Mycophenolate mofetil (MMF) is an immunosuppressive prodrug of mycophenolic acid (MPA). It is a potent, selective, non-competitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme crucial for the de novo pathway of guanosine nucleotide synthesis. This action selectively inhibits the proliferation of T and B lymphocytes, making it a cornerstone in preventing acute rejection in solid organ transplantation. In India, it is also widely used for autoimmune conditions like lupus nephritis.
Adult: Renal Transplant: 1g (two 500mg tablets) orally twice daily (2g/day total). Cardiac Transplant: 1.5g orally twice daily (3g/day total). Hepatic Transplant: 1g IV or 1.5g orally twice daily. Lupus Nephritis: 1-1.5g orally twice daily (2-3g/day total), often initiated at a lower dose (500mg BD) and titrated up.
Note: Administer on an empty stomach, 1 hour before or 2 hours after food to avoid reduced bioavailability. Tablets should be swallowed whole, not crushed, broken, or chewed. If a dose is missed, take it as soon as remembered unless it is nearly time for the next dose. Do not double the dose. For GI intolerance, may be administered with food after consulting physician, accepting reduced Cmax.
MMF is a prodrug that is hydrolyzed to mycophenolic acid (MPA). MPA is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), specifically the type II isoform which is upregulated in activated lymphocytes. Inhibition of IMPDH blocks the conversion of inosine monophosphate (IMP) to xanthine monophosphate (XMP), a critical step in the de novo synthesis of guanosine nucleotides (GDP, GTP).
Pregnancy: Pregnancy Category D. Contraindicated. MMF is associated with an increased risk of first trimester pregnancy loss and congenital malformations (including external ear, facial, cardiovascular, CNS, and limb abnormalities). Women of childbearing potential must use two reliable forms of contraception before, during, and for 6 weeks after stopping therapy. A negative pregnancy test is required prior to initiation.
Driving: May cause dizziness, somnolence, or blurred vision. Patients should not drive or operate machinery if they experience these effects.
| Acyclovir, Valacyclovir, Ganciclovir, Valganciclovir | Competition for renal tubular secretion may increase plasma levels of both MPA (as MPAG) and the antiviral drug, potentiating mutual toxicity (myelosuppression, neurotoxicity). | Major |
| Antacids containing Magnesium/Aluminum, Cholestyramine, Sevelamer | Significantly decrease MPA absorption by binding, reducing bioavailability by up to 40%. | Major |
| Proton Pump Inhibitors (PPIs), H2 Blockers | May alter gastric pH and potentially reduce MPA solubility and absorption, though clinical significance is variable. | Moderate |
| Rifampicin/Rifampin | Potent UGT inducer; increases metabolism of MPA to MPAG, reducing MPA exposure (AUC) by up to 70%. May lead to subtherapeutic immunosuppression. | Major |
| Phenytoin, Phenobarbital | Enzyme inducers; may reduce MPA levels. | Moderate |
| Oral Contraceptives (Ethinyl Estradiol, Norethindrone) | MPA may decrease plasma levels of contraceptives via induction of glucuronidation, reducing efficacy. Additional non-hormonal contraception is mandatory. | Major |
| Azathioprine | Concurrent use is not recommended due to overlapping myelosuppressive effects without proven synergistic benefit. | Contraindicated |
| Live Vaccines (e.g., MMR, Varicella, Yellow Fever, OPV) | Risk of disseminated vaccine-induced infection. Avoid. | Major |
| Warfarin | MPA may displace warfarin from protein binding sites, potentially increasing INR. Monitor INR closely. | Moderate |