N05BA01 - Diazepam |
Propably not porphyrinogenic |
PNP |
Rationale
Diazepam is metabolized by Cytochrome P450 enzymes, but there are no in vitro or clinical observations pointing to significant capacity for CYP-induction or irreversible CYP-inhibition. There are 18 EPNET reports on uneventful use of diazepam.
Chemical description
The chemical name for diazepam is chlorometylphenyl benzodiazepin-2-one.
Therapeutic characteristics
Diazepam has anticonvulsant, anxiolytic, sedative and muscle relaxant properties, and is used in the treatment of anxiety syndrome, acute alcohol abstinence symptoms, central and peripheral muscle spasms, epileptic state, tetanus, acute excitation and sedation prior to operation or diagnostic measures.
Diazepam can be administered via oral, parenteral or rectal formulations.
Metabolism and pharmacokinetics
Diazepam is mainly metabolized by CYP 2C19 under generation of the desmethyl metabolite norazepam, temazepam and oaxzepam, which are eliminated in glucuronide forms. There are no pharmacokinetic or drug interaction data in support of capacity for diazepam or its metabolites for significant CYP-induction or irreversible CYP-inhibition.
Personal communication
Thunell S: 3 reports of uneventful use.
Published experience
Kauppinen (1992): used uneventfully by two patients with acute porphyria.
Diazepam have been suspected to have contributed to cause porphyrick attacks in two AIP patients (Shipton (1984) and Stiefelhagen (2000)), but the attacks where poorly documented and other factors could have contributed to the attacks. These reports have therefore not been taken into account in the judgement of the porphyrinogenicity of diazepam.
IPNet drug reports
Uneventful use reported in 18 patients with acute porphyria.
References
- Scientific articles
- Preissner S, Kroll K, et al: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38 (Database issue):D237-43. Epub 2009 Nov 24 #2670
- Zhou, S.F., Zhou, Z.W. et al. Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development. Current Medicinal Chem 2009; 16: 3480-3675. #2353
- Fukasawa T, Suzuki A, et al. Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines. J Clin Pharm Ther. 2007 Aug;32(4):333-41. PMID 17635335. #4674
- Kauppinen R, Mustajoki P. Prognosis of acute porphyria: occurrence of acute attacks, precipitating factors, and associated diseases. Medicine (Baltimore). 1992 Jan;71(1):1-13. PMID 1549056. #1429
- Shipton EA, Roelofse JA. Anaesthesia in a patient with variegate porphyria undergoing coronary bypass surgery. A case report. S Afr Med J. 1984 Jan 14;65(2):53-4. #2671
- Stiefelhagen P. [Abdominal pain after taking drug tablets. Acute intermittent porphyria]. MMW Fortschr Med. 2000 Feb 3;142(5):47-8 PMID 10715942. #2672
- Drug reference publications
- Sweetman SC, editor. Martindale: The complete drug reference. Diazepam. Pharmaceutical Press 2009. #2673
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