Promethazine 12.5 mg / 25 mg / 50 mg Tablets: Prescription Phenothiazine Antihistamine for Severe Nausea and Vomiting, Motion Sickness, and Pre-operative Sedation

Information last reviewed: May 2026 — for educational purposes only.

Promethazine (Phenergan) is a prescription phenothiazine antihistamine with potent antiemetic, antihistamine, sedative, and anticholinergic properties. It was one of the first widely used antihistamines and remains clinically important for severe nausea and vomiting unresponsive to OTC antihistamines, for motion sickness prevention, for pre-operative and post-operative sedation and nausea prophylaxis, and as an adjunct for pain and anxiety management. Its mechanism combines H1 histamine receptor antagonism, muscarinic anticholinergic effects, and some D2 dopamine receptor antagonism in the CTZ — providing multi-pathway antiemetic activity.

Promethazine causes profound CNS sedation. This can be clinically advantageous (for procedural sedation, pre-operative use, or night-time nausea) but makes it unsuitable for daytime use in anyone who requires alertness. It should never be used IV via inadvertent intra-arterial injection or in peripheral IV lines due to the risk of severe tissue necrosis — IV administration (if done in hospital) must use a large, well-functioning central or good peripheral vein with extreme caution or, preferably, deep IM injection is used instead.

What Is Promethazine?

Promethazine is a first-generation phenothiazine (same family as chlorpromazine) that acts primarily as an H1 histamine receptor antagonist. Its antiemetic effect derives from H1 blockade in the vestibular apparatus and weak D2 dopamine antagonism in the CTZ. Its sedative effect derives from H1 blockade in the CNS plus anticholinergic activity. It also has alpha-adrenergic blocking and antiarrhythmic properties. It is indicated for nausea/vomiting in adults and children ≥2 years (FDA black box warning: NOT for children under 2 due to risk of fatal respiratory depression).

Prescription Status

Promethazine is prescription-only in the United States. It requires careful prescribing given its black box warnings, potential for respiratory depression, and significant drug interactions (sedatives, opioids, hypnotics). It is not available OTC despite its long history and relatively low cost.

Strengths and Available Forms

• 12.5 mg tablets — lower-dose antiemetic; used for nausea Q4–6H PRN
• 25 mg tablets — most commonly used antiemetic dose; also for motion sickness (25 mg 30–60 min before travel; may repeat after 8–12 hours)
• 50 mg tablets — sedation, pre-operative use, allergy (higher doses)
• 12.5 / 25 / 50 mg rectal suppositories — useful when oral route not possible due to severe vomiting; equivalent efficacy; onset in 20–40 minutes
• 6.25 mg/5 mL oral syrup — paediatric and adult use; useful for dysphagia
• 25 mg/mL injection solution (IM only preferred) — hospital use; IM deep injection into large muscle; IV use carries risk of severe tissue necrosis and is not recommended in current guidelines

Promethazine dosing varies by indication: for nausea/vomiting 12.5–25 mg every 4–6 hours PRN; for pre-operative sedation 25–50 mg the night before or 1–2 hours before procedure; for motion sickness 25 mg taken 30–60 min before travel then every 8–12 hours. Maximum daily dose is 150 mg for most indications in adults.

Price of Promethazine

Generic promethazine tablets and suppositories are available at very low cost at most US pharmacies. This is one of the most affordable prescription antiemetics available. Even without insurance, costs are modest. The injection form is used in hospital settings only.

Frequently Asked Questions

Why is promethazine contraindicated in children under 2 years old?

The FDA issued a black box warning against use of promethazine in children under 2 years old after reports of fatal respiratory depression in this age group. Young children are especially sensitive to the CNS-depressant effects of phenothiazines and antihistamines. The therapeutic window is extremely narrow in infants and toddlers — a dose that is antiemetic in adults can suppress brainstem respiratory drive in very young children. Promethazine must also be used with great caution and at the lowest effective dose in children aged 2–11.

What is the danger of intravenous promethazine injection?

Promethazine is highly vesicant (tissue-damaging) at high concentrations. Inadvertent intra-arterial injection or even extravasation from a peripheral IV line can cause severe local tissue necrosis, gangrene, and amputation in the worst cases. The FDA requires warnings on promethazine injectable products against IV administration. When injection is needed, deep intramuscular (IM) injection into the gluteus or vastus lateralis is recommended. If IV use is essential in a clinical setting, it should be highly diluted and given via large-bore central access only.

Can promethazine be used for pregnancy nausea (morning sickness)?

Promethazine is sometimes used off-label for nausea and vomiting of pregnancy, particularly when first-line options (pyridoxine-doxylamine combination, ondansetron) are not sufficient. While it has been used for decades in pregnancy, the available data on safety in the first trimester is less comprehensive than for other antiemetics. A physician should always weigh the benefit-risk ratio before prescribing promethazine to pregnant patients. It is FDA Pregnancy Category C.

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