Usage
Promethazine is primarily prescribed for the management of various conditions, including:
- Allergic conditions: Allergic rhinitis, allergic conjunctivitis, urticaria (hives), and angioedema.
- Nausea and vomiting: Postoperative, motion sickness, and chemotherapy-induced.
- Motion sickness: Prevention and treatment.
- Sedation: Preoperative and postoperative, insomnia.
Pharmacological Classifications:
- Antihistamine (H1 receptor antagonist)
- Antiemetic
- Sedative/Hypnotic
Mechanism of Action: Promethazine exerts its effects through multiple pathways:
- H1 receptor antagonism: Blocks the effects of histamine, reducing allergic symptoms.
- Anticholinergic activity: Inhibits acetylcholine, contributing to its drying and sedative effects.
- Dopamine receptor antagonism: Blocks dopamine receptors, reducing nausea and vomiting.
- Alpha-adrenergic receptor blockade: Contributes to its sedative and hypotensive effects.
Alternate Names
Promethazine hydrochloride
Brand Names: Phenergan, Promethegan, Avomine (in some regions)
How It Works
Pharmacodynamics: Promethazine’s effects are primarily mediated by H1 receptor antagonism, anticholinergic activity, dopamine receptor antagonism, and alpha-adrenergic receptor blockade.
Pharmacokinetics:
- Absorption: Well-absorbed after oral administration.
- Metabolism: Extensively metabolized in the liver via CYP450 enzymes (primarily CYP2D6).
- Elimination: Primarily eliminated through renal excretion (urine) as metabolites.
Mode of Action:
- Receptor Binding: Antagonist at H1 histamine receptors, muscarinic acetylcholine receptors, dopamine D2 receptors, and alpha-adrenergic receptors.
Elimination Pathways: Primarily renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Allergy: 12.5-25 mg orally every 4-6 hours or 25 mg at bedtime as needed. Maximum daily dose: 100 mg.
- Nausea/Vomiting: 12.5-25 mg orally every 4-6 hours as needed. Maximum daily dose: 100 mg.
- Motion Sickness: 25 mg orally 30-60 minutes before travel, then every 8-12 hours as needed.
- Sedation: 25-50 mg orally at bedtime.
Children:
- >2 years: Dosage varies depending on indication and weight. Consult specific pediatric guidelines. Promethazine is contraindicated in children under 2 years old.
Special Cases:
- Elderly Patients: Start with lower doses due to increased sensitivity.
- Patients with Renal Impairment: Caution advised; dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Caution advised; dose adjustment may be necessary.
- Patients with Comorbid Conditions: Individualized dosing based on specific condition and potential drug interactions.
Clinical Use Cases
- Intubation: Promethazine is sometimes used as an adjunct to pre-anesthetic medication.
- Surgical Procedures: Used pre- and postoperatively for sedation, nausea, and vomiting control.
- Mechanical Ventilation: Not specifically indicated.
- Intensive Care Unit (ICU) Use: May be used for nausea and vomiting control; caution is advised.
- Emergency Situations: Generally not recommended.
Dosage Adjustments
Dose adjustments are necessary based on patient factors like renal or hepatic dysfunction, drug interactions, and individual response. Always start with the lowest effective dose and titrate as needed.
Side Effects
Common Side Effects:
- Drowsiness
- Dizziness
- Blurred vision
- Dry mouth
- Constipation
- Urinary retention
Rare but Serious Side Effects:
- Neuroleptic malignant syndrome (NMS)
- Extrapyramidal symptoms (EPS)
- Seizures
- Agranulocytosis
- Leucopenia
- Thrombocytopenia
Long-Term Effects:
- Tardive dyskinesia (with prolonged use)
Adverse Drug Reactions (ADR):
Contraindications
- Hypersensitivity to promethazine or other phenothiazines.
- Coma.
- Children <2 years of age.
- Severe respiratory depression.
- Bone marrow suppression.
- Angle-closure glaucoma.
- Untreated bladder neck obstruction.
Drug Interactions
- CNS Depressants: Alcohol, opioids, benzodiazepines – increased sedation and respiratory depression.
- Anticholinergics: Increased anticholinergic effects (dry mouth, constipation, blurred vision).
- MAO Inhibitors: Hypertensive crisis.
- Epilepsy Medications: May lower seizure threshold.
Pregnancy and Breastfeeding
- Pregnancy: FDA Category C. Use only if the potential benefit justifies the risk to the fetus.
- Breastfeeding: Small amounts may be excreted in breast milk. Monitor infant for drowsiness and reduced milk production. If using short term, observe babies for excessive sedation.
Drug Profile Summary
- Mechanism of Action: H1 receptor antagonist, anticholinergic, antidopaminergic, alpha-adrenergic blocker.
- Side Effects: Drowsiness, dizziness, blurred vision, dry mouth, constipation, extrapyramidal symptoms (rare), NMS (rare).
- Contraindications: Hypersensitivity, coma, children <2 years, severe respiratory depression.
- Drug Interactions: CNS depressants, anticholinergics, MAOIs.
- Pregnancy & Breastfeeding: Use with caution; monitor infant.
- Dosage: Variable; see dosage guidelines.
- Monitoring Parameters: Respiratory rate, blood pressure, mental status.
Popular Combinations
Promethazine is sometimes combined with other medications for specific indications, but caution is needed due to potential drug interactions. It’s crucial to assess the individual patient’s situation before combining promethazine with other drugs.
Precautions
- General Precautions: Assess for allergies, underlying medical conditions, and concomitant medications.
- Specific Populations: See “Dosage - Special Cases” above.
- Lifestyle Considerations: Avoid alcohol and other CNS depressants. May impair driving ability.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Promethazine?
A: See “Dosage” section above for detailed guidelines.
Q2: What are the common side effects of Promethazine?
A: Drowsiness, dizziness, blurred vision, dry mouth, and constipation are the most common side effects.
Q3: Can Promethazine be used in children?
A: Promethazine is contraindicated in children under 2 years of age. For older children, dosages must be adjusted according to weight and indication. Consult pediatric guidelines.
Q4: Is it safe to take Promethazine during pregnancy?
A: Promethazine is FDA Pregnancy Category C. Use only if the potential benefit outweighs the potential risk to the fetus. Consult with an obstetrician.
Q5: What are the serious side effects to watch for with Promethazine?
A: Rare but serious side effects include neuroleptic malignant syndrome (NMS), extrapyramidal symptoms (EPS), and seizures.
Q6: Can I take Promethazine with other medications?
A: Many drug interactions are possible. Inform your doctor of all medications you are taking, including OTC drugs and supplements. Avoid alcohol and CNS depressants. See the “Drug Interactions” section.
Q7: How does Promethazine work for nausea and vomiting?
A: Promethazine blocks dopamine receptors, which reduces nausea and vomiting signals in the brain.
Q8: What should I do if a patient experiences an allergic reaction to Promethazine?
A: Discontinue the medication immediately and provide supportive care as needed. Severe reactions may require epinephrine and other emergency interventions.
Q9: Can Promethazine be administered intravenously (IV)?
A: Yes, but IV administration should be done slowly, following proper dilution guidelines, to avoid extravasation and tissue damage.
Q10: Is Promethazine addictive?
A: Promethazine is not considered addictive in the traditional sense, but tolerance and dependence can develop with prolonged use.
