M04AC01 - Colchicine |
Propably not porphyrinogenic |
PNP |
Side effects
Common adverse reactions of colchicine that can be confused with an acute porphyric attack are abdominal pain, nausea and vomiting. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Colchicine has a narrow therapeutic window and is extremely toxic in overdose. Patients with renal or hepatic impairment are at particular risk.
Rationale
Colchicine is a substrate of CYP 3A4, but is not found to be an inducer or mechanism-based inhibitor of CYP. In vitro colchicine has been shown to downregulate the formation and inducibility of CYP 2B6, 2C9, and 3A4. The observed in vitro effects on colchicines possible downregulation of CYP enzymes are not suspected to be porphyrinogenic.
Chemical description
Tricyclic herbal alkaloid
Therapeutic characteristics
Colchicine is an anti-inflammatory agent used in the treatment of acute gout attacks and as prophylaxis of gout attack during initiation of therapy with allopurinol and uricosuric drugs.
It is also used in the treatment of Familiar Mediterranean fever. It is administered orally.
Metabolism and pharmakokinetics
Colchicine is largely excreted in unchanged form, but is also dependent on biotransformation by CYP 3A4. The terminal half-life is 3 to 10 hours (SPC, Tateishi 1997).
Colchicine is not listed as a perpetrator of drug-drug interactions, but some case reports indicates that colchicine might have potential to inhibit CYP 2C9 (Gras-Chambel 2005).
In vitro, colchicine has shown the potential to downregulate CYP 2B6, 2C8, 2C9, and 3A4. The inductive effects of rifampicin and phenobarbital is impaired by affecting glucocorticoid receptor (GR)–mediated regulation. Colchicine may act by disrupting the microtubule network and thereby affecting the translocation of GR to the nucleus preventing activation of the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR). (Dvorak 2003)
Published experience
Wysenbeek et al. (1989) described that administration of colchicine in four patients with acute porphyrias during prodromal abdominal symptoms prevented development of full-blown attacks. Since the use of colchicine seemed to have beneficial effect on abdominal pain associated with acute porphyria, the authors propose this drug as a possible therapeutic regimen in acute porphyrias (Wysenbeek 1989).
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.
References
- Scientific articles
- Dvorak Z, Modriansky M et al. Colchicine down-regulates cytochrome P450 2B6, 2C8, 2C9, and 3A4 in human hepatocytes by affecting their glucocorticoid receptor-mediated regulation. Mol Pharmacol. 2003 Jul;64(1):160-9. PMID 12815172. #2408
- Gras-Champel V, Ohlmann P et al. Can colchicine potentiate the anticoagulant effect of fluindione? Eur J Clin Pharmacol. 2005 Aug;61(7):555-6. PMID 16007421. #2409
- Tateishi T, Soucek P et al. Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation. Biochem Pharmacol. 1997 Jan 10;53(1):111-6. PMID 8960070. #2410
- Wysenbeek AJ, Schoenfeld N, et al. Colchicine treatment of abdominal pains in porphyric patients. Isr J Med Sci. 1989 Feb;25(2):95-7. PMID 2703332. #4631
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Colchicine. #2411
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