HYDROXYZINE PAMOATE
Clinical safety rating: safe
CNS depressants may enhance sedative effects May cause marked drowsiness and QT prolongation.
Hydroxyzine pamoate is a piperazine derivative with antihistamine (H1 receptor antagonist) and anticholinergic properties. It also has sedative, anxiolytic, and antiemetic effects, likely mediated through suppression of subcortical regions of the central nervous system.
| Metabolism | Hydroxyzine is extensively metabolized in the liver primarily via CYP3A4 and CYP2D6 isoenzymes. The major metabolite is cetirizine, an active carboxylic acid metabolite. |
| Excretion | Primarily hepatic metabolism; <1% excreted unchanged in urine. Biliary/fecal elimination accounts for approximately 50% of metabolites. |
| Half-life | Terminal elimination half-life is approximately 20 hours (range 14-25 hours) in adults; may be prolonged in elderly or hepatic impairment. |
| Protein binding | Approximately 93% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 16 L/kg (range 13-20 L/kg); indicates extensive tissue distribution. |
| Bioavailability | Oral: approximately 100% (well absorbed); IM: approximately 100%. |
| Onset of Action | Oral: 15-30 minutes (antihistamine); 45-60 minutes (anxiolytic). IM: 15-30 minutes. |
| Duration of Action | Oral: 4-6 hours (antihistamine); 4-6 hours (anxiolytic). IM: 2-4 hours. Note: Sedative effects may persist longer. |
| Molecular Weight | 447.97 |
| Action Class | Antihistamine (first-generation, piperazine derivative) |
Oral: 50-100 mg every 6 hours as needed for pruritus or anxiety; maximum 600 mg/day. IM: 25-100 mg every 4-6 hours as needed.
| Dosage form | CAPSULE |
| Renal impairment | GFR 10-50 mL/min: Administer every 12 hours. GFR <10 mL/min: Administer every 24 hours or avoid use due to risk of accumulation. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Use with caution; maximum 50 mg/day or avoid use. |
| Pediatric use | Oral: For pruritus: 0.5-1 mg/kg/dose every 6-8 hours. For anxiety: <6 years: 50 mg/day divided; ≥6 years: 50-100 mg/day divided. IM: 0.5-1 mg/kg/dose every 4-6 hours. |
| Geriatric use | Start at lower end of dosing range (25 mg orally) due to increased sensitivity and anticholinergic effects; caution with sedation and hypotension. |
| 1st trimester | Hydroxyzine pamoate crosses the placenta. Limited data in first trimester; animal studies have shown fetal abnormalities at high doses. Use only if clearly needed. |
| 2nd trimester | Limited data; potential risk of neonatal respiratory depression if used near term. Use only if benefit outweighs risk. |
| 3rd trimester | Use near term may cause neonatal respiratory depression, hypotonia, and withdrawal symptoms. Avoid during labor and delivery. |
Clinical note
CNS depressants may enhance sedative effects May cause marked drowsiness and QT prolongation.
| FDA category | Animal |
| Placental transfer | Hydroxyzine crosses the placenta; fetal concentrations may approach maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | pruritus |
| Serious Effects | QT prolongation and torsade de pointes (especially with overdose or in patients with risk factors), Seizures, Severe hypotension, Acute dystonic reactions, Paradoxical CNS stimulation (especially in children or elderly), Blood dyscrasias (rare) |
Hypersensitivity to hydroxyzine or any componentEarly pregnancy (first trimester) unless absolutely necessaryPorphyriaQT prolongation or concurrent use of QT-prolonging drugs
| Precautions | May cause QT prolongation, especially in patients with risk factors (e.g., electrolyte abnormalities, concomitant QT-prolonging drugs)., Should be used with caution in elderly patients due to increased risk of anticholinergic effects and sedation., May impair cognitive function and motor skills; patients should avoid driving or operating machinery until effects are known., Use with caution in patients with hepatic impairment; dose adjustment may be required., May increase the risk of seizures in patients with a history of seizure disorder. |
Loading safety data…
| Hydroxyzine is excreted into breast milk in small amounts. Theoretical risk of sedation or irritability in infants. Consider alternative antihistamines with better safety profile. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Hydroxyzine pamoate is classified as FDA Pregnancy Category C. Data in humans are limited; however, animal studies have shown teratogenic effects at high doses. There are no adequate and well-controlled studies in pregnant women. First trimester: Potential risk of fetal abnormalities cannot be ruled out; use only if clearly needed. Second and third trimesters: May cause neonatal respiratory depression, hypotonia, and withdrawal symptoms if used near term. |
| Fetal Monitoring | Monitor maternal vital signs, level of sedation, and signs of anticholinergic effects. For the fetus, assess fetal heart rate and movement patterns; if used near term, observe neonate for respiratory depression, hypotonia, and withdrawal symptoms. |
| Fertility Effects | Hydroxyzine has no known direct effects on human fertility. Animal studies have not shown impairment of fertility at therapeutic doses. However, its anticholinergic effects may theoretically affect sexual function; no specific data in humans. |
| Food/Dietary | No significant food interactions. However, taking with food may reduce GI upset. Avoid alcohol and grapefruit juice, which can alter drug metabolism (minimal effect, but caution). |
| Clinical Pearls | Hydroxyzine pamoate is a first-generation antihistamine with sedative, anxiolytic, and antipruritic properties. It is often used for pre-operative sedation and management of anxiety. Note that it can cause significant QT prolongation, especially in patients with electrolyte abnormalities or concurrent use of other QT-prolonging drugs. Avoid use in patients with porphyria. Onset of sedation is rapid, making it useful for acute agitation. It is also effective for urticaria and other allergic pruritus. The pamoate salt is a long-acting formulation, with peak effects at 2-4 hours and a half-life of 20-25 hours. Always assess renal function in elderly patients to avoid excessive sedation and anticholinergic toxicity. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your healthcare provider. · This medication may cause drowsiness or dizziness; avoid driving or operating heavy machinery until you know how it affects you. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) as they can increase sedation. · Report any irregular heartbeat, fainting, or seizures immediately. · Do not take with other antihistamines or medications containing antihistamines (e.g., cold and allergy products). · If you are pregnant, planning to become pregnant, or breastfeeding, discuss with your doctor before use. · Store at room temperature, away from moisture and heat. · Do not crush or chew extended-release capsules; swallow whole. |