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  • CLASSES

    Anxiolytics, Non-Benzodiazepines
    First generation (sedating) Antihistamines
    Other Antiemetics and Antinauseants

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral sedating antihistamine of the piperazine class
    Used commonly for histamine-mediated pruritus due to atopy or for treating other allergic conditions
    Sometimes used perioperatively as a sedative/anxiolytic and antiemetic

    COMMON BRAND NAMES

    ANX, Atarax, Hyzine, Rezine, Vistaril

    HOW SUPPLIED

    ANX/Atarax/Hydroxyzine Hydrochloride/Rezine Oral Tab: 10mg, 25mg, 50mg
    Atarax/Hydroxyzine Hydrochloride Oral Sol: 5mL, 10mg
    Hydroxyzine Hydrochloride/Hyzine/Vistaril Intramuscular Inj Sol: 1mL, 25mg, 50mg
    Hydroxyzine Pamoate/Vistaril Oral Cap: 25mg, 50mg, 100mg
    Hydroxyzine Pamoate/Vistaril Oral Susp: 5mL, 25mg

    DOSAGE & INDICATIONS

    For the short-term treatment of anxiety, tension, and psychomotor agitation in conditions of emotional stress.
    Oral dosage
    Adults

    50 to 100 mg PO 4 times daily as needed, adjusted to patient response. The efficacy of hydroxyzine as an anti-anxiety agent in long-term use (i.e., more than 4 months) has not been established. Periodically reassess the clinical response of the individual patient.

    Geriatric Adults

    50 to 100 mg PO 4 times daily as needed is the usual adult dose, adjusted to patient response. In general, begin with a lower dose in the geriatric adult and monitor closely. The efficacy of hydroxyzine as an anti-anxiety agent in long-term use (i.e., more than 4 months) has not been established. Periodically reassess the clinical response of the individual patient. In general, begin with a lower dose in the geriatric adult and monitor closely. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of anxiolytics in long-term care facility (LTCF) residents. According to OBRA, hydroxyzine is considered inappropriate for use as an anxiolytic in skilled care residents.

    Children and Adolescents 6 years and older

    50 to 100 mg/day PO, given in divided doses. Alternatively, some pediatric texts recommend 2 mg/kg/day PO given in divided doses every 6 to 8 hours as needed. Other alternatives include 15 mg/m2/day given in divided doses.

    Children less than 6 years

    50 mg/day PO, given in divided doses. Alternatively, some pediatric texts recommend 2 mg/kg/day PO given in divided doses every 6 to 8 hours as needed. Other alternatives include 15 mg/m2/day given in divided doses.

    Intramuscular dosage
    Adults

    50 to 100 mg IM initially, may repeat every 4 to 6 hours as needed. Switch to oral therapy when practicable.

    Geriatric Adults

    50 to 100 mg IM initially, may repeat every 4 to 6 hours as needed. In general, begin with a lower dose and monitor closely. Switch to oral therapy when practicable. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of anxiolytics in long-term care facility (LTCF) residents. According to OBRA, hydroxyzine is considered inappropriate for use as an anxiolytic in skilled care residents.

    For the treatment of pruritus due to histamine-mediated conditions or due to allergic conditions like chronic urticaria (e.g., chronic idiopathic urticaria), atopic dermatitis or contact dermatitis.
    Oral dosage
    Adults

    25 mg PO 3 to 4 times per day as needed.

    Children and Adolescents 6 years and older

    50 to 100 mg/day PO, in divided doses. Alternatively, some pediatric texts recommend 2 mg/kg/day PO given in divided doses every 6 to 8 hours as needed. Other alternatives include 15 mg/m2/day given in divided doses.

    Children less than 6 years

    50 mg/day PO, in divided doses. Alternatively, some pediatric texts recommend 2 mg/kg/day PO given in divided doses every 6 to 8 hours as needed. Other alternatives include 15 mg/m2/day given in divided doses.

    For post-operative nausea/vomiting (PONV) and post-operative nausea/vomiting (PONV) prophylaxis.
    Intramuscular dosage
    Adults

    The recommended dose is 25 to 100 mg IM as a single dose.

    Children and Adolescents

    The recommended dose is 1.1 mg/kg IM as a single dose.

    For procedural sedation or adjunctively for pre-and postoperative or pre-and post-partum therapy to permit dosage reduction of narcotic analgesia.
    Oral dosage
    Adults

    50 to 100 mg PO is the recommended dose.

    Children and Adolescents

    0.6 mg/kg PO is the recommended dose.

    Intramuscular dosage
    Adults

    The recommended dose is 25 to 100 mg IM.

    Children and Adolescents

    The recommended dose is 1.1 mg/kg IM.

    For the short term treatment of insomnia†.
    Oral dosage
    Adults

    The recommended dose is 50 to 100 mg PO given 30 to 60 minutes before bedtime.

    Geriatric Adults

    The recommended adult dose is 50 mg to 100 mg PO given 30 to 60 minutes before bedtime. In general, start geriatric patients on a lower dose of hydroxyzine and closely monitor. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of sedative/hypnotics in long-term care facility (LTCF) residents. According to OBRA, hydroxyzine is not considered a medication of choice for the management of insomnia, especially in geriatric patients. Max: 50 mg/day PO in residents meeting criteria for treatment, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. All sleep medications should be used in accordance with approved product labeling when labeling is available. If the sleep agent is used routinely and is beyond the manufacturer's recommendations for duration of use, the facility should attempt a quarterly taper unless clinically contraindicated as defined in the OBRA guidelines.

    Intramuscular dosage
    Adults

    The recommended dose is 50 mg IM given 30 to 60 minutes before bedtime.

    For the treatment of allergic rhinitis† and for allergic rhinitis prophylaxis†.
    Oral dosage
    Adults

    Hydroxyzine is not commonly used for this purpose. However, doses of up to 150 mg/day PO total have been reported effective for seasonal allergies. Drowsiness and dry mouth are frequently reported.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    400 mg/day PO.

    Geriatric

    400 mg/day PO.

    Adolescents

    100 mg/day PO or 2 mg/kg/day PO.

    Children

    >= 6 years: 100 mg/day PO or 2 mg/kg/day PO.
    < 6 years: 50 mg/day PO or 2 mg/kg/day PO.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosage reduction may be necessary based on clinical response and degree of hepatic impairment; hydroxyzine is primarily metabolized by the liver.

    Renal Impairment

    CrCl > 50 mL/min: No dosage adjustment needed.
    CrCl <= 50 mL/min: Dosage reduction may be necessary; a 50% dosage reduction is recommended.
     
    Intermittent hemodialysis
    See dosage for CrCl < 10 mL/min. Hydroxyzine is not effectively removed by hemodialysis; may accumulate in ESRD.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    All dosage forms: May administer without regard to meals.

    Oral Liquid Formulations

    All dosage forms: May administer without regard to meals.
    Oral suspension: Shake well prior to each use. Measure with calibrated device for accurate dosage.
    Oral syrup: Measure with calibrated device for accurate dosage.

    Injectable Administration

    Hydroxyzine injection is intended only for intramuscular administration. Do NOT, under any circumstances, inject subcutaneously, intra-arterially or intravenously.
    Visually inspect products for particulate matter and discoloration prior to administration, whenever solution and container permit.

    Intramuscular Administration

    Inject intramuscularly well within the body of a relatively large muscle. Inadvertent subcutaneous injection may result in significant tissue damage.
    Adults: The preferred site is the upper outer quadrant of the buttock, (i.e., the gluteus maximus), or the mid-lateral thigh. The deltoid area should be used only if well developed such as in certain adults, and then only with caution to avoid radial nerve injury. Do NOT inject IM into the lower and mid-third of the upper arm.
    Children: Preferably administer in the mid-lateral muscles of the thigh. The deltoid area should be used only if well developed such as in certain older children, and then only with caution to avoid radial nerve injury. Do NOT inject IM into the lower and mid-third of the upper arm.
    Infants and small children: Preferably administer in the mid-lateral muscles of the thigh. The periphery of the upper outer quadrant of the gluteal region should be used only when necessary, such as in burn patients, to minimize the possibility of damage to the sciatic nerve.[47129]

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    ANX :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Atarax:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Hyzine :
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Rezine:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Vistaril:
    - Store below 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Hydroxyzine hypersensitivity

    Hydroxyzine is contraindicated for use in patients with a known hydroxyzine hypersensitivity or hypersensitivity to any of the formulation components. Also, hydroxyzine is contraindicated in patients with a cetirizine hypersensitivity or levocetirizine hypersensitivity, as these are known human metabolites of hydroxyzine. Hydroxyzine may rarely cause acute generalized exanthematous pustulosis (AGEP), a serious skin reaction characterized by fever and numerous small, superficial, non-follicular, sterile pustules, arising within large areas of edematous erythema. Inform patients about the signs of AGEP, and discontinue hydroxyzine at the first appearance of a skin rash, worsening of pre-existing skin reactions which hydroxyzine may be used to treat, or any other sign of hypersensitivity. If signs or symptoms suggest AGEP, do not resume hydroxyzine therapy and consider alternative therapy. Avoid cetirizine or levocetirizine in patients who have experienced AGEP or other hypersensitivity reactions with hydroxyzine, due to the risk of cross-sensitivity.  

    Asthma, chronic obstructive pulmonary disease (COPD)

    The anticholinergic activity of sedating antihistamines (H-1 blockers) like hydroxyzine may result in thickened bronchial secretions in the respiratory tract and may aggravate chronic obstructive pulmonary disease (COPD) in some patients. Although antihistamines should generally be avoided during an acute asthmatic attack, the use of antihistamines is not precluded in all patients with asthma or COPD. Antihistamines can reverse some of the harmful effects of histamine in patients with an allergic component to their asthma. Antihistamines are typically not contraindicated in asthma unless previous adverse reactions to the drugs have been observed.

    Bradycardia, cardiac disease, electrolyte imbalance, heart failure, hypokalemia, hypomagnesemia, long QT syndrome, myocardial infarction, QT prolongation, torsade de pointes, ventricular arrhythmias

    Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP); therefore, the drug is contraindicated in patients with a known history of QT prolongation. The majority of the post-marketing reports for QT prolongation with hydroxyzine occurred in patients with other risk factors for QT prolongation/TdP (e.g., pre-existing cardiac disease, uncorrected electrolyte imbalance such as hypokalemia or hypomagnesemia, or concomitant arrhythmogenic drug use). Hydroxyzine should be used with caution in patients with risk factors for QT prolongation, including congenital long QT syndrome, a family history of long QT syndrome, other conditions that predispose to QT prolongation and ventricular arrhythmias, as well as recent myocardial infarction, uncompensated heart failure, and bradycardia. Caution is recommended during the concomitant use of drugs known to prolong the QT interval. In addition, although cardiovascular effects of piperazine antihistamines like hydroxyzine are uncommon, antihistamines should generally be used conservatively in patients with cardiac disease. The quinidine-like local anesthetic and anticholinergic effects of some antihistamines are responsible for the adverse cardiac effects that have been observed including tachycardia, ECG changes, hypotension, and arrhythmias, particularly with overdosage. Hydroxyzine overdose may cause QT prolongation and TdP; ECG monitoring is recommended in cases of hydroxyzine overdose.

    Closed-angle glaucoma, contact lenses

    Hydroxyzine, like other antihistamines, should be used conservatively in patients with closed-angle glaucoma. Increased intraocular pressure may occur from the anticholinergic actions of the drug, precipitating or aggravating glaucoma. Elderly patients may be more susceptible to the anticholinergic ocular effects of antihistamines. Other ocular effects resulting from the anticholinergic effects of hydroxyzine include dry eyes or blurred vision. This may be of significance in the wearers of contact lenses.

    Ileus, prostatic hypertrophy, urinary retention

    Because of the anticholinergic effects inherent to antihistamine agents like hydroxyzine, a worsening of symptoms may be seen in patients with risks for urinary retention, such as patients with benign prostatic hypertrophy or a previous history of urinary retention. Antihistamines and other agents with anticholinergic activity should be avoided in patients with an ileus. The elderly are more susceptible to the anticholinergic effects of drugs since there is a decline in endogenous cholinergic activity that occurs with age.

    Dialysis, renal failure, renal impairment

    Use hydroxyzine with caution in patients with moderate to severe renal impairment. Prolongation of the drug half-life and reduced clearances of the drug and its metabolites may occur. Neither hydroxyzine or the metabolite, cetirizine, are appreciably removed during dialysis, and accumulation may occur in patients with renal failure. Dosage reduction of hydroxyzine may be necessary and has been recommended in patient populations with reduced renal function. Elderly patients may be more likely to have age-related decline in renal function; use care in dose selection.

    Biliary cirrhosis, hepatic disease

    Hydroxyzine is extensively metabolized in the liver. Although hydroxyzine may be prescribed for patients with pruritus secondary to hepatic disease, the metabolism of hydroxyzine may be reduced in the presence of hepatic impairment. Hydroxyzine elimination is impaired in patients with primary biliary cirrhosis. Those with other significant hepatic disease should be monitored for side effects. Dosage adjustments may be required for those with hepatic disease based on clinical response and tolerance.

    Labor, pregnancy

    No adequately large, controlled, prospective studies exist for the use of hydroxyzine in early human pregnancy. Thus the manufacturer of the drug considers use in the first trimester of pregnancy (early pregnancy) to be contraindicated, based on the lack of adequate human study and the fact that the drug is teratogenic in mice, rats, and rabbits. Smaller, earlier analyses of hydroxyzine exposure during early pregnancy indicate a possible relationship between drug exposure in the first trimester and minor congenital abnormalities in the fetus; more recent epidemiologic and prospective data have not concurred and appear to indicate a low potential for fetal risk in humans. However, prospective data of adequate sample size are not available to draw absolute conclusions. Antihistamines are usually not recommended for use in the last 2 weeks of pregnancy due to a possible association between these drugs and retrolental fibroplasia in premature babies. Seizures, thought to be due to hydroxyzine withdrawal, have also been reported in a newborn whose mother was taking hydroxyzine during the third trimester. Hydroxyzine is sometimes given intermittently during labor or around the time of obstetric delivery to relieve anxiety, and is usually considered safe and effective for this purpose; however, occasional fetal heart rate variability might be observed. When used during labor and concurrently with narcotics, the narcotic requirement may be reduced as much as 50% and this reduction in needed narcotic therapy may be of benefit to mother and fetus. Use concurrent narcotics with caution to avoid hypotension.

    Breast-feeding

    The manufacturer warns against the use of hydroxyzine during breast-feeding. It is unknown whether hydroxyzine is excreted into breast milk; however, the molecular weight of the drug is low enough that excretion into breast milk should be expected. The effects of the drug on the nursing infant are unknown. In general, many first-generation antihistamines are not recommended for use during lactation, since irritability, drowsiness, unusual excitement or other infant effects might be observed. Antihistamines can lower basal prolactin secretion and may interfere with the establishment of lactation. Consider treatment alternatives to hydroxyzine. Loratadine may be considered as an alternative for the treatment of allergy symptoms. Because of its lack of sedation and low milk concentrations, maternal use would not be expected to cause adverse effects in breast-fed babies and loratadine is considered usually compatible with breast-feeding. The British Society for Allergy and Clinical Immunology also recommends loratadine at the lowest dose as a preferred antihistamine in breast-feeding women. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Infants, neonates, premature neonates

    Hydroxyzine safety and efficacy has not been established in infants. Hydroxyzine may cause subjective somnolence in children, which may temporarily impair cognitive function. Paradoxically, hyperexcitability can occur in pediatric patients. Antihistamines should not be used in neonates or premature neonates; these age groups are especially sensitive to anticholinergic effects and the use of antihistamines may increase the risk of CNS stimulation or convulsions.

    Anticholinergic medications, geriatric

    The geriatric patient is generally more likely to experience anticholinergic or other CNS side effects of classic sedating antihistamines. Initially, low doses of hydroxyzine should be used in the older adult, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The anticholinergic effects of hydroxyzine are additive to those of other anticholinergic medications, particularly in the elderly. According to the Beers Criteria, first generation sedating antihistamines, including hydroxyzine, are considered potentially inappropriate medications (PIMs) for use in geriatric patients and should be avoided in this population because they are highly anticholinergic, there is reduced clearance in advanced age, tolerance develops when used as hypnotics, and there is a greater risk of anticholinergic effects including confusion, dry mouth, constipation, and other anticholinergic actions and toxicity compared to younger adults. The Beers expert panel recommends avoiding drugs with strong anticholinergic properties, such as hydroxyzine, in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: dementia/cognitive impairment (adverse CNS effects), delirium/high risk of delirium (possible new-onset or worsening delirium), or lower urinary tract symptoms/benign prostatic hyperplasia in men (possible urinary retention or hesitancy). The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, cough, cold, and allergy medications should be used only for a limited duration (less than 14 days) unless there is documented evidence of enduring symptoms that cannot otherwise be alleviated and for which a cause cannot be identified and corrected. Antihistamines (e.g., first generation agents) have strong anticholinergic properties and are not considered medications of choice in older individuals. If administered, antihistamines should be used in the smallest possible dose in individuals who are susceptible to anticholinergic side effects or who are receiving other medications with anticholinergic properties. Anticholinergics may cause excessive sedation, confusion, cognitive impairment, distress, dry mouth, constipation, and urinary retention. Many of these effects may lead to other adverse consequences, such as falls. The OBRA guidelines provide criteria for use and tapering requirements for sedating antihistamines used as sedative/hypnotics, such as hydroxyzine. OBRA considers hydroxyzine inappropriate for use as an anxiolytic.

    Coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion, ethanol intoxication

    Drowsiness has been reported with hydroxyzine; patients receiving this drug should be advised to avoid driving or operating machinery until the effects of the drug are known. The effects of ethanol may be additive to hydroxyzine; patients should be advised that ethanol ingestion, and particularly ethanol intoxication, should be avoided while taking hydroxyzine. Rarely, cardiac arrests and death have been reported in association with the combined use of hydroxyzine hydrochloride intramuscularly and other central nervous system (CNS) depressants. When coadministration with other CNS depressants occurs with hydroxyzine, such as preoperatively or prepartum, be alert that narcotic or other CNS depressant dose requirements may need to be reduced as much as 50%. The efficacy of hydroxyzine as an adjunctive pre- and post- surgery sedative medication has also been well established, especially with regard to its ability to relieve anxiety, control emesis, and reduce the amount of narcotic required.

    Intravenous administration, subcutaneous administration, tissue necrosis

    Intramuscular hydroxyzine injections may result in severe injection site reactions (including extensive tissue damage, tissue necrosis, and gangrene) requiring surgical intervention (including debridement, skin grafting and amputation). Hydroxyzine hydrochloride intramuscular solution is intended only for intramuscular administration and should not, under any circumstances, be injected via subcutaneous administration, intra-arterial administration, or intravenous administration.

    ADVERSE REACTIONS

    Severe

    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    tardive dyskinesia / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    tissue necrosis / Early / Incidence not known
    torsade de pointes / Rapid / Incidence not known

    Moderate

    blurred vision / Early / Incidence not known
    constipation / Delayed / Incidence not known
    urinary retention / Early / Incidence not known
    dysarthria / Delayed / Incidence not known
    impaired cognition / Early / Incidence not known
    palpitations / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    confusion / Early / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    dystonic reaction / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    psychosis / Early / Incidence not known
    dyskinesia / Delayed / Incidence not known
    hallucinations / Early / Incidence not known
    priapism / Early / Incidence not known
    hemolysis / Early / Incidence not known
    respiratory depression / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known

    Mild

    mydriasis / Early / Incidence not known
    xerophthalmia / Early / Incidence not known
    xerostomia / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    fatigue / Early / Incidence not known
    asthenia / Delayed / Incidence not known
    restlessness / Early / Incidence not known
    weakness / Early / Incidence not known
    headache / Early / Incidence not known
    dizziness / Early / Incidence not known
    drowsiness / Early / Incidence not known
    insomnia / Early / Incidence not known
    appetite stimulation / Delayed / Incidence not known
    agitation / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    rash / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    tremor / Early / Incidence not known
    injection site reaction / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Acetaminophen; Butalbital; Caffeine: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates. (Moderate) Concomitant use of codeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Codeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of codeine.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Dihydrocodeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of dihydrocodeine.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Codeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of codeine.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Additive CNS depression may occur if dichloralphenazone is used concomitantly with any of the sedating H1 blockers. Use caution with this combination. Dosage reduction of one or both agents may be necessary.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Acetaminophen; Oxycodone: (Moderate) Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Acetaminophen; Pentazocine: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with sedating H1-blockers may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
    Acetaminophen; Propoxyphene: (Moderate) Concomitant use of propoxyphene with other CNS depressants can potentiate respiratory depression and, or sedation. In addition, chlorpheniramine and diphenhydramine inhibit CYP2D6, an enzyme responsible for the metabolism of propoxyphene. Monitor these patients. Overdosage of propoxyphene in combination with other potent CNS depressants is a major cause of drug-related death; fatalities within the first hour of overdosage are not uncommon.
    Acetaminophen; Tramadol: (Moderate) An enhanced CNS depressant effect may occur when sedating h1-blockers are combined with other CNS depressants including tramadol.
    Albuterol: (Minor) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists, like albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.This risk may be more clinically significant with long-acting beta-agonists than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Albuterol; Ipratropium: (Minor) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists, like albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.This risk may be more clinically significant with long-acting beta-agonists than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution.
    Alfentanil: (Moderate) Concomitant use of alfentanil with other CNS depressants, such as sedating H1 blockers can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Alfuzosin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include alfuzosin.
    Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
    Amantadine: (Moderate) Medications with significant anticholinergic activity may potentiate the anticholinergic effects of amantadine, and may increase the risk of antimuscarinic-related side effects. Additive drowsiness may also occur.
    Ambenonium Chloride: (Moderate) The therapeutic benefits of ambenonium may be diminished when coadministered with drugs known to exhibit anticholinergic properties including sedating H1-blockers. When concurrent use cannot be avoided, monitor the patient for reduced ambenonium efficacy.
    Amiodarone: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include amiodarone.
    Amobarbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Amoxapine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating h1-blockers. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include clarithromycin.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include clarithromycin.
    Amphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
    Amphetamine; Dextroamphetamine Salts: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
    Amphetamine; Dextroamphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
    Anagrelide: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include anagrelide.
    Anticholinergics: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Apomorphine: (Major) Apomorphine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2 to 10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended. In addition, apomorphine causes significant somnolence. Concomitant administration of apomorphine and hydroxyzine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
    Apraclonidine: (Minor) No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as the anxiolytics, sedatives, and hypnotics, including barbiturates or benzodiazepines.
    Arformoterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Aripiprazole: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics.
    Arsenic Trioxide: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include arsenic trioxide.
    Artemether; Lumefantrine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include artemether; lumefantrine.
    Asenapine: (Major) Asenapine should be avoided with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect. In addition, using drugs that can cause CNS depression, such as sedating H1-blockers, concomitantly with asenapine may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates. (Moderate) Concomitant use of codeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Codeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of codeine.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Dihydrocodeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of dihydrocodeine.
    Aspirin, ASA; Carisoprodol: (Moderate) Carisoprodol is metabolized to meprobamate, a significant CNS depressant. Carisoprodol can cause additive CNS depression if used concomitantly with other CNS depressants. Additive effects of sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness, may occur if carisoprodol is taken with sedating H1-blockers. Utilize appropriate caution if carisoprodol is coadministered with another CNS depressant.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Carisoprodol is metabolized to meprobamate, a significant CNS depressant. Carisoprodol can cause additive CNS depression if used concomitantly with other CNS depressants. Additive effects of sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness, may occur if carisoprodol is taken with sedating H1-blockers. Utilize appropriate caution if carisoprodol is coadministered with another CNS depressant. (Moderate) Concomitant use of codeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Codeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of codeine.
    Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Atomoxetine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include atomoxetine.
    Atracurium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Atropine; Difenoxin: (Moderate) An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly.
    Atropine; Diphenoxylate: (Moderate) An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Azelastine: (Major) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including sedating H1-blockers; avoid concurrent use.
    Azelastine; Fluticasone: (Major) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including sedating H1-blockers; avoid concurrent use.
    Azithromycin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include azithromycin.
    Baclofen: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including skeletal muscle relaxants, such as baclofen.
    Barbiturates: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Bedaquiline: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include bedaquiline.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Belladonna; Opium: (Moderate) Enhanced CNS depressant effects may occur when opium is combined with other CNS depressants, such as sedating H1 blockers.
    Benzodiazepines: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Use caution with this combination.
    Benzphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include metronidazole.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include metronidazole.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Budesonide; Formoterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Buprenorphine: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Hydroxyzine has a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with buprenorphine. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, if concurrent use of sedating H1-blockers and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buprenorphine; Naloxone: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Hydroxyzine has a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with buprenorphine. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, if concurrent use of sedating H1-blockers and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buspirone: (Moderate) The combination of buspirone and other CNS depressants, such as sedating h1-blockers, can increase the risk for sedation.
    Butabarbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Butorphanol: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
    Capsaicin; Metaxalone: (Moderate) Concomitant administration of metaxalone with other CNS depressants can potentiate the sedative effects of either agent.
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers.
    Carbidopa; Levodopa; Entacapone: (Moderate) COMT inhibitors, such as entacapone or tolcapone, should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Cariprazine: (Moderate) Due to the CNS effects of cariprazine, caution should be used when cariprazine is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics like hydroxyzine.
    Carisoprodol: (Moderate) Carisoprodol is metabolized to meprobamate, a significant CNS depressant. Carisoprodol can cause additive CNS depression if used concomitantly with other CNS depressants. Additive effects of sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness, may occur if carisoprodol is taken with sedating H1-blockers. Utilize appropriate caution if carisoprodol is coadministered with another CNS depressant.
    Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and hydroxyzine; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Postmarketing data indicate that hydroxyzine also causes QT prolongation and torsade de pointes (TdP).
    Cetirizine: (Major) Dry mouth, drowsiness and other antihistamine-related side effects may occur in patients receiving cetirizine. Due to the duplicative and additive nature of the pharmacology of cetirizine, concurrent use of sedating antihistamines (H1-blockers) is not recommended.
    Cetirizine; Pseudoephedrine: (Major) Dry mouth, drowsiness and other antihistamine-related side effects may occur in patients receiving cetirizine. Due to the duplicative and additive nature of the pharmacology of cetirizine, concurrent use of sedating antihistamines (H1-blockers) is not recommended.
    Chlorcyclizine: (Moderate) Drugs that can cause CNS depression, if used concomitantly with iloperidone, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when iloperidone is given in combination with other centrally-acting medications, such as sedating H1-blockers.
    Chloroquine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include chloroquine.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Codeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of codeine.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Dihydrocodeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of dihydrocodeine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Dihydrocodeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of dihydrocodeine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpromazine: (Major) Chlorpromazine should be used cautiously and with close monitoring with hydroxyzine. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP).
    Chlorzoxazone: (Moderate) Additive CNS depression is possible if chlorzoxazone is used concomitantly with other CNS depressants including sedating H1-blockers. Additive effects of sedation and dizziness can occur, which can impair the ability to undertake tasks requiring mental alertness. Dosage adjustments of one or both medications may be necessary.
    Ciprofloxacin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ciprofloxacin.
    Cisapride: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of hydroxyzine with cisapride is contraindicated.
    Cisatracurium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Citalopram: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include citalopram.
    Clarithromycin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include clarithromycin.
    Clobazam: (Moderate) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects. Additive drowsiness may occur when clobazam is combined with CNS depressants such as sedating H1-blockers. In addition, caution is recommended when administering clobazam with medications extensively metabolized by CYP2D6 such as diphenhydramine because clobazam has been shown to inhibit CYP2D6 in vivo and may increase concentrations of drugs metabolized by this enzyme.
    Clozapine: (Major) Clozapine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation.
    Codeine: (Moderate) Concomitant use of codeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Codeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of codeine.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Codeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of codeine.
    Codeine; Phenylephrine; Promethazine: (Major) Promethazine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs with antimuscarinic activity like sedating H1-blockers. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants including sedating H1-blockers. (Moderate) Concomitant use of codeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Codeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of codeine.
    Codeine; Promethazine: (Major) Promethazine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs with antimuscarinic activity like sedating H1-blockers. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants including sedating H1-blockers. (Moderate) Concomitant use of codeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Codeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of codeine.
    COMT inhibitors: (Moderate) COMT inhibitors, such as entacapone or tolcapone, should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation.
    Crizotinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with hydroxyzine. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Postmarketing data indicate that hydroxyzine also causes QT prolongation as well as torsade de pointes (TdP).
    Cyclobenzaprine: (Moderate) The anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other medications with anticholinergic effects, such as cyclobenzaprine. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Dantrolene: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect (e.g., drowsiness) may occur when dantrolene is combined with other CNS depressants.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ritonavir.
    Dasatinib: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if hydroxyzine and dasatinib are coadministered. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Daunorubicin: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include certain anthracyclines. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Degarelix: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include degarelix.
    Desloratadine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
    Desloratadine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
    Deutetrabenazine: (Major) For patients taking a deutetrabenazine dosage more than 24 mg/day with hydroxyzine, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). Additionally, concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as hydroxyzine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Dexmedetomidine: (Moderate) Co-administration of dexmedetomidine with sedating antihistamines is likely to lead to an enhancement of CNS depression.
    Dextroamphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
    Dextromethorphan; Promethazine: (Major) Promethazine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs with antimuscarinic activity like sedating H1-blockers. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants including sedating H1-blockers.
    Dextromethorphan; Quinidine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include quinidine.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression, and death. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Dihydrocodeine should be used in reduced dosages if used concurrently with a CNS depressant. Also, consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Chlorpheniramine and diphenhydarmine are moderate inhibitors of CYP2D6. Coadministration may result in a reduction in the analgesic effect of dihydrocodeine.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Disopyramide: (Major) Disopyramide should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). In addition, the anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other medications with anticholinergic effects, such as disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Dofetilide: (Severe) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Because of the potential for TdP, use of hydroxyzine with dofetilide is contraindicated.
    Dolasetron: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include dolasetron.
    Dolutegravir; Rilpivirine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include rilpivirine.
    Donepezil: (Major) Donepezil should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP.
    Donepezil; Memantine: (Major) Donepezil should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP.
    Doxacurium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Dronabinol: (Moderate) Use caution if coadministration of dronabinol with antihistamines is necessary. Concurrent use of dronabinol, THC with antihistamines may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
    Dronedarone: (Severe) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Because of the potential for TdP, use of hydroxyzine with dronedarone is contraindicated.
    Droperidol: (Major) Droperidol should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
    Efavirenz: (Major) Coadministration of efavirenz and hydroxyzine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Post-marketing data indicate that hydroxyzine causes both QT prolongation and TdP.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of efavirenz and hydroxyzine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Post-marketing data indicate that hydroxyzine causes both QT prolongation and TdP.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and hydroxyzine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Post-marketing data indicate that hydroxyzine causes both QT prolongation and TdP.
    Eliglustat: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include eliglustat.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include rilpivirine.
    Encorafenib: (Major) Avoid coadministration of encorafenib and hydroxyzine due to QT prolongation. Encorafenib is associated with dose-dependent prolongation of the QT interval. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    Entacapone: (Moderate) COMT inhibitors, such as entacapone or tolcapone, should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation.
    Eribulin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include eribulin.
    Erythromycin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include erythromycin.
    Erythromycin; Sulfisoxazole: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include erythromycin.
    Escitalopram: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include escitalopram.
    Eszopiclone: (Moderate) A reduction in the dose of eszopiclone and concomitantly administered CNS depressants, such as sedating H1-blockers, should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Ethanol: (Moderate) Drowsiness may occur with the use of sedating antihistamines. Caution patients about the simultaneous use of alcohol, and caution that the effects of alcohol may be increased. Additive drowsiness and psychomotor impairment may occur.
    Etomidate: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Ezogabine: (Major) Ezogabine should be used cautiously and with close monitoring with hydroxyzine.Hydroxyzine is a sedating antihistamine (H1-blocker). Ezogabine has caused urinary retention requiring catheterization in some cases. The anticholinergic effects of hydroxyzine on the urinary tract may be additive. Additive sedation or other CNS effects may also occur. Post-marketing data indicate that hydroxyzine causes QT prolongation; ezogabine has also been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval.
    Fentanyl: (Major) Avoid coadministration of fentanyl with other CNS depressants when possible, as this significantly increases the risk for profound sedation, respiratory depression, hypotension, coma, and death. Reserve concomitant use of these drugs for patients in whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations possible and monitor patients closely for signs and symptoms of respiratory depression and sedation.
    Fingolimod: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include fingolimod.
    Flecainide: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include flecainide.
    Flibanserin: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
    Fluconazole: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include fluconazole.
    Fluoxetine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include fluoxetine.
    Fluoxetine; Olanzapine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include fluoxetine. (Moderate) Olanzapine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). In addition, olanzapine exhibits anticholinergic effects that may be clinically significant. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with olanzapine. Some medications exhibit additive anticholinergic effects include sedating H1-blockers. Olanzapine may also cause additive sedation with many of these drugs.
    Fluphenazine: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Fluphenazine, perphenazine, prochlorperazine, and trifluoperazine are associated with a possible risk for QT prolongation. Theoretically, these agents may increase the risk of QT prolongation if coadministered with drugs with a risk of QT prolongation. Administer these agents and drugs that can prolong the QT interval with caution. In addition, the anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other antimuscarinics. Other commonly used drugs with moderate to significant anticholinergic effects include most phenothiazines. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Fluticasone; Salmeterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluticasone; Vilanterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and hydroxyzine. Coadminister with caution. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP, particularly in patients with risk factors like pre-existing heart disease, electrolyte imbalances, or concomitant arrhythmogenic drug use. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Formoterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Formoterol; Mometasone: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as hydroxyzine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine also causes QT prolongation and TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fospropofol: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics like fospropofol.
    Gabapentin: (Moderate) Coadministration of gabapentin with anxiolytics, sedatives, and hypnotics may increase CNS depressive effects such as drowsiness and dizziness. Use caution when administering gabapentin with CNS depressants. Patients should limit activity until they are aware of how coadministration affects them.
    Galantamine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of galantamine.
    Gemifloxacin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include gemifloxacin.
    Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and hydroxyzine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Glycopyrrolate; Formoterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Granisetron: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include granisetron.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Halogenated Anesthetics: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include halogenated anesthetics. Also, because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Haloperidol: (Major) Haloperidol should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval.
    Heparin: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
    Histrelin: (Major) Consider periodic monitoring of EGCs for QT prolongation and monitor electrolytes if coadministration of histrelin and hydroxyzine is necessary; correct any electrolyte abnormalities. Androgen deprivation therapy (e.g., histrelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Postmarketing data indicate that hydroxyzine also causes QT prolongation and torsade de pointes (TdP).
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Hyaluronidase, Recombinant; Immune Globulin: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
    Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
    Hydantoins: (Moderate) Hydantoin anticonvulsants can theoretically add to the CNS depressant effects of other CNS depressants including the sedating H1 blockers.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as chlorpheniramine or diphenhydramine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydromorphone: (Moderate) Concomitant use of hydromorphone with other central nervous system (CNS) depressants can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include sedating H1-blockers. Prior to concurrent use of hydromorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If hydromorphone is used concurrently with a CNS depressant, a reduced dosage of hydromorphone and/or the CNS depressant is recommended; start with one-third to one-half of the estimated hydromorphone starting dose when using hydromorphone extended-release tablets. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and hydroxyzine. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Ibutilide: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ibutilide.
    Iloperidone: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include iloperidone. Drugs that can cause CNS depression, if used concomitantly with iloperidone, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when iloperidone is given in combination with other centrally-acting medications, such as sedating H1-blockers.
    Indacaterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Indacaterol; Glycopyrrolate: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with hydroxyzine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Isocarboxazid: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Consider alternative therapy to antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many non-prescription products for coughs, colds, allergy, hay fever or insomnia contain sedating antihistamines. Patients receiving an MAOI should be counseled that it is essential to consult their healthcare provider or pharmacist prior to the use of any non-prescription products. Patients should also be advised against driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
    Itraconazole: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include itraconazole.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with hydroxyzine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    Kava Kava, Piper methysticum: (Major) Any substance that acts on the CNS may interact with kava kava. These interactions are probably pharmacodynamic in nature. Patients should probably avoid concomitant administration.
    Ketamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Ketoconazole: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ketoconazole.
    Lapatinib: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include lapatinib.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with hydroxyzine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    Leuprolide: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include leuprolide.
    Leuprolide; Norethindrone: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include leuprolide.
    Levalbuterol: (Minor) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists, like albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.This risk may be more clinically significant with long-acting beta-agonists than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Levocetirizine: (Major) Dry mouth, drowsiness and other antihistamine-related side effects may occur in patients receiving cetirizine. Due to the duplicative and additive nature of the pharmacology of cetirizine, concurrent use of sedating antihistamines (H1-blockers) is not recommended.
    Levofloxacin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include levofloxacin.
    Levomethadyl: (Moderate) Enhanced CNS depressant effects may occur when levomethadyl is combined with other CNS depressants, such as sedating H1 blockers.
    Levorphanol: (Moderate) Concomitant use of levorphanol with other CNS depressants such as sedating H1-blockers can potentiate the effects of levorphanol on respiration, blood pressure, and alertness. Severe hypotension, respiratory depression, profound sedation, or coma may occur. Prior to concurrent use of levorphanol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. When concomitant treatment with levorphanol with another CNS depressant is necessary, reduce the dose of 1 or both drugs. The initial dose of levorphanol should be reduced by approximately 50% or more when levorphanol is used with another drug that may depress respiration.
    Lithium: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include lithium. In addition, because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including hydroxyzine.
    Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with hydroxyzine due to the potential for additive QT prolongation and torsade de pointes (TdP). Additionally, monitor for excessive hypotension and sedation during coadministration as lofexidine can potentiate the effects of CNS depressants. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Long-acting beta-agonists: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like hydroxyzine, should be used cautiously and with close monitoring with loperamide.
    Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like hydroxyzine, should be used cautiously and with close monitoring with loperamide.
    Lopinavir; Ritonavir: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ritonavir.
    Loratadine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers.
    Loratadine; Pseudoephedrine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers.
    Loxapine: (Moderate) Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with other drugs having anticholinergic activity and CNS depressant properties such as traditional antipsychotic agents, including loxapine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other CNS effects may also occur.
    Lurasidone: (Moderate) Due to the CNS effects of lurasidone, caution should be used when lurasidone is given in combination with other centrally acting medications. Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as hydroxyzine. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    Magnesium Salts: (Minor) Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as sedating H1-blockers. Caution should be exercised when using these agents concurrently.
    Maprotiline: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include maprotiline. In addition, the anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with medications with anticholinergic effects, such as maprotiline. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Meclizine: (Major) Meclizine is an H1-blocker which exhibits significant anticholinergic effects. The anticholinergic effects of meclizine may be enhanced when combined with other drugs with antimuscarinic activity, including other sedating H1-blockers. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive sedation may also occur.
    Mefloquine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include mefloquine.
    Melatonin: (Moderate) Concomitant administration of sedating antihistamines and melatonin may cause additive CNS depression and should be used cautiously in combination. Especially use caution when combining melatonin with sedating antihistamines found in OTC sleep products, since over-sedation, CNS effects, or sleep-related behaviors may occur. Use of more than one agent for hypnotic purposes may increase the risk for over-sedation, CNS effects, or sleep-related behaviors. Be alert for unusual changes in moods or behaviors. Patients reporting unusual sleep-related behaviors likely should discontinue melatonin use.
    Meperidine: (Moderate) Enhanced CNS depressant effects may occur when meperidine is combined with other CNS depressants, such as sedating H1 blockers.
    Meperidine; Promethazine: (Major) Promethazine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs with antimuscarinic activity like sedating H1-blockers. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants including sedating H1-blockers. (Moderate) Enhanced CNS depressant effects may occur when meperidine is combined with other CNS depressants, such as sedating H1 blockers.
    Mephobarbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including sedating H1-blockers.
    Mesoridazine: (Moderate) The anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other antimuscarinics. Other commonly used drugs with moderate to significant anticholinergic effects include most phenothiazines. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Metaproterenol: (Minor) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists, like metaproterenol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.This risk may be more clinically significant with long-acting beta-agonists than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Metaxalone: (Moderate) Concomitant administration of metaxalone with other CNS depressants can potentiate the sedative effects of either agent.
    Methadone: (Major) Hydroxyzine should be used cautiously and with close monitoring with methadone due to the potential for increased risk of QT prolongation, torsade de pointes (TdP), and additive CNS depressant effects. Post-marketing data indicate that hydroxyzine causes QT prolongation and TdP. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. In addition, concomitant use of methadone with another CNS depressant, like hydroxyzine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; in opioid-naive adults, use an initial methadone dose of 2.5 mg every 12 hours. Also consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Methamphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of sedating H1-blockers. This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine. Coadminister with caution and monitor for altered response to drug therapy.
    Methocarbamol: (Moderate) Methocarbamol may cause additive CNS depression if used concomitantly with other CNS depressants such as sedating H1-blockers. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
    Methohexital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Metoclopramide: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
    Metronidazole: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include metronidazole.
    Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Metyrosine: (Moderate) The concomitant administration of metyrosine with sedating H1-blockers can result in additive sedative effects.
    Midostaurin: (Major) The concomitant use of midostaurin and hydroxyzine may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QT prolongation and torsade de pointes have been reported in postmarketing surveillance of hydroxyzine.
    Mifepristone: (Major) Avoid use together if possible; consider alternative therapies to hydroxyzine. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). Mifepristone is associated with a risk of QT prolongation and torsade de pointes (TdP). To minimize risk, the lowest effective dose of mifepristone should be used. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Minocycline: (Minor) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants, such as sedating H1-blockers. Caution should be exercised when using these agents concurrently.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and hydroxyzine. Coadminister with caution. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP, particularly in patients with risk factors like pre-existing heart disease, electrolyte imbalances, or concomitant arrhythmogenic drug use. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Mitotane: (Moderate) Mitotane can cause sedation, lethargy, vertigo, and other CNS side effects. Concomitant administration of mitotane and CNS depressants, including sedating h1-blockers, may cause additive CNS effects.
    Mivacurium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Molindone: (Moderate) An enhanced CNS depressant effect may occur when sedating h1-blockers are combined with other CNS depressants including molindone.
    Monoamine oxidase inhibitors: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Consider alternative therapy to antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many non-prescription products for coughs, colds, allergy, hay fever or insomnia contain sedating antihistamines. Patients receiving an MAOI should be counseled that it is essential to consult their healthcare provider or pharmacist prior to the use of any non-prescription products. Patients should also be advised against driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
    Morphine: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include sedating H1-blockers. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
    Morphine; Naltrexone: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include sedating H1-blockers. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
    Moxifloxacin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include moxifloxacin.
    Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants, such as sedating H1-blockers, can potentiate the effects of nabilone on respiratory depression.
    Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants, such as sedating H1-blockers, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
    Nefazodone: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including nefazodone.
    Neuromuscular blockers: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and hydroxyzine; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Post-marketing data indicate that hydroxyzine causes QT prolongation and torsade de Pointes.
    Norfloxacin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include norfloxacin.
    Octreotide: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include octreotide.
    Ofloxacin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ofloxacin.
    Olanzapine: (Moderate) Olanzapine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). In addition, olanzapine exhibits anticholinergic effects that may be clinically significant. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with olanzapine. Some medications exhibit additive anticholinergic effects include sedating H1-blockers. Olanzapine may also cause additive sedation with many of these drugs.
    Olodaterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ritonavir.
    Ondansetron: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ondansetron.
    Orphenadrine: (Moderate) Orphenadrine has mild anticholinergic activity. Depending on the specific agent, additive anticholinergic effects may be seen when orphenadrine is used concomitantly with sedating H1-blockers.
    Osimertinib: (Major) Avoid coadministration of hydroxyzine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of hydroxyzine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with the use of both drugs in postmarketing experience.
    Oxycodone: (Moderate) Concomitant use of oxycodone with sedating H1-blockers may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxycodone, a reduced dosage of oxycodone and/or the CNS depressant is recommended; use an initial dose of oxycodone at 1/3 to 1/2 the usual dosage. Monitor for sedation and respiratory depression.
    Oxymorphone: (Moderate) Concomitant use of oxymorphone with other CNS depressants may produce additive CNS depressant effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants include sedating H1-blockers. Prior to concurrent use of oxymorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxymorphone, a reduced dosage of oxymorphone (1/3 to 1/2 of the usual dose) and/or the CNS depressant is recommended. If the extended-release oxymorphone tablets are used concurrently with a CNS depressant, it is recommended to use an initial dosage of 5 mg PO every 12 hours. Monitor for sedation or respiratory depression.
    Paliperidone: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include paliperidone. In addition, drugs that can cause CNS depression, if used concomitantly with paliperidone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when paliperidone is given in combination with other centrally-acting medications including sedating H1-blockers.
    Pancuronium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Panobinostat: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include panobinostat.
    Papaverine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as hydroxyzine could lead to enhanced sedation.
    Pasireotide: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include pasireotide.
    Pazopanib: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include pazopanib.
    Pentamidine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include pentamidine.
    Pentazocine: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with sedating H1-blockers may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
    Pentazocine; Naloxone: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with sedating H1-blockers may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
    Pentobarbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as sedating H1-blockers.
    Perphenazine: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Fluphenazine, perphenazine, prochlorperazine, and trifluoperazine are associated with a possible risk for QT prolongation. Theoretically, these agents may increase the risk of QT prolongation if coadministered with drugs with a risk of QT prolongation. Administer these agents and drugs that can prolong the QT interval with caution. In addition, the anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other antimuscarinics. Other commonly used drugs with moderate to significant anticholinergic effects include most phenothiazines. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Perphenazine; Amitriptyline: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Fluphenazine, perphenazine, prochlorperazine, and trifluoperazine are associated with a possible risk for QT prolongation. Theoretically, these agents may increase the risk of QT prolongation if coadministered with drugs with a risk of QT prolongation. Administer these agents and drugs that can prolong the QT interval with caution. In addition, the anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other antimuscarinics. Other commonly used drugs with moderate to significant anticholinergic effects include most phenothiazines. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Phenelzine: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Consider alternative therapy to antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many non-prescription products for coughs, colds, allergy, hay fever or insomnia contain sedating antihistamines. Patients receiving an MAOI should be counseled that it is essential to consult their healthcare provider or pharmacist prior to the use of any non-prescription products. Patients should also be advised against driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
    Phenobarbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Phentermine; Topiramate: (Major) Although not specifically studied, coadministration of CNS depressant drugs with topiramate may potentiate CNS depression such as dizziness or cognitive adverse reactions, or other centrally mediated effects of these agents. Monitor for increased CNS effects if coadministering.
    Phenylephrine; Promethazine: (Major) Promethazine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs with antimuscarinic activity like sedating H1-blockers. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants including sedating H1-blockers.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Coadministration may increase the risk for QT prolongation.
    Pimozide: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of hydroxyzine with pimozide is contraindicated.
    Pirbuterol: (Minor) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists, like pirbuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.This risk may be more clinically significant with long-acting beta-agonists than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Posaconazole: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include posaconazole.
    Pramipexole: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
    Pregabalin: (Moderate) Concomitant administration of pregabalin with CNS-depressant drugs, including sedating H1-blockers, can potentiate the CNS effects of either agent. Pregabalin can cause considerable somnolence and the combined use of ethanol or other CNS depressants with pregabalin may lead to an additive drowsy effect.
    Primaquine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include primaquine.
    Primidone: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Procainamide: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include procainamide.
    Procarbazine: (Moderate) Use procarbazine and sedating H1-blockers together with caution; additive central nervous system depression may occur.
    Prochlorperazine: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Fluphenazine, perphenazine, prochlorperazine, and trifluoperazine are associated with a possible risk for QT prolongation. Theoretically, these agents may increase the risk of QT prolongation if coadministered with drugs with a risk of QT prolongation. Administer these agents and drugs that can prolong the QT interval with caution. In addition, the anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other antimuscarinics. Other commonly used drugs with moderate to significant anticholinergic effects include most phenothiazines. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Promethazine: (Major) Promethazine should be used cautiously and with close monitoring with hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs with antimuscarinic activity like sedating H1-blockers. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants including sedating H1-blockers.
    Propafenone: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include propafenone.
    Propofol: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Propoxyphene: (Moderate) Concomitant use of propoxyphene with other CNS depressants can potentiate respiratory depression and, or sedation. In addition, chlorpheniramine and diphenhydramine inhibit CYP2D6, an enzyme responsible for the metabolism of propoxyphene. Monitor these patients. Overdosage of propoxyphene in combination with other potent CNS depressants is a major cause of drug-related death; fatalities within the first hour of overdosage are not uncommon.
    Quetiapine: (Major) Avoid coadminsitration of quetiapine and hydroxyzine. Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may also result in additive effects. Additive drowsiness or other CNS effects may occur.
    Quinidine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include quinidine.
    Quinine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include quinine.
    Ramelteon: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as ramelteon.
    Ranolazine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ranolazine.
    Rapacuronium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Rasagiline: (Moderate) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Rasagiline may be less likely to produce these interactions than other MAOIs, due to MAO-B selectivity. However, consider alternatives therapy to antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many non-prescription products for coughs, colds, allergy, hay fever or insomnia contain sedating antihistamines. Patients receiving rasagiline should be counseled that it is essential to consult their healthcare provider or pharmacist prior to the use of any non-prescription products. Patients should also be advised against driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
    Remifentanil: (Moderate) Concomitant use of remifentanil with other CNS depressants can potentiate the effects of remifentanil on respiration, sedation, and hypotension. A dose reduction of one or both drugs may be warranted.
    Ribociclib: (Major) Avoid coadministration of ribociclib with hydroxyzine due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with hydroxyzine due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Concomitant use may increase the risk for QT prolongation.
    Rilpivirine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include rilpivirine.
    Risperidone: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include risperidone. In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including risperidone.
    Ritonavir: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include ritonavir.
    Rituximab; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
    Rivastigmine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
    Rocuronium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Romidepsin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include romidepsin.
    Ropinirole: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
    Rotigotine: (Major) Concomitant use of rotigotine with other CNS depressants, such as hydroxyzine, can potentiate the sedation effects of rotigotine.
    Safinamide: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
    Salmeterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Saquinavir: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include saquinavir.
    Secobarbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Selegiline: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Consider alternative therapy to antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many non-prescription products for coughs, colds, allergy, hay fever or insomnia contain sedating antihistamines. Patients receiving an MAOI should be counseled that it is essential to consult their healthcare provider or pharmacist prior to the use of any non-prescription products. Patients should also be advised against driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
    Sertraline: (Major) There have been postmarketing reports of QT prolongation and torsade de pointes (TdP) during treatment with sertraline and the manufacturer of sertraline recommends avoiding concurrent use with drugs known to prolong the QTc interval. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent medications, including H1-blockers. False study results are possible; thorough patient history is important in the interpretation of procedure results.
    Sodium Iodide: (Moderate) Antihistamines may alter sodium iodide I-131 pharmacokinetics and dynamics for up to 1 week after administration. In addition, medications that decrease salivation increase the time of radiation exposure to salivary glands. Consider discontinuing sedating H1-blockers prior to sodium iodide I-131 administration.
    Sodium Oxybate: (Severe) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs.
    Solifenacin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include solifenacin. In addition, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
    Sorafenib: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include sorafenib.
    Sotalol: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include sotalol.
    Succinylcholine: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Sufentanil: (Moderate) Concomitant use of sufentanil with other CNS depressants can potentiate sufentanil-induced CNS and cardiovascular effects and the duration of these effects. A dose reduction of one or both drugs may be warranted.
    Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of hydroxyzine with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation as well as TdP.
    Suvorexant: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Tacrine: (Moderate) Concurrent use of sedating H1-blockers and tacrine should be avoided if possible. Tacrine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of tacrine.
    Tacrolimus: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include tacrolimus.
    Tamoxifen: (Major) Caution is advised with the concomitant use of tamoxifen and hydroxyzine due to an increased risk of QT prolongation and torsade de pointes (TdP). Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Tapentadol: (Moderate) Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants. Severe hypotension, profound sedation, coma, or respiratory depression may occur. Prior to concurrent use of tapentadol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with tapentadol, a reduced dosage of tapentadol and/or the CNS depressant is recommended. If the extended-release tapentadol tablets are used concurrently with a CNS depressant, it is recommended to use an initial tapentadol dose of 50 mg PO every 12 hours. Monitor patients for sedation and respiratory depression.
    Tasimelteon: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
    Telavancin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include telavancin.
    Telithromycin: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include telithromycin.
    Terbutaline: (Minor) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists, like terbutaline, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.This risk may be more clinically significant with long-acting beta-agonists than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Tetrabenazine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include tetrabenazine. In addition, concurrent use of tetrabenazine and drugs that can cause CNS depression, such as hydroxyzine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
    Thalidomide: (Major) Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
    Thiethylperazine: (Moderate) The anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other antimuscarinics. Other commonly used drugs with moderate to significant anticholinergic effects include most phenothiazines. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Thiopental: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates.
    Thioridazine: (Severe) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of hydroxyzine with thioridazine is contraindicated.
    Thiothixene: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
    Tiotropium; Olodaterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Tizanidine: (Major) Use tizanidine and hydroxyzine together with caution due to additive CNS depression. Consider tizanidine dosage reduction and monitor patients for symptoms of excess sedation.
    Tolcapone: (Moderate) COMT inhibitors, such as entacapone or tolcapone, should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation.
    Tolterodine: (Major) Postmarketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include tolterodine. Additive anticholinergic effects may be seen when tolterodine is used concomitantly with other drugs with anticholinergic properties, such as sedating antihistamines. Blurred vision, constipation, and dry mouth may be more prominent additive effects.
    Topiramate: (Major) Although not specifically studied, coadministration of CNS depressant drugs with topiramate may potentiate CNS depression such as dizziness or cognitive adverse reactions, or other centrally mediated effects of these agents. Monitor for increased CNS effects if coadministering.
    Toremifene: (Major) Avoid coadministration of hydroxyzine with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    Tramadol: (Moderate) An enhanced CNS depressant effect may occur when sedating h1-blockers are combined with other CNS depressants including tramadol.
    Tranylcypromine: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Consider alternative therapy to antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many non-prescription products for coughs, colds, allergy, hay fever or insomnia contain sedating antihistamines. Patients receiving an MAOI should be counseled that it is essential to consult their healthcare provider or pharmacist prior to the use of any non-prescription products. Patients should also be advised against driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
    Trazodone: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include trazodone. In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including trazodone.
    Tricyclic antidepressants: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include tricyclic antidepressants. In addition, the anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with medications with anticholinergic effects, such as tricyclic antidepressants. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Trifluoperazine: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Fluphenazine, perphenazine, prochlorperazine, and trifluoperazine are associated with a possible risk for QT prolongation. Theoretically, these agents may increase the risk of QT prolongation if coadministered with drugs with a risk of QT prolongation. Administer these agents and drugs that can prolong the QT interval with caution. In addition, the anticholinergic effects of hydroxyzine are moderate and may be enhanced when combined with other antimuscarinics. Other commonly used drugs with moderate to significant anticholinergic effects include most phenothiazines. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Trimethobenzamide: (Moderate) The concurrent use of trimethobenzamide with other medications that cause CNS depression, like the sedating h1-blockers, may potentiate the effects of either trimethobenzamide or the sedating h1-blocker.
    Trospium: (Moderate) Additive anticholinergic effects may be seen when trospium is used concomitantly with drugs that are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function and temperature regulation. While CNS-related side effects such as drowsiness and blurred vision are not typically noted with trospium, they may occur in some patients.
    Tubocurarine: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Umeclidinium; Vilanterol: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated.
    Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib; post-marketing data indicate that hydroxyzine causes QT prolongation and TdP. If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose.
    Vardenafil: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include vardenafil.
    Vecuronium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Vemurafenib: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include vemurafenib.
    Venlafaxine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include venlafaxine.
    Vigabatrin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Vilazodone: (Moderate) Due to the CNS effects of vilazodone, caution should be used when vilazodone is given in combination with other centrally acting medications such as anxiolytics, sedatives, and hypnotics. Also, Cyproheptadine is an antagonist of serotonin in the CNS, a property which may oppose some of the pharmacologic effects of vilazodone. Cyproheptadine has been used for the management of orgasm dysfunction caused by the serotonergic antidepressants and for the adjunctive treatment of serotonin syndrome; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the antidepressant. Clinically, cyproheptadine reportedly has interfered with the antidepressant and anti-bulimia actions of fluoxetine, but more data are needed to confirm a direct drug-drug interaction.
    Voriconazole: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include voriconazole.
    Vorinostat: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include vorinostat.
    Zaleplon: (Moderate) In premarketing studies, zaleplon potentiated the CNS effects of ethanol, imipramine, and thioridazine for at least 2 to 4 hours. Other drugs that may have additive CNS effects with zaleplon but have not been studied include other sedating H1-blockers. If used together, a reduction in the dose of one or both drugs may be needed.
    Ziconotide: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
    Ziprasidone: (Severe) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including hydroxyzine.
    Zolpidem: (Moderate) The CNS-depressant effects of zolpidem can be potentiated with concomitant administration of other drugs known to cause CNS depression, such as sedating H1-blockers. A dose reduction of either or both drugs should be considered to minimize additive sedative effects. For Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night. The risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving. In addition, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of zolpidem and other CNS depressants than with zolpidem alone.

    PREGNANCY AND LACTATION

    Pregnancy

    The manufacturer warns against the use of hydroxyzine during breast-feeding. It is unknown whether hydroxyzine is excreted into breast milk; however, the molecular weight of the drug is low enough that excretion into breast milk should be expected. The effects of the drug on the nursing infant are unknown. In general, many first-generation antihistamines are not recommended for use during lactation, since irritability, drowsiness, unusual excitement or other infant effects might be observed. Antihistamines can lower basal prolactin secretion and may interfere with the establishment of lactation. Consider treatment alternatives to hydroxyzine. Loratadine may be considered as an alternative for the treatment of allergy symptoms. Because of its lack of sedation and low milk concentrations, maternal use would not be expected to cause adverse effects in breast-fed babies and loratadine is considered usually compatible with breast-feeding. The British Society for Allergy and Clinical Immunology also recommends loratadine at the lowest dose as a preferred antihistamine in breast-feeding women. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Hydroxyzine competes with histamine for H1-receptor sites on the effector cell surface. Blockade of H1-receptors also suppresses the formation of edema, flare, and pruritus that result from histaminic activity. The sedative properties of hydroxyzine occur at the subcortical level of the CNS, and, as mentioned above, this effect may be dose-related. Hydroxyzine has some antiemetic actions secondary to its central anticholinergic actions. Hydroxyzine also demonstrates antiarrhythmic, analgesic, local anesthetic, and skeletal muscle relaxant properties as well as bronchodilatory and mild antisecretory effects. Although antihistamines possess intrinsic analgesic properties (perhaps secondary to interfering with nociception), they should not be considered potent analgesics.

    PHARMACOKINETICS

    Hydroxyzine is administered orally and intramuscularly. Distribution of hydroxyzine has not been fully described and it is unknown whether it crosses the placenta or is distributed into breast milk. Hydroxyzine, like most first-generation antihistamines, is metabolized in the liver. One active metabolite is cetirizine; cetirizine is mostly excreted renally as unchanged drug. Another hydroxyzine metabolite, norchlorcyclizine, has chemical similarities to a trazodone metabolite, m-chlorophenylpiperazine, but the activity and elimination of this compound are not certain. The elimination half-life of hydroxyzine is variably reported to be between 14 to 25 hours.

    Oral Route

    Hydroxyzine is rapidly absorbed following oral administration. The oral dosages of hydroxyzine pamoate and hydroxyzine hydrochloride are considered equivalent. The onset of effect for hydroxyzine occurs between 15 to 60 minutes, with a usual duration of action of 4 to 6 hours. The inflammatory response and pruritus can be suppressed for up to 4 days.

    Intramuscular Route

    Hydroxyzine is rapidly absorbed following intramuscular administration.