Promethazine
Promethazine hydrochloride
Also known as: Phenergan · Phenadoz · Promethegan · Promethazine HCl · Lilly 01516 · PM 284 · RP 3277 · prometazina · Promethazine hydrochloride · Promethazini hydrochloridum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| As an antiemetic | 2 mg/kg PO or IM once daily | PO/IM | q24h | — | 🌎 NA |
| As an antihistamine | 0.2-0.4 mg/kg PO three to four times a day | PO | q6-8h | — | 🌎 NA |
| As an antihistamine | 1-2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| As an antiemetic | 2 mg/kg PO or IM once daily | PO/IM | q24h | — | 🌎 NA |
| As an antihistamine | 0.2-0.4 mg/kg PO three to four times a day | PO | q6-8h | — | 🌎 NA |
| As an antihistamine | 1-2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Promethazine is a phenothiazine derivative utilized in veterinary medicine primarily as an antiemetic and antihistamine.
- Primary Uses: It is occasionally used to manage nausea and vomiting in dogs and cats, and has been trialed for pruritus in atopic dogs (though efficacy for the latter is generally poor).
- Pharmacological Profile: While structurally related to tranquilizers like acepromazine, promethazine is distinguished by its potent antihistaminic properties alongside its antiemetic, anticholinergic, sedative, and mild local anesthetic effects.
Clinical Pearl: Promethazine is relatively uncommonly prescribed in modern veterinary practice compared to newer, more targeted antiemetics (e.g., maropitant, ondansetron) or standard antihistamines (e.g., diphenhydramine), largely due to its potential for sedation and extrapyramidal side effects.
Mechanism of action
Promethazine exerts its effects through competitive antagonism at multiple receptor sites centrally and peripherally:
- H1-Receptor Antagonism: Competitively blocks histamine at H1 receptors → reduces allergic responses and pruritus.
- D2-Dopaminergic Antagonism: Blocks dopamine receptors in the Chemoreceptor Trigger Zone (CRTZ) of the medulla → provides central antiemetic effects.
- Muscarinic Antagonism: Blocks acetylcholine at muscarinic receptors → contributes to antiemetic efficacy and causes anticholinergic side effects (e.g., dry mouth).
- Alpha-1 Adrenergic Antagonism: Blocks peripheral alpha-1 receptors → can lead to vasodilation and subsequent hypotension.
Safety & warnings
Contraindications
- Hypovolemia or shock (due to hypotensive effects)
- Tetanus or strychnine intoxication (due to extrapyramidal effects)
- Human label black box warning: Contraindicated in children < 2 years old (fatal respiratory depression)
- Known hypersensitivity to phenothiazines
- Severe central nervous system depression
- Comatose patients
- Use with caution in patients with seizure disorders
- Use with caution in patients with severe hepatic or cardiovascular disease
Adverse effects
- Sedation or lethargy
- Anticholinergic effects (dry mouth, urinary retention, decreased GI motility)
- Hypotension (especially with rapid IV administration or in hypovolemic patients)
- Extrapyramidal signs (tremors, rigidity, torticollis) - rare but possible
- Sedation / Lethargy
- Dry mucous membranes (anticholinergic effect)
- Tachycardia
- Paradoxical excitation (especially in cats)
- Gastrointestinal disturbances
Precautions
Use cautiously and at smaller doses in animals with hepatic dysfunction, cardiac disease, or general debilitation. Animals may require lower dosages of general anesthetics following phenothiazine administration. Use with extreme caution in very young or severely debilitated animals. Promethazine can cause false-positive results for salicylates in urine and false-positive/negative results for chorionic gonadotropin in urine.
Drug interactions
May cause reduced GI absorption of oral phenothiazines.
May cause reduced GI absorption of oral phenothiazines.
May have additive anticholinergic effects when used with promethazine.
May cause additive CNS depression if used with phenothiazines.
Phenothiazines block alpha-adrenergic receptors; concomitant epinephrine can lead to unopposed beta-activity causing vasodilation and increased cardiac rate (epinephrine reversal).
Phenothiazines may potentiate the extrapyramidal effects of metoclopramide.
May potentiate extrapyramidal effects.
May enhance the hypotensive effects of phenothiazines; dosages may need to be reduced.
Phenothiazines should not be given within one month of worming with these agents as their toxic effects may be potentiated.
Additive central nervous system depression and sedation.
Additive anticholinergic effects (tachycardia, dry mouth, ileus).
Monitoring
- Clinical efficacy (resolution of vomiting or pruritus)
- Degree of sedation
- Hydration status (if vomiting persists)
- Heart rate and rhythm
- Blood pressure (especially with IV use)
- Level of consciousness / CNS status
- Respiratory rate
Pharmacokinetics
Half-life
Absorption
Little veterinary data available. In humans, well absorbed following oral, rectal, or IM administration.
Distribution
Presumed to follow general phenothiazine patterns (widely distributed, crosses blood-brain barrier).
Metabolism
Metabolized in the liver.
Elimination
Metabolites are eliminated primarily in the urine.
Overdose
Overdose may result in profound sedation, severe hypotension, or acute extrapyramidal clinical signs (e.g., torticollis, tremors, excessive salivation, rigidity).
- Treatment: Supportive care is primary. Acute extrapyramidal signs have been successfully treated with injectable diphenhydramine in humans. Hypotension should be treated with IV fluids; avoid epinephrine due to the risk of epinephrine reversal (use alpha-agonists like phenylephrine if pressors are required).
Available products
Formulations
- Oral tablets
- Oral syrup
- Injection (IV/IM)
- Rectal suppositories
- 10 mg tablet
- 25 mg tablet
- 1 mg/ml syrup
- 25 mg/ml injectable solution
Human-labeled
- Promethazine HCl for Injection: 25 mg/mL & 50 mg/mL in 1 mL ampules
- Promethazine HCl Oral syrup: 1.25 mg/mL
- Promethazine HCl Oral Tablets: 12.5 mg, 25 mg & 50 mg
- Promethazine HCl Rectal Suppositories: 12.5 mg, 25 mg, & 50 mg
- Phenergan 10 mg tablets
- Phenergan 25 mg tablets
- Phenergan 1 mg/ml syrup
- Phenergan 25 mg/ml injectable solution
Regulatory status
Available as a human prescription product (POM).
Phenergan is a POM (Prescription Only Medicine) in the UK.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store tablets at room temperature (20-25°C) in tight, light-resistant containers. Syrup should be stored at 15-25°C and protected from light. Injection should be stored at room temperature (20-25°C) and protected from light; do not use if precipitate forms or solution is discolored. Suppositories should be stored in the refrigerator (2-8°C). Promethazine can adsorb to plastic IV bags and tubing.
Client information
Promethazine is used to help control nausea and vomiting, or occasionally to treat allergic reactions.
- Dry Mouth: This medication can cause a dry mouth. You can relieve this by applying small amounts of water to your pet's tongue for 10-15 minutes.
- Sedation: It may cause drowsiness, sedation, or mild behavior changes. Contact your veterinarian if these effects are severe or concerning.
- When to Call the Vet: Protracted vomiting or diarrhea can be serious; contact your veterinarian if your pet's clinical signs do not improve.
- Warning Signs: Immediately contact your veterinarian if your animal exhibits abnormal, jerky movements, tremors, or becomes rigid.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.