Acute Porphyria Drugs

Acute Porphyria Drug Database

N06AX03 - Mianserin
Propably not porphyrinogenic
PNP
Rationale
Mianserin is most probably not an inhibitor or an inducer of any major CYP enzymes.
Chemical description
Mianserin is a racemic mixture, in which S-mianserin is considered as the more potent enantiomer.
Therapeutic characteristics
Mianserin is indicated for the treatment of depression.
Metabolism and pharmakokinetics
Mianserin is metabolised via 8-hydroxylation, N-demethylation, N-oxidation and glucuronidation (Eap 1999). In vitro data indicates that mianserin is metabolised by CYP2D6, CYP3A and CYP1A (Koyama 1996 and Wang 2009). In vivo data indicates that CYP2D6 is involved in the metabolism of mianserin with enantioselectivity for S(+)-mianserin (Dahl 1994, Yasui 1997 and Wang 2009). Mianserin has two main metabolites, 8-hydroxymianserin and desmethylmianserin. 8-hydroxymianserin contributes to the pharmacological activity of the drug (Eap 1999). The half-life elimination is 21-61 hours (SPC). Co-administration of carbamazepine and mianserin, reduced the AUC of mianserin. Carbamazepine is a known inducer of CYP3A4 and the data therefore indicates that mianserin is a substrate of CYP3A (Eap 1999). Mianserin is not listed as an inducer or inhibitor of any major CYP enzymes (FDA, Hisaka 2010, Isoherranen 2009 and Pelkonen 2008) and no drug-drug interaction with mianserin as a perpetrator has been reported in the literature.
Published experience
Mianserin is listed as unsafe because it has been shown to be porphyrinogenic in animals or in vitro systems, or to have been associated with acute attacks in humans (Moore 1997).
IPNet drug reports
Uneventful use reported in 3 patients with acute porphyria.

References

  1. Scientific articles
  2. Eap CB, Yasui N,et al. Effects of carbamazepine coadministration on plasma concentrations of the enantiomers of mianserin and of its metabolites. Ther Drug Monit. 1999 Apr;21(2):166-70. PMID 10217335. #4699
  3. 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
  4. 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. #1005
  5. Koyama E, Chiba K, et al. Identification of human cytochrome P450 isoforms involved in the stereoselective metabolism of mianserin enantiomers. J Pharmacol Exp Ther. 1996 Jul;278(1):21-30. PMID 8764331. #4700
  6. Moore MR, Hift RJ. Drugs in the acute porphyrias--toxicogenetic diseases. Cell Mol Biol (Noisy-le-grand). 1997 Feb;43(1):89-94. PMID 9074793. #1110
  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. Wang B, Zhou SF. Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. PMID 19754423. #1203
  9. Yasui N, Tybring G, et al. Effects of thioridazine, an inhibitor of CYP2D6, on the steady-state plasma concentrations of the enantiomers of mianserin and its active metabolite, desmethylmianserin, in depressed Japanese patients. Pharmacogenetics. 1997 Oct;7(5):369-74. PMID 9352572. #4701
  10. Government bodies
  11. U.S Food and Drug Administration (FDA). #1450
  12. Summary of Product Characteristics
  13. Norwegian medicines agency. Summary of Product Characteristics (SPC). Mianserin. #2777
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