L03AB04 - Interferon Alfa-2a |
Propably not porphyrinogenic |
PNP |
Rationale
Interferon alfa-2a 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 alfa-2a, 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-2a might therefore protect against attacks of acute porphyria. However, very common side effects such as anorexia, diarrhoea, nausea and vomiting are potentially porphyrogenic through reduction in caloric intake.
Interaction studies performed on pegylated interferon alfa-2a show no effect on CYP3A4, 2C9, 2D6 or 2C19 activities.
Chemical description
Interferon alfa-2a is a cytokine glycoprotein produced by a method based on recombinant DNA technology using bacteria as host cells.
Therapeutic characteristics
Interferon alfa-2a is a cytokine with antiviral, antiproliferative and immunomodulating effects. It is used in chronic hepatitis B and chronic hepatitis C, AIDS-related Kaposis sarcoma, hairy-cell leukemia, chronic myeloid leukemia, follicular lymphoma, cutaneous T-cell lymphoma, stadium II malignant melanoma, and renal cell carcinoma.
It is administered subcutaneously.
In recurrent chronic hepatitis C it is administered in combination with ribavirin.
Common adverse reactions of interferon alfa-2a are that can be confused with an acute porphyric attack are muscle pain, fatigue, diarrhoea, nausea and vomiting.
Common side effects such as anorexia, diarrhoea, nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmakokinetics
Interferon alfa-2a is mainly eliminated by the kidneys.
Interaction studies performed on pegylated interferon alfa-2a show no effect on CYP3A4, 2C9, 2D6 or 2C19 activities, but it has shown to have inhibitory effects on CYP1A2 activity (SPC, pegasys).
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 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). Roceron. #2207
- Swedish medicines agency. Summary of Product Characteristics (SPC). Roferon-A. #2208
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Roferon-A, Pegasys. #2209
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