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. |
| Molecular Weight | 374.9 |
| Action Class | First-generation antihistamine (piperazine class); also classified as an anxiolytic and sedative. |
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 | Hydroxyzine crosses the placenta. Animal studies have shown fetal abnormalities at high doses. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus. |
| 2nd trimester | Hydroxyzine crosses the placenta. Limited human data. Use only if clearly needed. |
| 3rd trimester | Hydroxyzine may cause neonatal respiratory depression, hypotonia, and withdrawal symptoms if used near term. Avoid use in late pregnancy, especially during labor and delivery. |
Clinical note
CNS depressants may enhance sedative effects May cause marked drowsiness and QT prolongation.
| Placental transfer | Hydroxyzine crosses the placenta. The degree of transfer is likely moderate based on its molecular weight and lipophilicity. Animal studies show fetal exposure. |
| Breastfeeding | Hydroxyzine is excreted into human breast milk in small amounts. Effects on the nursing infant are unknown, but may cause drowsiness or irritability. Use with caution, especially in neonates or preterm infants. |
■ FDA Black Box Warning
There is no FDA black box warning for hydroxyzine.
| Common Effects | pruritus |
| Serious Effects | QT prolongation and torsade de pointes (especially with overdose or in patients with risk factors), Seizures, Severe drowsiness and impaired psychomotor function, Urinary retention, Acute angle-closure glaucoma (in predisposed patients), Paradoxical excitation (especially in children and elderly), Hypotension, Respiratory depression (especially with concomitant CNS depressants) |
Hypersensitivity to hydroxyzine or any component of the formulationEarly pregnancy (first trimester) - contraindicated based on FDA labeling (old classification)PorphyriaQT interval prolongation (use with other QT-prolonging drugs)
| 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. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Food/Dietary | Hydroxyzine may be taken with or without food. Grapefruit juice may increase hydroxyzine serum concentrations and risk of adverse effects; avoid concurrent consumption. High-fat meals can delay but not significantly reduce absorption. No other food restrictions are required. |
| Clinical Pearls | Hydroxyzine is a first-generation antihistamine with anxiolytic, sedative, and antiemetic properties. It is commonly used for pruritus, anxiety, and premedication. Avoid concurrent use with CNS depressants due to additive sedation. In elderly patients, risk of confusion and falls is increased; consider alternative therapies. Hydroxyzine has anticholinergic effects; use cautiously in patients with glaucoma, urinary retention, or prostatic hyperplasia. Note that hydroxyzine can cause QT prolongation at high doses or in combination with other QT-prolonging drugs. |
| Patient Advice | Take hydroxyzine exactly as prescribed and do not exceed the recommended dose. · Avoid driving or operating heavy machinery until you know how hydroxyzine affects you, as it may cause drowsiness or dizziness. · Avoid alcohol and other central nervous system depressants (e.g., benzodiazepines, opioids) while taking hydroxyzine. · Notify your doctor if you experience blurred vision, dry mouth, difficulty urinating, or rapid heartbeat. · Do not stop taking hydroxyzine abruptly if using for anxiety; consult your doctor for a taper plan. · Store at room temperature, away from moisture and heat. |