MYCOPHENOLATE MOFETIL
Clinical safety rating: avoid
Contraindicated (not allowed)
Mycophenolate mofetil is a prodrug that is rapidly hydrolyzed to mycophenolic acid (MPA), a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), which inhibits the de novo pathway of guanosine nucleotide synthesis. This inhibition preferentially blocks proliferation of T- and B-lymphocytes, as they are critically dependent on this pathway, thereby suppressing cell-mediated immune responses and antibody formation.
| Metabolism | Mycophenolate mofetil is rapidly and completely metabolized by esterases (primarily in plasma, liver, and kidney) to the active moiety mycophenolic acid (MPA). MPA is then glucuronidated by UDP-glucuronosyltransferases (UGT1A9, UGT1A8, UGT1A7, UGT1A10) to form the inactive glucuronide metabolite (MPAG). MPAG undergoes enterohepatic recirculation and is excreted in urine. A small fraction of MPAG is converted back to MPA in the intestine. |
| Excretion | Mycophenolate mofetil is extensively metabolized to mycophenolic acid (MPA), which is primarily eliminated in urine as MPA glucuronide (MPAG). Approximately 87% of the dose is excreted in urine as MPAG, with less than 1% as unchanged MPA. Fecal excretion accounts for about 6% of the dose, mainly as MPAG. Biliary excretion contributes to enterohepatic recirculation of MPA, enhancing its exposure. |
| Half-life | The terminal elimination half-life of mycophenolic acid (MPA) is approximately 8-16 hours in healthy volunteers and renal transplant patients. In patients with renal impairment, the half-life may be prolonged due to accumulation of MPAG. The half-life supports twice-daily dosing. |
| Protein binding | Mycophenolic acid is highly protein bound (97%) primarily to serum albumin. This binding is saturable, and unbound fraction increases at higher concentrations, potentially affecting pharmacodynamics. |
| Volume of Distribution | The apparent volume of distribution of mycophenolic acid is approximately 3.6 L/kg, indicating extensive tissue distribution. The high Vd reflects distribution into extravascular spaces, including lymphoid tissues where its immunosuppressive effects occur. |
| Bioavailability | Oral bioavailability of mycophenolate mofetil is approximately 94% for the oral suspension and 93% for the capsule. Mycophenolate mofetil is a prodrug that is rapidly and completely hydrolyzed to mycophenolic acid after absorption. Food decreases peak concentration (Cmax) by 40% but does not significantly affect overall exposure (AUC). |
| Onset of Action | After oral administration of mycophenolate mofetil, peak plasma concentrations of MPA occur within 1-2 hours. Clinical immunosuppressive effects are typically observed within days to weeks, with maximal effects on lymphocyte proliferation seen after several doses. |
| Duration of Action | The immunosuppressive effect of mycophenolate mofetil lasts for the dosing interval of 12 hours, maintained through twice-daily administration. Continuous therapy is required to sustain immunosuppression. |
1 g orally twice daily; intravenous infusion 1 g over 2 hours twice daily for up to 14 days.
| Dosage form | CAPSULE |
| Renal impairment | For GFR <25 mL/min/1.73 m2 (not on dialysis): avoid doses >1 g twice daily; for GFR 25-50 mL/min/1.73 m2: no adjustment; for dialysis: not recommended. |
| Liver impairment | No specific Child-Pugh based adjustments; use with caution in severe hepatic impairment. |
| Pediatric use | Children ≥1 year: 600 mg/m2 orally or IV twice daily; maximum 2 g/day. |
| Geriatric use | No specific dose adjustment; monitor for adverse effects due to potential age-related renal decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Antacids and cholestyramine can decrease absorption Can cause severe myelosuppression and increased risk of infections.
| Breastfeeding | Mycophenolate is excreted into human milk; M/P ratio is approximately 0.7–1.2. Due to potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment. |
| Teratogenic Risk | Mycophenolate mofetil is contraindicated in pregnancy due to high risk of first trimester pregnancy loss and congenital malformations including microtia, external auditory canal atresia, cleft lip and palate, and cardiac anomalies. Risk persists throughout pregnancy. |
■ FDA Black Box Warning
Increased risk of congenital malformations and pregnancy loss when used during pregnancy. Females of reproductive potential must be counseled regarding pregnancy prevention and planning. Mycophenolate mofetil is available only under a Risk Evaluation and Mitigation Strategy (REMS) program. Increased risk of lymphomas and other malignancies, particularly of the skin. Increased susceptibility to infections, including opportunistic infections and reactivation of latent viruses (e.g., CMV, BK virus, herpes simplex).
| Common Effects | autoimmune disorders |
| Serious Effects |
["Hypersensitivity to mycophenolate mofetil, mycophenolic acid, or any component of the formulation","Pregnancy (due to increased risk of first trimester pregnancy loss and congenital malformations)","Females of reproductive potential not using effective contraception (unless not at risk)","Patients with active serious infections (relative contraindication)"]
| Precautions | ["Pregnancy: Can cause fetal harm; must be used only after negative pregnancy test and effective contraception.","Lymphomas and malignancies: Increased risk, especially skin cancers; limit sun exposure.","Infections: Increased susceptibility to bacterial, viral, fungal, and protozoal infections; monitor for CMV, BK virus, and herpes.","Neutropenia: Monitor CBCs; risk of severe neutropenia, especially during first month.","Pure red cell aplasia (PRCA): Has been reported; consider dose reduction or discontinuation.","Gastrointestinal bleeding: Risk of serious GI ulceration and bleeding, especially in patients with prior GI disease.","Vaccinations: Avoid live attenuated vaccines during treatment.","Renal impairment: Dose adjustment required for severe chronic kidney disease (GFR < 25 mL/min/1.73 m^2).","Teratogenicity: Females of reproductive potential must use two forms of contraception."] |
Loading safety data…
| Fetal Monitoring |
| Monitor for myelosuppression (CBC with differential weekly for first month, then monthly), liver function tests, and renal function. In pregnancy, confirm negative pregnancy test before initiation, ensure effective contraception, and perform ultrasound to assess fetal anatomy if exposed. |
| Fertility Effects | No evidence of impairment of fertility in humans; animal studies showed effects on spermatogenesis and oogenesis at high doses. Reversible upon discontinuation. |