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Promethazine is a first-generation H1 receptor antagonist used medically as an antihistamine and antiemetic. It can also have strong sedative effects and in some countries is prescribed for insomnia when benzodiazepines are contraindicated. It is a prescription drug in the United States and Australia but is available over the counter in the United Kingdom, Canada, Switzerland, and many other countries (brand names Phenergan, Promethegan, Romergan, Fargan, Farganesse, Prothiazine, Avomine, Atosil, Receptozine, Lergigan).

Chemically, promethazine hydrochloride appears as a white to faint yellow crystaline powder that is practically odorless. Slow oxidation may occur upon prolonged exposure to air usually causing blue discoloration. Promethazine as the hydrochloride salt is freely soluble in water and somewhat soluble in alcohol. Promethazine is a chiral compound, occurring as a mixture of enantiomers (pictured).


Mechanism of action

  • Promethazine is a phenothiazine derivative that competitively blocks histamine H1 receptors without blocking the secretion of histamine. It also is a very weak dopamine antagonist .
  • It has sedative, anti-motion-sickness, anti-emetic, and anti-cholinergic effects

Side effects

Some common side effects include:
  • Confusion in the elderly
  • Drowsiness, dizziness, fatigue, more rarely vertigo
  • Dry mouth
  • Respiratory depression in patients under age of 2 and in those with severely compromised pulmonal function
  • Constipation
  • Euphoria (very rare with high IV doses and/or coadministration with opioids/CNS depressants)
  • Restless legs
  • Paresthesia

Extremely rare side effects include:

It is recommended that promethazine only be given through an existing intravenous set in a large vein and diluted to concentration no greater than 25mg per mL, not to exceed a rate of administration of 25mg a min. Serious complications including those listed above have resulted from improper parenteral administration, including those requiring surgical intervention and amputation.

Because of potential for more severe side effects, this drug is on the list to avoid in the elderly. (See NCQA’s HEDIS Measure: Use of High Risk Medications in the Elderly).

Laboratory examinations

All patients should have their blood pressure measured frequently. During long-term therapy, blood cell counts, liver function studies, EKG, and EEG are recommended. The intervals should be determined according to the risk profile of the patient.In high doses, promethazine can create auditory and visual hallucinations causing panic and intense fear.

Case law

The U.S.marker Supreme Courtmarker accepted a case involving promethazine that influences product liability. Diana Levine, a woman suffering from a migraine, was administered Wyeth's Phenergan via IV push. The drug was injected improperly resulting in gangrene and subsequent amputation of her right forearm below the elbow. A state jury awarded her $6 million in punitive damages. The case was appealed to the Supreme Court on grounds of federal pre-emption and substantive due process. The Supreme Court upheld the lower courts' rulings stating that "Wyeth could have unilaterally added a stronger warning about IV-push administration" without acting in opposition to federal law. In effect, this means that drug manufacturers can be held liable for injuries if the FDA-approved warnings of potential adverse affects is deemed insufficient by state courts.

See Also


  1. RxList: Promethazine
  2. RxList: Promethazine Description
  3. RxList Indications for Promethazine
  4. [1]
  5. David J. McCann and Brett Roth, Toxicity, Antihistamine, eMedicine Toxicology, updated June 21, 2007
  6. Cordingley Neurology
  7. Baxter: Promethazine HCl Injection, USP Information

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