ATARAX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATARAX (ATARAX).
Hydroxyzine is a piperazine derivative with antihistaminic (H1-receptor antagonist) and anticholinergic properties; also exhibits sedative, anxiolytic, and antiemetic effects due to suppression of activity in subcortical areas of the CNS.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2D6; major metabolite is cetirizine. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and CYP2D6; renal excretion of metabolites accounts for approximately 70-80% of the dose, with less than 1% excreted unchanged; fecal excretion is about 10-15%. |
| Half-life | Terminal elimination half-life is approximately 20-25 hours in healthy adults; may be prolonged in elderly, hepatic impairment, or renal insufficiency (up to 30-40 hours); steady-state achieved within 3-4 days. |
| Protein binding | Approximately 93% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 10-15 L/kg; large Vd indicates extensive tissue distribution, including penetration into the central nervous system. |
| Bioavailability | Oral bioavailability is approximately 100% (nearly complete absorption) with peak plasma concentrations at 2 hours; intramuscular bioavailability is similar to oral but with faster absorption. |
| Onset of Action | Oral: 15-30 minutes for antihistaminic effect; 30-60 minutes for anxiolytic effect. Intramuscular: 15-20 minutes. Intravenous: 5-10 minutes. |
| Duration of Action | Antihistaminic effect: 4-6 hours (may persist up to 12 hours). Anxiolytic and sedative effects: 6-24 hours; duration depends on dose and individual response. |
| Molecular Weight | 374.9 |
| Action Class | H1 Antihistaminics (First Generation) |
| Brand Substitutes | HD Zine 25mg Tablet, Hyzox 25 Tablet, Hizet 25mg Tablet, Hydil 25mg Tablet, Zyzine 25mg Tablet, Evall 10mg Tablet, Hydil 10mg Tablet, Stoprax 10mg Tablet, Hynorax 10mg Tablet, Hydrobal 10 Tablet, Hydil 10mg Syrup, Pru 10mg Syrup, Hedosat 10mg Syrup, Livrox 10mg Syrup, Anzine 10mg Syrup |
25 mg orally 3-4 times daily; maximum 100 mg per day. Also available as 50 mg intramuscular injection every 4-6 hours.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: administer every 24 hours. GFR <10 mL/min: contraindicated or reduce dose to 50% every 24 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment. Class B: reduce dose by 50%. Class C: contraindicated. |
| Pediatric use | Children >6 years: 0.6 mg/kg orally every 6 hours; maximum 2 mg/kg/day. Children <6 years: 0.5 mg/kg orally every 4-6 hours; maximum 50 mg/day. |
| Geriatric use | Initiate at 12.5 mg orally twice daily; may increase gradually. Avoid use in patients with significant renal impairment or dementia due to anticholinergic effects. |
| 1st trimester | Hydroxyzine is generally avoided during the first trimester due to limited safety data and potential risk of fetal harm; animal studies have shown embryotoxicity at high doses. Use only if clearly needed and benefit outweighs risk. |
| 2nd trimester | Use with caution during the second trimester; no well-controlled human studies, but animal data suggest low risk at therapeutic doses. Consider alternative agents if possible. |
| 3rd trimester | Use near term may increase the risk of neonatal respiratory depression, hypotonia, or withdrawal symptoms. Avoid use during labor and delivery. |
Clinical note
Comprehensive clinical and safety monograph for ATARAX (ATARAX).
| Placental transfer | Hydroxyzine readily crosses the placenta; maternal serum levels are similar to fetal serum levels, indicating extensive placental transfer. |
| Breastfeeding | Hydroxyzine is excreted into human breast milk in small amounts. Due to its long half-life and potential for sedation or irritability in the nursing infant, caution is advised. Use only if clearly needed and monitor infant for drowsiness or feeding difficulties. |
■ FDA Black Box Warning
Not applicable; no black box warning.
| Serious Effects |
Hypersensitivity to hydroxyzine or any component of the formulationKnown hypersensitivity to cetirizine or levocetirizinePorphyriaEarly pregnancy (first trimester) – generally contraindicated due to potential teratogenicityBreastfeeding – caution, but not an absolute contraindication; avoid if possible
| Precautions | Drowsiness and impairment of alertness; avoid driving or operating machinery, Potentiation of CNS depressants (alcohol, barbiturates, opioids), Anticholinergic effects (urinary retention, blurred vision, constipation), QT prolongation risk (especially with electrolyte disturbances, pre-existing QT prolongation, or concurrent QT-prolonging drugs), Use with caution in elderly due to increased risk of sedation and falls, Tardive dyskinesia with prolonged high-dose use |
| Food/Dietary | No significant food interactions reported. However, alcohol should be avoided due to additive CNS depression. Grapefruit juice may theoretically increase hydroxyzine levels via CYP3A4 inhibition, but clinical significance is minimal; caution is advised. |
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| Lactation Rating | L3 (Moderately Safe) - Limited data suggest low risk, but caution due to possible adverse effects in some infants. |
| Teratogenic Risk | First trimester: Considered safe; large studies show no increased risk of major malformations. Second trimester: No known specific risks. Third trimester: Use near term may cause neonatal withdrawal or CNS depression (drowsiness, irritability, tremors) due to placental transfer. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and CNS effects (sedation, dizziness). Assess fetal heart rate and uterine activity if used in labor. In neonates exposed near term, observe for withdrawal symptoms (irritability, hypertonia, tremor). |
| Fertility Effects | Hydroxyzine has no known adverse effects on fertility in either men or women. Animal studies show no impairment of fertility at therapeutic doses. |
| Clinical Pearls | ATARAX (hydroxyzine) is a first-generation antihistamine with anxiolytic and sedative properties. It is commonly used for pruritus, anxiety, and preoperative sedation. Note: QT prolongation risk at high doses; avoid in patients with known QT interval prolongation or concurrent use of other QT-prolonging agents. Onset of sedation is rapid, making it useful for sleep induction, but tolerance develops with chronic use. Anticholinergic effects (dry mouth, urinary retention) are dose-dependent. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) as they may increase drowsiness and dizziness. · Do not drive or operate heavy machinery until you know how this medication affects you. · Report any signs of allergic reaction (rash, difficulty breathing) or irregular heartbeat (palpitations, syncope) immediately. · Hydrate adequately to reduce dry mouth; sugar-free gum or candy can help. · Do not discontinue abruptly; follow your doctor's instructions for tapering if needed. |