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    Opioid Agonists

    BOXED WARNING

    Accidental exposure, ethanol ingestion, ethanol intoxication, parenteral administration, potential for overdose or poisoning, requires an experienced clinician

    Like all opioid analgesics, oxycodone is associated with significant potential for overdose or poisoning; proper patient selection and counseling is recommended. The extended-release formulations are not intended for use in the management of pain following surgery, acute pain, or on an as-needed basis; extended-release tablets or capsules are intended only for patients requiring continuous, around-the-clock opioid analgesia for an extended period of time and requires an experienced clinician who is knowledgeable in the use of long-acting opioids for the management of chronic pain. In pediatric patients >= 11 years, the extended-release tablet formulation should only be used in those who are already receiving opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for the 2 days immediately preceding initiation. Further, the misuse of oxycodone by crushing, chewing, snorting, or injecting the dissolved product (parenteral administration) poses a significant risk to the abuser and may result in overdose and death. Advise patients and caregivers to strictly adhere to the recommended dosing. Oxycodone should be kept out of the reach of pediatric patients, others for whom the drug was not prescribed, and pets as accidental exposure or improper use may cause respiratory failure and a fatal overdose. Consumption with ethanol will result in additive CNS depressant effects. Advise patients to avoid ethanol ingestion and ethanol intoxication, including the ingestion of alcohol contained in prescription or non-prescription medications, during therapy. Care should be taken to avoid dosing errors due to confusion between oxycodone oral solution 20 mg/mL and other lower concentrations; the 20 mg/mL concentration should not be used in opioid-naive patients, as a fatal overdose could occur.

    Alcoholism, depression, substance abuse

    Oxycodone is an opioid agonist and therefore has abuse potential and risk of fatal overdose from respiratory failure. Addiction may occur in patients who obtain oxycodone illicitly or in those appropriately prescribed the drug. The risk of addiction in any individual is unknown. However, patients with mental illness (e.g., major depression) or a family history of substance abuse (including alcoholism) have an increased risk of opioid abuse. Assess patients for risks of addiction, abuse, or misuse before drug initiation, and monitor patients who receive opioids routinely for development of these behaviors or conditions. A potential risk of abuse should not preclude appropriate pain management in any patient, but requires more intensive counseling and monitoring. Abuse and addiction are separate and distinct from physical dependence and tolerance; patients with addiction may not exhibit tolerance and symptoms of physical dependence. The misuse of oxycodone by crushing, chewing, snorting, or injecting the dissolved product can result in overdose and death. To discourage abuse, the smallest appropriate quantity of oxycodone should be dispensed, and proper disposal instructions for unused drug should be given to patients.

    Asthma, chronic obstructive pulmonary disease (COPD), coadministration with other CNS depressants, coma, cor pulmonale, hypoxemia, obesity, pulmonary disease, respiratory depression, respiratory insufficiency, scoliosis, sleep apnea, status asthma...

    Oxycodone use is contraindicated in patients with significant respiratory depression and in patients with acute or severe asthma (e.g., status asthmaticus) or hypercarbia in unmonitored care settings or in the absence of resuscitative equipment. Oxycodone immediate-release tablets, oral liquid, and capsules are specifically contraindicated in patients with hypercarbia; receipt of moderate oxycodone doses in these patients may significantly decrease pulmonary ventilation. Additionally, avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for respiratory depression, low blood pressure, and death. As with other opioid agonists, oxycodone should be avoided in patients with severe pulmonary disease. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to oxycodone, as even usual therapeutic doses may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Oxycodone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention; use of oxycodone extended-release tablets or capsules is not recommended in these patients. Respiratory depression, if left untreated, may cause respiratory arrest and death. Symptoms of respiratory depression include a reduced urge to breathe, a decreased respiratory rate, or deep breaths separated by long pauses (a "sighing" breathing pattern). Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Careful monitoring is required, particularly when CYP450 3A4 inhibitors or inducers are used concomitantly; concurrent use of a CYP3A4 inhibitor or discontinuation of a concurrently used CYP3A4 inducer may increase plasma oxycodone concentrations and potentiate the risk of fatal respiratory depression. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with oxycodone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep-apnea syndrome and/or decreased respiratory reserve. In these patients, opioid agonists should be used only under careful medical supervision at the lowest effective dose. Due to an unreasonable risk of fatal respiratory depression in patients who are not tolerant to opioids, 60 mg and 80 mg extended-release tablets are only for use in opioid tolerant patients; single extended-release tablet doses more than 40 mg and a total daily dose more than 80 mg are also only indicated in those who are opioid tolerant. Similarly, single extended-release capsule doses more than 36 mg and a total daily dose more than 72 mg are only indicated in patients who are opioid tolerant. In pediatric patients 11 years or older, the extended-release tablet should only be used in those who are already receiving opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for the 2 days immediately preceding initiation. Respiratory depression may persist for a significant period of time following the discontinuation of oxycodone controlled-release preparations, and patients require close monitoring until their respiratory rate has stabilized. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

    Opioid-naive patients, surgery

    To reduce the risk of life-threatening adverse effects, do not use oxycodone oral solution in 100 mg/5 mL (20 mg/mL) concentration and oxycodone extended-release 60 mg and 80 mg tablets in opioid-naive patients; these patients should also not receive a single dose of extended-release tablets more than 40 mg or a total daily dose more than 80 mg. Similarly, do not use a single dose of oxycodone extended-release capsules more than 36 mg or a total daily dose more than 72 mg in opioid-naive patients. Use great caution when prescribing all other formulations of oxycodone in non-tolerant patients. Adult patients who are opioid tolerant are those receiving at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, 60 mg oral hydrocodone/day, or an equianalgesic dose of another opioid for one week or longer. Further, oxycodone extended-release tablets are not indicated for pain in the immediate postoperative period (the first 12 to 24 hours following surgery) unless the patient is already receiving oxycodone extended-release therapy, or if the pain is expected to be moderate to severe and persist for an extended period of time. Extended-release tablets or capsules should also not be used for the treatment of mild pain or pain that is not expected to persist for an extended period of time, acute pain, or as an as-needed (prn) analgesic. Reserve use of the extended-release tablets or capsules for patients in whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Extended-release oxycodone tablets should only be used in opioid-tolerant pediatric patients 11 years or older who have received opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for 2 days immediately preceding dosing with extended-release oxycodone. The extended-release tablets must be swallowed whole and are not to be cut, broken, chewed, crushed, or dissolved. When the tablet is crushed or broken and/or if its contents are given by intravenous administration or snorted into the nostrils, the extended-release mechanism is defeated and a potentially lethal dose of oxycodone is immediately released.

    Labor, neonatal opioid withdrawal syndrome, obstetric delivery, pregnancy

    Pregnancy exposure data are insufficient to inform a drug-associated risk of birth defects or miscarriage with oxycodone. In animal studies with rats and rabbits, no embryo-fetal toxicity was detected when oxycodone was given during organogenesis at doses 0.5- to 15-times the adult human dose of 160 mg/day. In a pre- and post-natal study in rats, oxycodone given during gestation and lactation at a dose approximately 0.4 times an adult human dose of 160 mg/day was not associated with any long-term developmental or reproductive adverse effects in pups; however, pup weight was transiently decreased during lactation and the early post-weaning period. No drug-related effects on reproductive performance in female rats was observed. Published data with rats indicate that oxycodone may result in neurobehavioral effects, including altered stress response, increased anxiety-like behavior, and altered learning and memory, in offspring when given at clinically relevant doses and below. Oxycodone is not recommended for use in women during and immediately prior to labor and obstetric delivery because oral opioid agonists may cause respiratory depression in the newborn. Further, prolonged maternal use of long-acting opioids, such as oxycodone, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.

    DEA CLASS

    Rx, schedule II

    DESCRIPTION

    Phenanthrene opioid agonist
    For moderate to severe pain
    Some products are formulated to help deter abuse by inhalation or injection

    COMMON BRAND NAMES

    Dazidox, Endocodone, ETH-Oxydose, Oxaydo, OxyContin, Oxydose, OxyFast, OxyIR, Percolone, Roxicodone, XTAMPZA

    HOW SUPPLIED

    Dazidox/Endocodone/Oxaydo/Oxycodone/Oxycodone Hydrochloride/Percolone/Roxicodone Oral Tab: 5mg, 7.5mg, 10mg, 15mg, 20mg, 30mg
    ETH-Oxydose/Oxycodone/Oxycodone Hydrochloride/Oxydose/OxyFast/Roxicodone Oral Sol: 1mL, 5mg, 5mL, 20mg
    Oxycodone/Oxycodone Hydrochloride/OxyContin Oral Tab ER: 10mg, 15mg, 20mg, 30mg, 40mg, 60mg, 80mg
    Oxycodone/Oxycodone Hydrochloride/OxyIR Oral Cap: 5mg
    Oxycodone/XTAMPZA Oral Cap ER: 9mg, 13.5mg, 18mg, 27mg, 36mg

    DOSAGE & INDICATIONS

    For the relief of moderate pain to severe pain.
    For the treatment of acute and chronic moderate to severe pain.
    Oral dosage (immediate-release)
    Adults

    5 to 15 mg PO every 4 to 6 hours as needed for pain for opioid-naive patients. For conversion from other opioid therapy, factor the potency of the prior opioid relative to oxycodone into the selection of the total daily dose of oxycodone. The usual dose after titration is 10 to 30 mg PO every 4 hours as needed. In opioid-tolerant patients with chronic cancer pain, it is not unusual for patients to require doses of 20 to 45 mg PO every 4 hours, with some patients requiring as much as 120 mg PO every 4 hours.

    Children† and Adolescents† 5 years or older

    0.2 mg/kg PO given 30 minutes preprocedure reduced pain associated with wound care in children aged 5 to 14 years (16.6 to 56 kg); the oxycodone regimen was compared to an oral transmucosal fentanyl regimen. As rated by the children, pain scores were not significantly different between the 2 treatment groups before drug receipt, immediately before wound care, or at the end of wound care. Both drugs were well tolerated. 0.2 mg/kg PO then 0.1 to 0.3 mg/kg PO every 3 to 4 hours has been used successfully for acute bone fracture pain management.

    For the management of chronic severe pain in patients who require daily, around-the-clock, long-term opioid treatment.
    NOTE: Extended-release oxycodone should be reserved for patients in whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would otherwise provide inadequate pain management. Discontinue all other around-the-clock opioid drugs upon initiation of oxycodone extended-release tablets.
    NOTE: Extended-release oxycodone 60 or 80 mg tablets, a single tablet dose more than 40 mg, or a total tablet daily dose more than 80 mg should be reserved for opioid-tolerant patients. A single extended-release oxycodone capsule dose of 36 mg (equivalent to 40 mg oxycodone hydrochloride) or more or a total capsule daily dose of 72 mg (equivalent to 80 mg oxycodone hydrochloride) or more should be reserved for opioid-tolerant patients. Adult patients who are opioid tolerant are those receiving, for a minimum of 1 week, 60 mg or more oral morphine daily, 30 mg or more oral oxycodone daily, 8 mg or more oral hydromorphone daily, 25 mg or more oral oxymorphone daily, 25 mcg or more transdermal fentanyl per hour, 60 mg or more oral hydrocodone per day, or an equivalent dose of another opioid. Extended-release oxycodone tablets should only be used in pediatric patients 11 years or older receiving opioids for at least 5 consecutive days and taking a minimum of 20 mg per day of oxycodone or its equivalent for 2 days immediately preceding dosing with extended-release oxycodone.
    Oral dosage (extended-release tablet, Oxycontin or generic equivalents) for use as the first opioid analgesic or in patients who are not opioid-tolerant
    Adults

    10 mg PO every 12 hours. Reduce the starting dose to one-third to one-half the usual dosage in debilitated, nonopioid-tolerant patients and those receiving concomitant central nervous system depressants. Titrate the total daily oxycodone dose by 25% to 50% every 1 to 2 days.

    Oral dosage (extended-release tablet, Oxycontin or generic equivalents) for conversion from other oral oxycodone formulations
    Adults

    Convert to an equivalent total daily oxycodone dose and divide the 24-hour oxycodone requirements into 2 equal doses given PO every 12 hours. Titrate the total daily oxycodone dose by 25% to 50% every 1 to 2 days.

    Children and Adolescents 11 years or older

    Use only in patients receiving opioids for 5 or more consecutive days and taking 20 mg/day or more of oxycodone or its equivalent for 2 days immediately preceding dosing. Convert to an equivalent total daily oxycodone dose and divide the 24-hour oxycodone requirements into 2 equal doses given PO every 12 hours. If rounding is necessary, always round the dose down to the nearest available tablet strength. If the calculated dose is less than 20 mg/dose, there is no safe strength for conversion; do not initiate extended-release oxycodone. Titrate the total daily oxycodone dose by 25% every 1 to 2 days as needed.

    Oral dosage (extended-release tablet, Oxycontin or generic equivalents) for conversion from fentanyl transdermal patch
    Adults

    10 mg PO every 12 hours for each 25 mcg/hour fentanyl transdermal patch beginning 18 hours after removal of the fentanyl transdermal patch. Titrate the total daily oxycodone dose by 25% to 50% every 1 to 2 days.

    Children and Adolescents 11 years or older

    Limited data in pediatric patients. Use only in patients receiving opioids for 5 or more consecutive days and taking 20 mg/day or more of oxycodone equivalent for 2 days immediately preceding dosing. 10 mg PO every 12 hours for each 25 mcg/hour fentanyl transdermal patch beginning at least 18 hours after removal of the fentanyl transdermal patch. If rounding is necessary, always round the dose down to the nearest available tablet strength. If the calculated dose is less than 20 mg/dose, there is no safe strength for conversion; do not initiate extended-release oxycodone. Titrate the total daily oxycodone dose by 25% every 1 to 2 days.

    Oral dosage (extended-release tablet, Oxycontin or generic equivalents) for conversion from other opioid agonist analgesics
    Adults

    10 mg PO every 12 hours. Titrate the total daily oxycodone dose by 25% to 50% every 1 to 2 days. Use extreme caution when converting patients from methadone as the ratio between methadone and other opioid agonists can vary widely.

    Children and Adolescents 11 years or older

    Use only in patients receiving opioids for 5 or more consecutive days and taking 20 mg/day or more of oxycodone or its equivalent for 2 days immediately preceding dosing. To convert to extended-release oxycodone, calculate the 24-hour opioid requirement and multiply this amount by the conversion factor provided in the FDA-approved labeling. The conversion factors are as follows: 0.9 for oral hydrocodone, 4 for oral hydromorphone, 20 for parenteral hydromorphone, 0.5 for oral morphine, 3 for parenteral morphine, 0.17 for oral tramadol, and 0.2 for parenteral tramadol. For patients receiving high-dose parenteral opioids, a more conservative conversion is warranted; for example, use a conversion factor of 1.5 instead of 3 for patients receiving high-dose parenteral morphine. Divide the calculated total daily dose into 2 equal doses given PO every 12 hours. If rounding is necessary, always round the dose down to the nearest available tablet strength. If the calculated dose is less than 20 mg/dose, there is no safe strength for conversion; do not initiate extended-release oxycodone. Titrate the total daily oxycodone dose by 25% every 1 to 2 days.

    Oral dosage (extended-release capsule, Xtampza ER) for use as the first opioid analgesic or in patients who are not opioid-tolerant
    Adults

    9 mg PO every 12 hours. Titrate the total daily oxycodone dose by 25% to 50% every 1 to 2 days. Use an alternate analgesic for patients who require a dose less than 9 mg.

    Oral dosage (extended-release capsule, Xtampza ER) for conversion from other oral oxycodone formulations
    Adults

    Convert to an equivalent total daily oxycodone dose and divide the 24-hour oxycodone requirements into 2 equal doses given PO every 12 hours. Titrate the total daily oxycodone dose by 25% to 50% every 1 to 2 days. Because extended-release capsules are not bioeqivalent to other extended-release oxycodone products, monitor patients for possible dosage adjustment. Use an alternate analgesic for patients who require a dose less than 9 mg.

    Oral dosage (extended-release capsule, Xtampza ER) for conversion from fentanyl transdermal patch
    Adults

    9 mg PO every 12 hours for each 25 mcg/hour fentanyl transdermal patch beginning 18 hours after removal of the fentanyl transdermal patch. Titrate the total daily oxycodone dose by 25% to 50% every 1 to 2 days. Use an alternate analgesic for patients who require a dose less than 9 mg.

    Oral dosage (extended-release capsule, Xtampza ER) for conversion from other opioid agonist analgesics
    Adults

    9 mg PO every 12 hours. Titrate the total daily oxycodone dose by 25% to 50% every 1 to 2 days. Use extreme caution when converting patients from methadone as the ratio between methadone and other opioid agonists can vary widely. Use an alternate analgesic for patients who require a dose less than 9 mg.

    For the treatment of painful diabetic neuropathy†.
    Oral dosage (extended-release tablets, e.g., Oxycontin or generic equivalent)
    Adults

    10 mg PO every 12 hours initially. Titrate dosage every 2—7 days up to a maximum of 120 mg/day PO, given in divided doses. The American Academy of Neurology guidelines consider extended-release oxycodone as probably effective in lessening the pain of diabetic neuropathy.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Immediate-release dosage forms, extended-release tablets: There is no maximum dose of oxycodone; however, careful titration of oxycodone, especially in opiate-naive patients, is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.
    Extended-release capsules (Xtampza ER): 288 mg/day PO (equivalent to 320 mg/day oxycodone hydrochloride).

    Geriatric

    Immediate-release dosage forms, extended-release tablets: There is no maximum dose of oxycodone; however, careful titration of oxycodone, especially in opiate-naive patients, is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.
    Extended-release capsules (Xtampza ER): 288 mg/day PO (equivalent to 320 mg/day oxycodone hydrochloride).

    Adolescents

    Extended-release tablets: With appropriate dosage titration, there is no maximum dose of extended-release oxycodone in opioid-tolerant pediatric patients; however, careful titration is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.
    Immediate-release dosage forms and extended-release capsules (Xtampza ER): Safety and efficacy have not been established.

    Children

    Extended-release tablets in Children 11 years or older: With appropriate dosage titration, there is no maximum dose of extended-release oxycodone in opioid-tolerant pediatric patients; however, careful titration is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.
    Extended-release tablets in Children younger than 11 years, immediate-release dosage forms, and extended-release capsules (Xtampza ER): Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Start initial therapy at one-third to one-half the normal dose and titrate dose carefully. Patients with hepatic impairment have higher plasma oxycodone and noroxycodone and lower oxymorphone concentrations than those with normal hepatic function.

    Renal Impairment

    Conservative initial dose and dose titration are required. Dosage should be modified depending on clinical response and degree of renal impairment. In patients with CrCl < 60 mL/minute, the serum concentration of oxycodone is about 50% higher than in patients with normal renal function.

    ADMINISTRATION

    Oral Administration

    Oxycodone should be titrated from the initial recommended dosage to the dose required to relieve the patient's pain and minimize adverse reactions.
    There is no maximum dose of oxycodone; however, careful titration is required to avoid adverse reactions (i.e., drowsiness and respiratory depression).

    Oral Solid Formulations

    Immediate-release tablets:
    May be administered with food or milk to minimize GI irritation.
    Oxecta and Oxaydo brand tablets: Swallow whole; do not crush or dissolve. Do not pre-soak, lick, or otherwise wet tablet prior to dose administration. Administer 1 tablet at a time; allow patient to swallow each tablet separately with sufficient liquid to ensure prompt and complete transit through the esophagus. Do not use this brand for administration via nasogastric, gastric, or other feeding tubes as it may cause obstruction of feeding tubes. 
     
    Extended-release tablets (e.g., OxyContin):
    Administer whole; do not crush, chew, cut, dissolve, or break in half. Taking chewed, broken, cut, dissolved, or crushed extended-release tablets could lead to the rapid release and absorption of a potentially fatal dose of oxycodone.
    OxyContin brand tablets: Do not pre-soak, lick, or otherwise wet tablet prior to dose administration. Administer 1 tablet at a time; allow patient to swallow each tablet separately with sufficient liquid to ensure prompt and complete transit through the esophagus.
    May be administered with or without food.
    Take with a full glass of water to ensure complete swallowing.
    In general, administer one-half of the patient's total daily dose every 12 hours. If asymmetric dosing is necessary, instruct patient to take the higher dose in the morning.
    Extended-release 60 mg and 80 mg tablets are for use ONLY in opioid-tolerant patients.
    Monitor patients closely for respiratory depression, particularly within the first 24 to 72 hours after initiation or dose escalation.
     
    Extended-release capsules (Xtampza ER):
    Always take with food and with approximately the same amount of food in order to ensure consistent plasma concentrations.
    The capsule contents may be taken by sprinkling the contents onto soft foods (e.g., applesauce, pudding, yogurt, ice cream, or jam) or into a cup and then giving directly into the mouth. Swallow immediately and rinse mouth to ensure all capsule contents have been swallowed. Discard capsule shells following administration.
    The capsule contents may be given through a nasogastric or gastrostomy tube. Flush the tube with water. Open a capsule and pour the contents directly into the tube. Do not pre-mix capsule contents with the liquid that will be used to flush the tube. Draw up 15 mL of water into a syringe, insert the syringe into the tube, and flush the contents through the tube. Repeat flushing twice using 10 mL of water with each flush. Milk or liquid nutritional supplement may be used as an alternative to water when flushing capsule contents through the tube.
    Extended-release 36 mg capsules are for use ONLY in opioid-tolerant patients.
    Monitor patients closely for respiratory depression, particularly within the first 24 to 72 hours after initiation or dose escalation.

    Oral Liquid Formulations

    Oral concentrate solution:
    Always use an enclosed oral syringe when administering the highly concentrated solution (20 mg/mL); care should be taken in dispensing and administering this medication.
    For ease of administration, Oxyfast concentrated 20 mg/mL solution may be added to 30 mL of a liquid or semi-solid food. If the medication is placed in liquid or food, the patient needs to immediately consume; do not store diluted oxycodone for future use.

    STORAGE

    Dazidox :
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Endocodone :
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    ETH-Oxydose:
    - Do not freeze
    - Store between 68 to 77 degrees F
    Oxaydo:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    OXECTA:
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    OxyContin:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Oxydose :
    - Do not freeze
    - Store between 68 to 77 degrees F
    OxyFast:
    - Do not freeze
    - Store between 68 to 77 degrees F
    OxyIR:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Percolone:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Roxicodone:
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    XTAMPZA :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Accidental exposure, ethanol ingestion, ethanol intoxication, parenteral administration, potential for overdose or poisoning, requires an experienced clinician

    Like all opioid analgesics, oxycodone is associated with significant potential for overdose or poisoning; proper patient selection and counseling is recommended. The extended-release formulations are not intended for use in the management of pain following surgery, acute pain, or on an as-needed basis; extended-release tablets or capsules are intended only for patients requiring continuous, around-the-clock opioid analgesia for an extended period of time and requires an experienced clinician who is knowledgeable in the use of long-acting opioids for the management of chronic pain. In pediatric patients >= 11 years, the extended-release tablet formulation should only be used in those who are already receiving opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for the 2 days immediately preceding initiation. Further, the misuse of oxycodone by crushing, chewing, snorting, or injecting the dissolved product (parenteral administration) poses a significant risk to the abuser and may result in overdose and death. Advise patients and caregivers to strictly adhere to the recommended dosing. Oxycodone should be kept out of the reach of pediatric patients, others for whom the drug was not prescribed, and pets as accidental exposure or improper use may cause respiratory failure and a fatal overdose. Consumption with ethanol will result in additive CNS depressant effects. Advise patients to avoid ethanol ingestion and ethanol intoxication, including the ingestion of alcohol contained in prescription or non-prescription medications, during therapy. Care should be taken to avoid dosing errors due to confusion between oxycodone oral solution 20 mg/mL and other lower concentrations; the 20 mg/mL concentration should not be used in opioid-naive patients, as a fatal overdose could occur.

    Acute abdomen, constipation, diarrhea, diverticulitis, dysphagia, esophageal stricture, gastric cancer, GI disease, GI obstruction, ileus, inflammatory bowel disease, ulcerative colitis

    Oxycodone is contraindicated in patients who have or are suspected of having paralytic ileus. Use of oxycodone extended-release tablets or capsules is contraindicated in patients with any type of GI obstruction, and other dosage forms of oxycodone should be avoided in these conditions. Due to the effects of opioid agonists on the gastrointestinal tract, oxycodone should be used cautiously in patients with GI disease such as ulcerative colitis (UC). Patients with UC or other inflammatory bowel disease may be more sensitive to constipation caused by opioid agonists. Rarely, intestinal obstruction and exacerbation of diverticulitis requiring surgical intervention to remove the tablet has been reported with OxyContin tablets. Patients at greatest risk of developing these complications include those with underlying GI disease such as gastric cancer (i.e., esophageal cancer or colon cancer with small gastrointestinal lumen); use of alternative analgesics should be considered in these patients. Use the extended-release tablets and Oxecta brand tablets with caution in patients with pre-existing esophageal stricture or dysphagia, as the tablets may swell when exposed to liquids including saliva; choking, gagging, and related events have been reported with post-market use. Choking, gagging, regurgitation, and tablets getting stuck in the throat have also occurred with OxyContin; do not pre-soak, lick, or wet the tablet prior to ingestion. Do not use Oxecta brand immediate-release products in nasogastric, gastric, or other feeding tubes as obstruction may occur; never crush, cut, chew, break, or dissolve extended-release tablets. Opioid agonists may obscure the diagnosis or clinical course in patients with an acute abdomen. Opioid agonists may exacerbate cases of diarrhea secondary to poisoning or infectious diarrhea, as a reduction in GI motility may occur with use. Antimotility agents have been used successfully in these patients. If possible, opioid agonists should not be given until the toxic substance has been eliminated.

    Alcoholism, depression, substance abuse

    Oxycodone is an opioid agonist and therefore has abuse potential and risk of fatal overdose from respiratory failure. Addiction may occur in patients who obtain oxycodone illicitly or in those appropriately prescribed the drug. The risk of addiction in any individual is unknown. However, patients with mental illness (e.g., major depression) or a family history of substance abuse (including alcoholism) have an increased risk of opioid abuse. Assess patients for risks of addiction, abuse, or misuse before drug initiation, and monitor patients who receive opioids routinely for development of these behaviors or conditions. A potential risk of abuse should not preclude appropriate pain management in any patient, but requires more intensive counseling and monitoring. Abuse and addiction are separate and distinct from physical dependence and tolerance; patients with addiction may not exhibit tolerance and symptoms of physical dependence. The misuse of oxycodone by crushing, chewing, snorting, or injecting the dissolved product can result in overdose and death. To discourage abuse, the smallest appropriate quantity of oxycodone should be dispensed, and proper disposal instructions for unused drug should be given to patients.

    Asthma, chronic obstructive pulmonary disease (COPD), coadministration with other CNS depressants, coma, cor pulmonale, hypoxemia, obesity, pulmonary disease, respiratory depression, respiratory insufficiency, scoliosis, sleep apnea, status asthma...

    Oxycodone use is contraindicated in patients with significant respiratory depression and in patients with acute or severe asthma (e.g., status asthmaticus) or hypercarbia in unmonitored care settings or in the absence of resuscitative equipment. Oxycodone immediate-release tablets, oral liquid, and capsules are specifically contraindicated in patients with hypercarbia; receipt of moderate oxycodone doses in these patients may significantly decrease pulmonary ventilation. Additionally, avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for respiratory depression, low blood pressure, and death. As with other opioid agonists, oxycodone should be avoided in patients with severe pulmonary disease. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to oxycodone, as even usual therapeutic doses may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Oxycodone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention; use of oxycodone extended-release tablets or capsules is not recommended in these patients. Respiratory depression, if left untreated, may cause respiratory arrest and death. Symptoms of respiratory depression include a reduced urge to breathe, a decreased respiratory rate, or deep breaths separated by long pauses (a "sighing" breathing pattern). Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Careful monitoring is required, particularly when CYP450 3A4 inhibitors or inducers are used concomitantly; concurrent use of a CYP3A4 inhibitor or discontinuation of a concurrently used CYP3A4 inducer may increase plasma oxycodone concentrations and potentiate the risk of fatal respiratory depression. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with oxycodone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep-apnea syndrome and/or decreased respiratory reserve. In these patients, opioid agonists should be used only under careful medical supervision at the lowest effective dose. Due to an unreasonable risk of fatal respiratory depression in patients who are not tolerant to opioids, 60 mg and 80 mg extended-release tablets are only for use in opioid tolerant patients; single extended-release tablet doses more than 40 mg and a total daily dose more than 80 mg are also only indicated in those who are opioid tolerant. Similarly, single extended-release capsule doses more than 36 mg and a total daily dose more than 72 mg are only indicated in patients who are opioid tolerant. In pediatric patients 11 years or older, the extended-release tablet should only be used in those who are already receiving opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for the 2 days immediately preceding initiation. Respiratory depression may persist for a significant period of time following the discontinuation of oxycodone controlled-release preparations, and patients require close monitoring until their respiratory rate has stabilized. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

    Opioid-naive patients, surgery

    To reduce the risk of life-threatening adverse effects, do not use oxycodone oral solution in 100 mg/5 mL (20 mg/mL) concentration and oxycodone extended-release 60 mg and 80 mg tablets in opioid-naive patients; these patients should also not receive a single dose of extended-release tablets more than 40 mg or a total daily dose more than 80 mg. Similarly, do not use a single dose of oxycodone extended-release capsules more than 36 mg or a total daily dose more than 72 mg in opioid-naive patients. Use great caution when prescribing all other formulations of oxycodone in non-tolerant patients. Adult patients who are opioid tolerant are those receiving at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, 60 mg oral hydrocodone/day, or an equianalgesic dose of another opioid for one week or longer. Further, oxycodone extended-release tablets are not indicated for pain in the immediate postoperative period (the first 12 to 24 hours following surgery) unless the patient is already receiving oxycodone extended-release therapy, or if the pain is expected to be moderate to severe and persist for an extended period of time. Extended-release tablets or capsules should also not be used for the treatment of mild pain or pain that is not expected to persist for an extended period of time, acute pain, or as an as-needed (prn) analgesic. Reserve use of the extended-release tablets or capsules for patients in whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Extended-release oxycodone tablets should only be used in opioid-tolerant pediatric patients 11 years or older who have received opioids for at least 5 consecutive days and are taking a minimum of 20 mg/day of oxycodone or its equivalent for 2 days immediately preceding dosing with extended-release oxycodone. The extended-release tablets must be swallowed whole and are not to be cut, broken, chewed, crushed, or dissolved. When the tablet is crushed or broken and/or if its contents are given by intravenous administration or snorted into the nostrils, the extended-release mechanism is defeated and a potentially lethal dose of oxycodone is immediately released.

    Dental work

    Patients who are taking oxycodone as part of ongoing analgesia therapy may be safely continued on the drug following surgery or dental work, if appropriate dosage adjustments are made considering the procedure, other drugs given, and temporary changes in physiology caused by the surgical intervention. Monitor for decreased bowel motility in postoperative patients receiving opiate agonists.

    Biliary tract disease, pancreatitis

    As with other opiate agonists, oxycodone may cause spasm of the sphincter of Oddi. Biliary effects due to opiate agonists have resulted in plasma amylase and lipase concentrations up to 2—15 times the normal values. Oxycodone should be used with caution in patients with biliary tract disease, including pancreatitis, or undergoing biliary tract surgery.

    Abrupt discontinuation

    Abrupt discontinuation of prolonged oxycodone therapy can result in withdrawal symptoms. Gradually taper patients off prolonged oxycodone therapy to avoid a withdrawal reaction. Generally, oxycodone therapy can be decreased by 25% to 50% per day with careful monitoring. Avoid use of partial agonists (e.g., buprenorphine), mixed agonist/antagonists (e.g., nalbuphine) or pure antagonists (e.g., naloxone) in patients physically dependent on opioids, as an acute withdrawal syndrome may precipitate. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and on the administered dose of the concomitant drug. If treatment of respiratory depression in an individual physically dependent on opioids is necessary, administer the opioid antagonist with extreme care; titrate the antagonist dose by using smaller than usual doses. In addition, the use of partial agonists or mixed agonist/antagonists in patients who have received or are receiving oxycodone should be avoided as these medications may reduce the analgesic effect of oxycodone.

    CNS depression, head trauma, increased intracranial pressure, intracranial mass, psychosis

    Use oxycodone with caution in patients with CNS depression, toxic psychosis, head trauma, intracranial mass, or increased intracranial pressure. Monitor for signs of drowsiness and depressed respirations, particularly when initiating oxycodone. Opioids may aggravate such conditions and alter neurologic parameters (e.g., level of consciousness, pupillary responses). Oxycodone-induced hypoventilation can produce cerebral hypoxia, carbon dioxide retention, and raise CSF pressure. Avoid the use of oxycodone in patients with impaired consciousness.

    Angina, cardiac arrhythmias, cardiac disease, dehydration, heart failure, hypotension, hypovolemia, orthostatic hypotension, shock

    Opioid agonists, such as oxycodone, produce cholinergic side effects (by stimulating medullary vagal nuclei) causing bradycardia and vasovagal syncope, and induce the release of histamine. In patients who are unable to maintain blood pressure due to hypovolemia or dehydration, or in those who concurrently receive other agents that compromise vasomotor tone (e.g., phenothiazines or general anesthetics), opioid agonists may induce peripheral vasodilatation and severe hypotension. These effects can cause problems in patients with cardiac disease (e.g., angina, heart failure). Oxycodone should be used with caution in patients with cardiac arrhythmias or orthostatic hypotension. Extended-release tablets and capsules should not be used in patients with circulatory shock; caution should be exercised if other dosage forms are used. Monitor patients for hypotension following oxycodone initiation and dose titrations.

    Bladder obstruction, hepatic disease, oliguria, prostatic hypertrophy, renal disease, renal failure, renal impairment, urethral stricture, urinary retention

    Oxycodone and other opioid agonists can cause urinary retention and oliguria, due to increasing the tension of the detrusor muscle. Patients more prone to these effects include those with prostatic hypertrophy, urethral stricture, bladder obstruction, pelvic tumors, or renal disease. Drug accumulation or prolonged duration of action may occur in patients with renal failure or hepatic disease. In acute situations, patients require close monitoring to avoid excessive toxicity. In patients with renal impairment (creatinine clearance < 60 mL/minute), the concentrations of oxycodone are approximately 50% higher than patients with normal renal function. Dose initiation in these patients should be conservative and dosage adjustments based on individual patient response. In patients with hepatic impairment, oxycodone therapy should be initiated at doses one-third to one-half the usual dose and careful dose titration is warranted.

    Seizure disorder, seizures

    Seizures can be precipitated by opiate agonists in patients with a preexisting seizure disorder. The incidence of these effects during oxycodone therapy is not known, but appears to be rare at normal doses. Monitor patients with a history of seizure disorders for worsened seizure control during therapy.

    Geriatric

    Use oxycodone with caution in geriatric or debilitated patients. Geriatric or debilitated patients are more susceptible to adverse reactions, especially sedation and respiratory depression, probably as a result of altered distribution of the drug and decreased elimination. Initial doses may need to be reduced, and dosages should be carefully titrated taking into account analgesic effects, adverse reactions, and concomitant drugs that may depress respiration. When using the extended-release tablets, reduce the starting dose to one-third to one-half the usual dosage in debilitated, non-opioid tolerant patients. According to the Beers Criteria, opioid agonists are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, with the exception of pain management due to recent fractures or joint replacement, since opioids can produce ataxia, impaired psychomotor function, syncope, and additional falls. If an opioid must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. Individuals receiving palliative care or those in hospice settings are excluded from the Beers Criteria; the balance of benefits and harms of medication management for these patients may differ from those of the general population of older adults.

    Children, infants, neonates

    Opiate agonists may be used in children for moderate to severe pain; however, all formulations of oxycodone should be used with caution in children. Immediate-release formulations have not been FDA-approved in neonates, infants, children, or adolescents. Oxycodone extended-release tablets are one of the few long-acting opioid products labeled for pediatric use; use may be considered in opioid tolerant patients >= 11 years who have received opioids for at least 5 consecutive days and are taking a minimum of 20 mg per day of oxycodone or its equivalent for 2 days immediately preceding extended-release oxycodone initiation. It must be remembered that these tablets cannot be crushed or broken for administration. If the calculated oxycodone dose does not coincide with an available tablet size, the dose should always rounded down to the nearest available tablet strength. If the calculated dose is less than 20 mg/dose, there is no safe strength for conversion and the patient should not be initiated on extended-release oxycodone. Accidental ingestion or unintended exposure by children can be fatal. Instruct patients and caregivers to keep all oxycodone dosage forms out of the reach of children and to properly discard all unneeded product. Neonates and infants < 6 months of age have highly variable clearance of opiate agonists. Therefore, infants younger than 6 months of age given opiate agonists must be closely monitored for apnea until 24 hours after their last dose. Clinical practice guidelines suggest close monitoring of children up to 1 year of age.

    Labor, neonatal opioid withdrawal syndrome, obstetric delivery, pregnancy

    Pregnancy exposure data are insufficient to inform a drug-associated risk of birth defects or miscarriage with oxycodone. In animal studies with rats and rabbits, no embryo-fetal toxicity was detected when oxycodone was given during organogenesis at doses 0.5- to 15-times the adult human dose of 160 mg/day. In a pre- and post-natal study in rats, oxycodone given during gestation and lactation at a dose approximately 0.4 times an adult human dose of 160 mg/day was not associated with any long-term developmental or reproductive adverse effects in pups; however, pup weight was transiently decreased during lactation and the early post-weaning period. No drug-related effects on reproductive performance in female rats was observed. Published data with rats indicate that oxycodone may result in neurobehavioral effects, including altered stress response, increased anxiety-like behavior, and altered learning and memory, in offspring when given at clinically relevant doses and below. Oxycodone is not recommended for use in women during and immediately prior to labor and obstetric delivery because oral opioid agonists may cause respiratory depression in the newborn. Further, prolonged maternal use of long-acting opioids, such as oxycodone, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.

    Breast-feeding

    Oxycodone is distributed into breast milk at varying degrees depending upon the dose. There is no information available on the effects of oxycodone on milk production. Because of the potential for serious adverse reactions in nursing infants, such as respiratory depression, sedation, and withdrawal symptoms upon cessation by the mother, breast-feeding is not recommended during treatment with oxycodone. As with all opioid-containing products, if oxycodone is used by a breast-feeding mother, the infant should be monitored for sedation, respiratory depression, and changes in feeding patterns. A retrospective study compared central nervous system (CNS) depression in breast-feeing infants of mothers receiving oxycodone (n = 139), codeine (n = 210), or acetaminophen (n = 184). Symptoms of CNS depression were determined through questionnaires completed by the mothers. CNS depression was significantly higher in breast-fed infants exposed to oxycodone compared to acetaminophen (20.1% vs. 0.5%, p < 0.0001) and was not significantly different compared to infants exposed to codeine (16.7%, p > 0.05). The doses of both oxycodone and codeine in the mothers with infants that experienced symptoms were significantly higher compared to those that did not (oxycodone median 0.4 mg/kg/day vs. 0.15 mg/kg/day, p = 0.0005; codeine median 1.4 mg/kg/day vs. 0.9 mg/kg/day, p < 0.001).

    Infertility, reproductive risk

    Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression) and pose a reproductive risk. Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence, amenorrhea, or infertility. It is not known whether the effects on fertility are reversible.

    Driving or operating machinery

    Any patient receiving oxycodone should be warned about the possibility of sedation and to use caution when driving or operating machinery.

    Latex hypersensitivity, opiate agonist hypersensitivity

    Although true opiate agonist hypersensitivity is rare, use of oxycodone is contraindicated in patients with a history of oxycodone hypersensitivity. Use this medication with caution, if at all, in patients who have demonstrated a prior hypersensitivity reaction to other opioid agonists of the phenanthrene subclass including morphine, codeine and hydromorphone. It may be possible to treat these patients with an opioid agonist from the phenylpiperidine subclass (meperidine or fentanyl) or the diphenylheptane subclass (methadone). Patients with latex hypersensitivity should not handle the dropper that comes with the OxyFast product. The dropper contains dry natural rubber.

    Adrenal insufficiency, hypothyroidism, myxedema

    Use oxycodone with caution in patients with adrenal insufficiency (i.e., Addison's disease), hypothyroidism, or myxedema. Such patients may be at increased risk of adverse events. Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH); however, the thyroid stimulating hormone may be either stimulated or inhibited by opioids. Rarely, adrenal insufficiency has been reported in association with opioid use. Patients should seek immediate medical attention if they experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or hypotension. If adrenocortical insufficiency is suspected, confirm with diagnostic testing as soon as possible. If diagnosed, the patient should be treated with physiologic replacement doses of corticosteroids, and if appropriate, weaned off of opioid therapy. If the opioid can be discontinued, a follow-up assessment of adrenal function should be performed to determine if corticosteroid treatment can be discontinued. Other opioids may be tried; some cases reported use of a different opioid with no recurrence of adrenocortical insufficiency. It is unclear which, if any, opioids are more likely to cause adrenocortical insufficiency. In addition, chronic opioid use may lead to symptoms of hypogonadism, resulting from changes in the hypothalamic-pituitary-gonadal axis. Monitor patients for symptoms of opioid-induced endocrinopathy, particularly those receiving a daily dose equivalent to 100 mg or more of morphine. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.

    ADVERSE REACTIONS

    Severe

    thrombosis / Delayed / 0-3.0
    heart failure / Delayed / 0-3.0
    apnea / Delayed / 0-3.0
    laryngospasm / Rapid / 0-3.0
    bone fractures / Delayed / 0-3.0
    seizures / Delayed / 0-1.0
    exfoliative dermatitis / Delayed / 0-1.0
    ileus / Delayed / Incidence not known
    neonatal abstinence syndrome / Early / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    biliary obstruction / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    SIADH / Delayed / Incidence not known
    cardiac arrest / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    respiratory arrest / Rapid / Incidence not known
    GI obstruction / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 3.0-23.0
    gastritis / Delayed / 1.0-5.0
    withdrawal / Early / 0-5.0
    depression / Delayed / 0-5.0
    dysphoria / Early / 1.0-5.0
    confusion / Early / 0-5.0
    migraine / Early / 0-5.0
    euphoria / Early / 1.0-5.0
    hypochloremia / Delayed / 1.0-5.0
    hyponatremia / Delayed / 1.0-5.0
    edema / Delayed / 0-5.0
    orthostatic hypotension / Delayed / 1.0-5.0
    sinus tachycardia / Rapid / 0-5.0
    hypertension / Early / 1.0-5.0
    blurred vision / Early / 0-5.0
    urinary retention / Early / 0-5.0
    dyspnea / Early / 0-5.0
    neutropenia / Delayed / 1.0-5.0
    thrombocytopenia / Delayed / 1.0-5.0
    dysuria / Early / 0-5.0
    hyperglycemia / Delayed / 0-5.0
    glossitis / Early / 0-3.0
    peripheral vasodilation / Rapid / 0-3.0
    peripheral edema / Delayed / 0-3.0
    bleeding / Early / 0-3.0
    hypotension / Rapid / 0-3.0
    palpitations / Early / 0-3.0
    hypertonia / Delayed / 0-3.0
    dysphagia / Delayed / 0-3.0
    gout / Delayed / 0-3.0
    bone pain / Delayed / 0-3.0
    leukopenia / Delayed / 0-3.0
    anemia / Delayed / 0-3.0
    amblyopia / Delayed / 0-3.0
    stomatitis / Delayed / 0-1.0
    hypotonia / Delayed / 0-1.0
    amnesia / Delayed / 0-1.0
    hallucinations / Early / 0-1.0
    ataxia / Delayed / 0-1.0
    dysphonia / Delayed / 0-1.0
    hyperesthesia / Delayed / 0-1.0
    impotence (erectile dysfunction) / Delayed / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    dehydration / Delayed / 0-1.0
    lymphadenopathy / Delayed / 0-1.0
    hematuria / Delayed / 0-1.0
    tolerance / Delayed / Incidence not known
    psychological dependence / Delayed / Incidence not known
    physiological dependence / Delayed / Incidence not known
    hyperalgesia / Delayed / Incidence not known
    impaired cognition / Early / Incidence not known
    respiratory depression / Rapid / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    infertility / Delayed / Incidence not known
    adrenocortical insufficiency / Delayed / Incidence not known
    myoclonia / Delayed / Incidence not known

    Mild

    nausea / Early / 0-23.0
    drowsiness / Early / 3.0-23.0
    vomiting / Early / 0-21.0
    fever / Early / 1.0-11.0
    diarrhea / Early / 0-6.0
    xerostomia / Early / 0-6.0
    asthenia / Delayed / 1.0-6.0
    abdominal pain / Early / 0-5.0
    anorexia / Delayed / 0-5.0
    dyspepsia / Early / 0-5.0
    gastroesophageal reflux / Delayed / 1.0-5.0
    hiccups / Early / 1.0-5.0
    anxiety / Delayed / 0-5.0
    hypoesthesia / Delayed / 0-5.0
    paresthesias / Delayed / 0-5.0
    agitation / Early / 0-5.0
    rash (unspecified) / Early / 0-5.0
    hyperhidrosis / Delayed / 1.0-5.0
    flushing / Rapid / 1.0-5.0
    tremor / Early / 0-5.0
    chills / Rapid / 1.0-5.0
    diaphoresis / Early / 5.0-5.0
    irritability / Delayed / 1.0-5.0
    fatigue / Early / 1.0-5.0
    cough / Delayed / 0-5.0
    arthralgia / Delayed / 0-5.0
    musculoskeletal pain / Early / 1.0-5.0
    myalgia / Early / 0-5.0
    back pain / Delayed / 0-5.0
    gingivitis / Delayed / 0-3.0
    rhinitis / Early / 0-3.0
    epistaxis / Delayed / 0-3.0
    sinusitis / Delayed / 0-3.0
    pharyngitis / Delayed / 0-3.0
    infection / Delayed / 0-3.0
    photosensitivity / Delayed / 0-3.0
    appetite stimulation / Delayed / 0-1.0
    flatulence / Early / 0-1.0
    eructation / Early / 0-1.0
    restlessness / Early / 0-1.0
    hyperkinesis / Delayed / 0-1.0
    lethargy / Early / 0-1.0
    vertigo / Early / 0-1.0
    emotional lability / Early / 0-1.0
    dysgeusia / Early / 0-1.0
    syncope / Early / 0-1.0
    malaise / Early / 0-1.0
    night sweats / Early / 0-1.0
    tinnitus / Delayed / 0-1.0
    polyuria / Early / 0-1.0
    xerosis / Delayed / 0-1.0
    dizziness / Early / 3.0
    insomnia / Early / 1.0
    headache / Early / 3.0
    pruritus / Rapid / 2.6
    miosis / Early / 10.0
    dental caries / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    gonadal suppression / Delayed / Incidence not known
    amenorrhea / Delayed / Incidence not known
    libido decrease / Delayed / Incidence not known
    mydriasis / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital; Caffeine; Codeine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Acetaminophen; Caffeine; Dihydrocodeine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Acetaminophen; Codeine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Acetaminophen; Dextromethorphan; Doxylamine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Acetaminophen; Diphenhydramine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Acetaminophen; Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Acetaminophen; Pentazocine: Avoid the concomitant use of pentazocine and opiate agonists, such as oxycodone. Pentazocine is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of oxycodone. Pentazocine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of pentazocine with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
    Acetaminophen; Propoxyphene: Propoxyphene is a weak mu-opiate receptor agonist. As other opiate agonists bind to mu-opiate receptors, concurrent use of an opiate agonist with propoxyphene is not desirable. Also, propoxyphene will only partially suppress the withdrawal syndrome in patients physically dependent on morphine or other narcotics. The choice of one mu-opiate receptor agonist needs to be made to avoid duplicate therapy and possible adverse effects. For example, concomitant use of propoxyphene with other CNS depressants (e.g., other opiate agonists) can potentiate the effects of respiratory depression and/or sedation. Propoxyphene in combination with other CNS depressants is a major cause of drug-related death. Fatalities within the first hour of overdosage are not uncommon. Extreme caution is needed during concomitant use of any CNS-depressant drug and propoxyphene. Assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Acetaminophen; Tramadol: Concomitant use of tramadol increases the seizure risk in patients taking opiate agonists. Also, tramadol can cause additive CNS depression and respiratory depression when used with opiate agonists; avoid concurrent use whenever possible. If used together, extreme caution is needed, and a reduced tramadol dose is recommended.
    Acrivastine; Pseudoephedrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Aldesleukin, IL-2: Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psychotropic activity such as opiate agonists. Particular caution should be paid to combination with oxycodone. Aldesleukin, IL-2, is a CYP3A4 inhibitor, and the drug may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust oxycodone dosage as necessary.
    Alfentanil: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Aliskiren; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Almotriptan: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor agonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Alosetron: Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
    Alprazolam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminphen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Alvimopan: Patients should not take alvimopan if they have received therapeutic doses of opiate agonists for more than 7 consecutive days immediately before initiation of alvimopan therapy. Patients recently exposed to opioids are expected to be more sensitive to the effects of mu-opioid receptor antagonists and may experience adverse effects localized to the gastrointestinal tract such as abdominal pain, nausea/vomiting, and diarrhea.
    Amide local anesthetics: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Amiloride; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Amiodarone: Coadministration of amiodarone, an inhibitor of CYP3A4 and CYP2D6, and oxycodone, a substrate of CYP3A4 and CYP2D6, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Amitriptyline: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Amitriptyline; Chlordiazepoxide: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Amoxapine: Concomitant use of oxycodone with other CNS depressants, such as amoxapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking amoxapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower amoxapine dose. Monitor patients for sedation and respiratory depression.
    Amoxicillin; Clarithromycin; Lansoprazole: Clarithromycin is an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4. Oxycodone is a CYP3A4 substrate. Coadministration of clarithormycin and oxycodone may result in increased oxycodone plasma concentrations and a higher risk for adverse or prolonged effects. If coadministration of these agents is necessary, patients should be monitored at frequent intervals and dosage adjustments made if warranted.
    Amoxicillin; Clarithromycin; Omeprazole: Clarithromycin is an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4. Oxycodone is a CYP3A4 substrate. Coadministration of clarithormycin and oxycodone may result in increased oxycodone plasma concentrations and a higher risk for adverse or prolonged effects. If coadministration of these agents is necessary, patients should be monitored at frequent intervals and dosage adjustments made if warranted.
    Amyl Nitrite: Administration of nitrates such as amyl nitrite to patients receiving other hypotension-producing agents, such as opiate agonists, can cause additive hypotensive or orthostatic effects.
    Anticholinergics: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Apomorphine: Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
    Apraclonidine: No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as opiate agonists.
    Aprepitant, Fosaprepitant: Use caution if oxycodone and aprepitant, fosaprepitant are used concurrently and monitor for an increase in oxycodone-related adverse effects, including excess sedation, for several days after administration of a multi-day aprepitant regimen. Oxycodone is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of oxycodone. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Articaine; Epinephrine: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Asenapine: Drugs that can cause CNS depression, if used concomitantly with asenapine, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when asenapine is given in combination with other centrally-acting medications including opiate agonists.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Aspirin, ASA; Caffeine; Dihydrocodeine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Aspirin, ASA; Carisoprodol: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Aspirin, ASA; Carisoprodol; Codeine: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Atazanavir: Coadministration of atazanavir, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Atazanavir; Cobicistat: Coadministration of atazanavir, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold. The plasma concentrations of oxycodone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while oxycodone is a CYP3A4 and CYP2D6 substrate.
    Atenolol; Chlorthalidone: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Atomoxetine: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin norepinephrine reuptake inhibitors (SNRIs). Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Atracurium: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as methylene blue. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Atropine; Difenoxin: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events.
    Atropine; Diphenoxylate: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events.
    Azelastine: An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including opiate agonists. A dose reduction of one or both drugs may be warranted.
    Azelastine; Fluticasone: An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including opiate agonists. A dose reduction of one or both drugs may be warranted.
    Azilsartan; Chlorthalidone: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Baclofen: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Basiliximab: Coadministration of basiliximab, an indirect down-regulator of CYP3A4, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Belladonna; Opium: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Benazepril; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Bendroflumethiazide; Nadolol: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as methylene blue. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Benzonatate: The vagal effects and respiratory depression induced by opiate agonists may be increased by the use of benzonatate.
    Bethanechol: Bethanechol facilitates intestinal and bladder function via parasympathomimetic actions. Opiate agonists impair the peristaltic activity of the intestine. Thus, these drugs can antagonize the beneficial actions of bethanechol on GI motility.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Bismuth Subsalicylate: Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Bisoprolol; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Boceprevir: Close clinical monitoring is advised when administering oxycodone with boceprevir due to an increased potential for oxycodone-related adverse events. If oxycodone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
    Brexpiprazole: Due to the CNS effects of brexpiprazole, caution is advisable when brexpiprazole is given in combination with other centrally-acting medications including opiate agonists.
    Brimonidine: Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
    Brimonidine; Brinzolamide: Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
    Brimonidine; Timolol: Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
    Brompheniramine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Brompheniramine; Carbetapentane; Phenylephrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Brompheniramine; Dextromethorphan; Guaifenesin: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Brompheniramine; Guaifenesin; Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Brompheniramine; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Brompheniramine; Pseudoephedrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Bupivacaine Liposomal: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Bupivacaine: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Bupivacaine; Lidocaine: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Buprenorphine: Buprenorphine is a mixed opiate agonist/antagonist with strong affinity for the mu-receptor that may partially block the effects of full mu-receptor opiate agonists and reduce analgesic effects. In some cases of acute pain, trauma, or during surgical management, opiate-dependent patients receiving buprenorphine maintenance therapy may require concurrent treatment with opiate agonists, such as oxycodone. In these cases, health care professionals must exercise caution in opiate agonist dose selection, as higher doses of an opiate agonist may be required to compete with buprenorphine at the mu-receptor. Management strategies may include adding a short-acting opiate agonist to achieve analgesia in the presence of buprenorphine, discontinuation of buprenorphine and use of an opiate agonist to avoid withdrawal and achieve analgesia, or conversion of buprenorphine to methadone while using additional opiate agonists if needed. Closely monitor patients for CNS or respiratory depression. When buprenorphine is used for analgesia, avoid co-use with opiate agonists. Buprenorphine may cause withdrawal symptoms in patients receiving chronic opiate agonists as well as possibly potentiate CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
    Buprenorphine; Naloxone: Buprenorphine is a mixed opiate agonist/antagonist with strong affinity for the mu-receptor that may partially block the effects of full mu-receptor opiate agonists and reduce analgesic effects. In some cases of acute pain, trauma, or during surgical management, opiate-dependent patients receiving buprenorphine maintenance therapy may require concurrent treatment with opiate agonists, such as oxycodone. In these cases, health care professionals must exercise caution in opiate agonist dose selection, as higher doses of an opiate agonist may be required to compete with buprenorphine at the mu-receptor. Management strategies may include adding a short-acting opiate agonist to achieve analgesia in the presence of buprenorphine, discontinuation of buprenorphine and use of an opiate agonist to avoid withdrawal and achieve analgesia, or conversion of buprenorphine to methadone while using additional opiate agonists if needed. Closely monitor patients for CNS or respiratory depression. When buprenorphine is used for analgesia, avoid co-use with opiate agonists. Buprenorphine may cause withdrawal symptoms in patients receiving chronic opiate agonists as well as possibly potentiate CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. Naloxone can antagonize the therapeutic efficacy of oxycodone in addition to precipitating withdrawal symptoms in patients who are physically dependent on opiate drugs including oxycodone.
    Bupropion: Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures.
    Bupropion; Naltrexone: When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures.
    Buspirone: Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of oxycodone, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Butorphanol: Avoid the concomitant use of butorphanol and opiate agonists, such as oxycodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
    Candesartan; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Capsaicin; Metaxalone: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Captopril; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Carbamazepine: Inducers of CYP3A4 such as carbamazepine, may induce the hepatic metabolism of opiate agonists, which may lead to opiate withdrawal or inadequate pain control. This interaction is most significant if the enzyme-inducing agent is added after opiate therapy has begun in patients who are opiate tolerant. Clinicians should be alert to changes in the effect of the opioid agonist. Opiate doses may need to be increased if carbamazepine is added. Conversely, doses may need to be decreased if carbamazepine is discontinued.
    Carbetapentane; Chlorpheniramine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Carbetapentane; Chlorpheniramine; Phenylephrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Carbetapentane; Diphenhydramine; Phenylephrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Carbetapentane; Guaifenesin: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Carbetapentane; Guaifenesin; Phenylephrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Carbetapentane; Phenylephrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Carbetapentane; Phenylephrine; Pyrilamine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Carbetapentane; Pseudoephedrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Carbetapentane; Pyrilamine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including morphine.
    Carbidopa; Levodopa; Entacapone: Concomitant use of opiate agonists with other central nervous system (CNS) depressants such as COMT inhibitors can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of an opiate in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Carbinoxamine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Carbinoxamine; Hydrocodone; Phenylephrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Carbinoxamine; Phenylephrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Carbinoxamine; Pseudoephedrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Cariprazine: Due to the CNS effects of cariprazine, caution is advisable when cariprazine is given in combination with other centrally-acting medications including opiate agonists.
    Carisoprodol: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Ceritinib: Avoid the use of ceritinib, a time-dependent inhibitor of CYP3A4, with substrates that are primarily metabolized by CYP3A4, such as oxycodone, as oxycodone exposure may be increased. If co-administration is unavoidable, consider an oxycodone dose reduction and monitor for oxycodone toxicity.
    Cetirizine: Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, including opiate agonists.
    Cetirizine; Pseudoephedrine: Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, including opiate agonists.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chloramphenicol: Coadministration of chloramphenicol, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Chlorcyclizine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlordiazepoxide: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlordiazepoxide; Clidinium: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chloroprocaine: Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Chloroquine: Closely monitor for excessive toxicity in patients receiving oxycodone and chloroquine, as chloroquine may theoretically increase concentrations of oxycodone. Chloroquine inhibits CYP2D6 and oxycodone is metabolized in part by CYP2D6 to oxymorphone, which represents < 15% of the total administered dose.
    Chlorothiazide: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Chlorpheniramine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Codeine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Dextromethorphan: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Hydrocodone; Phenylephrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Phenylephrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpheniramine; Pseudoephedrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Chlorpromazine: Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Chlorthalidone: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Chlorthalidone; Clonidine: Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including opiate agonists. Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Chlorzoxazone: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Cimetidine: When used in high doses, cimetidine has decreased the metabolism of certain opiate agonists leading to increased opiate levels and opiate toxicity in some patients.
    Cinacalcet: Cinacalcet, a strong in vitro inhibitor of the CYP2D6 cytochrome P450 enzyme, may theoretically increase serum concentrations of other drugs metabolized by this enzyme, such as oxycodone.
    Cisatracurium: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Citalopram: Citalopram impairs metabolism via the CYP2D6 pathway at therapeutic doses. This can result in increased concentrations of drugs metabolized via the same pathway, including oxycodone.
    Clarithromycin: Clarithromycin is an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4. Oxycodone is a CYP3A4 substrate. Coadministration of clarithormycin and oxycodone may result in increased oxycodone plasma concentrations and a higher risk for adverse or prolonged effects. If coadministration of these agents is necessary, patients should be monitored at frequent intervals and dosage adjustments made if warranted.
    Clemastine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Clobazam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Clomipramine: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Clonazepam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Clonidine: Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including opiate agonists.
    Clorazepate: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Clozapine: Concomitant use of oxycodone with other CNS depressants, such as clozapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. In addition, this drug combination may result in additive effects on intestinal motility or bladder function. Prior to concurrent use of oxycodone in patients taking clozapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower clozapine dose. Monitor patients for sedation and respiratory depression.
    Cobicistat: The plasma concentrations of oxycodone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while oxycodone is a CYP3A4 and CYP2D6 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: The plasma concentrations of oxycodone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while oxycodone is a CYP3A4 and CYP2D6 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: The plasma concentrations of oxycodone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while oxycodone is a CYP3A4 and CYP2D6 substrate.
    Codeine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Codeine; Guaifenesin: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Codeine; Phenylephrine; Promethazine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Codeine; Promethazine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    COMT inhibitors: Concomitant use of opiate agonists with other central nervous system (CNS) depressants such as COMT inhibitors can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of an opiate in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Conivaptan: Coadministration of conivaptan, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Crizotinib: Concomitant use of crizotinib and oxycodone may result in increased oxycodone concentrations. Crizotinib is a CYP3A4 and P-glycoprotein (PGP) inhibitor, while oxycodone is a CYP3A4 substrate. Monitor patients for toxicity, such as CNS or respiratory depression, with coadministration.
    Crofelemer: Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
    Cyclizine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Cyclobenzaprine: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Cyproheptadine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Dalfopristin; Quinupristin: Coadministration of dalfopristin; quinupristin, a potent CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Danazol: Coadministration of danazol, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Dantrolene: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Darunavir: Coadministration of darunavir, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Darunavir; Cobicistat: Coadministration of darunavir, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold. The plasma concentrations of oxycodone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while oxycodone is a CYP3A4 and CYP2D6 substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Oxycodone is metabolized by CYP3A4. Concomitant administration of ritonavir, a CYP3A4 inhibitor, may cause an increase in oxycodone plasma concentrations, which could increase or prolong adverse effects and may cause potentially fatal respiratory depression. If coadministration of these agents is necessary, patients should be monitored for an extended period of time and dosage adjustments made if warranted. In addition, oxycodone is metabolized in part by CYP2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 has not been shown to result in clinically significant interactions. However, potent inhibitors of CYP2D6, such as ritonavir, may potentially increase the effects of oxycodone. Caution and close monitoring are advised if these drugs are administered together. Initiate oxycodone a low dosages and tritrate carefully.
    Dasatinib: Coadministration of dasatinib, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Delavirdine: Delavirdine, a potent CYP3A4 inhibitor, CYP3A4 substrate, and CYP2D6 inhibitor, may increase plasma concentrations of oxycodone, a substrate of CYP3A4 and CYP2D6. This may increase or prolong oxycodone-related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Desflurane: Concurrent use with opiate agonists can decrease the minimum alveolar concentration (MAC) of desflurane needed to produce anesthesia.
    Desipramine: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Desloratadine: Although desloratadine is considered a 'non-sedating' antihistamine, rare CNS effects such as dizziness and sedation have been reported. For this reason, it would be prudent to monitor for drowsiness or dizziness when used concurrently with other CNS depressants such as opiate agonists.
    Desloratadine; Pseudoephedrine: Although desloratadine is considered a 'non-sedating' antihistamine, rare CNS effects such as dizziness and sedation have been reported. For this reason, it would be prudent to monitor for drowsiness or dizziness when used concurrently with other CNS depressants such as opiate agonists.
    Desmopressin: Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including opiate agonists. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
    Dexchlorpheniramine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Dexmedetomidine: Co-administration of dexmedetomidine with opiate agonists likely to lead to an enhancement of CNS depression.
    Dexpanthenol: Use caution when using dexpanthenol with drugs that decrease gastrointestinal motility, such as opiate agonists, as it may decrease the effectiveness of dexpanthenol.
    Dextromethorphan; Diphenhydramine; Phenylephrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Dextromethorphan; Quinidine: Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Diazepam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. If parental diazepam is used with an opiate agonist, reduce the opiate agonist dosage by at least 1/3. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Diltiazem: Coadministration of diltiazem, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Similarly, an interaction may occur if diltiazem; enalapril and oxycodone are coadministered. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Dimenhydrinate: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Diphenhydramine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Diphenhydramine; Hydrocodone; Phenylephrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression. Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Diphenhydramine; Ibuprofen: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Diphenhydramine; Phenylephrine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Dolasetron: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Doxacurium: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Doxepin: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Doxylamine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Doxylamine; Pyridoxine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Dronabinol, THC: Concomitant use of opiate agonists and other CNS depressants such as dronabinol, THC may result in respiratory depression, CNS depression, and/or hypotension. Prior to concurrent use of opiate agonists in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. When concomitant treatment is necessary, reduce the dose of 1 or both drugs. When levorphanol is used with dronabinol, reduce the initial levorphanol dose by approximately 50% or more.
    Dronedarone: Dronedarone is metabolized by CYP3A and is an inhibitor of CYP2D6 and CYP3A4. Oxycodone is a substrate for CYP2D6 and CYP3A4. The concomitant administration of dronedarone and CYP2D6 and CYP3A4 substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
    Droperidol: Concomitant use of oxycodone with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Drugs that may cause additive CNS effects include droperidol. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Ethanol abuse and the use of benzodiazepines and intravenous opiates are risk factors for the development of prolonged QT syndrome in patients receiving droperidol. Oxycodone should be used in reduced dosages if used concurrently with droperidol; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving droperidol. Monitor patients for sedation and respiratory depression.
    Echinacea: Echinacea inhibits intestinal CYP3A4, but induces hepatic CYP3A4. The overall effects on orally administered drugs metabolized by CYP3A4 are unknown and may be negligible. Monitor for changes in efficacy or toxicity when echinacea is coadministered with drugs that are metabolized by CYP3A4, including oxycodone
    Efavirenz: Oxycodone is metabolized by CYP3A4. Efavirenz, an inducer of CYP3A4, may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed. Similarly, an interaction may occur if efavirenz; emtricitabine; tenofovir and oxycodone are coadministered.
    Efavirenz; Emtricitabine; Tenofovir: Oxycodone is metabolized by CYP3A4. Efavirenz, an inducer of CYP3A4, may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed. Similarly, an interaction may occur if efavirenz; emtricitabine; tenofovir and oxycodone are coadministered.
    Elbasvir; Grazoprevir: Administering oxycodone with elbasvir; grazoprevir may result in elevated oxycodone plasma concentrations. Oxycodone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eletriptan: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor agonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Eliglustat: Coadministration of oxycodone and eliglustat may result in increased concentrations of oxycodone, although the interaction does not appear to be clinically significant unless a 3A4 inhibitor is used concomitantly. Eliglustat is a CYP2D6 inhibitor. Although primarily metabolized by CYP3A, CYP2D6 also contributes to conversion of oxycodone to oxymorphone. If coadministration is necessary, use caution and monitor patients closely for opioid-related adverse effects such as respiratory depression and sedation at frequent intervals. Consider reducing the dosage of oxycodone until stable drug effects are achieved, and titrating to clinical effect.
    Eltrombopag: Eltrombopag is a UDP-glucuronyltransferase inhibitor. Opiate agonists are substrates of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of morphine is possible. Monitor patients for morphine-related adverse reactions if these drugs are coadministered.
    Eluxadoline: Avoid use of eluxadoline with medications that may cause constipation, such as opiate agonists. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. In addition, the CYP3A4 metabolism of some opiate agonists may be inhibited by eluxadoline. Although the CYP3A4 inhibitory effects of eluxadoline have not been definitively established, the manufacturer recommends caution when administering eluxadoline concurrently with CYP3A4 substrates that have a narrow therapeutic index, such as fentanyl and alfentanil. Closely monitor for increased side effects if these drugs are administered together. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
    Enalapril; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Enflurane: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Entacapone: Concomitant use of opiate agonists with other central nervous system (CNS) depressants such as COMT inhibitors can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of an opiate in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Eprosartan; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Erythromycin: Oxycodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as erythromycin, may cause an increase in oxycodone plasma concentrations, which could increase or prolong adverse effects and may cause potentially fatal respiratory depression. If coadministration of these agents is necessary, patients should be monitored for an extended period of time and dosage adjustments made if warranted.
    Erythromycin; Sulfisoxazole: Oxycodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as erythromycin, may cause an increase in oxycodone plasma concentrations, which could increase or prolong adverse effects and may cause potentially fatal respiratory depression. If coadministration of these agents is necessary, patients should be monitored for an extended period of time and dosage adjustments made if warranted.
    Escitalopram: Escitalopram modestly inhibits metabolism via the CYP2D6 pathway. Theoretically, this can result in increased concentrations of drugs metabolized via the same pathway, including oxycodone.
    Eslicarbazepine: In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Oxycodone is metabolized by CYP3A4. Coadministration may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed.
    Estazolam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Eszopiclone: Concomitant use of oxycodone with eszopiclone may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If eszopiclone is used concurrently with oxycodone, a reduced dosage of oxycodone and/or eszopiclone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Ethanol: Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use of alcohol or illicit drugs when prescribing CNS depressant medications. In many cases, the patient should receive a lower dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol.
    Ethotoin: Oxycodone is metabolized by CYP3A4. Phenytoin or fosphenytoin, an inducer of CYP3A4, may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed.
    Etomidate: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Fentanyl: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Flibanserin: The concomitant use of flibanserin with CNS depressants, such as opiate agonists, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
    Fluconazole: Coadministration of fluconazole, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong oxycodone-related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Fluoxetine: Fluoxetine is a relatively potent inhibitor of CYP2D6 resulting in increased concentrations of opiate agonists metabolized via this same pathway including oxycodone. Clinicians should be alert for an exaggerated opiate response if fluoxetine is given with oxycodone.
    Fluoxetine; Olanzapine: Concomitant use of oxycodone with other CNS depressants, such as olanzapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking olanzapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower olanzapine dose. Monitor patients for sedation and respiratory depression. Fluoxetine is a relatively potent inhibitor of CYP2D6 resulting in increased concentrations of opiate agonists metabolized via this same pathway including oxycodone. Clinicians should be alert for an exaggerated opiate response if fluoxetine is given with oxycodone.
    Fluphenazine: Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Flurazepam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Fluvoxamine: Coadministration of fluvoxamine, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold. Also, oxycodone may interact with fluvoxamine because of the possible risk of serotonin syndrome.
    Fosamprenavir: Coadministration of fosamprenavir, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Fosinopril; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Fosphenytoin: Oxycodone is metabolized by CYP3A4. Phenytoin or fosphenytoin, an inducer of CYP3A4, may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed.
    Fospropofol: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Frovatriptan: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor agonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Gabapentin: Pain medications that contain opiate agonists may intensify CNS depressive adverse effects seen with gabapentin use, such as drowsiness or dizziness. Patients should limit activity until they are aware of how coadministration affects them.
    Gefitinib: Monitor for an increased incidence of oxycodone-related adverse effects if gefitinib and oxycodone are used concomitantly. At high concentrations, gefitinib is an inhibitor of CYP2D6, which is partially responsible for the metabolism of oxycodone. As < 15% of the total administered dose is metabolized by CYP2D6 to oxymorphone, concurrent use of some agents that inhibit CYP2D6 has not been shown to result in clinically significant interactions. However, potent inhibitors of CYP2D6, such as ritonavir, may potentially increase the effects of oxycodone. In patients with solid tumors, exposure to metoprolol, another CYP2D6 substrate, was increased by 30% when given on day 15 of gefitinib dosing (500 mg daily); the effect of gefitinib on CYP2D6-dependent drugs is only likely to be clinically relevant when given with CYP2D6 substrates with a narrow therapeutic index or that are individually dose titrated such as oxycodone.
    General anesthetics: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Granisetron: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Grapefruit juice: Grapefruit juice, a CYP3A4 inhibitor, may increase plasma concentrations of oxycodone, a CYP3A4 substrate. This may increase or prolong oxycodone-related toxicities including potentially fatal respiratory depression. Advise patients accordingly; patient monitoring and dosage adjustments may be necessary if grapefruit is consumed regularly. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Guaifenesin; Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Guanabenz: Guanabenz is associated with sedative effects. Guanabenz can potentiate the effects of CNS depressants such as opiate agonists, when administered concomitantly.
    Guanfacine: Central-acting adrenergic agonists like guanfacine have CNS depressive effects and can potentiate the actions of other CNS depressants including opiate agonists.
    Haloperidol: Haloperidol can potentiate the actions of other CNS depressants such as opiate agonists. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
    Halothane: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Homatropine; Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Hydantoins: Oxycodone is metabolized by CYP3A4. Phenytoin or fosphenytoin, an inducer of CYP3A4, may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed.
    Hydralazine; Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Irbesartan: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Lisinopril: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Losartan: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Methyldopa: Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants, such as opiate agonists, when administered concomitantly. Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Metoprolol: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Moexipril: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Olmesartan: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Propranolol: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Quinapril: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Spironolactone: Opiate agonists like oxycodone may potentiate orthostatic hypotension when given concomitantly with spironolactone. Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Telmisartan: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Triamterene: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Valsartan: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Hydrocodone; Ibuprofen: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Hydrocodone; Phenylephrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Hydrocodone; Potassium Guaiacolsulfonate: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Hydromorphone: Concomitant use of hydromorphone with other central nervous system (CNS) depressants, such as other opiate agonists, can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of hydromorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If hydromorphone is used concurrently with a CNS depressant, a reduced dosage of hydromorphone and/or the CNS depressant is recommended; start with one-third to one-half of the estimated hydromorphone starting dose when using hydromorphone extended-release tablets. Use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydroxyzine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as methylene blue. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Idelalisib: Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with oxycodone, a CYP3A substrate, as oxycodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: Concomitant use of iloperidone with other centrally-acting medications such as opiate agonists, may increase both the frequency and the intensity of adverse effects including drowsiness, sedation, and dizziness.
    Imatinib, STI-571: Imatinib is a potent inhibitor of cytochrome P450 2D6 and may increase concentrations of other drugs metabolized by this enzyme including oxycodone.
    Imipramine: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Indinavir: Coadministration of indinavir, a potent CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Isavuconazonium: Coadministration of isavuconazonium, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Isoflurane: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Isoniazid, INH: Coadministration of isoniazid, INH, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: Coadministration of isoniazid, INH, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold. Coadministration of oxycodone, a CYP3A4 substrate, with rifampin, a CYP3A4 inducer, may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. Coadministration of rifampin and oxycodone decreased oxycodone AUC by 86% and the Cmax by 63%. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed. In addition, oxycodone is metabolized in part by CYP2D6 to oxymorphone, which represents < 15% of the total administered dose. An inducer of CYP2D6, such as rifampin, could convert a greater percentage of the dose to oxymorphone, which has analgesic activity. In the presence of a CYP2D6 inducer, more oxycodone could be converted to oxymorphone. Also, conversion of oxycodone to noroxycodone may be enhanced. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Monitor the patient for excessive adverse effects of oxycodone or reduced efficacy of oxycodone. A lower or higher oxycodone dose may be needed if used with rifampin.
    Isoniazid, INH; Rifampin: Coadministration of isoniazid, INH, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold. Coadministration of oxycodone, a CYP3A4 substrate, with rifampin, a CYP3A4 inducer, may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. Coadministration of rifampin and oxycodone decreased oxycodone AUC by 86% and the Cmax by 63%. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed. In addition, oxycodone is metabolized in part by CYP2D6 to oxymorphone, which represents < 15% of the total administered dose. An inducer of CYP2D6, such as rifampin, could convert a greater percentage of the dose to oxymorphone, which has analgesic activity. In the presence of a CYP2D6 inducer, more oxycodone could be converted to oxymorphone. Also, conversion of oxycodone to noroxycodone may be enhanced. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Monitor the patient for excessive adverse effects of oxycodone or reduced efficacy of oxycodone. A lower or higher oxycodone dose may be needed if used with rifampin.
    Itraconazole: Coadministration of itraconazole, a potent CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Ivacaftor: Use caution when administering ivacaftor and oxycodone concurrently. Ivacaftor is an inhibitor of CYP3A and oxycodone is partially metabolized by CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as oxycodone, can theoretically increase oxycodone exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Ketamine: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Ketoconazole: Oxycodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as ketoconazole, may cause an increase in oxycodone plasma concentrations, which could increase or prolong adverse effects and may cause potentially fatal respiratory depression. If coadministration of these agents is necessary, patients should be monitored for an extended period of time and dosage adjustments made if warranted.
    Lactobacillus: Concurrent use of antidiarrheals and opiate agonists, can lead to severe constipation and possibly additive CNS depression. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
    Lanreotide: Coadministration of lanreotide, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Lapatinib: Coadministration of lapatinib, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Levobupivacaine: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Levocetirizine: Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, including opiate agonists.
    Levorphanol: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Lidocaine: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Lincosamides: Lincosamides, which have been shown to exhibit neuromuscular blocking action, can enhance the effects of opiate agonists if used concomitantly, enhancing respiratory depressant effects. They should be used together with caution and the patient carefully monitored.
    Linezolid: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as linezolid. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Loperamide: Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Concurrent use of selected antidiarrheals (e.g., loperamide, diphenoxylate) and opiate agonists can lead to additive CNS depression.
    Loperamide; Simethicone: Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Concurrent use of selected antidiarrheals (e.g., loperamide, diphenoxylate) and opiate agonists can lead to additive CNS depression.
    Lopinavir; Ritonavir: Oxycodone is metabolized by CYP3A4. Concomitant administration of ritonavir, a CYP3A4 inhibitor, may cause an increase in oxycodone plasma concentrations, which could increase or prolong adverse effects and may cause potentially fatal respiratory depression. If coadministration of these agents is necessary, patients should be monitored for an extended period of time and dosage adjustments made if warranted. In addition, oxycodone is metabolized in part by CYP2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 has not been shown to result in clinically significant interactions. However, potent inhibitors of CYP2D6, such as ritonavir, may potentially increase the effects of oxycodone. Caution and close monitoring are advised if these drugs are administered together. Initiate oxycodone a low dosages and tritrate carefully.
    Loratadine: Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as opiate agonists.
    Loratadine; Pseudoephedrine: Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as opiate agonists.
    Lorazepam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Loxapine: Loxapine can potentiate the actions of other CNS depressants such as opiate agonists. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
    Luliconazole: Theoretically, luliconazole may increase the side effects of oxycodone, which is a CYP3A4 substrate. Monitor patients for adverse effects of oxycodone, such as CNS and respiratory depression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
    Lumacaftor; Ivacaftor: Lumacaftor; ivacaftor may induce the metabolism of oxycodone, which could result in lack of therapeutic efficacy or the development of an abstinence syndrome in patients who are physically dependent on opioids. If coadministration is necessary, monitor the patient closely at frequent intervals for appropriate pain control and signs of opioid withdrawal. Consider oxycodone dosage adjustments until stable drug effects are achieved. If lumacaftor; ivacaftor is subsequently discontinued, oxycodone plasma concentrations will increase. Monitor the patient closely at frequent intervals for oversedation and respiratory depression and reduce the oxycodone dosage as appropriate. Oxycodone is primarily metabolized by CYP3A4, and lumacaftor is a strong CYP3A inducer. Coadministration of oxycodone with rifampin, another strong CYP3A inducer, resulted in an 86% and 63% decrease in oxycodone AUC and Cmax, respectively, during drug-interaction studies.
    Lumacaftor; Ivacaftor: Use caution when administering ivacaftor and oxycodone concurrently. Ivacaftor is an inhibitor of CYP3A and oxycodone is partially metabolized by CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as oxycodone, can theoretically increase oxycodone exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Lurasidone: Due to the CNS effects of lurasidone, caution should be used when lurasidone is given in combination with other centrally acting medications such as opiate agonists.
    Magnesium Salts: Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as opiate agonists. Caution should be exercised when using these agents concurrently.
    Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as opiate agonists. Caution should be exercised when using these agents concurrently.
    Maprotiline: Concomitant use of oxycodone with other CNS depressants, such as maprotiline, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking maprotiline, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower maprotiline dose. Monitor patients for sedation and respiratory depression.
    Meclizine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Meperidine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Meperidine; Promethazine: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Mepivacaine: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Mepivacaine; Levonordefrin: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Meprobamate: Concomitant use of oxycodone with meprobamate may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If meprobamate is used concurrently with oxycodone, a reduced dosage of oxycodone and/or meprobamate is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Mesoridazine: Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Metaxalone: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Methadone: Concomitant use of methadone with another CNS depressant can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; in opioid-naive adults, use an initial methadone dose of 2.5 mg every 12 hours. Also consider a using a lower dose of the CNS depressant; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor patients for sedation and respiratory depression.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as methylene blue. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Methocarbamol: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Methyclothiazide: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Methyldopa: Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants, such as opiate agonists, when administered concomitantly.
    Methylene Blue: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as methylene blue. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Metoclopramide: Opiate agonists antagonize GI motility and can decrease the GI motility enhancing effects of metoclopramide. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as metoclopramide, may result in a reduction in the analgesic effect of hydrocodone.
    Metolazone: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Metyrapone: Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Additive drowsiness and/or dizziness is possible. Also, hydrocodone is metabolized by CYP3A4. Metyrapone, an inducer of CYP3A4, may cause increased clearance of hydrocodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. Monitor the patient for reduced efficacy of hydrocodone. A higher hydrocodone dose may be needed if used with metyrapone.
    Metyrosine: The concomitant administration of metyrosine with opiate agonists can result in additive sedative effects.
    Midazolam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Mifepristone, RU-486: Coadministration of mifepristone, RU-486, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Minocycline: Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as opiate agonists. Caution should be exercised when using these agents concurrently.
    Mirabegron: Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs partially metabolized by CYP2D6, such as oxycodone, may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
    Mirtazapine: Concomitant use of oxycodone with other CNS depressants, such as mirtazapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking mirtazapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower mirtazapine dose. Monitor patients for sedation and respiratory depression.
    Mitotane: Use caution if mitotane and oxycodone are used concomitantly, and monitor for decreased efficacy of oxycodone, a possible change in dosage requirements, and possible development of an abstinence syndrome in a patient with physical dependence to oxycodone. Mitotane is a strong CYP3A4 inducer and oxycodone is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of oxycodone. Coadministration of rifampin and oxycodone decreased oxycodone AUC by 86% and the Cmax by 63%.
    Mivacurium: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Molindone: Concomitant use of opiate agonists with other central nervous system (CNS) depressants, such as molindone, can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of an opiate in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or molindone is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Monoamine oxidase inhibitors: Concomitant use of oxycodone with other CNS depressants, such as MAOIs, can lead to additive respiratory or CNS depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Advise patients against driving or performing other tasks requiring alertness until they know how the combination affects them.
    Morphine: Concomitant use of oxycodone with morphine may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of oxycodone and/or morphine is recommended; use an initial dose of oxycodone at one-third to one-half the usual dosage. For extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor for sedation and respiratory depression.
    Morphine; Naltrexone: Concomitant use of oxycodone with morphine may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of oxycodone and/or morphine is recommended; use an initial dose of oxycodone at one-third to one-half the usual dosage. For extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor for sedation and respiratory depression.
    Nabilone: Concomitant use of opiate agonists with other central nervous system (CNS) depressants, such as nabilone, can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of an opiate in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Nalbuphine: Avoid the concomitant use of nalbuphine and opiate agonists, such as oxycodone. Nalbuphine is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of acetaminophen; oxycodone. Nalbuphine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of nalbuphine with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
    Naloxone: Naloxone can antagonize the therapeutic efficacy of oxycodone in addition to precipitating withdrawal symptoms in patients who are physically dependent on opiate drugs including oxycodone.
    Naltrexone: When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
    Naproxen; Sumatriptan: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor agonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Naratriptan: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor agonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Nefazodone: Concomitant use of oxycodone with other CNS depressants, such as nefazodone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking nefazodone, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower nefazodone dose. Monitor patients for sedation and respiratory depression.
    Nesiritide, BNP: The potential for hypotension may be increased when coadministering nesiritide with opiate agonists.
    Netupitant; Palonosetron: Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as oxycodone. The plasma concentrations of oxycodone can increase when co-administered with netupitant; the inhibitory effect on CYP3A4 can last for multiple days.
    Neuromuscular blockers: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Nicardipine: Coadministration of nicardipine, a CYP3A4 inhibitor according to in vitro data, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Nilotinib: Concomitant use of nilotinib, a CYP3A4 and CYP2D6 inhibitor, and oxycodone, a CYP3A4 and CYP2D6 substrate, may result in increased oxycodone levels. If these drugs are used together, consider a oxycodone dose reduction and monitor patients for toxicity (e.g., sedation, respiratory depression).
    Nitroglycerin: Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
    Nortriptyline: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Octreotide: Octreotide can cause additive constipation with opiate agonists such as oxycodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use. Also, coadministration of octreotide, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Olanzapine: Concomitant use of oxycodone with other CNS depressants, such as olanzapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking olanzapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower olanzapine dose. Monitor patients for sedation and respiratory depression.
    Ombitasvir; Paritaprevir; Ritonavir: Oxycodone is metabolized by CYP3A4. Concomitant administration of ritonavir, a CYP3A4 inhibitor, may cause an increase in oxycodone plasma concentrations, which could increase or prolong adverse effects and may cause potentially fatal respiratory depression. If coadministration of these agents is necessary, patients should be monitored for an extended period of time and dosage adjustments made if warranted. In addition, oxycodone is metabolized in part by CYP2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 has not been shown to result in clinically significant interactions. However, potent inhibitors of CYP2D6, such as ritonavir, may potentially increase the effects of oxycodone. Caution and close monitoring are advised if these drugs are administered together. Initiate oxycodone a low dosages and tritrate carefully.
    Ondansetron: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Oritavancin: Oxycodone is metabolized by CYP3A4 and CYP2D6; oritavancin is a weak CYP3A4 and CYP2D6 inducer. Plasma concentrations and efficacy of oxycodone may be reduced if these drugs are administered concurrently.
    Orphenadrine: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Oxazepam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Oxymorphone: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. a reduced dosage of oxymorphone (1/3 to 1/2 of the usual dose) and/or the CNS depressant is recommended. If the extended-release oxymorphone tablets are used concurrently with a CNS depressant, it is recommended to use an initial dosage of 5 mg PO every 12 hours. Monitor for sedation and respiratory depression.
    Paliperidone: Drugs that can cause CNS depression such as opiate agonists, if used concomitantly with paliperidone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Palonosetron: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Pancuronium: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Papaverine: Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with opiate agonists. Concurrent use of papaverine with potent CNS depressants could lead to enhanced sedation.
    Paroxetine: Paroxetine is a potent inhibitor of drug metabolism via the CYP2D6 pathway. This can result in increased concentrations of drugs metabolized via the same pathway, including oxycodone. Clinicians should be alert for increased opiate effects if these drugs are used concurrently. In addition, there is a case report of possible serotonin syndrome caused by the combination of oxycodone and paroxetine.
    Pazopanib: Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and oxycodone, a CYP3A4 substrate, may cause an increase in systemic concentrations of oxycodone. Use caution when administering these drugs concomitantly.
    Peginterferon Alfa-2b: Oxycodone is metabolized in part by CYP2D6 to oxymorphone, which represents < 15% of the total administered dose. In theory, concurrent use of a CYP2D6 inhibitor, such as peginterferon alfa-2b, may inhibit the conversion of oxycodone to oxymorphone. In addition, concurrent use with a CYP2D6 inhibitor may increase the adverse effects of oxycodone. Close monitoring for pronounced opioid effects is advisable.
    Pegvisomant: In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
    Pentazocine: Avoid the concomitant use of pentazocine and opiate agonists, such as oxycodone. Pentazocine is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of oxycodone. Pentazocine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of pentazocine with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
    Pentazocine; Naloxone: Avoid the concomitant use of pentazocine and opiate agonists, such as oxycodone. Pentazocine is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of oxycodone. Pentazocine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of pentazocine with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. Naloxone can antagonize the therapeutic efficacy of oxycodone in addition to precipitating withdrawal symptoms in patients who are physically dependent on opiate drugs including oxycodone.
    Perampanel: Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as opiate agonists.
    Perphenazine: Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Perphenazine; Amitriptyline: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued. Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Phenothiazines: Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Phenytoin: Oxycodone is metabolized by CYP3A4. Phenytoin or fosphenytoin, an inducer of CYP3A4, may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed.
    Pimozide: Concomitant use of oxycodone with other CNS depressants, such as pimozide, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking pimozide, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower pimozide dose. Monitor patients for sedation and respiratory depression.
    Posaconazole: Coadministration of posaconazole, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Pramipexole: Concomitant use of oxycodone with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Pramlintide: Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. Medications with the potential to slow GI motility, such as opiate agonists, should be used with caution, if at all, with pramlintide until more data are available from the manufacturer. Monitor blood glucose.
    Pregabalin: Concomitant use of opiate agonists with other central nervous system (CNS) depressants can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include pregabalin. Prior to concurrent use of an opiate in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Prilocaine: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Prilocaine; Epinephrine: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Procaine: Due to the CNS depression potential of all local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Procarbazine: Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Prochlorperazine: Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Propafenone: Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as propafenone, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Propofol: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Propoxyphene: Propoxyphene is a weak mu-opiate receptor agonist. As other opiate agonists bind to mu-opiate receptors, concurrent use of an opiate agonist with propoxyphene is not desirable. Also, propoxyphene will only partially suppress the withdrawal syndrome in patients physically dependent on morphine or other narcotics. The choice of one mu-opiate receptor agonist needs to be made to avoid duplicate therapy and possible adverse effects. For example, concomitant use of propoxyphene with other CNS depressants (e.g., other opiate agonists) can potentiate the effects of respiratory depression and/or sedation. Propoxyphene in combination with other CNS depressants is a major cause of drug-related death. Fatalities within the first hour of overdosage are not uncommon. Extreme caution is needed during concomitant use of any CNS-depressant drug and propoxyphene. Assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Protriptyline: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Quazepam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Quetiapine: Concomitant use of oxycodone with other CNS depressants, such as quetiapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking quetiapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower quetiapine dose. Monitor patients for sedation and respiratory depression.
    Quinidine: Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as quinidine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Quinine: Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions including oxycodone.
    Ranolazine: Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Ranolazine and/or metabolites partially inhibit CYP2D6 isoenzymes based on data available. Although the concomitant use of ranolazine with oxycodone has not been studied, ranolazine may theoretically increase plasma concentrations of oxycodone, Studies of interactions with other CYP2D6 inhibitors and oxycodone have not demonstrated clinical significance.
    Rapacuronium: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Rasagiline: Opiate agonists (e.g., alfentanil, codeine, hydrocodone, morphine, sufentanil, etc.) may cause additive CNS depression, drowsiness, dizziness or hypotension, so use with MAOIs should be cautious; lower initial dosages of the opiate are recommended followed by careful titration.
    Remifentanil: Concomitant use of oxycodone with other opiate agonists may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Rifampin: Coadministration of oxycodone, a CYP3A4 substrate, with rifampin, a CYP3A4 inducer, may cause increased clearance of oxycodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. Coadministration of rifampin and oxycodone decreased oxycodone AUC by 86% and the Cmax by 63%. If coadministration of these agents is necessary, monitor patients at frequent intervals and consider dose adjustments if needed. In addition, oxycodone is metabolized in part by CYP2D6 to oxymorphone, which represents < 15% of the total administered dose. An inducer of CYP2D6, such as rifampin, could convert a greater percentage of the dose to oxymorphone, which has analgesic activity. In the presence of a CYP2D6 inducer, more oxycodone could be converted to oxymorphone. Also, conversion of oxycodone to noroxycodone may be enhanced. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Monitor the patient for excessive adverse effects of oxycodone or reduced efficacy of oxycodone. A lower or higher oxycodone dose may be needed if used with rifampin.
    Risperidone: Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
    Ritonavir: Oxycodone is metabolized by CYP3A4. Concomitant administration of ritonavir, a CYP3A4 inhibitor, may cause an increase in oxycodone plasma concentrations, which could increase or prolong adverse effects and may cause potentially fatal respiratory depression. If coadministration of these agents is necessary, patients should be monitored for an extended period of time and dosage adjustments made if warranted. In addition, oxycodone is metabolized in part by CYP2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 has not been shown to result in clinically significant interactions. However, potent inhibitors of CYP2D6, such as ritonavir, may potentially increase the effects of oxycodone. Caution and close monitoring are advised if these drugs are administered together. Initiate oxycodone a low dosages and tritrate carefully.
    Rizatriptan: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor agonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Rocuronium: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Rolapitant: Use caution if oxycodone and rolapitant are used concurrently, and monitor for oxycodone-related adverse effects. Oxycodone is a CYP2D6 substrate where an increase in exposure may significantly increase adverse effects, and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant lasts for at least 7 days, and may last longer after single dose administration. The Cmax and AUC of another CYP2D6 substrate, dextromethorphan, were increased by 120% and 160%, respectively, on day 1 with rolapitant, and by 180% and 230%, respectively, on day 8 after rolapitant administration.
    Ropinirole: Concomitant use of opiate agonists with other central nervous system (CNS) depressants such as ropinirole can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of an opiate in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Ropivacaine: Due to the CNS depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists.
    Saquinavir: Coadministration of saquinavir, a potent CYP3A4 inhibitor and CYP3A4 substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Sedating H1-blockers: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Selective norepinephrine reuptake inhibitors: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin norepinephrine reuptake inhibitors (SNRIs). Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Serotonin-Receptor Agonists: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor agonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Serotonin-Receptor Antagonists: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Sertraline: Sertraline is a mild to moderate inhibitor of drug metabolism via the CYP2D6 pathway. Theoretically, this can result in increased concentrations of drugs metabolized via CYP2D6, including some opiate agonists like oxycodone.
    Sevoflurane: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Sildenafil: Prolonged erections have been reported in two patients taking sildenafil with dihydrocodeine. Although more data are needed, use caution when prescribing opiate agonists and sildenafil concomitantly.
    Simeprevir: Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of oxycodone, which is a CYP3A4 substrate. Monitor patients for adverse effects of oxycodone, such as CNS and respiratory depression.
    Skeletal Muscle Relaxants: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Sodium Oxybate: Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with opiate agonists.
    Solifenacin: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Spironolactone: Opiate agonists like oxycodone may potentiate orthostatic hypotension when given concomitantly with spironolactone.
    Streptogramins: Coadministration of dalfopristin; quinupristin, a potent CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Succinylcholine: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Sumatriptan: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor agonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Suvorexant: CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Tamoxifen: Coadministration of tamoxifen, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Tapentadol: Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants, including other opiate agonists. Severe hypotension, profound sedation, coma, or respiratory depression may occur. Prior to concurrent use of tapentadol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If an opiate agonist is used concurrently with tapentadol, a reduced dosage of tapentadol and/or the opiate agonist is recommended. If the extended-release tapentadol tablets are used concurrently with a CNS depressant, it is recommended to use an initial tapentadol dose of 50 mg PO every 12 hours. Monitor patients for sedation and respiratory depression.
    Telaprevir: Close clinical monitoring is advised when administering oxycodone with telaprevir due to an increased potential for oxycodone-related adverse events. If oxycodone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of oxycodone. Oxycodone is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated oxycodone plasma concentrations.
    Telithromycin: Coadministration of telithromycin and oxycodone may result in increased oxycodone plasma concentrations and a higher risk for adverse or prolonged effects, such as potentially fatal respiratory depression. Oxycodone is metabolized by CYP3A4; telithromycin is a CYP3A4 inhibitor. If coadministration of these agents is necessary, patients should be monitored for an extended period of time and dosage adjustments made if warranted.
    Temazepam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Terbinafine: Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as terbinafine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Tetrabenazine: Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Tetracaine: Due to the central nervous system depression potential of local anesthetics, they should be used with caution with other agents that can cause respiratory depression, such as opiate agonists. Excitation or depression of the CNS may be the first manifestation of CNS toxicity. Restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. After each local anesthetic injection, careful and constant monitoring of ventilation adequacy, cardiovascular vital signs, and the patient's state of consciousness is advised.
    Thalidomide: Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Thiazide diuretics: Opiate agonists may potentiate orthostatic hypotension when used concurrently with thiazide diuretics.
    Thiethylperazine: Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Thioridazine: Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Thiothixene: Thiothixene can potentiate the CNS-depressant action of other drugs such as opiate agonists. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Tipranavir: Coadministration of tipranavir, a potent CYP3A4 inhibitor and CYP3A4 substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Tizanidine: Concomitant use of opiate agonists with skeletal muscle relaxants may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with skeletal muscle relaxants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone or oxycodone; naloxone is initiated in a patient taking a skeletal muscle relaxant, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage and titrate to clinical response; reduced initial doses of oxycodone; naltrexone, aspirin, ASA; oxycodone, and ibuprofen; oxycodone are also recommended. If a decision is made to start treatment with acetaminophen; oxycodone extended-release tabIets, start with 1 tablet PO every 12 hours. If a skeletal muscle relaxant is prescribed for a patient taking an opiate agonist, use a lower initial dose of the skeletal muscle relaxant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Tolcapone: Concomitant use of opiate agonists with other central nervous system (CNS) depressants such as COMT inhibitors can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of an opiate in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Tolterodine: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Tramadol: Concomitant use of tramadol increases the seizure risk in patients taking opiate agonists. Also, tramadol can cause additive CNS depression and respiratory depression when used with opiate agonists; avoid concurrent use whenever possible. If used together, extreme caution is needed, and a reduced tramadol dose is recommended.
    Trandolapril; Verapamil: Coadministration of verapamil, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Trazodone: Concomitant use of oxycodone with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Triazolam: Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. For acetaminophen; oxycodone extended-release tablets, start with 1 tablet PO every 12 hours, and for other oxycodone products, use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Tricyclic antidepressants: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Trifluoperazine: Concomitant use of oxycodone with phenothiazines may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. Furthermore, oxycodone is metabolized in part by cytochrome P450 (CYP) 2D6 to oxymorphone, which represents < 15% of the total administered dose. Concurrent use of some agents that inhibit CYP2D6 (e.g., quinidine) has not been shown to result in clinically significant interactions. However, many phenothiazines are potent inhibitors of CYP2D6 (e.g., chlorpromazine, perphenazine, thioridazine) and may potentially increase the effects of oxycodone. Also, severe hypotension may be potentiated with concurrent phenothiazine usage or other drug that compromises vasomotor tone.
    Trimethobenzamide: The concurrent use of trimethobenzamide with other medications that cause CNS depression, like opiate agonists, may potentiate the effects of either trimethobenzamide or the opiate agonist.
    Trimipramine: Concomitant use of oxycodone and tricyclic antidepressants (TCAs) may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Orthostasis may occur in ambulatory patients. Constipation occurs wtih both oxycodone and TCA use. Prior to concurrent use of oxycodone in patients taking a TCAt, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a TCA is used concurrently with oxycodone, a reduced dosage of oxycodone is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression and for reduced GI motility. Caution should also be observed when administering TCAs with opiates having serotonergic properties such as oxycodonel. Serotonin syndrome may rarely occur and is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma). If serotonin syndrome is suspected, both the TCA and concurrent serotonergic agents should be discontinued.
    Triprolidine: Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression. In addition, chlorpheniramine and diphenhydramine inhibit cytochrome P450 (CYP) 2D6, the enzyme responsible of metabolizing oxycodone to oxymorphone, which represents < 15% of the total administered dose. Close monitoring for potential side effects in patients receiving oxycodone and chlorpheniramine or diphenhydramine is recommended.
    Trospium: Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may be seen.
    Tubocurarine: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Valerian, Valeriana officinalis: Any substances that act on the CNS may theoretically interact with valerian, Valeriana officinalis. The valerian derivative, dihydrovaltrate, binds at barbiturate binding sites; valerenic acid has been shown to inhibit enzyme-induced breakdown of GABA in the brain; the non-volatile monoterpenes (valepotriates) have sedative activity. The sedative effect may be additive to other drugs with sedative actions, such as the opiate agonists. Consider the patient's use of alcohol or illicit drugs. If valerian is used concurrently with a CNS depressant, a reduced dosage of the CNS depressant may be required, or, the valerian supplement may be discontinued. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
    Vecuronium: Concomitant use of oxycodone with other CNS depressants, such as neuromuscular blockers, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Vemurafenib: Concomitant use of vemurafenib and oxycodone may result in altered concentrations of oxycodone. Vemurafenib is a weak inhibitor of CYP2D6 and an inducer of CYP3A4. Oxycodone is a substrate of CYP2D6 and CYP3A4. Use caution and monitor patients for toxicity and efficacy.
    Verapamil: Coadministration of verapamil, a CYP3A4 inhibitor and substrate, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Vigabatrin: Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Vilazodone: Due to the CNS effects of vilazodone, caution should be used when vilazodone is given in combination with other centrally acting medications such as opiate agonists.
    Voriconazole: Oxycodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as voriconazole, may cause an increase in oxycodone plasma concentrations, which could increase or prolong adverse effects and may cause potentially fatal respiratory depression. Coadministration of voriconazole and oxycodone increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold. If coadministration of these agents is necessary, patients should be monitored for an extended period of time and dosage adjustments made if warranted.
    Zafirlukast: Coadministration of zafirlukast, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Zaleplon: Concomitant use of oxycodone with zaleplon may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If zaleplon is used concurrently with oxycodone, a reduced dosage of oxycodone and/or zaleplon is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Ziconotide: Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion.
    Ziprasidone: Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including oxycodone.
    Zolmitriptan: Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor agonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Zolpidem: Concomitant use of oxycodone with zolpidem may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. In addition, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of zolpidem and other CNS depressants than with zolpidem alone. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If zolpidem is used concurrently with oxycodone, a reduced dosage of oxycodone and/or zolpidem is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. For Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night. Monitor for sedation and respiratory depression.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy exposure data are insufficient to inform a drug-associated risk of birth defects or miscarriage with oxycodone. In animal studies with rats and rabbits, no embryo-fetal toxicity was detected when oxycodone was given during organogenesis at doses 0.5- to 15-times the adult human dose of 160 mg/day. In a pre- and post-natal study in rats, oxycodone given during gestation and lactation at a dose approximately 0.4 times an adult human dose of 160 mg/day was not associated with any long-term developmental or reproductive adverse effects in pups; however, pup weight was transiently decreased during lactation and the early post-weaning period. No drug-related effects on reproductive performance in female rats was observed. Published data with rats indicate that oxycodone may result in neurobehavioral effects, including altered stress response, increased anxiety-like behavior, and altered learning and memory, in offspring when given at clinically relevant doses and below. Oxycodone is not recommended for use in women during and immediately prior to labor and obstetric delivery because oral opioid agonists may cause respiratory depression in the newborn. Further, prolonged maternal use of long-acting opioids, such as oxycodone, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.

    MECHANISM OF ACTION

    Mechanism of Action: Oxycodone is a potent µ-opiate receptor agonist. Opiate receptors include µ (mu), kappa (kappa), and delta (delta), which have been reclassified by an International Union of Pharmacology subcommittee as OP1 (delta), OP2 (kappa), and OP3 (µ). These receptors are coupled with G-protein (guanine-nucleotide-binding protein) receptors and function as modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Opioid-G-protein systems include adenylyl cyclase-cyclic adenosine monophosphate (cAMP) and phospholipase3 C (PLC)-inositol 1,4,5 triphosphate (Ins(1,4,5)P3)-Ca2). Opiates do not alter the pain threshold of afferent nerve endings to noxious stimuli, nor do they affect the conductance of impulses along peripheral nerves. Analgesia is mediated through changes in the perception of pain at the spinal cord (µ2- , delta,- kappa-receptors) and higher levels in the CNS (µ1- and kappa3 receptors). There is no ceiling effect of analgesia for opiates. The emotional response to pain is also altered. Opioids close N-type voltage-operated calcium channels (kappa-receptor agonist) and open calcium-dependent inwardly-rectifying potassium channels (µ and delta receptor agonist) resulting in hyperpolarization and reduced neuronal excitability. Binding of the opiate stimulates the exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP) on the G-protein complex. Binding of GTP leads to a release of the G-protein subunit, which acts on the effector system. In this case of opioid-induced analgesia, the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane. Thus, opioids decrease intracellular cAMP by inhibiting adenylate cyclase that modulates the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and norepinephrine. Opioids also modulate the endocrine and immune systems. Opioids inhibit the release of vasopressin, somatostatin, insulin and glucagon.The stimulatory effects of opioids are the result of 'disinhibition' as the release of inhibitory neurotransmitters such as GABA and acetylcholine is blocked. The exact mechanism how opioid agonists cause both inhibitory and stimulatory processes is not well understood. Possible mechanisms including differential susceptibility of the opioid receptor to desensitization or activation of more than one G-protein system or subunit (one excitatory and one inhibitory) by an opioid receptor.Clinically, stimulation of µ-receptors produces analgesia, euphoria, respiratory depression, miosis, decreased gastrointestinal motility, and physical dependence. Kappa-receptor stimulation also produces analgesia, miosis, respiratory depression, as well as, dysphoria and some psychomimetic effects (i.e., disorientation and/or depersonalization). Miosis is produced by an excitatory action on the autonomic segment of the nucleus of the oculomotor nerve. Respiratory depression is caused by direct action of opiate agonists on respiratory centers in the brain stem. Opiate agonists increase smooth muscle tone in the antral portion of the stomach, the small intestine (especially the duodenum), the large intestine, and the sphincters. Opiate agonists also decrease secretions from the stomach, pancreas, and biliary tract. The combination of effects of opiate agonists on the GI tract results in constipation and delayed digestion. Urinary smooth muscle tone is also increased by opiate agonists. The tone of the bladder detrusor muscle, ureters, and vesical sphincter is increased, which sometimes causes urinary retention.Several other clinical effects occur with opiate agonists including cough suppression, hypotension, and nausea/vomiting. The antitussive effects of opiate agonists are mediated through direct action on receptors in the cough center of the medulla. Cough suppression can be achieved at lower doses than those required to produce analgesia. Hypotension is possibly due to an increase in histamine release and/or depression of the vasomotor center in the medulla. Induction of nausea and vomiting possibly occurs from direct stimulation of the vestibular system and/or the chemoreceptor trigger zone.

    PHARMACOKINETICS

    Oxycodone is administered orally. It is about 45% protein bound. Once absorbed, it is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and the CNS; oxycodone has been found in breast milk. Metabolism occurs in the liver with excretion principally in the urine. Oxycodone is metabolized to noroxycodone by CYP3A4, noroxymorphone by both CYP2D6 and CYP3A4, and oxymorphone by CYP2D6. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. The analgesic effect is primarily due to the parent compound; oxymorphone has analgesic effects, but it is only present in low concentrations. The elimination half-life of oxycodone is 3 to 5 hours with the duration of analgesia lasting 3 to 4 hours. The extended-release tablet has a slightly longer half-life (4.5 hours) than the immediate-release preparations (3.2 hours). The extended-release capsule half-life is 5.6 hours when dosed in the fed state.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2D6

    Oral Route

    Immediate-release preparations: Oral bioavailability is 60% to 87%, which is more than other opioid agonists due to low pre-systemic and first-pass metabolism. The Cmax occurs approximately 1 hour after administration of the oral solution and 1.3 hours after administration of tablets. Oxecta brand is bioequivalent to other immediate-release tablet formulations in the fasted state. The onset of analgesia begins in about 15 minutes following dose administration, with maximal analgesic effect seen at 1 to 2 hours post-dose.
     
    Extended-release tablets: Oral bioavailability is 60% to 87%. The relative oral bioavailability of the extended-release tablets to the immediate-release tablets is 100%. Release of oxycodone is pH independent. Peak plasma concentration and systemic exposure are dose-proportional for the 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80 mg tablet strengths. Food has no significant effect on the extent of absorption from the extended-release tablets. Steady-state plasma concentrations are reached within 24 to 36 hours after initiating dosing. Doses of 10 mg every 12 hours of the extended-release tablets were equivalent to the AUC and Cmax of 5 mg every 6 hours of the immediate-release tablets.
     
    Extended-release capsules (Xtampza ER): Extended-release capsules are not bioequivalent to extended-release tablets. In the fed state, the AUC of the tablet and capsule is similar; however, the Cmax is lower for the capsule. In the fasted state, Cmax and AUC are both lower for the capsule. Time to peak concentration is approximately 3 hours longer for the capsule compared to immediate-release oral solution. The mean Cmax of oxycodone from the capsule compared to Cmax from oral solution is lower (73% and 43% lower for fasted and fed conditions, respectively). The relative bioavailability of the capsules to oxycodone immediate release oral solution is 75% in the fasted state and 114% in the fed state. The bioavailability of oxycodone from the capsule is greater when taken with food; bioavailability is dependent on the type of food consumed and fat content. Following a high-fat and high-calorie meal, increases in Cmax of 100% to 150% and AUC of 50% to 60% were seen. Following a medium-fat, medium calorie meal, Cmax increased by 84% and AUC by 28%. Following a low-fat, low-calorie meal, Cmax increased by 19% and AUC was comparable to the fasted state. Tmax occurs approximately 4.5 hours after administration in the fed state. Steady state concentrations are reached within 24 to 36 hours. Pharmacokinetic studies demonstrated no clinically relevant differences in Cmax, Tmax, and AUC when the capsule was given intact vs. sprinkled capsule contents under fed conditions.