HYDROXYZINE
Clinical safety rating: safe
Animal studies have demonstrated safety
Hydroxyzine is a first-generation antihistamine that acts as a competitive antagonist at histamine H1 receptors in the gastrointestinal tract, blood vessels, and respiratory tract. It also exhibits sedative, anxiolytic, and antiemetic properties, possibly through central nervous system depression and anticholinergic effects.
| Metabolism | Hydroxyzine is primarily metabolized by the liver via CYP3A4 and CYP2D6 isoenzymes. The major active metabolite is cetirizine, which is also a histamine H1 receptor antagonist. |
| Excretion | Renal: approximately 70% as metabolites, less than 1% unchanged. Fecal/biliary: minor. Cetirizine (active metabolite) also renally eliminated. |
| Half-life | Terminal elimination half-life: 14-25 hours (mean ~20 h). In elderly or hepatic impairment, may be prolonged; antihistamine effect persists beyond half-life due to active metabolite. |
| Protein binding | 93% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 16 L/kg (range 7-20 L/kg), indicating extensive tissue distribution; higher Vd suggests large extravascular binding. |
| Bioavailability | Oral: approximately 80%; IM: >80% (almost complete and rapid); IV: 100%. |
| Onset of Action | Oral: 15-30 minutes for generalized anxiety; IM: 15-30 minutes for sedation or antihistaminic effect; IV: immediate (minutes) for sedation or as premedication. |
| Duration of Action | Oral: 4-6 hours for antihistamine effect, 6-24 hours for anxiolytic/sedative effect (dose-dependent). IM/IV: 4-6 hours for sedation, may last up to 24 hours for anxiolysis. |
25-100 mg orally 3-4 times daily; 50-100 mg IM every 4-6 hours as needed. Maximum oral dose: 600 mg/day in divided doses.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: administer every 12 hours. GFR <10 mL/min: administer every 24 hours. Not recommended for use in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) due to increased risk of neurotoxicity. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50% and/or increase dosing interval to every 12-24 hours. Child-Pugh Class C: use with caution; consider alternative agent or reduce dose by 75% and administer every 24 hours. |
| Pediatric use | Oral: 2 mg/kg/day in divided doses every 6-8 hours. Maximum: 50 mg/day for children <6 years; 100 mg/day for 6-12 years. IM: 0.5-1 mg/kg every 6-8 hours, not to exceed 50 mg per dose. |
| Geriatric use | Initiate at lowest dose (25 mg orally 3-4 times daily) and titrate cautiously due to increased risk of sedation, confusion, and anticholinergic effects. Maximum recommended dose: 100 mg/day in divided doses. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects May cause marked drowsiness and QT prolongation.
| Breastfeeding | Hydroxyzine is excreted into breast milk in small amounts. The milk-to-plasma ratio is estimated at approximately 0.5. In infants, it may cause sedation, irritability, or poor feeding. Because of the potential for serious adverse reactions in nursing infants, consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for hydroxyzine and any potential adverse effects on the breastfed infant. Alternatives with better safety profiles may be preferred. |
| Teratogenic Risk | Hydroxyzine is generally considered low risk for teratogenicity. Animal studies have shown no consistent evidence of fetal harm. Human data are limited but do not indicate a significant increase in major malformations. In the first trimester, use only if clearly needed. In the second and third trimesters, there is a potential risk of neonatal respiratory depression, hypotonia, and withdrawal symptoms if used near term or in high doses. Avoid use during labor and delivery due to potential maternal hypotension and fetal effects. |
■ FDA Black Box Warning
There is no FDA black box warning for hydroxyzine.
| Common Effects | pruritus |
| Serious Effects |
["Hypersensitivity to hydroxyzine or any of its components.","Early pregnancy (first trimester) due to potential teratogenic effects; use in later pregnancy only if clearly needed.","Breastfeeding: caution advised as hydroxyzine is excreted in breast milk.","Concomitant use of other CNS depressants may potentiate sedation.","Avoid in patients with known QT prolongation or history of arrhythmias."]
| Precautions | ["May cause sedation and impair ability to drive or operate machinery.","May cause QT prolongation, especially in patients with risk factors such as electrolyte imbalance, bradycardia, or concurrent use of other QT-prolonging drugs.","Use with caution in patients with hepatic impairment, as metabolism may be reduced.","Anticholinergic effects: may exacerbate conditions such as glaucoma, urinary retention, hyperthyroidism, or asthma.","May increase the risk of seizures in susceptible patients."] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate during intravenous administration. Assess for signs of excessive sedation, hypotension, or respiratory depression in the mother, especially near term. For neonates exposed near delivery, monitor for respiratory depression, hypotonia, jitteriness, and withdrawal symptoms (e.g., irritability, poor feeding) for 24-48 hours after birth. |
| Fertility Effects | Hydroxyzine has no known direct effects on human fertility. In animal studies, no impairment of fertility was observed. However, its anticholinergic and sedative properties may indirectly affect libido or sexual function, but no specific data exist. Use in women of childbearing potential is not restricted based on fertility concerns. |