From the Guidelines
Promethazine is a phenothiazine with antihistamine, sedative, antiemetic, and anticholinergic effects, and its use should be cautious, especially in children under 2 years due to the risk of fatal respiratory depression 1.
Key Characteristics of Promethazine
- It works by blocking postsynaptic dopaminergic receptors in the brain and has a strong-adrenergic inhibitory effect, as well as being a competitive histamine H-receptor antagonist 1.
- The clinical effects of promethazine are evident within 5 minutes of intravenous administration, with a duration of action of 4 to 6 hours, and a plasma half-life of 9 to 16 hours 1.
- The usual dose of promethazine is 12.5 to 25 mg intravenously, infused slowly to minimize the risk of hypotension 1.
Important Considerations
- Promethazine has been used for the management of allergic reactions and anaphylaxis, as treatment of postoperative nausea and vomiting, and as an adjuvant for postoperative pain and sedation 1.
- It should be used cautiously in elderly patients and is not recommended for children under 2 years due to potential respiratory depression risks 1.
- The medication can cause significant sedation, so users should avoid driving or operating machinery after taking it.
Side Effects and Interactions
- Common side effects include drowsiness, dry mouth, blurred vision, and constipation.
- Promethazine may interact with other medications, such as narcotics and benzodiazepines, and its use may require a reduction in the dosage of standard sedation agents 1.
From the FDA Drug Label
Promethazine is a phenothiazine derivative which differs structurally from the antipsychotic phenothiazines by the presence of a branched side chain and no ring substitution. Promethazine hydrochloride, a phenothiazine derivative, is designated chemically as 10 H-Phenothiazine-10-ethanamine, N, N,α-trimethyl-, monohydrochloride, (±)- Promethazine is an H1 receptor blocking agent with antihistaminic, sedative, and antiemetic effects 2.
- It is a phenothiazine derivative
- Chemically designated as 10 H-Phenothiazine-10-ethanamine, N, N,α-trimethyl-, monohydrochloride, (±)- 2
From the Research
Definition and Uses of Promethazine
- Promethazine is a histamine H1 receptor competitive antagonist with antihistaminic, sedative, anti-kinetotic, antiemetic, and antimuscarinic effects 3.
- It is utilized for the treatment of nausea and vomiting, a common reason for emergency department (ED) visits 3.
- Promethazine is also used as a sedative and/or as an antiemetic 4.
Pharmacological Aspects
- Promethazine selectively inhibits NMDA receptors, whereas AMPA- and kainate receptors are hardly affected 4.
- The inhibition of NMDA-induced membrane currents occurs in a reversible manner with a half-maximal effect at around 20 μM promethazine 4.
- Promethazine directly blocks the hERG K(+) channel, which may lead to QT prolongation and torsades de pointes 5.
Therapeutic Uses and Toxicity
- Promethazine offers a suitable alternative antiemetic for use in the ED due to its distinct mechanism of action 3.
- However, injectable promethazine must be used with caution to minimize the risk of serious patient harm in the event of intra-arterial or perivascular extravasation when given parenterally 3.
- Promethazine has significant sedative effects, especially when used in conjunction with narcotic analgesics 6.
- Low-dose intravenous promethazine (6.25 or 12.5 mg) relieves nausea and vomiting as effectively as intravenous ondansetron 4 mg 6.