Promethazine
Promethazine hydrochloride
Brand names:Phenergan, Promethegan
A first-generation phenothiazine with antihistamine, antiemetic, and sedative properties. Promethazine carries FDA boxed warnings for severe tissue injury from IV extravasation and for respiratory depression in children under 2 years. Ondansetron has displaced promethazine as the first-line antiemetic in most tactical and EMS protocols. Remaining role is severe nausea unresponsive to 5-HT3 antagonists.
Pharmacology and Actions
Promethazine is a phenothiazine derivative with strong H1 antihistamine, anticholinergic, dopaminergic D2 antagonist, and weak alpha-adrenergic blocking activity. Antiemetic effect comes primarily from central D2 antagonism in the chemoreceptor trigger zone and H1 antihistamine activity in the vestibular system. Crosses blood-brain barrier readily, producing significant sedation. Anticholinergic burden contributes to dry mouth, urinary retention, and confusion.
Indications
- Nausea and vomiting (when 5-HT3 antagonists ineffective)
- Motion sickness (less common; antihistamine and anticholinergic effects)
- Allergic reactions (adjunct)
- Sedation (off-label)
- Preoperative sedation
Absolute Contraindications
- Known hypersensitivity to promethazine or phenothiazines
- Children under 2 years (FDA boxed warning - fatal respiratory depression)
- Comatose patients
- Concurrent use with high-dose CNS depressants
Precautions and Side Effects
FDA boxed warnings: severe tissue injury from IV extravasation (gangrene, amputation) - IM or PO routes strongly preferred; respiratory depression and death in children under 2 years. Common: significant sedation (the dominant operational issue), dizziness, dry mouth, blurred vision. Extrapyramidal: dystonia, akathisia, tardive dyskinesia (less than typical antipsychotics but present). Cardiovascular: hypotension, especially orthostatic. Anticholinergic: urinary retention, confusion, constipation. Photosensitivity. Lowers seizure threshold. Drug interactions: additive sedation with CNS depressants (alcohol, opioids, benzodiazepines); additive anticholinergic effects with TCAs, other antihistamines; concurrent MAOI - hypertensive crisis risk; reduced levodopa effect. Half-life 9 to 16 hours. Pregnancy Category C (extensively used for hyperemesis gravidarum despite category designation). Passes into breast milk; may cause infant sedation. Elderly: high anticholinergic burden and fall risk. If IV use is unavoidable, dilute in at least 10 mL NS, give through running IV line in large vein, never in hand or wrist - and stop immediately at any complaint of burning.
Adult Dosing
Pediatric Dosing
Contraindicated under 2 years. Children 2 years and older: 0.25 to 0.5 mg/kg PO/IM/PR every 4 to 6 hours, max 25 mg per dose.
Pharmacokinetics
Peak Effect: IV: rapid. IM/PO: 1 to 2 hours.
Duration: 4 to 6 hours (can be longer in elderly due to extended half-life).
Storage and Handling
Store at room temperature (15 to 30 degrees C). Protect from light. Injectable formulation in amber vials. Tablets, suppositories, and oral solution all stable in standard EMS conditions.
Reconstitution:
Injectable typically supplied at 25 mg/mL or 50 mg/mL. For IV (if unavoidable): dilute 25 mg in at least 10 mL of NS or compatible IV fluid. Some institutions require dilution to 1 mg/mL or lower. IM administration: undiluted, deep muscular injection.
TCCC and TECC Role
Promethazine is not in the TCCC core formulary; ondansetron is the TCCC and TECC standard antiemetic. Promethazine appears in tactical EMS supplemental formularies as a backup antiemetic when ondansetron has failed or is unavailable. Mission impact is substantial - significant sedation makes the operator non-mission-capable after administration. Operational use is primarily for casualties already being evacuated who need stronger antiemetic effect than ondansetron alone provides.
Promethazine has fallen far down the antiemetic ladder in modern tactical practice. Ondansetron's clean profile makes it the default; metoclopramide has its niche for prokinetic needs; promethazine is largely reserved for refractory nausea where sedation is acceptable or even desirable (a vomiting patient who needs to rest during evac, for instance). The FDA boxed warning about IV extravasation injury is real and severe - patients have lost limbs from inadvertent IV promethazine extravasation. If you must give it parenterally in the field, use IM. The sedation is also genuinely useful as a sleep aid in some prolonged field care scenarios, though zaleplon is a cleaner choice when available.
IV administration into a hand or wrist vein. The vesicant injury risk is severe and the resulting damage can include compartment syndrome, gangrene, and limb loss. Use IM whenever possible; if IV is unavoidable, use a large antecubital vein, dilute to at least 10 mL, infuse slowly, and stop at any complaint of burning. The other mistake is using promethazine in any patient under 2 years - the FDA boxed warning for fatal respiratory depression in this age group is absolute.
This drug profile is provided as educational reference material for trained medical providers. It is not medical advice, not a substitute for formal training, and not a substitute for current published guidelines or medical direction.
Drug administration is governed by your scope of practice, agency standing orders, medical director protocols, and applicable state and federal regulations. Controlled substances are subject to additional handling, accountability, and documentation requirements per DEA and state law. Always verify dosing, indications, contraindications, and route of administration against current published guidelines and your local protocols before administration.
If this content is being viewed during a medical emergency, call 911 immediately and follow the direction of your local emergency dispatch and medical control. Do not use this reference as a substitute for emergency medical services.
Drug information evolves. Last reviewed dates and source citations are provided for each entry. Confirm currency against the cited source before clinical use.
Penn Tactical Solutions publishes this reference for educational purposes. PTS does not provide medical direction and does not assume responsibility for clinical decisions made in the field. Clinical responsibility rests with the administering provider, their medical director, and their agency.
Educational reference for trained medical providers. Not medical advice. Not a substitute for formal training, current published guidelines, or medical direction. Drug administration is governed by your scope of practice, agency standing orders, medical director protocols, and applicable state and federal regulations. Controlled substances require additional storage, accountability, and documentation per DEA and state law.
In a medical emergency, call 911. This reference is not a substitute for emergency medical services.
Verify dosing, indications, and contraindications against current published guidelines and your local protocols before administration. Confirm content currency against the source citation. Penn Tactical Solutions does not provide medical direction. Clinical responsibility rests with the administering provider, their medical director, and their agency.
Promethazine
| IV/IO | Avoid IV use when possible (FDA boxed warning). If unavoidable: 6.25 to 12.5 mg IV maximum, diluted to at least 10 mL in NS, administered slowly (over 10 to 15 minutes) through a running IV line in a large vein. Stop immediately at any complaint of burning or pain. (3 to 5 minutes) |
| IM | 12.5 to 25 mg IM every 4 to 6 hours as needed. IM is the preferred parenteral route - reliable absorption, much lower risk than IV. (20 minutes) |
| IN | None (None) |
| PO | 12.5 to 25 mg PO every 4 to 6 hours as needed. Tablets 12.5, 25, 50 mg. (20 minutes) |