Acute Porphyria Drug Database

J01XD02 - Tinidazole
Propably not porphyrinogenic
PNP

Rationale
Tinidazole is metabolized by CYP 3A4 but no capacity to induce or inhibit any of the CYP enzymes is found either in in vitro studies or in clinical use. Risk for gastrointestinal adverse events in the form of nausea, vomiting and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.
Chemical description
Ethylsulphonyl metylnitroimidazole. Differs from metronidazole only in the cyclic 1-N substituent (ethylsulphonyl instead of etahnol).
Therapeutic characteristics
Tinidazole is a nitroimidazole antiprotozoal agent used in the treatment of Trichomonas vaginalis, Giaria lamblia, Entamoeba histolytica, and bacterial vaginosis. Tinidazole is also used as a prophylactic agent against post-operative infections caused by anaerobic bacteria. Common side effects that can be confused with an acute porphyria attack are nausea, vomiting, diarrhoea, and abdominal pain. Dark colouring of urine may take place.
Metabolism and pharmacokinetics
The pharmacokinetics of tinidazole is stated to resemble that of metronidazol, but with longer half-life (12-14 hours). Orally administered timidazole is almost completely absorbed. In vitro data indicates that tinidazole is metabolized by CYP 3A4 and to a less extent 2B6 (Li 2003). In spite of carrying a cyclic tertiary amine with sulphonyl substituent, and thus possibly with irreversible CYP-inhibiting capacity, tinidazole is not observed to be an inducer or inhibitor of CYP3A4 (FDA, Hisaka 2010, Isoherranen 2008, Pelkonen 2008). Imidazole derivatives are listed as possible inhibitors of CYP 2C9 (reversible inhibition), and thus having the potential for enhancing the action of warfarin. However, this effect has not been observed specifically for tinidazole. An in vitro study showed no effect of tinidazole on the activity of CYP 1A2, 2C9, 2C19, 3A4 or 2D6 (Bapiro 2012).
Published experience
Zoanetti (2011), described a patient suffering from a possible acute attack after receiving tinidazole and other drugs as prophylaxis prior to elective surgery. The administration of potentially porphyrinogenic drugs was suspected by the authors to be a triggering factor. However, other triggering factors like anxiety and psychological stress prior to surgery may well have precipitated the attack.

References

  1. Scientific articles
  2. Bapiro TE, The Interaction of Antiparasitic Drugs with the Drug-metabolizing Cytochrome P450s (CYPs) and Characterization of a CYP Variant Unique to African Populations. University of Zimbabwe. Thesis. #1655
  3. Fung HB, Doan TL. Tinidazole: a nitroimidazole antiprotozoal agent. Clin Ther. 2005 Dec;27(12):1859-84. PMID 16507373. #1656
  4. Hisaka A, Ohno Y, et al. Prediction of pharmacokinetic drug-drug interaction caused by changes in cytochrome P450 activity using in vivo information. Pharmacol Ther. 2010 Feb;125(2):230-48. #1138
  5. Isoherranen N, Hachad H, et al. Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database. Chem Res Toxicol. 2009 Feb;22(2):294-8 #1657
  6. Li XQ, Björkman A et al. Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42. PMID 12920490. #1658
  7. Pelkonen O, Turpeinen M, et al. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol. 2008 Oct;82(10):667-715. PMID 18618097. #4347
  8. Government bodies
  9. U.S Food and Drug Administration (FDA) #1660
  10. Summary of Product Characteristics
  11. The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). (Fasigyn). (Last edition: November 2012). #1659
  12. Other sources
  13. Zoanetti G. AIP, It’s the real thing. Br J Dermatol 2011; 164: 1162 (Poster presentation, International porphyria congress, Cardiff 2011). #1661

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