L03AB07 - Interferon Beta-1a |
Propably not porphyrinogenic |
PNP |
Rationale
Interferon beta-1a is a recombinant cytokine and fever and flu-like symptoms are very common adverse reactions.
Experience seems to be that infection may trigger attacks of acute porphyria. However, infections are not commonly reported in the treatment with interferon beta-1a, and there is no evidence to show that inflammation and fever alone are triggering factors. Chronic inflammatory diseases are not associated with higher incidence of porphyric attacks.
Inflammation has also shown to down-regulate the activity and expression of cytochrome P450 enzymes involved in hepatic drug clearance. Through inhibition of ALAS1-induction, interferon beta-1a might therefore protect against attacks of acute porphyria.
However, common side effects such as anorexia, nausea, diarrhoea and vomiting are potentially porphyrogenic through reduction in caloric intake.
Chemical description
Interferon beta-1a is a cytokine glycoprotein produced by a method based on recombinant DNA technology using bacteria as host cells.
Therapeutic characteristics
Interferon beta-1a is used in the treatment of relapsing multiple sclerosis.
The mechanism of action is not known.
It is administered subcutaneously.
Common adverse reactions of interferon beta-1b that can be confused with an acute porphyric attack are nausea, vomiting, depression, insomnia and myalgia. Common side effects such as anorexia, diarrhoea, nausea and vomiting are potentially porphyrogenic through reduction in caloric intake.
Metabolism and pharmacokinetics
Interferon beta-1a is mainly metabolised and excreted by the liver and the kidneys.
Probably CYP-inhibing effects.
Inflammation suppresses the expression of several hepatic transporters and detoxifying CYPs including CYP3A4 (Aitken, 2005; Moreau, 2008).
References
- Scientific articles
- Aitken AE, Richardson TA, et al. Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol. 2006;46:123-49. #2197
- Moreau A, Vilarem MJ, et al. Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm. 2008;5(1):35-41. PMID 18159929. #4604
- Drug reference publications
- McEvoy GK, editor. Interferon beta. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (18.10.10). #2220
- Sweetman SC, editor. Martindale: The complete drug reference. Interferon beta. Pharmaceutical Press 2009. #2222
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Avonex. #2221
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Rebif. edition: Sept.2010) #2223
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