L03AB01 - Interferon Alfa Natural |
Propably not porphyrinogenic |
PNP |
Rationale
Interferon alfa natural is a mixture of cytokines 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 alfa natural, 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 alfa natural 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 alfa natural is a mixture of naturally occurring human interferon alfa proteins recovered from supernate of primary human leukocyte cultures incubated with Sendai virus.
Therapeutic characteristics
Interferon alfa natural is used as adjuvant therapy of high-risk patients with cutaneous melanoma and in the treatment of patients that have initially responded to recombinant interferon alpha, but who have become resistent.
It is administered subcutaneously.
Common adverse reactions of interferon alfa natural are influenza-like symptoms like fever, fatigue, musculoskeletal pain, diarrhea and nausea. Several of these effects can be confused with an acute porphyric attack.
Side effects such as anorexia, nausea and diarrhea may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmakokinetics
Interferon alfa natural is mainly eliminated by the kidneys.
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 alfa. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (10.08.10). #2198
- Sweetman SC, editor. Martindale: The complete drug reference. Interferon alfa. Pharmaceutical Press 2009. #2201
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Multiferon. #2200
- Swedish medicines agency. Summary of Product Characteristics (SPC). (Multiferon). #2202
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