HYDROXYZINE HYDROCHLORIDE
Clinical safety rating: safe
CNS depressants may enhance sedative effects May cause marked drowsiness and QT prolongation.
Hydroxyzine hydrochloride is a first-generation antihistamine that acts as a competitive antagonist at histamine H1 receptors. It also possesses anticholinergic, antiemetic, and sedative properties. Its mechanism involves binding to H1 receptors in the gastrointestinal tract, uterus, blood vessels, and bronchial muscles, thereby inhibiting histamine-mediated effects.
| Metabolism | Hydroxyzine is extensively metabolized in the liver primarily via CYP3A4 and CYP2D6 enzymes. The major metabolite is cetirizine, which is pharmacologically active. Additional minor metabolites include oxycetirizine and p-hydroxyhydroxyzine. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and CYP3A5; <1% excreted unchanged in urine. Renal elimination of metabolites (approx. 50-60% of total clearance), with minor fecal excretion (<10%). |
| Half-life | Terminal elimination half-life is approximately 20-25 hours in adults. In elderly or hepatic impairment, may be prolonged. Clinical context: Achieves steady-state after ~4-5 days; detectable for >72 hours after cessation. |
| Protein binding | 93% bound primarily to albumin, with some binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 7-16 L/kg (range 7-16 L/kg). Large Vd indicates extensive tissue distribution, including CNS. |
| Bioavailability | Oral: approximately 70-80% due to first-pass metabolism, but variable. IM: 100% (complete absorption). |
| Onset of Action | Oral: 15-30 minutes for anxiolytic/sedative effects; IM: 15-30 minutes; IV: immediate (within minutes). Antihistaminic effect: 1 hour oral. |
| Duration of Action | Antihistaminic: 4-6 hours; sedative/anxiolytic: 6-24 hours depending on dose. Clinical note: Duration may be longer in elderly or hepatic impairment. Not for rapid onset of antiallergic action. |
25-100 mg orally or intramuscularly 3-4 times daily; maximum 600 mg/day.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required; however, use with caution and consider reducing dose in severe renal impairment (CrCl < 10 mL/min) due to risk of accumulation. |
| Liver impairment | In Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use or reduce dose by 75%. |
| Pediatric use | Children > 6 years: 0.5-1 mg/kg/dose orally or IM every 4-6 hours as needed; maximum 100 mg/day. |
| Geriatric use | Initiate at 25 mg orally or IM 3-4 times daily; titrate slowly due to increased risk of sedation, anticholinergic effects, and falls. |
| 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.
| FDA category | Animal |
| Breastfeeding | Hydroxyzine is excreted into human milk in small amounts. M/P ratio is approximately 0.6. Caution is advised; use during breastfeeding only if clearly needed. Monitor infant for drowsiness, irritability, or feeding difficulties. The American Academy of Pediatrics considers hydroxyzine compatible with breastfeeding. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warnings.
| Common Effects | pruritus |
| Serious Effects |
["Hypersensitivity to hydroxyzine or any of its components","Early pregnancy (first trimester) based on teratogenic risk","Porphyria","QT prolongation or concomitant use of QT-prolonging drugs","Severe hepatic impairment"]
| Precautions | ["May cause QT prolongation; avoid in patients with preexisting QT prolongation or those taking other QT-prolonging drugs.","Use with caution in patients with bradycardia, hypokalemia, hypomagnesemia, or concomitant use of Class IA or III antiarrhythmics.","May cause sedation and impair ability to drive or operate machinery.","Use cautiously in elderly patients and those with hepatic or renal impairment.","May cause anticholinergic effects such as dry mouth, urinary retention, and blurred vision."] |
Loading safety data…
| Hydroxyzine hydrochloride is a pregnancy category C drug. First trimester: limited human data suggest a possible increased risk of congenital malformations, but risk cannot be excluded. Animal studies have shown teratogenic effects at high doses. Second and third trimesters: no evidence of fetal harm from controlled human studies, but avoid use near term due to potential neonatal adverse effects (e.g., respiratory depression, hypotonia, withdrawal symptoms). |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate; observe for signs of excessive sedation and respiratory depression. Fetal monitoring is not routinely required but consider in late pregnancy or with prolonged high-dose use. Assess neonatal adaptation after delivery if used near term. |
| Fertility Effects | No significant effects on fertility reported in human studies. Animal studies with high doses showed some impairment of fertility, but clinical relevance is unknown. Use with caution in women planning pregnancy. |