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. |
| Molecular Weight | 357.87 |
| Action Class | Antihistamine (first-generation, piperazine derivative) |
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 | Animal studies have shown fetal abnormalities; human data limited. Use only if potential benefit justifies risk. |
| 2nd trimester | May be used with caution; no known teratogenicity in second trimester but limited data. |
| 3rd trimester | Risk of neonatal CNS depression, extrapyramidal signs if used near term. Avoid in late pregnancy. |
Clinical note
CNS depressants may enhance sedative effects May cause marked drowsiness and QT prolongation.
| FDA category | Animal |
| Placental transfer | Hydroxyzine crosses the placenta, with fetal plasma concentrations similar to maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA black box warnings.
| Common Effects | pruritus |
| Serious Effects | QT prolongation and torsades de pointes (especially with overdose or in patients with risk factors), Seizures, Severe hypotension, Acute angle-closure glaucoma (in predisposed patients), Urinary retention (in patients with prostatic hypertrophy or bladder neck obstruction), Paradoxical CNS stimulation (especially in children or elderly), Severe allergic reactions (e.g., anaphylaxis, angioedema) |
Hypersensitivity to hydroxyzine or cetirizine/levocetirizineEarly pregnancy (first trimester) unless clearly necessaryPorphyria
| 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 is excreted in breast milk in small amounts; however, effects on infant are unclear. Caution advised, especially with prolonged use, due to potential CNS depressant effects. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | 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. |
| Food/Dietary | No clinically significant food interactions. However, alcohol should be avoided as it potentiates the sedative effects of hydroxyzine. |
| Clinical Pearls | Hydroxyzine hydrochloride is an antihistamine with sedative, anxiolytic, and antiemetic properties. It is contraindicated in patients with prolonged QT interval or those taking other QT-prolonging drugs due to risk of torsades de pointes. Onset of sedation occurs within 15-30 minutes; avoid driving or operating heavy machinery. For pruritus, it is more effective than diphenhydramine but causes less drowsiness at lower doses. Rapid IV administration can cause hemolysis; administer IM only. In elderly patients, risk of dizziness and falls is increased; use with caution. |
| Patient Advice | May cause drowsiness; avoid driving or operating heavy machinery until you know how the drug affects you. · Avoid alcohol and other CNS depressants as they can increase drowsiness. · If you have an allergy to hydroxyzine or cetirizine, do not take this medication. · Notify your doctor if you have a history of heart problems (QT prolongation), liver disease, or seizures. · Take exactly as prescribed; do not increase dose without consulting your doctor. · For itching, use as directed; if symptoms persist, contact your healthcare provider. |