Obat

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
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
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.
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.
Adults
The recommended dose is 25 to 100 mg IM as a single dose.
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.
0.6 mg/kg PO is the recommended dose.
Adults
The recommended dose is 25 to 100 mg IM.
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.
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 :
Atarax:
Hyzine :
- Discard product if it contains particulate matter, is cloudy, or discolored
- Discard unused portion. Do not store for later use.
- Protect from light
Rezine:
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
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
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with hydroxyzine
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
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
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
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
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
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
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
other CNS depressants including barbiturates. (Major) Concomitant use of opioid agonists with
Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with
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
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
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
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
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
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
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
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
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
Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been
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; Phenylephrine: (Moderate) Drowsiness has been reported during
Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported
during administration of carbetapentane. An enhanced CNS depressant effect may occur when
Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during
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
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid
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
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
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid
Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Concomitant use of opioid
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
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with
Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid
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.
Cisatracurium: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-
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
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
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with hydroxyzine may
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with
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
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
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
Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid
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).
Dolasetron: (Moderate) Caution is recommended if hydroxyzine is administered with dolasetron
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
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-
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
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
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
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
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
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
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
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
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.
(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
Fluticasone; Salmeterol: (Moderate) Caution is recommended if hydroxyzine is administered
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
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-
Formoterol; Mometasone: (Moderate) Caution is recommended if hydroxyzine is administered
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: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients
for symptoms of sedation and somnolence during coadministration of gabapentin and
hydroxyzine. Reduce the gabapentin dose by 50% or more when used with hydroxyzine
intramuscular injection. Concomitant use of gabapentin with hydroxyzine may cause additive
CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
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
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
Glycopyrrolate; Formoterol: (Moderate) Caution is recommended if hydroxyzine is
Goserelin: (Moderate) Caution is recommended if hydroxyzine is administered with goserelin
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
Granisetron has been associated with QT prolongation.
Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with hydroxyzine may
Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists
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
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
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
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
depression.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with hydroxyzine may
Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with hydroxyzine
Hydrocodone; Potassium Guaiacolsulfonate: (Major) Concomitant use of opioid agonists with
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
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with
Hydromorphone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause
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
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-
Indacaterol; Glycopyrrolate: (Moderate) Caution is recommended if hydroxyzine is
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
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
Ketamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant
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
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.
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.
(TdP).
Leuprolide: (Moderate) Caution is recommended if hydroxyzine is administered with leuprolide
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
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
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
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,
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
Long-acting beta-agonists: (Moderate) Caution is recommended if hydroxyzine is administered
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
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
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.
Meperidine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive
Meperidine; Promethazine: (Major) Concomitant use of opioid agonists with hydroxyzine may
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.
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-
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
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
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
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-
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
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
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
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
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
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-
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
Oxymorphone: (Major) Concomitant use of opioid agonists with hydroxyzine may cause
desired clinical effect. Reduce the initial oxymorphone dosage by 1/3 to 1/2. Educate patients
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
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-
Panobinostat: (Major) Coadministration of hydroxyzine and panobinostat is not recommended
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
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
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
Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Perphenazine is
Perphenazine; Amitriptyline: (Moderate) Caution is recommended if hydroxyzine is
administered with perphenazine due to the potential for additive QT prolongation and risk of
Perphenazine is associated with a possible risk for QT prolongation.
Phenelzine: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating
Phenobarbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS
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
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
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
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: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients
for symptoms of sedation and somnolence during coadministration of pregabalin and
hydroxyzine. Reduce the pregabalin dose by 50% or more when used with hydroxyzine
intramuscular injection. Concomitant use of pregabalin with hydroxyzine may cause additive
CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
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
Primaquine has been associated with prolongation of the QT interval.
Primidone: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS
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
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
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
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
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
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
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
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
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-
Rasagiline: (Moderate) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating
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
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
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
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.
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-
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-
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
Secobarbital: (Major) Because hydroxyzine can cause pronounced sedation, an enhanced CNS
barbiturates.
Selegiline: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-
blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or
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
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-
Sufentanil: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive
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) Monitor for excessive sedation and somnolence during
coadministration of suvorexant and sedating antihistamines (H1-blockers). Dosage adjustments
of suvorexant and sedating H1-blockers may be necessary when administered together because
of potentially additive CNS effects. The risk of next-day impairment, including impaired driving,
is increased if suvorexant is taken with other CNS depressants. Patients should generally avoid
nonprescription antihistamine products that are marketed as sleep-aids concurrently with
suvorexant.
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
Tamoxifen: (Moderate) Caution is recommended if hydroxyzine is administered with tamoxifen
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
Tasimelteon: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS
anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Telavancin: (Moderate) Caution is recommended if hydroxyzine is administered with telavancin
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
Telithromycin is also associated with QT prolongation and TdP.
Terbutaline: (Minor) Caution is recommended if hydroxyzine is administered with short-acting
Tetrabenazine: (Major) Avoid coadministration of hydroxyzine and tetrabenazine due to the
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
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
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
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
Tramadol: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive
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
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
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
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
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
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-
Umeclidinium; Vilanterol: (Moderate) Caution is recommended if hydroxyzine is administered
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
Vardenafil: (Moderate) Caution is recommended if hydroxyzine is administered with vardenafil
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-
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.
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
Voriconazole has been associated with QT prolongation and rare cases of TdP.
Vorinostat: (Moderate) Caution is recommended if hydroxyzine is administered with vorinostat
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,
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
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.
https://www.pdr.net/drug-summary/Hydroxyzine-Pamoate-hydroxyzine-pamoate-744 diakses tanggal

19 Januari 2020 pukul 22.22 WITA
8 Donner NC, Lowry CA. Sex differences in anxiety and emotional behavior. Pflügers Archiv-
European Journal of Physiology. 2013 May 1;465(5):601-26.

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CLASSES

Oral and parenteral sedating antihistamine of the piperazine class

COMMON BRAND NAMES

ANX, Atarax, Hyzine, Rezine, Vistaril

ANX/Atarax/Hydroxyzine Hydrochloride/Rezine Oral Tab: 10mg, 25mg, 50mg

DOSAGE & INDICATIONS

50 to 100 mg PO 4 times daily as needed, adjusted to patient response. The efficacy of

Children and Adolescents 6 years and older

Children less than 6 years

For the treatment of pruritus due to histamine-mediated conditions or due to allergic

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

Children and Adolescents 6 years and older

Children less than 6 years

Children and Adolescents

1.1 mg/kg IM.

For post-operative nausea/vomiting (PONV) and post-operative nausea/vomiting (PONV)

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

50 to 100 mg PO is the recommended dose.

Children and Adolescents

0.6 mg/kg PO is the recommended dose.

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†.

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

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

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

For the treatment of seasonal allergic rhinitis† (seasonal allergies†).

†Indicates off-label use

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

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

Safety and efficacy have not been established.

Safety and efficacy have not been established.

CrCl > 50 mL/min: No dosage adjustment needed.

All dosage forms: May administer without regard to meals.

Oral Liquid Formulations

All dosage forms: May administer without regard to meals.

Asthma, chronic obstructive pulmonary disease (COPD)

Bradycardia, cardiac disease, electrolyte imbalance, heart failure, hypokalemia,

Closed-angle glaucoma, contact lenses

Ileus, prostatic hypertrophy, urinary retention

Because of the anticholinergic effects inherent to antihistamine agents like hydroxyzine, a

Dialysis, renal failure, renal impairment

Biliary cirrhosis, hepatic disease

Hydroxyzine is extensively metabolized in the liver. Although hydroxyzine may be prescribed

Infants, neonates, premature neonates

Anticholinergic medications, geriatric

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

Intravenous administration, subcutaneous administration, tissue necrosis

acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known

blurred vision / Early / Incidence not known

mydriasis / Early / Incidence not known

Acetaminophen; Butalbital: (Major) Because hydroxyzine can cause pronounced sedation, an

PREGNANCY AND LACTATION

Hydroxyzine is administered orally and intramuscularly. Distribution of hydroxyzine has not

Hydroxyzine is rapidly absorbed following intramuscular administration.

https://www.pdr.net/drug-summary/Hydroxyzine-Pamoate-hydroxyzine-pamoate-744 diakses tanggal

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