L03AX15 - Mifamurtide |
Propably not porphyrinogenic |
PNP |
Rationale
Mifamurtide has non CYP metabolism and no capacity for CYP-induction or inhibition. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in carbohydrate intake.
Chemical description
Acetamido dideoxy glucopyranose propyl alanyl isoglutaminyl alanyl amino bishexadecanoyl propyl hydrogen phosphate (muramyltripeptide phosphatidylethanolamine, MTP-PE).
Therapeutic characteristics
Mifamurtide is a fully synthetic derivative of muramuyl dipeptide (MDP), the smallest naturally-occurring immune stimulatory component of cell walls from Mycobacterium sp.
Common side effects of mifamurtide that can be confused with an acute porphyria attack are nausea, vomiting, obstipation, diarrhoea, anorexia, tachycardia, myalgia, arthralgia, abdominal pain and pain in arms and legs. Other common side effects are insomnia, infections (sepsis, cellulitis, nasopharyngitis, catheter site infections, upper respiratory tract infection, urinary tract infection, pharyngitis and Herpes simplex infection).
The liberated pro-inflammatory cytokines modulate the expression of the nuclear transcription factors PXR, CAR, HNF-4 and NF-kB, in a way to damp clinically significant the expression of hepatic drug-metabolizing CYPs, including Cyp3A4 (Breslin, 2007, Christensen 2012, Morgan 2008).
Hepatic exposure
Irrelevant
Metabolism and pharmacokinetics
Mifamurtide has non CYP metabolism. It is phagocytosed by monocytes and macrophages which degrades the liposomal vesicles, and in that way releases mifamurtide into the cytosol. There are no in vitro CYP-inhibiting or CYP-inducing effects (EMEA).
References
- Scientific articles
- Breslin S. Cytokine-release syndrome: overview and nursing implications. Clin J Oncol Nurs. 2007 Feb;11(1):37-42. PMID 17471824. #2248
- Christensen H, Hermann M. Immunological response as a source to variability in drug metabolism and transport. Front Pharmacol. 2012;3:8. PMID 22363283. #2249
- Morgan ET, Goralski KB et al. Regulation of drug-metabolizing enzymes and transporters in infection, inflammation, and cancer. Drug Metab Dispos. 2008 Feb;36(2):205-16. PMID 18218849. #2251
- Government bodies
- EMEA - European Medicines Agency. Assessment report for Mepact [online]. Available from URL: [Accsessed 26.02.2013] #2250
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Mifamurtid. #2252
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