L03AB03 - Interferon Gamma |
Propably not porphyrinogenic |
PNP |
Rationale
Interferon gamma 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 gamma, 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 gamma might therefore protect against attacks of acute porphyria. However, very common side effects such as nausea and vomiting are potentially porphyrogenic through reduction in caloric intake.
Chemical description
Interferon gamma is a cytokine glycoprotein produced by a method based on recombinant DNA technology using bacteria as host cells.
Therapeutic characteristics
Interferon gamma is a recombinant cytokine with antiviral and immunomodulating effects. It is used in chronic granulomatous disease to reduce the incidence of serious infections, and in the rare inborn disease malignant osteopetrosis where macrophage oxidative metabolism is impaired.
It is administered by subcutaneous injection.
Common adverse reactions of interferon gamma that can be confused with an acute porphyric attack are nausea, vomiting, myalgia and fatigue. Flu-like symptoms including fever is also very common.
Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmacokinetics
Mainly hepatic elimination. Plasma half life about 5 hours.
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. Epub 2007 Dec 27. PMID 18159929. #4603
- Drug reference publications
- McEvoy GK, editor. Interferon gamma. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (18.10.2010). #2203
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). (Imukin). #2204
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Immukin. #2205
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