Hydroxyzine Pamoate
Hydroxyzine pamoate
Generic Name
Hydroxyzine pamoate
Mechanism
- Competitive inhibition of histamine binding at peripheral and central H₁ receptors → ↓ vasodilation, vascular permeability, and pruritus.
- Central sedative effects through blockade of cholinergic pathways and reduced acetylcholine release → anxiolytic and hypnotic properties.
- Anticholinergic activity (M₁ receptor blockade) contributes to dry mouth, tachycardia, and antispasmodic effects.
Pharmacokinetics
| Parameter | Detail | Notes |
| Absorption | Oral bioavailability ~30%; peak serum conc. 1–3 h post‑dose; slower with pamoate salt. | IV dosing provides immediate effect. |
| Distribution | High protein binding (~90 %); crosses BBB → central action. | Lipophilic, enabling sedation. |
| Metabolism | Hepatic via CYP2D6 & CYP3A4 → N‑dealkylated metabolites. | Metabolite activity similar to parent. |
| Elimination | Renal excretion (~70 %); half‑life 20–25 h (IV faster). | Reduced clearance in renal impairment. |
| Special Populations | 1‑2 × dose reduction in elderly; caution in hepatic/renal disease. | In pregnancy, drug passes placenta & into breast milk. |
Indications
- Allergic Dermatitis/Pruritus – 25–100 mg PO q4–6 h, max 25 mg q1 h for severe itch.
- Acute Anxiety & Pre‑operative Sedation – 25 mg PO or 25 mg IV 30–60 min before surgery.
- Psychogenic Irritability in Children – 0.5 mg/kg PO q6–8 h, max 25 mg.
- Adjunct for Post‑operative nausea/vomiting – adjunct to 5‑HT₃ antagonists.
Contraindications
- Absolute Contraindications: Hypersensitivity to hydroxyzine or any excipient.
- Relative Contraindications:
- Severe hepatic or renal insufficiency.
- Known QT prolongation, long QT syndrome, or history of torsades de pointes.
- Glaucoma (raised intra‑ocular pressure).
- Prostatic hypertrophy, urinary retention.
- Warnings:
- Sedative‑dose: avoid alcohol, opioids, benzodiazepines.
- Use cautiously in elderly: delirium, falls, confusion.
- Use with caution in pregnancy (category B) & lactation – minimal data but drug crosses into breast milk.
Dosing
| Form | Adult Dose | Pediatric Dose | Notes |
| Oral (pamoate) | 25–200 mg PO q4–6 h, max 400 mg/day | 0.5–2 mg/kg PO q6–8 h (≤ 12 yrs) | Slow release; avoid crushing. |
| IV | 25 mg IV q4–6 h or 25 mg IV bolus 30 min pre‑op | 0.5–2 mg/kg IV q6–8 h (≤ 12 yrs) | Rapid onset; monitor respiratory status. |
| Sublingual | 25 mg SL q6–8 h | 0.5 mg/kg SL q6–8 h | Rapid absorption, useful for acute anxiety. |
Adverse Effects
- Common
- Somnolence, dizziness, dry mouth, constipation.
- Blurred vision, headache.
- Mild tachycardia or hypotension (post‑prandial).
- Serious
- Anticholinergic toxicity: delirium, urinary retention, pupil dilation.
- Cardiovascular: QT prolongation → torsades de pointes; orthostatic hypotension.
- Respiratory: bronchospasm (rare), especially in asthmatics.
- Seizures: as part of anticholinergic crisis.
- Allergic Reactions: rash, pruritus, anaphylaxis (rare).
Monitoring
- CNS: Level of sedation; avoid driving/safety‑critical tasks until effect wears off.
- Cardiac: Monitor ECG for QTc changes, especially in patients on other QT‑prolonging agents.
- Renal/Hepatic: Periodic LFTs and creatinine in long‑term users.
- Therapeutic Drug Levels: Usually not required but may be checked in pharmacotherapy‑intensive cases.
Clinical Pearls
1. Dual‑action “quick fix” – Hydroxyzine’s antihistamine plus anxiolytic action makes it ideal for acute itch + anxiety episodes.
2. Pre‑operative “chemo‑sedation” – Administer 25 mg IV 30–60 min pre‑op to reduce drug‑sedation from anesthetics and enable smoother induction.
3. Metoclopramide alternative for post‑op nausea – Hydroxyzine’s anti‑emetic profile is useful when 5‑HT₃ antagonists fail, but watch for additive QT risk when combined with ondansetron.
4. Equivocal abuse potential – Not a Schedule‑IV drug, but it is readily available OTC as antihistamine; counsel patients on opioid‑sedation conflicts.
5. Pediatric dosing nuance – Start at the lower end (0.5 mg/kg) and titrate to effect to mitigate sedation seizures.
6. Pregnancy & lactation – Category B: low‑dose short‑term therapy acceptable; prudently weigh risk vs benefit in breastfeeding mothers.
7. Drug interactions – Concomitant use of CYP2D6 or CYP3A4 inhibitors (e.g., fluoxetine, ketoconazole) can elevate hydroxyzine levels; dose adjustment may be required.
Key Takeaway: Hydroxyzine pamoate remains a versatile, inexpensive option for symptomatic relief of itch, anxiety, and pre‑operative sedation, provided clinicians vigilantly monitor anticholinergic and cardiac safety markers.