Promethazine

Generic Name: Promethazine

Brand Names: Phenergan

Promethazine is a first-generation antihistamine with antiemetic, sedative, and antihistamine properties.

AntiemeticsAntihistaminesAllergy

Drug Class

First-Generation Phenothiazine Antihistamine (H1 Antagonist) with Antiemetic and Sedative Properties

Pregnancy

Category C — Animal studies have shown adverse effects at high doses. Limited human data have not consistently demonstrated teratogenicity, but use near term may cause neonatal sedation, hypotonia, or extrapyramidal symptoms. Reserve for situations where benefit clearly outweighs risk; ondansetron or doxylamine-pyridoxine are preferred for pregnancy-associated nausea.

Available Forms

Oral tablet (12.5 mg, 25 mg, 50 mg), Oral syrup (6.25 mg/5 mL), Rectal suppository (12.5 mg, 25 mg, 50 mg), Injection for IM or deep IV use (25 mg/mL, 50 mg/mL — IV use carries FDA Boxed Warning for severe tissue injury)

What It's Used For

Nausea and vomiting prevention and treatment
Allergic rhinitis and other allergic conditions
Motion sickness prevention
Sedation (preoperative and postoperative)
Adjunct in anaphylaxis treatment

Dosage Quick Reference

These are general dosage guidelines. Your doctor will determine the appropriate dose for your specific situation.

Condition	Starting Dose	Maintenance Dose
Nausea and vomiting (adult)	12.5–25 mg orally, rectally, or IM every 4–6 hours as needed	Same dose; reassess after 24 hours
Allergic rhinitis or urticaria (adult)	12.5 mg before meals and at bedtime	25 mg at bedtime if needed
Motion sickness (adult)	25 mg orally 30–60 minutes before travel	25 mg every 8–12 hours during travel
Preoperative or postoperative sedation	25–50 mg IM	Repeat every 4–6 hours as needed
Pediatric (>= 2 years; nausea, allergy)	0.25–0.5 mg/kg per dose every 4–6 hours	Use lowest effective dose; max 25 mg/dose

Side Effects

Common Side Effects:

Drowsiness and sedation
Dizziness
Dry mouth
Blurred vision
Constipation
Confusion (especially in elderly)
Urinary retention

Serious Side Effects (seek immediate medical attention):

Severe respiratory depression (especially in children)
Severe tissue injury at injection site
Neuroleptic malignant syndrome (fever, rigidity, altered consciousness)
Severe hypotension
Seizures
Extrapyramidal symptoms (involuntary movements)

Drug Interactions

Promethazine has wide receptor activity (H1, dopamine D2, muscarinic, alpha-adrenergic) which produces both pharmacodynamic and pharmacokinetic interactions of concern.

CNS depressants (opioids, benzodiazepines, alcohol, sedating antihistamines, gabapentin, sleep aids): Profound additive sedation and respiratory depression. The FDA has highlighted risk when combined with opioids; use the lowest effective dose and avoid combining with other sedating agents whenever possible.
Anticholinergic agents (oxybutynin, tricyclic antidepressants, diphenhydramine, scopolamine): Additive dry mouth, urinary retention, blurred vision, constipation, confusion, and anticholinergic delirium — especially in older adults.
Dopamine antagonists (haloperidol, metoclopramide, prochlorperazine): Additive risk of extrapyramidal symptoms, akathisia, and neuroleptic malignant syndrome.
MAO inhibitors: May intensify and prolong promethazine anticholinergic effects and contribute to hypotension. Use cautiously and at reduced doses.
Epinephrine: Promethazine alpha-adrenergic blockade can cause paradoxical further fall in blood pressure when epinephrine is given in shock. Use norepinephrine or phenylephrine in patients on phenothiazines.
QT-prolonging agents (e.g., ondansetron, methadone, amiodarone, ciprofloxacin): Additive QT prolongation. Obtain ECG and monitor electrolytes when combinations are unavoidable.

Additional Information

Promethazine is a first-generation antihistamine with additional antiemetic, sedative, and anticholinergic properties. Originally developed as an antihistamine, it has found widespread use for prevention and treatment of nausea and vomiting, as a sedative, and as an adjunct in pain management. Its versatility makes it valuable in multiple clinical settings, though safety considerations limit its use in certain populations.

Mechanism of Action

Promethazine exerts its effects through multiple receptor interactions. As a histamine H1 receptor antagonist, it blocks the effects of histamine on capillaries, bronchial smooth muscle, and the gastrointestinal tract. Its antiemetic effect results primarily from blocking H1 receptors and muscarinic receptors in the vomiting center and chemoreceptor trigger zone. The sedative effects are mediated through central H1 blockade. Promethazine also has significant anticholinergic activity and weak antidopaminergic properties, contributing to both therapeutic effects and side effects.

The medication has local anesthetic properties due to its membrane-stabilizing effects, which may contribute to its ability to relieve itching and irritation associated with allergic reactions.

Available Formulations

Promethazine (Phenergan) is available in multiple formulations including oral tablets (12.5 mg, 25 mg, 50 mg), oral solution (6.25 mg/5 mL), suppositories (12.5 mg, 25 mg, 50 mg), and injectable solution (25 mg/mL, 50 mg/mL) for deep intramuscular or intravenous use. The variety of formulations allows administration even when nausea prevents oral intake. Combination products with codeine (Phenergan with Codeine) are available for cough suppression.

FDA-Approved Indications

Promethazine is FDA-approved for allergic conditions (perennial and seasonal allergic rhinitis, allergic conjunctivitis, uncomplicated allergic skin manifestations of urticaria and angioedema), prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery, therapy adjunct in anaphylactic reactions (after acute symptoms controlled with epinephrine), preoperative, postoperative, or obstetric sedation, and prevention and treatment of motion sickness.

Dosing Guidelines

For allergic conditions, the typical adult dose is 25 mg orally at bedtime, or 12.5 mg before meals and at bedtime. For nausea and vomiting, 12.5-25 mg every 4-6 hours as needed is typical. For sedation, 25-50 mg at bedtime or preoperatively. For motion sickness, 25 mg 30-60 minutes before travel, repeated every 8-12 hours as needed. Doses should be reduced in elderly patients and those with hepatic impairment.

Boxed Warning for Respiratory Depression in Children

Promethazine carries a boxed warning contraindicated in children less than 2 years of age due to the potential for fatal respiratory depression. In children 2 years and older, use the lowest effective dose and avoid combination with other respiratory depressants. Promethazine should not be used for treatment of uncomplicated vomiting in children; use should be limited to prolonged vomiting of known etiology.

Important Safety Considerations

Beyond the pediatric concerns, promethazine causes significant sedation and impairs mental and physical abilities required for tasks such as driving. Anticholinergic effects include dry mouth, urinary retention, constipation, and blurred vision. The medication can lower the seizure threshold and should be used cautiously in patients with seizure disorders. Neuroleptic malignant syndrome has been reported. Avoid concurrent use with other CNS depressants including opioids, sedatives, and alcohol.

Injection Site Concerns

Intravenous administration of promethazine has been associated with severe tissue injury including gangrene requiring amputation. The preferred route is deep intramuscular injection. If IV administration is necessary, it should be given through a running IV line at the port furthest from the patient's vein, at a concentration no greater than 25 mg/mL, at a rate not exceeding 25 mg/minute. Subcutaneous and intra-arterial injection are contraindicated.

Drug Interactions

CNS depressants (opioids, benzodiazepines, alcohol) have additive effects and may cause profound sedation or respiratory depression. Anticholinergic drugs increase the risk of adverse effects. MAO inhibitors may prolong and intensify anticholinergic effects. Promethazine may enhance the hypotensive effects of antihypertensive agents. It may interfere with pregnancy tests and glucose tolerance tests.

Learn more at MedlinePlus

Frequently Asked Questions

Promethazine is highly caustic to vessels and tissues. Inadvertent arterial injection or extravasation can cause severe vasospasm, gangrene, and limb amputation, prompting an FDA Boxed Warning. The IM route is much safer, and many institutions now prefer alternative antiemetics such as ondansetron when an IV agent is needed.

No, not for at least several hours and possibly longer. Promethazine causes substantial sedation, slows reaction time, and impairs judgment in ways patients often underestimate. Avoid driving, operating heavy machinery, or making important decisions until you know how the drug affects you, and never combine it with alcohol.

Promethazine carries an FDA Boxed Warning against use in children younger than 2 years because of fatal respiratory depression. Even in older children, lower doses and careful patient selection are required. Discuss safer alternatives such as ondansetron with your pediatrician for nausea and vomiting in young children.

Promethazine appears on the Beers Criteria of medications best avoided in adults over 65 due to strong anticholinergic effects, sedation, fall risk, confusion, and contribution to delirium. When a sedating antiemetic or antihistamine is needed in older patients, your physician will usually choose alternatives with a more favorable safety profile.

Onset is typically within 20 minutes by mouth or IM and 30 to 60 minutes rectally. Effects, including sedation, usually last 4 to 6 hours but can persist for 12 hours in sensitive individuals or higher doses. Plan dosing so you can rest and avoid activities requiring full alertness.

Questions to Ask Your Doctor

Consider discussing these topics at your next appointment:

✓Is promethazine the safest option for my symptoms, or would another antiemetic or antihistamine be better?
✓Could any of my current medications interact with promethazine to cause sedation or heart rhythm problems?
✓How long should I plan to take promethazine, and what symptoms should prompt me to stop?
✓If I am over 65 or care for an older adult, are there safer alternatives I should consider?

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Related Health Conditions

This medication is commonly used to treat or manage the following conditions:

Rhinitis

Rhinitis, or inflammation of the nasal mucous membrane, presents with symptoms like a runny nose and congestion, stemming from allergies, irritants, infections, or hormonal changes.

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Medical Disclaimer: This information is for educational purposes only and should not be considered medical advice. Always consult with your healthcare provider before starting, stopping, or changing any medication. Your doctor can provide personalized recommendations based on your specific health condition and medical history.