Promethazine

Promethazine

Clinical data
Trade names	Phenergan, Histantil
AHFS/Drugs.com	Monograph
MedlinePlus	a682284
Pregnancy category	AU: C US: C (Risk not ruled out)
Routes of administration	Oral, rectal, IV, IM, topical
ATC code	D04AA10 (WHO) R06AD02 (WHO)
Legal status
Legal status	AU: S3 (Pharmacist only) CA: OTC UK: Pharmacy medicines US: ℞-only (injection POM(UK))
Pharmacokinetic data
Bioavailability	88% absorbed but after first-pass metabolism reduced to 25% absolute bioavailability
Protein binding	93%
Metabolism	Hepatic glucuronidation and sulfoxidation
Biological half-life	16-19 hours
Excretion	Renal and biliary
Identifiers
IUPAC name (RS)-N,N-dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine
CAS Number	60-87-7 Y 58-33-3 (hydrochloride)
PubChem (CID)	4927
IUPHAR/BPS	7282
DrugBank	DB01069 Y
ChemSpider	4758 Y
UNII	FF28EJQ494 Y
KEGG	D00494 Y
ChEBI	CHEBI:8461 Y
ChEMBL	CHEMBL643 Y
ECHA InfoCard	100.000.445
Chemical and physical data
Formula	C17H20N2S
Molar mass	284.42 g/mol
3D model (Jmol)	Interactive image
Chirality	Racemic mixture
SMILES S2c1ccccc1N(c3c2cccc3)CC(N(C)C)C
InChI InChI=1S/C17H20N2S/c1-13(18(2)3)12-19-14-8-4-6-10-16(14)20-17-11-7-5-9-15(17)19/h4-11,13H,12H2,1-3H3 Y Key:PWWVAXIEGOYWEE-UHFFFAOYSA-N Y

Promethazine is a neuroleptic medication and first-generation antihistamine of the phenothiazine family. The drug has strong sedative and weak antipsychotic effects. It also reduces motion sickness and has antiemetic and anticholinergic properties (via its action on the dopamine receptor D₂). In some countries it is prescribed for insomnia when benzodiazepines are contraindicated. It is available in many countries under many brand names. Promethazine was developed in the mid 1940s when a team of scientists from Rhône-Poulenc laboratories were able to synthesize it from phenothiazine and a diamine side chain of diphenhydramine.

Some documented side effects include:

Extremely rare side effects include:

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). In many countries (including the US and UK), promethazine is contraindicated in children less than two years of age, and strongly cautioned against in children between two and six, due to problems with respiratory depression and sleep apnea.

Promethazine is listed as one of the drugs of highest anticholinergic activity in a study of anticholinergenic burden, including long-term cognitive impairment.