L04AA06 - Mycophenolic Acid |
Propably not porphyrinogenic |
PNP |
Important Information
Patients on immunosuppressive therapy have an increased risk of infections. Since infections have a potential to trigger acute porphyric attacks vigilance is motivated regarding signs or symptoms of infection and/or possible symptoms of a porphyric attack. Side effects like nausea and vomiting may potentially be porphyrinogenic through reduction in carbohydrate intake.
Side effects
Infections are common in patients using immunosuppressants and since infections might trigger an acute porphyric attack, vigilance regarding signs and symptoms of an infection and/ or a porphyric attack is recommended. Common adverse reactions of mycophenolic acid that can be confused with an acute porphyric attack are nausea and vomiting. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Mycophenolic acid is not metabolized by cytochrome P450 enzymes. No pharmacokinetic porphyrinogenic effects are suspected.
Chemical description
Mycophenolic acid (or mycophenolate), derived from Penicillium stoloniferuma, is a reversible inhibitor of inosine monophosphate dehydrogenase and thus inhibits purine synthesis. The most commonly used form of the drug is mycophenolate mofetil, the 2-morpholinoethyl ester of mycophenolic acid.
Therapeutic characteristics
Mycophenolic acid is an immunosuppressant used for the prevention of graft rejection, and has also been tried in diseases with an auto-immune or immune-mediated inflammatory component. It is administered orally or as an intravenous infusion.
Metabolism and pharmakokinetics
Mycophenolate undergoes presystemic metabolism to active mycophenolic acid (MPA). MPA undergoes enterohepatic recirculation and secondary increases in plasma MPA concentrations are seen. MPA is metabolised by glucuronidation to the inactive mycophenolic acid glucuronide.
Published experience
Mycophenolate was used uneventfully after kidney transplants in two female AIP patients (Barone, 2001; Warholm, 2003), one 49 year old male AIP patient (El-Haggan, 2002) and one female HCP patient (Telkes 2013).
IPNet drug reports
Uneventful use reported in 4 patients with acute porphyria.
References
- Scientific articles
- Barone GW, Gurley BJ et al. The tolerability of newer immunosuppressive medications in a patient with acute intermittent porphyria. J Clin Pharmacol. 2001;41(1):113-5. #2259
- El-Haggan W, Lobbedez T, et al. Sirolimus tolerability in a kidney transplant recipient with acute intermittent porphyria. Nephrol Dial Transplant. 2002;17(6):1147. #2255
- Telkes G, Pusztai A et al. Kidney transplantation in hereditary coproporphyria using tacrolimus and mycophenolate mofetil: a case report. Transplant Proc. 2013;45(10):3703-4. PMID 24315002. #2262
- Warholm C, Wilczek H. Renal transplantation in a case of acute intermittent porphyria. J Clin Pharmacol. 2003;43(10):1158-60. #2264
- Drug reference publications
- McEvoy GK, editor. Mycophenolate. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (23.08.10). #2260
- Sweetman SC, editor. Martindale: The complete drug reference. Mycophenolic acid. Pharmaceutical Press 2009. #2261
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). CellCept. #2263
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