Promethazine
Promethazine
Generic Name
Promethazine
Brand Names
Phenergan®, Banan) is a first‑generation phenothiazine antihistamine with antiemetic, sedative, and anticholinergic properties. It is widely used for allergy relief, nausea/vomiting, and procedural sedation.
Mechanism
- H1‑Histamine Receptor Antagonist – competitively blocks peripheral and central H1 receptors, reducing wheal‑and‑flare, pruritus, and bronchospasm.
- Dopamine D2 Receptor Antagonism – contributes to antiemetic effect by inhibiting the chemoreceptor trigger zone.
- Weak Anticholinergic Activity – diminishes secretions and smooth‑muscle tone.
- α‑Adrenergic Blockade & Central Nervous System Depression – responsible for the drug’s sedative and hypotensive effects.
> *Note:* The combination of H1 antagonism with dopamine blockade underlies its high antiemetic efficacy.
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Pharmacokinetics
| Parameter | Details |
| Absorption | Rapid oral absorption (T_max ≈ 30–60 min). Adequate bioavailability (~70 % when taken with food). |
| Distribution | Widely distributed; highly lipophilic → significant brain penetration. Protein binding ~ 70 %. |
| Metabolism | Hepatic via CYP450 enzymes (mainly CYP2D6 & CYP3A4) to inactive metabolites. |
| Half‑Life | 6–18 h (depends on age, hepatic function).
| Excretion | Renal (≈ 50 %) and biliary. Elimination in urine and feces. |
| Special Populations | Reduced clearance in hepatic impairment; caution with chronic alcoholism and severe renal disease. |
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Indications
- Allergic reactions: urticaria, rhinitis, asthma (as an adjunct), allergic conjunctivitis.
- Anti‑emetic: motion sickness, postoperative nausea/vomiting, chemotherapy‑induced emesis.
- Sedation: pre‑operative anxiolysis, short‑term management of agitation.
- Premedication: for mild procedural sedation, especially in infants/children.
- Adjunct in severe asthma: combined with β₂‑agonists for refractory bronchospasm.
- Other: treatment of nausea in pregnancy (Class II); occasionally used in irritable bowel syndrome for anticholinergic effect.
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Contraindications
| Category | Precautions |
| Contraindicated | Asthma or reactive airway disease (except used as adjunct with β₂‑agonists), severe hepatic/renal disease, pregnancy > 3rd trimester, neonatal use (excessive sedation). |
| Warnings |
• CNS depression: avoid concomitant alcohol, benzodiazepines, opioids. • Anticholinergic overload: risk of orthostatic hypotension, urinary retention. • Seizures: prolonged use > 14 days may lower seizure threshold. • Children under 2 yrs: risk of sudden infant death syndrome (SIDS) with oral suspension. |
| Drug‑Drug Interactions | CYP2D6 inhibitors (e.g., fluoxetine) ↑ plasma levels; warfarin ↑ bleeding risk; other CNS depressants—additive sedation. |
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Dosing
| Population | Dose | Frequency | Notes |
| Adults (oral) | 25–50 mg q8–12 h | ≥ 4 h intervals | 300 mg not to exceed per day. |
| Adults (IV/IM) | 5–20 mg PO/IV/IM | q4–6 h | Use 2.5–10 mg IV for sedation. |
| Children ≥2 yrs | 1 mg/kg PO up to 50 mg | q6–8 h | Not recommended Administration tip: For IV use a 2.5 % Promethazine solution. Slowly infuse over 2–3 min to reduce hypotension.
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Adverse Effects
Common (≥ 10 %)
• Drowsiness, sedation
• Dry mouth, blurred vision
• Headache, dizziness
• Hypotension (postural)
• Nausea, constipation
Serious (≤ 1 %)
• Severe respiratory depression (esp. with opioids or alcohol)
• Hypersensitivity/anaphylaxis
• Prolonged QTc (rare)
• Seizures or status epilepticus with prolonged use or high dose
• Anticholinergic crisis (urinary retention, hyperthermia)
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Monitoring
| Parameter | Frequency | Rationale |
| Vital signs (BP, HR, RR) | Every 2–4 h in high‑dose or elderly | Detect orthostatic hypotension, respiratory depression. |
| Sedation level | At bedtime or during infusion | Avoid oversedation, monitor for overdose. |
| QTc interval | Baseline and if high dose (> 20 mg IV) | Screen for arrhythmia risk, especially with other QT‑prolonging meds. |
| Renal/hepatic function | Before therapy and periodically in impaired patients | Adjust dose, prevent accumulation. |
| Respiratory function | In opioid‑co‑administered patients | Detect hypoventilation early. |
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Clinical Pearls
1. Use a “Low‑Dose Pre‑op” Protocol: 1 mg/kg IV Promethazine 30 min before surgery yields adequate anxiolysis with minimal hypotension compared to larger doses.
2. Avoid in Geriatric Patients → higher sensitivity to anticholinergic effects and risk of confusion. Start at 25 mg PO bid, titrate to effect.
3. Pregnancy‑Safe Alternative? When anti‑nausea is needed, consider ondansetron; Promethazine is Class II (risk/benefit).
4. Check for CYP2D6 Inhibitors → these can up‑dose Promethazine dramatically; monitor for increased anticholinergic toxicity.
5. Combination with Anticholinergics (e.g., diphenhydramine) → additive sedation and dry‑mouth; use caution.
6. SIDS Alert: Never prescribe oral Promethazine to infants These points help differentiate Promethazine from other antihistamines and inform safe, effective use in varied patient populations.
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• *For citation, see: Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th Ed.), Drugs.com Pharmacology, and FDA prescribing information.*