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  • CLASSES

    Agents for Opioid Dependence
    Agents Used In Alcohol Dependence

    DEA CLASS

    Rx

    DESCRIPTION

    Opiate antagonist.
    Used as an aid in relapse prevention in alcohol and/or opiate dependence; has been used as part of rapid and ultrarapid detoxification techniques.
    Better bioavailability and longer duration of action than naloxone; will not prevent opiate withdrawal.

    COMMON BRAND NAMES

    Depade, ReVia, Vivitrol

    HOW SUPPLIED

    Depade/Naltrexone/Naltrexone Hydrochloride/ReVia Oral Tab: 50mg
    Vivitrol Intramuscular Inj Pwd F/Susp ER: 380mg

    DOSAGE & INDICATIONS

    For the maintenance treatment of alcohol dependence.
    Oral dosage
    Adults

    50 mg PO once daily with food for 12 weeks has been shown to be effective. Other regimens or durations have not been evaluated in placebo-controlled trials, but include 50 mg PO once daily on weekdays and 100 mg PO on Saturdays; 100 mg PO every other day; or 150 mg PO every third day. A consensus panel recommends naltrexone treatment be individualized to meet the patient's needs. Some patients may require naltrexone doses of 100 mg/day PO. Initially, patients may require 3 to 6 months of naltrexone treatment. Certain patients may benefit from up to 1 year of treatment. To decrease gastrointestinal side effects, start with 12.5 mg to 25 mg PO once daily and gradually titrate the dose, split the daily dose, or adjust the administration times. Pharmacotherapy should be used as a part of a comprehensive management program that includes psychosocial support and treatment. Naltrexone does not eliminate or reduce alcohol withdrawal symptoms. If naltrexone is initiated early in the abstinence process, it will not prevent signs and symptoms that would be experienced if the drug had not been started.

    Intramuscular dosage
    Adults

    380 mg IM every 4 weeks. Use is indicated in patients who are able to abstain from alcohol in an outpatient setting prior to treatment initiation. Patients should not be actively drinking alcohol at the time of initial naltrexone IM administration. Pretreatment with oral naltrexone is not required before using naltrexone IM. There are no data to specifically address treatment re-initiation in patients who discontinue naltrexone use. There are no systematic data that specifically address switching from oral naltrexone to IM naltrexone.

    For relapse prevention following opioid detoxification in patients with opiate agonist dependence.
    Oral dosage
    Adults

    Initial dose of 25 mg PO with food. If no withdrawal signs occur, the patient may be started on 50 mg PO once daily therafter. NOTE: Naltrexone should be used as part of a comprehensive treatment plan that includes psychosocial support and medication compliance techniques. Patients must be opioid-free for a minimum of 7—10 days before starting naltrexone to avoid precipitation of opioid withdrawal.

    Intramuscular dosage

    NOTE: Intramuscular naltrexone must be prepared and administered by a healthcare professional. Pretreatment with oral naltrexone is not required before using Vivitrol. There are no data to specifically address treatment re-initiation in patients who stopped therapy, and there are no systematically collected data that specifically address the switch from oral naltrexone to IM naltrexone or from buprenorphine, buprenorphine; naloxone or methadone. Some patients may experience severe manifestations of precipitated withdrawal when being switched from opioid agonist therapy to opioid antagonist therapy. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks. Be prepared to manage withdrawal symptomatically with non-opioid medications.

    Adults

    380 mg IM every 4 weeks or once a month. The drug should be administered as a gluteal injection, alternating buttocks for each subsequent injection, and using the carton components provided by the manufacturer, which include customized needles. Naltrexone must not be injected using any other needle. The body size of the patient should be assessed prior to each injection to ensure that the needle length is adequate. Alternate treatment should be considered in those whose body size precludes gluteal administration using the manufacturer-provided needles.

    For the opiate agonist withdrawal induction† during detoxification.
    NOTE: Rapid and ultrarapid opiate detoxification should only be done in a controlled setting under the supervision of a physician experienced in the management of opiate withdrawal. Severe withdrawal symptoms and death have been reported in patients undergoing ultrarapid opiate detoxification.
    For rapid opiate detoxification†.
    Oral dosage
    Adults

    Various titration regimens leading up to a full dose of naltrexone 50 mg PO once daily have been used during rapid opiate detoxification. In some cases patients have been treated with naloxone prior to naltrexone. Many studies also use concomitant adjuvant medications to decrease withdrawal symptoms including phenothiazines, benzodiazepines, and non-opiate analgesics (NSAIDs).

    For ultrarapid opiate detoxification†.
    Oral dosage
    Adults

    Naltrexone with or without naloxone has been given during ultrarapid opiate detoxification. In a study using naltrexone alone, 50 mg PO was given prior to sedation with midazolam. Other medications used in ultrarapid detoxification include clonidine, benzodiazepines, antiemetic agents (e.g., metoclopramide and ondansetron), and general anesthesia.

    For the treatment of pruritus†.
    Due to cholestatic liver disease.
    Oral dosage
    Adults

    50 mg PO once daily for 7 days to 4 weeks resulted in significant improvement in itching and sleep in patients with pruritus resistant to cholestyramine or ursodiol. Nausea may be limited by using an initial dose of naltrexone 25 mg PO once daily, followed by subsequent titration.

    Due to systemic or dermatologic disease.
    Oral dosage
    Adults

    Limited data suggest 50 mg PO once daily may be effective. In an open-label pilot study of 50 patients with severe pruritus, naltrexone for up to 20 months significantly reduced symptoms in 35 patients, with 13 patients experiencing complete resolution. Six patients experienced tachyphylaxis within 1—9 months of treatment; 2 patients with chronic prurigo nodularis overcame tachyphylaxis by administration of 50 mg twice a day. Adverse effects, including fatigue, dizziness, heartburn, and diarrhea were rare and were restricted to the first 2 weeks of treatment. Nausea, which occurred in 11 patients, was generally controlled by metoclopramide; however, 2 patients required discontinuation of therapy.

    For uremic pruritus†.
    Oral dosage
    Adults

    Limited data suggest 50 mg PO once daily may be effective. In a randomized, double-blind, placebo-controlled crossover trial of 15 hemodialysis patients with severe resistant pruritus, treatment with naltrexone for 7 days resulted in a significant reduction in pruritus compared to placebo. Relief from pruritus occurred within the first 48 hours of treatment. Adverse reactions were reported by a total of 5 patients and included heartburn and upper abdominal discomfort.

    For use as an adjunct to psychosocial interventions for tobacco cessation† (smoking cessation†).
    Oral dosage
    Adults

    Limited data are available. Naltrexone 50 mg PO once daily has been used alone or in combination with nicotine transdermal patches as a treatment or adjuvant therapy in patients attempting to stop smoking. In a trial comparing nicotine patches alone or with naltrexone, the results showed a decreased urge to smoke in response to smoking cues, a decrease in withdrawal scored, and reduced negative effects following exposure to smoking cues in patients treated with the combination. The conclusions of this study are considered preliminary and require more extensive follow-up.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    150 mg/day PO; 380 mg/dose IM.

    Elderly

    150 mg/day PO; 380 mg/dose IM.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Naltrexone undergoes significant liver metabolism. In patients with severe hepatic dysfunction, up to a 10-fold increase in naltrexone AUC may be observed. Dosage adjustment may be necessary in patients with hepatic impairment. However, specific guidelines for dosage adjustments in patients with hepatic dysfunction are not available.

    Renal Impairment

    Both naltrexone and its active metabolite are excreted renally, and naltrexone doses may need adjustment for patients with renal impairment. However, specific guidelines for dosage adjustment in patients with renal impairment are not available.

    ADMINISTRATION

     
    In general, do not attempt treatment with naltrexone unless, in the medical judgment of the prescribing physician, there is no reasonable possibility of short-acting opiate agonist use within the past 7—10 days, and up to two weeks for long-acting opioids. If there is any question of occult opiate dependence, perform a challenge test. If the challenge test is positive, do NOT initiate naltrexone therapy. Repeat the test in 24 hours. If the test is negative and there are no other contraindications, naltrexone therapy may be started. If there is any doubt about the results of the test, hold naltrexone and repeat the challenge in 24 hours. Advise patient not to self-administer opiates while receiving naltrexone therapy.

    Oral Administration

    Administer tablets by mouth with food to decrease nausea. Tablets are scored for splitting, if needed.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intramuscular Administration

    NOTE: Naltrexone for extended-release injectable suspension must be correctly administered by a health care professional; proper administration is imperative to reduce the likelihood of a severe injection site reaction. Administration MUST be with the provided needle into the gluteal muscle. The risk of serious injection site reactions may be increased when Vivitrol is deposited in subcutaneous or fatty tissue. Body habitus should be assessed prior to each injection for each patient to assure that the proper needle is selected and that the needle length is adequate for intramuscular administration. The needles provided are customized needles. Vivitrol must not be injected using any other needle. Consider alternate treatment for those patients whose body habitus precludes an intramuscular gluteal injection with one of the provided needles.
     
    Preparation:
    Take the carton out of the refrigerator for about 45 minutes before preparation to allow the product to reach room temperature.
    Firmly tap the bottom of the vial on a hard surface to ensure that the powder moves freely. Remove the flip caps off the drug and diluent vials.
    Using aseptic technique, place the one inch preparation needle on the syringe and withdraw 3.4 ml diluent from diluent vial; inject the 3.4 ml diluent into naltrexone microsphere vial. Do not use any other diluent or needle.
    Vigorously shake the vial for 1 minute. A properly mixed suspension will be milky white, will not contain clumps, and will move freely down the wall of the vial. If these conditions do not exist, do not administer.
    Immediately after suspension, withdraw 4.2 ml of the suspension into the syringe using the same preparation needle.
    Select the appropriate needle for intramuscular injection based on patient's body habitus: 1.5 inch needle for very lean patients or 2 inch needle for patients with larger amount of subcutaneous tissue overlying the gluteal muscle; patients with average body habitus may use either needle.
     
    Intramuscular injection:
    Hold the syringe with the needle pointing upward and tap the syringe. Expel the syringe contents to get rid of any air bubbles and until only 4 ml remains in the syringe.
    Insert the needle into the gluteal muscle, and aspirate before injection to avoid injection into a blood vessel. If blood aspirates or the needle clogs, remove the needle and replace with the supplied spare administration needle. Repeat the procedure at an adjacent site in the same gluteal muscle. If no blood appears, inject the medicine (4 ml) using a slow and continuous delivery. Alternate the right and left buttock for the injection site each month.

    STORAGE

    Depade:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    ReVia:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Vivitrol:
    - Do not expose product to temperatures above 77 degrees F
    - Do not freeze
    - Store between 36 to 46 degrees F
    - Unrefrigerated product can be stored at temperatures not exceeding 77 degrees F for no more than 7 days prior to administration

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Naltrexone is contraindicated in patients with hypersensitivity to naltrexone or any components of the commercially available product. Naltrexone is incorporated in 75:25 polylactide-co-glycolide (PLG) at a concentration of 337 mg of naltrexone per gram of microspheres. The diluent is composed of carboxymethylcellulose sodium salt, polysorbate 20, sodium chloride, and water for injection. Naltrexone should also not be used in patients with a known hypersensitivity to naloxone or nalmefene because these three drugs are all structurally similar.

    Hepatic disease, hepatitis

    The use of naltrexone in patients with hepatic disease should be carefully considered due to the hepatotoxic effects of naltrexone and the potential for decreased clearance of naltrexone. Naltrexone does not appear to be hepatotoxic at recommended doses. However, the margin between a safe dose and a hepatotoxic dose appears to be five-fold or less. There may be a higher risk of hepatocellular injury with single doses above 50 mg, and use of higher doses and extended dosing intervals should balance the possible risks against the probable benefits. There are reports of hepatitis and significant hepatic dysfunction in association with exposure to naltrexone oral tablets and parenteral naltrexone. In patients treated with naltrexone tablets or injection who presented with elevated transaminases, other potential causes were often identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs. Opioid withdrawal does not typically manifest as clinically significant hepatic dysfunction, however, abruptly precipitated opioid withdrawal may lead to systemic sequelae including acute liver injury. Warn patients of the potential risk of hepatic injury and advise them to seek medical attention if they experience symptoms of acute hepatitis. Discontinue use of naltrexone if signs/symptoms of acute hepatitis occur.

    Depression, suicidal ideation

    Depression, suicide, attempted suicide and suicidal ideation have been reported in patients receiving naltrexone for the treatment of opioid dependence. No causal relationship has been demonstrated. In the literature, endogenous opioids have been theorized to contribute to a variety of conditions. Monitor alcohol and opioid dependent patients, including those taking naltrexone, for the development of depression or suicidal thinking. Inform families and caregivers of patients being treated with naltrexone to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient’s healthcare provider.

    Acute opioid withdrawal

    Naltrexone is contraindicated in patients who are receiving opioid analgesics, partial opiate agonists (e.g., buprenorphine), those with current physiologic opioid dependence, and those in acute opioid withdrawal. Administration of naltrexone to these patients may precipitate an abrupt withdrawal severe enough to require hospitalization, and in some cases management in the intensive care unit. To prevent precipitation of withdrawal, patients should be opioid-free (including tramadol) for a minimum of 7—10 days prior to initiation of naltrexone. When transitioning from buprenorphine or methadone, patients may be vulnerable to precipitation of withdrawal symptoms for up to two weeks. In every case, be prepared to manage withdrawal symptomatically with non-opioid medications because there is no completely reliable method for determining whether a patient has had an adequate opioid-free period. Since the absence of an opiate drug in the urine is often not sufficient proof that a patient is opiate-free, a naloxone challenge should be done if there is any question of occult opioid dependence. A naloxone challenge test may be helpful; however, a few case reports have indicated that patients may experience precipitated withdrawal despite having a negative urine toxicology screen or tolerating a naloxone challenge test (usually in the setting of transitioning from buprenorphine treatment). Make patients aware of the risks associated with precipitated withdrawal and the need to give an accurate account of last opioid use. A positive reaction to the naloxone challenge predicts a similar response to naltrexone. Use of naltrexone is contraindicated in an individual who fails the naloxone challenge test or who has a positive urine test for opioids.The naloxone challenge can be repeated in 24 hours. Assess patients treated for alcohol dependence for underlying opioid dependence and for any recent use of opioids prior to initiation of treatment with naltrexone. Precipitated opioid withdrawal has been observed in alcohol-dependent patients in circumstances where the prescriber had been unaware of the additional use of opioids or co-dependence on opioids.

    Surgery

    If a painful procedure such as surgery is planned, then naltrexone should be discontinued 72 hours prior to the procedure. Patients should be abstinent from opiate analgesia for at least 7 days before restarting naltrexone.

    Respiratory depression

    Naltrexone treated patients who require emergent opiate analgesia may require the administration of large opiate doses to provide adequate pain control, which may increase the risk of deep or prolonged respiratory depression. A rapidly acting opiate agonist is preferred for emergent analgesia to limit the duration of respiratory depression. Non-opiate receptor mediated actions (i.e., histamine-mediated) may occur with the use of opiates and should be expected (e.g., facial swelling, itching, generalized erythema or bronchoconstriction). Other alternatives for emergent analgesia in patients taking naltrexone include the use of regional analgesia, conscious sedation, non-opiate analgesics, or general anesthetics.

    Opioid use disorder, potential for overdose or poisoning

    Attempts to overcome the antagonistic effects of naltrexone with large doses of an opioid agonist by patients maintained on naltrexone may result in potential for overdose or poisoning that may be fatal; cases of opioid overdose with fatal outcomes have been reported in patients after discontinuing treatment. Despite a prolonged pharmacologic effect, the blockade produced by naltrexone is surmountable. As the naltrexone blockade wanes and eventually dissipates, patients may respond to lower doses of opioids than previously used, potentially resulting in life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.) if the patient uses previously tolerated doses of opioids. Patients are at particular risk at the end of the dosing interval, after missing a scheduled dose or after discontinuing naltrexone treatment. Patients should be informed of the serious consequences of attempting to overcome the opioid blockade and that they may be more sensitive to lower doses of opioid agonists once naltrexone therapy is stopped. Advise patients to inform family members and those closest to them of this increased sensitivity and risk of overdose. Discuss the availability of naloxone with all patients and strongly consider prescribing it in patients treated for opioid use disorder (OUD) because of the potential for relapse. Inform patients and caregivers of their options for obtaining naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program).

    Renal impairment

    Naltrexone and its major active metabolite are excreted primarily by the kidney. Use caution in administering naltrexone to patients with renal impairment. Pharmacokinetic parameters of naltrexone given intramuscularly are essentially unchanged in patients with a creatinine clearance of 50—80 ml/minute. The disposition of naltrexone in patients with moderate to severe renal impairment has not been evaluated. Dosage adjustments may be necessary in patients with renal dysfunction.

    Pregnancy

    The use of naltrexone for a substance abuse disorder during pregnancy should be considered only if supportive substance abuse prevention measures are ineffective. There are no adequate and well-controlled studies of naltrexone use in pregnant women to be informative of any drug-associated risks for birth defects or miscarriage, adverse maternal outcomes, or fetal outcomes. If treatment with naltrexone is selected, the potential benefit to the mother versus the potential risk to the fetus should be evaluated. There are known risks of opiate and alcohol addiction to the fetus. Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Published studies have also demonstrated that alcohol is associated with fetal harm including growth restriction, facial abnormalities, central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Daily oral administration of naltrexone to female rats and rabbits increased the incidence of early fetal loss at exposures 11 times or more and 2 times or more the human exposure, respectively. Daily oral administration of naltrexone to pregnant rats and rabbits during the period of organogenesis did not induce malformation at exposures up to 175 times and 14 times the human exposure, respectively. The effects of naltrexone during labor and delivery are unknown.

    Breast-feeding

    The developmental health benefits of breast-feeding should be considered along with the mother's clinical need for naltrexone and any potential adverse effects on the breastfed infant from naltrexone or the mother's underlying maternal condition. Naltrexone and its metabolite 6-beta-naltrexol are present in human breast milk. There are no data on the effects on the breastfed infant or the effects on milk production. Alcohol dependence and opiate addiction are known to have potential adverse drug risks to the nursing infant; alcohol and many opiates are excreted in breast milk.

    Children, infants, neonates

    The safe use of naltrexone in neonates, infants, children, and adolescents has not been established.

    Driving or operating machinery

    Naltrexone may cause dizziness. Tell patients about the importance of not driving or operating machinery, or performing other potentially hazardous tasks, until they know how this medicine will affect them.

    Coagulopathy, females, hemophilia, intravenous administration, obesity, subcutaneous administration, thrombocytopenia, tissue necrosis

    Naltrexone extended-release injectable suspension (e.g., Vivitrol) is for intramuscular administration only; intravenous administration and subcutaneous administration should be avoided. Serious injection site reactions have been reported. The risk of severe injection site reactions may be increased when the extended-release injectable suspension is deposited in subcutaneous or fatty tissue. Proper administration techniques and patient selection are imperative. Consider alternate treatment for patients whose body habitus (obesity) precludes a gluteal intramuscular injection with the provided needle. Also, variable depth of subcutaneous tissue exists between patients; the depth is dependent on the gender and weight of the patient. Women may be physiologically at higher risk for injection site reactions because of increased gluteal fat thickness vs. males, and in fact, postmarketing reports of injection site reactions have occurred primarily in females. Patients should be informed that any concerning injection site reactions should be brought to the attention of the healthcare provider. Patients exhibiting signs of abscess, cellulitis, tissue necrosis, or extensive swelling should be evaluated by a physician to determine if referral to a surgeon is warranted. As with any intramuscular injection, naltrexone extended-release injectable suspension should be administered with caution to patients with thrombocytopenia or any coagulation disorder (e.g., hemophilia or coagulopathy) due to the risk for hematoma or bleeding.[32954]

    ADVERSE REACTIONS

    Severe

    peptic ulcer / Delayed / 0-1.0
    seizures / Delayed / Incidence not known
    stroke / Early / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    eosinophilic pneumonia / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    tissue necrosis / Early / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    heart failure / Delayed / Incidence not known
    atrial fibrillation / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    cholecystitis / Delayed / Incidence not known

    Moderate

    elevated hepatic enzymes / Delayed / 7.0-20.0
    constipation / Delayed / 0-10.0
    ejaculation dysfunction / Delayed / 0-10.0
    hypertension / Early / 0-5.0
    confusion / Early / 0-1.0
    hallucinations / Early / 0-1.0
    hot flashes / Early / 0-1.0
    hemorrhoids / Delayed / 0-1.0
    dyspnea / Early / 0-1.0
    sinus tachycardia / Rapid / 0-1.0
    phlebitis / Rapid / 0-1.0
    edema / Delayed / 0-1.0
    palpitations / Early / 0-1.0
    dysuria / Early / 0-1.0
    ocular inflammation / Early / 0-1.0
    photophobia / Early / 0-1.0
    blurred vision / Early / 0-1.0
    hyperbilirubinemia / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    euphoria / Early / Incidence not known
    migraine / Early / Incidence not known
    depression / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    colitis / Delayed / Incidence not known
    hematoma / Early / Incidence not known
    angina / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    cholelithiasis / Delayed / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    dehydration / Delayed / Incidence not known
    withdrawal / Early / Incidence not known

    Mild

    injection site reaction / Rapid / 0-69.0
    nausea / Early / 10.0-33.0
    headache / Early / 3.0-25.0
    asthenia / Delayed / 23.0-23.0
    insomnia / Early / 3.0-14.0
    vomiting / Early / 3.0-14.0
    anorexia / Delayed / 9.0-14.0
    abdominal pain / Early / 0-14.0
    dizziness / Early / 4.0-13.0
    syncope / Early / 0-13.0
    diarrhea / Early / 0-13.0
    anxiety / Delayed / 2.0-12.0
    irritability / Delayed / 0-10.0
    rash / Early / 0-10.0
    polydipsia / Early / 0-10.0
    chills / Rapid / 0-10.0
    muscle cramps / Delayed / 8.0-8.0
    back pain / Delayed / 6.0-6.0
    xerostomia / Early / 0-5.0
    drowsiness / Early / 0-4.0
    dental pain / Delayed / 4.0-4.0
    yawning / Early / 0-1.0
    restlessness / Early / 0-1.0
    nightmares / Early / 0-1.0
    paranoia / Early / 0-1.0
    appetite stimulation / Delayed / 0-1.0
    flatulence / Early / 0-1.0
    weight loss / Delayed / 0-1.0
    weight gain / Delayed / 0-1.0
    sneezing / Early / 0-1.0
    cough / Delayed / 0-1.0
    fever / Early / 0-1.0
    nasal congestion / Early / 0-1.0
    hoarseness / Early / 0-1.0
    rhinorrhea / Early / 0-1.0
    epistaxis / Delayed / 0-1.0
    tremor / Early / 0-1.0
    acne vulgaris / Delayed / 0-1.0
    pruritus / Rapid / 0-1.0
    alopecia / Delayed / 0-1.0
    increased urinary frequency / Early / 0-1.0
    libido decrease / Delayed / 0-1.0
    libido increase / Delayed / 0-1.0
    tinnitus / Delayed / 0-1.0
    ocular irritation / Rapid / 0-1.0
    otalgia / Early / 0-1.0
    fatigue / Early / 4.0
    arthralgia / Delayed / 10.0
    myalgia / Early / 10.0
    hyperkinesis / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    agitation / Early / Incidence not known
    dysgeusia / Early / Incidence not known
    purpura / Delayed / Incidence not known
    gastroesophageal reflux / Delayed / Incidence not known
    ecchymosis / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    laryngitis / Delayed / Incidence not known
    infection / Delayed / Incidence not known
    sinusitis / Delayed / Incidence not known
    influenza / Delayed / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    night sweats / Early / Incidence not known
    malaise / Early / Incidence not known
    lethargy / Early / Incidence not known

    DRUG INTERACTIONS

    Acamprosate: (Minor) The administration of naltrexone with acamprosate results in an increase in acamprosate exposure (AUC) by 25% and in peak concentration (Cmax) by 33%. However, acamprosate dosage adjustments are not required.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) 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.
    Acetaminophen; Codeine: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Acetaminophen; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Acetaminophen; Oxycodone: (Major) 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.
    Acetaminophen; Pentazocine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 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 (respiratory insufficiency or arrest or circulatory collapse) 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.
    Acetaminophen; Propoxyphene: (Major) 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.
    Alfentanil: (Major) 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. The usual doses of alfentanil will be ineffective in patients receiving naltrexone. 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. However, respiratory depression from alfentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. 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.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) 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.
    Aspirin, ASA; Carisoprodol; Codeine: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Aspirin, ASA; Oxycodone: (Major) 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.
    Atropine; Difenoxin: (Major) 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.
    Bremelanotide: (Major) Avoid using bremelanotide with an orally-administered naltrexone-containing product that is intended to treat alcohol and opioid addiction due to the severe consequence of naltrexone treatment failure. In pharmacokinetic studies, bremelanotide significantly affected the oral absorption of naltrexone.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Buprenorphine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 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 (respiratory insufficiency or arrest or circulatory collapse) 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.
    Buprenorphine; Naloxone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 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 (respiratory insufficiency or arrest or circulatory collapse) 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.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Butorphanol: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 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 (respiratory insufficiency or arrest or circulatory collapse) 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.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Chlorpheniramine; Codeine: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) 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.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) 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.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Codeine: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Codeine; Guaifenesin: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Codeine; Phenylephrine; Promethazine: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Codeine; Promethazine: (Major) 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. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. 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.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) 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.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Diphenoxylate; Atropine: (Major) 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.
    Disulfiram: (Major) The safety and efficacy of concomitant use of naltrexone and disulfiram is unknown. There is the possibility of additive hepatotoxicity and concurrent use of these agents is not recommended. If concomitant use of naltrexone and disulfiram is required, liver function tests should be performed prior to beginning combination therapy, then they should be repeated every 2 weeks for 1 to 2 months. Continue monitoring LFTs monthly after the third month of combined use.
    Dronabinol: (Moderate) Concomitant administration of naltrexone and oral THC like dronabinol enhances the positive subjective effects of oral THC. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers.
    Fentanyl: (Major) 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.
    Guaifenesin; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Homatropine; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Hydrocodone; Ibuprofen: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Hydrocodone; Phenylephrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Hydrocodone; Pseudoephedrine: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
    Hydromorphone: (Major) 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. Opiate antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to hydromorphone. 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.
    Ibuprofen; Oxycodone: (Major) 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.
    Levomethadyl: (Major) 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.
    Levorphanol: (Major) 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.
    Lofexidine: (Major) Separate administration of lofexidine and oral naltrexone by 2 hours as simultaneous administration may reduce the efficacy of naltrexone. Coadministration of lofexidine and oral naltrexone resulted in statistically significant differences in the steady state pharmacokinetics of naltrexone. This interaction is not expected if naltrexone is administered by non-oral routes.
    Meperidine: (Major) 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.
    Meperidine; Promethazine: (Major) 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.
    Methadone: (Major) 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.
    Methylnaltrexone: (Major) Avoid concomitant use of methylnaltrexone with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
    Morphine: (Major) 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 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7 to 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.
    Morphine; Naltrexone: (Major) 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 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7 to 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.
    Nabilone: (Moderate) Concomitant administration of naltrexone and nabilone enhances the 'positive' subjective effects of nabilone. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers.
    Nalbuphine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 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 (respiratory insufficiency or arrest or circulatory collapse) 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.
    Naldemedine: (Major) Avoid concomitant use of naldemedine with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
    Naloxegol: (Major) Avoid concomitant use of naloxegol with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
    Opiate Agonists-Antagonists: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 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 (respiratory insufficiency or arrest or circulatory collapse) 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.
    Oxycodone: (Major) 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.
    Oxymorphone: (Major) 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. Naltrexone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxymorphone overdose. 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.
    Pentazocine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 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 (respiratory insufficiency or arrest or circulatory collapse) 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.
    Pentazocine; Naloxone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 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 (respiratory insufficiency or arrest or circulatory collapse) 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.
    Phenothiazines: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
    Propoxyphene: (Major) 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.
    Remifentanil: (Major) 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. The usual doses of remifentanil will be ineffective in patients receiving naltrexone. 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. However, respiratory depression from remifentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. 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.
    Sufentanil: (Major) 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. The usual doses of sufentanil will be ineffective in patients receiving naltrexone. 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. However, respiratory depression from sufentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. 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.
    Tapentadol: (Major) 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 (respiratory insufficiency or arrest or circulatory collapse) 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.

    PREGNANCY AND LACTATION

    Pregnancy

    The use of naltrexone for a substance abuse disorder during pregnancy should be considered only if supportive substance abuse prevention measures are ineffective. There are no adequate and well-controlled studies of naltrexone use in pregnant women to be informative of any drug-associated risks for birth defects or miscarriage, adverse maternal outcomes, or fetal outcomes. If treatment with naltrexone is selected, the potential benefit to the mother versus the potential risk to the fetus should be evaluated. There are known risks of opiate and alcohol addiction to the fetus. Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Published studies have also demonstrated that alcohol is associated with fetal harm including growth restriction, facial abnormalities, central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Daily oral administration of naltrexone to female rats and rabbits increased the incidence of early fetal loss at exposures 11 times or more and 2 times or more the human exposure, respectively. Daily oral administration of naltrexone to pregnant rats and rabbits during the period of organogenesis did not induce malformation at exposures up to 175 times and 14 times the human exposure, respectively. The effects of naltrexone during labor and delivery are unknown.

    The developmental health benefits of breast-feeding should be considered along with the mother's clinical need for naltrexone and any potential adverse effects on the breastfed infant from naltrexone or the mother's underlying maternal condition. Naltrexone and its metabolite 6-beta-naltrexol are present in human breast milk. There are no data on the effects on the breastfed infant or the effects on milk production. Alcohol dependence and opiate addiction are known to have potential adverse drug risks to the nursing infant; alcohol and many opiates are excreted in breast milk.

    MECHANISM OF ACTION

    Mechanism of Action: Like naloxone, naltrexone is a competitive antagonist at opiate receptors mu, kappa, and delta. Opiate receptors have been reclassified by an International Union of Pharmacology subcommittee as OP1 (delta), OP2 (kappa), and OP3 (mu). Naltrexone can either displace opiate agonists from binding at these receptors or prevent opiate binding. Naltrexone does not antagonize the effects of non-opiates such as cocaine, ethanol, amphetamines, barbiturates, or benzodiazepines. Blockade of opiate receptors by naltrexone is a competitive phenomenon and results in elimination of the euphoric effect of opiates. At usual opiate concentrations, naltrexone's greater affinity for the receptor prevents the binding of the opiate agonist to the receptor. However, when opiate concentrations are extremely high, the opiate can displace naltrexone, and respiratory depression and/or death is possible. Although naltrexone itself may possess some agonistic properties, these are minor compared to its potent antagonistic actions. Naltrexone is 17-times more potent than nalmorphine and twice as potent as naloxone. In patients who are physically dependent on opiates, naltrexone will precipitate an opiate withdrawal syndrome. Naltrexone use is not associated with tolerance or dependence, therefore, withdrawal from naltrexone does not occur. When co-administered with opiate agonists, naltrexone blocks the physical dependence to morphine, heroin, and other opiate agonists. Depending on the dose, the clinical effects of naltrexone can persist for up to 72 hours.Endogenous opiods such as beta-endorphins and enkephalins may play an important role in alcoholism. An opioid reward system mediated by mu- and delta-receptors and an opposing aversions system mediated by kappa-receptors must be in balance to maintain a neutral state in regards to the development of addiction. Several therories regarding alcohol addiction and the function of endongeous opioids exist. All of these therories are based on an imbalance in favor of the endongenous reward pathways due to alcohol. Naltrexone inhibits the effects of endogenous opioids and decreases the positive or reward pathways associated with alcoholism. Naltrexone is not aversive therapy and will not produce a disulfiram-like reaction if opiates or ethanol are ingested while receiving naltrexone.

    PHARMACOKINETICS

    Naltrexone is administered orally or intramuscularly. Naltrexone is widely distributed throughout the body, and antagonistic activity appears to be related to plasma and tissue concentrations.CSF concentrations are not known. Protein binding is roughly 21—28%. Naltrexone is metabolized to 6-beta-naltrexol, which also has antagonistic activity but is less potent than its parent. Significantly less 6-beta-naltrexol is generated following IM administration of naltrexone compared to administration of oral naltrexone due to a reduction in first-pass hepatic metabolism. Two other minor metabolites have been identified: 2-hydroxy-3-methoxy-6-beta-naltrexol and 2-hydroxy-3-methyl-naltrexone. The cytochrome P450 system is not involved in the metabolism of naltrexone. There appears to be little accumulation of naltrexone and 6-beta-naltrexol after chronic administration. Naltrexone is a highly extracted drug (> 98% metabolized), and extra-hepatic sites of metabolism may exist. Following hepatic metabolism, both naltrexone and its metabolites conjugate with glucuronic acid. The maximum serum concentration and systemic exposure for both naltrexone and 6-beta-naltrexol are dose proportional. Total naltrexone exposure is 3—4 fold higher after a single, 380 mg IM injection as compared with daily oral doses of 50 mg for 28 days.
     
    Both naltrexone and its metabolite are excreted primarily by the kidney (53—79% of the dose). Only about 2% of naltrexone is excreted in the urine unchanged within 24 hours. 6-beta-naltrexol appears to undergo renal tubular secretion. Although naltrexone and its metabolites may undergo enterohepatic recycling, fecal elimination is a minor elimination pathway. The mean elimination half-life of naltrexone after oral administration is 4 hours, and the elimination half-life of 6-beta-naltrexol is roughly 14 hours. The mean elimination half-life of both naltrexone and 6-beta-naltrexol after intramuscular administration is 5—10 days; elimination of naltrexone is dependent on erosion of the polymer.

    Oral Route

    Oral absorption is rapid and almost complete (roughly 96%). Due to extensive first-pass metabolism in the liver, however, only 5—40% of the drug reaches the systemic circulation unchanged. Studies indicate that oral naltrexone 50 mg will block the pharmacologic effects of 25 mg IV heroin for as long as 24 hours. Additional data suggest that doubling the dose of naltrexone provides blockade for 48 hours and tripling the dose provides blockade for up to 72 hours.

    Intramuscular Route

    After IM naltrexone administration, an initial drug peak occurs around 2 hours after the injection. A second peak occurs 2—3 days later; measurable concentrations are available for more than 1 month. Steady-state is achieved at the end of the dosing interval after the first injection. First pass metabolism is reduced with IM administration.