A first-generation phenothiazine antihistamine with antiemetic, sedative, and anticholinergic properties. Promethazine is used for prevention and treatment of nausea and vomiting from various causes, motion sickness, allergic conditions, and as a pre- and postoperative sedative adjunct.
Children under 2 years of age (risk of fatal respiratory depression)
Known hypersensitivity to phenothiazines
The bottom line
Evidence rating strong. Most-documented uses: prevention and treatment of nausea and vomiting, motion sickness prevention, sedation (pre- and postoperative adjunct). 10 sources indexed (2003–2025), with 3 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Blocks histamine H1 receptors (antihistaminic and antiemetic activity), dopamine receptors in the chemoreceptor trigger zone (antiemetic activity), and muscarinic cholinergic receptors (anticholinergic and anti-motion-sickness activity). The combination of these receptor antagonisms provides broad antiemetic and sedative effects.
Class
Antiemetic (Phenothiazine)
Absorption
Fat-soluble; take with food
Dosing
Dosing & protocol.
Common range
12.5–25 mg every 4–6 hours as needed (as prescribed by your physician)
Recommended form
Tablet, oral solution, rectal suppository, or IM injection
Can be taken with or without food; take 30–60 minutes before travel for motion sickness
Safety
Full safety detail.
Side effects
Pronounced sedation and drowsiness
Dry mouth
Blurred vision
Urinary retention
Constipation
Dizziness
Severe tissue injury with IV or subcutaneous injection
Respiratory depression (especially in children)
Contraindications
Children under 2 years of age (risk of fatal respiratory depression)
Known hypersensitivity to phenothiazines
Comatose states
Concurrent use with other respiratory depressants in children
Intra-arterial or subcutaneous injection (severe tissue necrosis)
Alcohol can add to promethazine's sedating, anticholinergic, and coordination-impairing effects. Human studies show promethazine impairs psychomotor performance, and ethanol produces overlapping deficits in performance monitoring and reaction tasks. The combination is especially unsafe with opioids, sleep medicines, respiratory disease, or fall risk.
Recommendation: Avoid alcohol while taking promethazine for nausea, allergy, cough, or sleep. Do not drive or combine it with other sedatives if alcohol was used. Get urgent care for severe confusion, fainting, shallow breathing, or inability to wake.
THC-dominant cannabis can add to promethazine-related sedation, slowed reactions, and impaired coordination. Promethazine impairs psychomotor function in controlled human studies, while THC acutely impairs driving-related performance. The combination is especially concerning with nausea/cough products that also contain opioids or other sedatives.
Recommendation: Do not combine THC-dominant cannabis with promethazine before driving or any safety-sensitive task. If both were used, stay in a safe setting and avoid adding alcohol, opioids, or sleep medicines. Use the lowest effective promethazine dose only as prescribed.
Melatonin can add to promethazine-related drowsiness, slowed reaction time, and next-day grogginess. Promethazine significantly impairs psychomotor function in healthy-volunteer studies, and melatonin can affect sleepiness and performance depending on timing and dose. The combination is more concerning when promethazine is used as a nighttime sedative or alongside cough products containing opioids.
Recommendation: Do not use melatonin to intensify promethazine's sedating effect. If your prescriber approves both, use the lowest effective doses and avoid driving until you know how you respond. Avoid adding alcohol, cannabis, opioids, or other sleep medicines.
Miuli A, Stigliano G, Lalli A et al.. "Purple Drank" (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon with Medical Implications. Journal of psychoactive drugs. 2020
Huf G, Coutinho ES, Adams CE. [Haloperidol plus promethazine for agitated patients--a systematic review]. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999). 2009
Ruijuan L, Jiqiang Z, Ruirui B et al.. Promethazine for nausea and vomiting prevention after gynaecological laparoscopic surgery: A randomized controlled trial. Scientific reports. 2025
Liu R, Bi R, Zhang J et al.. Promethazine Combined with Metoclopramide for the Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Colorectal Cancer Surgery: A Randomized Controlled Trial. Drug design, development and therapy. 2025
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