PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • 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

    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 the treatment of nausea/vomiting, excluding the nausea and vomiting of pregnancy.
    Intramuscular dosage
    Adults

    25 to 100 mg IM.

    Children and Adolescents

    1.1 mg/kg IM.

    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 seasonal allergic rhinitis† (seasonal allergies†).
    Oral dosage
    Adults

    Hydroxyzine is not commonly used for this purpose. Up to 150 mg/day PO, given in divided doses, has been reported effective for seasonal allergies. Drowsiness and dry mouth are frequently reported.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    400 mg/day PO; 600 mg/day IM.

    Geriatric

    400 mg/day PO; 600 mg/day IM.

    Adolescents

    100 mg/day PO or 2 mg/kg/day PO; 1.1 mg/kg IM as a single dose.

    Children

    6 years and older: 100 mg/day PO or 2 mg/kg/day PO; 1.1 mg/kg IM as a single dose.
    5 years and younger: 50 mg/day PO or 2 mg/kg/day PO; 1.1 mg/kg IM as a single dose.

    Infants

    Safety and efficacy have not been established.

    Neonates

    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 between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Atarax:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 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 between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Vistaril:
    - Store at controlled room temperature (between 68 and 77 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 the 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 antihistamines are considered potentially inappropriate medications (PIMs) in geriatric patients and should be avoided 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 (e.g., confusion, dry mouth, constipation) and toxicity compared to younger adults. Avoid drugs with strong anticholinergic activity in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: dementia/cognitive impairment (adverse CNS effects), delirium/high risk of delirium (new-onset or worsening delirium), or lower urinary tract symptoms/benign prostatic hyperplasia in men (urinary retention or hesitancy). The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities; 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, use the smallest possible dose. 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 also 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 in the geriatric skilled care resident.

    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. (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS 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; Tramadol: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Aclidinium; Formoterol: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol: (Minor) Caution is recommended if hydroxyzine is administered with short-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol; Ipratropium: (Minor) Caution is recommended if hydroxyzine is administered with short-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Alfuzosin: (Moderate) Caution is recommended if hydroxyzine is administered with alfuzosin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Alfuzosin may prolong the QT interval in a dose-dependent manner.
    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) Avoid coadministration of amiodarone and hydroxyzine due to the risk of additive QT prolongation and torsade de pointes (TdP). Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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. 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) Avoid coadministration of clarithromycin with hydroxyzine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Clarithromycin is associated with an established risk for QT prolongation and TdP. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with hydroxyzine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Clarithromycin is associated with an established risk for QT prolongation and TdP. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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) Do not use anagrelide with other drugs that prolong the QT interval, such as hydroxyzine. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide; dose-related increases in mean QTc and heart rate were observed in healthy subjects Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with apomorphine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including apomorphine. Postmarketing data indicate that hydroxyzine causes QT prolongation and 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.
    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) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Aripiprazole: (Moderate) Caution is recommended if hydroxyzine is administered with aripiprazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including aripiprazole. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Arsenic Trioxide: (Major) Avoid coadministration of hydroxyzine and arsenic trioxide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP); discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. Monitor ECG frequently if coadministration is required. QT interval prolongation, TdP, and complete atrioventricular block have been reported with arsenic trioxide use. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Artemether; Lumefantrine: (Major) Avoid coadministration of hydroxyzine and artemether; lumefantrine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Monitor ECG for QT prolongation if coadministration is required. Artemether; lumefantrine is associated with QT interval prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Asenapine: (Major) Avoid coadministration of hydroxyzine and asenapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additive CNS depression may also occur. Asenapine has been associated with QT prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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. (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (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; Oxycodone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Atomoxetine: (Moderate) Caution is recommended if hydroxyzine is administered with atomoxetine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    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: (Moderate) Consider the risk of QT prolongation, which can be fatal, when administering azithromycin to patients on other QT prolonging agents such as hydroxyzine. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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) Monitor ECGs if bedaquiline is coadministered with hydroxyzine. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 ms. Bedaquiline prolongs the QT interval. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with metronidazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Potential QT prolongation has been reported in limited case reports with metronidazole.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Caution is recommended if hydroxyzine is administered with metronidazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Potential QT prolongation has been reported in limited case reports with 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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Budesonide; Formoterol: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Buprenorphine: (Major) Caution is recommended if hydroxyzine is administered with buprenorphine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, if concurrent use of hydroxyzine 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. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Buprenorphine has been associated with QT prolongation and has a possible risk of TdP. 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.
    Buprenorphine; Naloxone: (Major) Caution is recommended if hydroxyzine is administered with buprenorphine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, if concurrent use of hydroxyzine 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. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Buprenorphine has been associated with QT prolongation and has a possible risk of TdP. 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.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    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) Avoid coadministration of ceritinib with hydroxyzine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; 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: (Moderate) Due to the duplicative and additive pharmacology, concurrent use of cetirizine/levocetirizine with sedating H1-blockers should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
    Cetirizine; Pseudoephedrine: (Moderate) Due to the duplicative and additive pharmacology, concurrent use of cetirizine/levocetirizine with sedating H1-blockers should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
    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) Caution is recommended if hydroxyzine is administered with chloroquine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Chloroquine is associated with an increased risk of QT prolongation and TdP; fatalities have been reported. The risk of QT prolongation is increased with higher chloroquine doses. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes.
    Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpromazine: (Major) Caution is recommended if hydroxyzine is administered with chlorpromazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes. Chlorpromazine is associated with an established risk of QT prolongation and 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: (Moderate) Caution is recommended if hydroxyzine is administered with ciprofloxacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance.
    Cisapride: (Severe) Coadministration of cisapride with hydroxyzine is contraindicated due to the risk of additive QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Cisatracurium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Citalopram: (Major) Avoid coadministration of hydroxyzine and citalopram due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Monitor ECG for QT prolongation if coadministration is required. Citalopram causes dose-dependent QT interval prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Clarithromycin: (Major) Avoid coadministration of clarithromycin with hydroxyzine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Clarithromycin is associated with an established risk for QT prolongation and TdP. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with hydroxyzine. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Clozapine: (Major) Caution is recommended if hydroxyzine is administered with clozapine due to the potential for additive QT prolongation, increased risk of torsade de pointes (TdP), significant sedation, and anticholinergic effects. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death.
    Codeine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Caution is recommended if hydroxyzine is administered with promethazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Promethazine is associated with a possible risk for QT prolongation.
    Codeine; Promethazine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Caution is recommended if hydroxyzine is administered with promethazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Promethazine is associated with a possible risk for QT prolongation.
    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) Avoid coadministration of crizotinib with hydroxyzine due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Postmarketing data indicate that hydroxyzine also causes QT prolongation and torsade de pointes (TdP).
    Cyclobenzaprine: (Moderate) Cyclobenzaprine and sedating antihistamines such as hydroxyzine both exhibit anticholinergic activity, and anticholinergic side effects can be additive. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
    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.
    Dasatinib: (Moderate) 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.
    Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving hydroxyzine. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    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: (Moderate) 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: (Moderate) Caution is recommended if hydroxyzine is administered with promethazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Promethazine is associated with a possible risk for QT prolongation.
    Dextromethorphan; Quinidine: (Major) Caution is recommended if hydroxyzine is administered with quinidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Quinidine administration is associated with QT prolongation and TdP.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Disopyramide: (Major) Disopyramide should be used cautiously and with close monitoring with hydroxyzine. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). Disopyramide administration is associated with QT prolongation and 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. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
    Dofetilide: (Major) Coadministration of dofetilide and hydroxyzine is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Dolasetron: (Moderate) Caution is recommended if hydroxyzine is administered with dolasetron due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Moderate) Caution is recommended if hydroxyzine is administered with rilpivirine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Donepezil: (Moderate) Caution is recommended if hydroxyzine is administered with donepezil due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
    Donepezil; Memantine: (Moderate) Caution is recommended if hydroxyzine is administered with donepezil due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
    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) Coadministration of dronedarone with hydroxyzine is contraindicated due to the risk of additive 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. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as hydroxyzine. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with hydroxyzine as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Consider alternatives to efavirenz when coadministering with hydroxyzine as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with hydroxyzine as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes.
    Eliglustat: (Moderate) Caution is recommended if hydroxyzine is administered with eliglustat due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is recommended if hydroxyzine is administered with rilpivirine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Caution is recommended if hydroxyzine is administered with rilpivirine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Encorafenib: (Major) Avoid coadministration of encorafenib and hydroxyzine due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. 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.
    Entrectinib: (Major) Avoid coadministration of entrectinib with hydroxyzine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    Eribulin: (Major) Monitor ECG if eribulin is administered with hydroxyzine as coadministration may increase the risk for additive QT prolongation and torsade de pointes (TdP). Eribulin has been associated with QT prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Erythromycin: (Major) Caution is recommended if hydroxyzine is administered with erythromycin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Both hydroxyzine and erythromycin have been associated with QT prolongation and TdP.
    Erythromycin; Sulfisoxazole: (Major) Caution is recommended if hydroxyzine is administered with erythromycin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Both hydroxyzine and erythromycin have been associated with QT prolongation and TdP.
    Escitalopram: (Moderate) Caution is recommended if hydroxyzine is administered with escitalopram due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Escitalopram has also been associated with a risk of QT prolongation and TdP.
    Esketamine: (Major) Closely monitor patients receiving esketamine and hydroxyzine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with ezogabine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, 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. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Ezogabine has been associated with QT prolongation.
    Fentanyl: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Fingolimod: (Moderate) Caution is recommended if hydroxyzine is administered with fingolimod due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Caution is recommended if hydroxyzine is administered with flecainide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with fluconazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Fluconazole has also been associated with QT prolongation and rare cases of TdP.
    Fluoxetine: (Moderate) Caution is recommended if hydroxyzine is administered with fluoxetine. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    Fluoxetine; Olanzapine: (Moderate) Caution is recommended if hydroxyzine is administered with fluoxetine. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). (Moderate) Caution is recommended if hydroxyzine is administered with olanzapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including olanzapine. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
    Fluphenazine: (Moderate) Caution is recommended if hydroxyzine is administered with fluphenazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Fluphenazine is associated with a possible risk for QT prolongation.
    Fluticasone; Salmeterol: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluvoxamine: (Moderate) Caution is recommended if hydroxyzine is administered with fluvoxamine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Formoterol: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Formoterol; Mometasone: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Foscarnet: (Major) Avoid use of foscarnet with hydroxyzine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Both QT prolongation and TdP have been reported during postmarketing use of foscarnet and hydroxyzine.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with gemifloxacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Moderate) 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.
    Gilteritinib: (Moderate) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and hydroxyzine is necessary. Gilteritinib has been associated with QT prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). Coadministration has the potential for additive QT effects.
    Glasdegib: (Major) Avoid coadministration of glasdegib with hydroxyzine due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    Glycopyrrolate; Formoterol: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Goserelin: (Moderate) Caution is recommended if hydroxyzine is administered with goserelin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Androgen deprivation therapy may prolong the QT/QTc interval.
    Granisetron: (Moderate) Caution is recommended if hydroxyzine is administered with granisetron due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Granisetron has been associated with QT prolongation.
    Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Halogenated Anesthetics: (Major) Caution is recommended if hydroxyzine is administered with halogenated anesthetics due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including halogenated anesthetics. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Halogenated anesthetics can prolong the QT interval.
    Haloperidol: (Moderate) Caution is recommended if hydroxyzine is administered with haloperidol due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. QT prolongation and 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.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with histrelin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Androgen deprivation therapy may prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydromorphone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Ibutilide: (Major) Caution is recommended if hydroxyzine is administered with ibutilide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
    Iloperidone: (Major) Avoid coadministration of iloperidone with hydroxyzine due to the potential for additive QT prolongation and torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including iloperidone. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Iloperidone has also been associated with QT prolongation.
    Indacaterol: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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 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: (Moderate) Caution is recommended if hydroxyzine is administered with itraconazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Itraconazole has been associated with prolongation of the QT interval.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with ketoconazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Ketoconazole has been associated with prolongation of the QT interval.
    Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with hydroxyzine as concurrent use may increase the risk of QT prolongation. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Lefamulin: (Major) Avoid coadministration of lefamulin with hydroxyzine as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    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: (Moderate) Caution is recommended if hydroxyzine is administered with leuprolide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Androgen deprivation therapy may prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Moderate) Caution is recommended if hydroxyzine is administered with leuprolide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Androgen deprivation therapy may prolong the QT/QTc interval.
    Levalbuterol: (Minor) Caution is recommended if hydroxyzine is administered with short-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Levocetirizine: (Moderate) Due to the duplicative and additive pharmacology, concurrent use of cetirizine/levocetirizine with sedating H1-blockers should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
    Levofloxacin: (Moderate) Caution is recommended if hydroxyzine is administered with levofloxacin. Postmarketing data indicate that both hydroxyzine and levofloxacin cause QT prolongation and torsade de pointes (TdP).
    Levomethadyl: (Moderate) Enhanced CNS depressant effects may occur when levomethadyl is combined with other CNS depressants, such as sedating H1 blockers.
    Levorphanol: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial dose of levorphanol by approximately 50% or more. Educate patients about the risks and symptoms of excessive CNS depression.
    Lithium: (Moderate) Caution is recommended if hydroxyzine is administered with lithium due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including lithium. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Lithium has been associated with QT prolongation.
    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) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Loperamide: (Moderate) Caution is recommended if hydroxyzine is administered with loperamide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
    Loperamide; Simethicone: (Moderate) Caution is recommended if hydroxyzine is administered with loperamide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
    Lopinavir; Ritonavir: (Moderate) Caution is recommended if hydroxyzine is administered with lopinavir; ritonavir due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Lopinavir; ritonavir is associated with QT prolongation.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with maprotiline due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with mefloquine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Meperidine; Promethazine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Caution is recommended if hydroxyzine is administered with promethazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Promethazine is associated with a possible risk for QT prolongation.
    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) Caution is recommended if hydroxyzine is administered with short-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and QT prolongation. 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.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with metronidazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Potential QT prolongation has been reported in limited case reports with 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 coadministration of hydroxyzine with mifepristone due to the risk for additive QT prolongation and torsade de pointes (TdP). Mifepristone has been associated with dose-dependent prolongation of the QT interval. 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: (Moderate) Caution is recommended if hydroxyzine is administered with mirtazapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. TdP has been reported postmarketing, primarily in overdose or in patients with other risk factors for 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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
    Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
    Moxifloxacin: (Major) Caution is recommended if hydroxyzine is administered with moxifloxacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    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. Postmarketing 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: (Moderate) Caution is recommended if hydroxyzine is administered with octreotide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Moderate) Caution is recommended if hydroxyzine is administered with ofloxacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Olanzapine: (Moderate) Caution is recommended if hydroxyzine is administered with olanzapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including olanzapine. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
    Olodaterol: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ondansetron: (Major) Monitor ECGs if hydroxyzine is coadministered with ondansetron due to the potential for additive QT prolongation and torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of TdP.
    Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Oxymorphone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial oxymorphone dosage by 1/3 to 1/2. Educate patients about the risks and symptoms of excessive CNS depression.
    Paliperidone: (Major) Avoid coadministration of hydroxyzine and paliperidone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including paliperidone. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose.
    Pancuronium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Panobinostat: (Major) Coadministration of hydroxyzine and panobinostat is not recommended due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Panobinostat can cause QT prolongation.
    Papaverine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as hydroxyzine could lead to enhanced sedation.
    Paroxetine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as hydroxyzine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
    Pasireotide: (Moderate) Caution is recommended if hydroxyzine is administered with pasireotide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
    Pazopanib: (Major) Coadministration of hydroxyzine and pazopanib is not recommended due to the risk of additive QT prolongation and torsade de pointes (TdP). Monitor the ECG for QT prolongation if coadministration is required. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Pazopanib is associated with QT interval prolongation.
    Pentamidine: (Major) Caution is recommended if hydroxyzine is administered with pentamidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Systemic pentamidine has been associated with QT prolongation.
    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) Caution is recommended if hydroxyzine is administered with perphenazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Perphenazine is associated with a possible risk for QT prolongation.
    Perphenazine; Amitriptyline: (Moderate) Caution is recommended if hydroxyzine is administered with perphenazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Perphenazine is associated with a possible risk for QT prolongation.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with promethazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Promethazine is associated with a possible risk for QT prolongation.
    Pimavanserin: (Major) Avoid coadministration of hydroxyzine and pimavanserin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Pimavanserin may cause QT prolongation.
    Pimozide: (Severe) Coadministration of pimozide with hydroxyzine is contraindicated due to the risk of additive QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Pirbuterol: (Minor) Caution is recommended if hydroxyzine is administered with short-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Pitolisant: (Major) Avoid coadministration of pitolisant with hydroxyzine as the effect of pitolisant may be decreased; concurrent use may also increase the risk of QT prolongation. Pitolisant increases histamine concentrations in the brain; therefore, H1-receptor antagonists like hydroxyzine, may reduce pitolisant efficacy. Pitolisant prolongs the QT interval. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP).
    Posaconazole: (Moderate) Caution is recommended if hydroxyzine is administered with posaconazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with primaquine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Primaquine has been associated with prolongation of the QT interval.
    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) Caution is recommended if hydroxyzine is administered with procainamide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Procainamide is also associated with a well-established risk of QT prolongation and TdP.
    Procarbazine: (Moderate) Use procarbazine and sedating H1-blockers together with caution; additive central nervous system depression may occur.
    Prochlorperazine: (Moderate) Caution is recommended if hydroxyzine is administered with prochlorperazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Prochlorperazine is associated with a possible risk for QT prolongation.
    Promethazine: (Moderate) Caution is recommended if hydroxyzine is administered with promethazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Promethazine is associated with a possible risk for QT prolongation.
    Propafenone: (Major) Caution is recommended if hydroxyzine is administered with propafenone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval.
    Propofol: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Quetiapine: (Major) Avoid coadministration of hydroxyzine and quetiapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including quetiapine. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Quinidine: (Major) Caution is recommended if hydroxyzine is administered with quinidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Quinidine administration is associated with QT prolongation and TdP.
    Quinine: (Major) Avoid coadministration of hydroxyzine and quinine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Quinine has also been associated with QT prolongation and rare cases of TdP.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with ranolazine as concurrent use may increase the risk of QT prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval.
    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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with rilpivirine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Risperidone: (Moderate) Use risperidone and hydroxyzine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with hydroxyzine. Romidepsin has been reported to prolong the QT interval. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes.
    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) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Saquinavir: (Major) Avoid coadministration of saquinavir boosted with ritonavir and hydroxyzine due to the risk of QT prolongation or torsade de pointes (TdP). Monitor ECG at baseline and during therapy if coadministration cannot be avoided. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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: (Moderate) Use caution and monitor patients for QT prolongation when administering hydroxyzine with sertraline. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Short-acting beta-agonists: (Minor) Caution is recommended if hydroxyzine is administered with short-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving hydroxyzine due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with solifenacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
    Sorafenib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of sorafenib with hydroxyzine is necessary; correct any electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). Sorafenib has also been associated with QT prolongation.
    Sotalol: (Major) Caution is recommended if hydroxyzine is administered with sotalol due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Succinylcholine: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Sufentanil: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with hydroxyzine. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). Sunitinib can prolong the QT interval.
    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: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with hydroxyzine. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Tamoxifen: (Moderate) Caution is recommended if hydroxyzine is administered with tamoxifen due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and 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.
    Tapentadol: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS 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: (Moderate) Caution is recommended if hydroxyzine is administered with telavancin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Telavancin has been associated with QT prolongation.
    Telithromycin: (Moderate) Caution is recommended if hydroxyzine is administered with telithromycin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Telithromycin is also associated with QT prolongation and TdP.
    Terbutaline: (Minor) Caution is recommended if hydroxyzine is administered with short-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Tetrabenazine: (Major) Avoid coadministration of hydroxyzine and tetrabenazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including tetrabenazine. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    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) Coadministration of thioridazine with hydroxyzine is contraindicated due to the risk of additive QT prolongation and torsades de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with tolterodine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additive anticholinergic effects may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
    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 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: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    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.
    Trastuzumab; 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.
    Trazodone: (Major) Avoid coadministration of hydroxyzine and trazodone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including trazodone. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of TdP.
    Tricyclic antidepressants: (Moderate) Caution is recommended if hydroxyzine is administered with tricyclic antidepressants due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Trifluoperazine: (Moderate) Caution is recommended if hydroxyzine is administered with trifluoperazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, additive anticholinergic effects and CNS depression may also occur. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Trifluoperazine is associated with a possible risk for QT prolongation.
    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.
    Triptorelin: (Moderate) Caution is recommended if hydroxyzine is administered with triptorelin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Androgen deprivation therapy may prolong the QT/QTc interval.
    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) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Vandetanib: (Major) Avoid coadministration of vandetanib with hydroxyzine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Vardenafil: (Moderate) Caution is recommended if hydroxyzine is administered with vardenafil due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
    Vecuronium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including neuromuscular blockers.
    Vemurafenib: (Major) Monitor ECG if hydroxyzine is coadministered with vemurafenib due to the potential for additive QT prolongation and torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Vemurafenib has also been associated with QT prolongation and TdP.
    Venlafaxine: (Moderate) Use caution if venlafaxine is coadministered with hydroxyzine due to the potential for QT prolongation and torsade de pointes (TdP). Venlafaxine administration is associated with a possible risk of QT prolongation; TdP has reported with postmarketing use. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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: (Moderate) Caution is recommended if hydroxyzine is administered with voriconazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Voriconazole has been associated with QT prolongation and rare cases of TdP.
    Vorinostat: (Moderate) Caution is recommended if hydroxyzine is administered with vorinostat due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Vorinostat therapy is associated with a risk of QT prolongation.
    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: (Major) Concomitant use of ziprasidone and hydroxyzine should be avoided due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including ziprasidone. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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.