CELLCEPT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CELLCEPT (CELLCEPT).
Mycophenolate mofetil is a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), inhibiting de novo purine synthesis in T and B lymphocytes, thereby suppressing lymphocyte proliferation.
| Metabolism | Mycophenolate mofetil is hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is primarily metabolized by glucuronidation via UDP-glucuronosyltransferases (UGT1A9 and UGT2B7) to MPA-glucuronide (MPAG), which is excreted in urine. |
| Excretion | Mycophenolic acid (MPA) is primarily excreted in urine as mycophenolic acid glucuronide (MPAG) (87% of dose); <1% excreted as unchanged MPA. Fecal excretion accounts for approximately 6% of dose. |
| Half-life | Terminal elimination half-life of MPA is approximately 17.9 ± 6.5 hours in renal transplant patients. Clinical significance: dosing interval of 12 hours maintains therapeutic levels. |
| Protein binding | 97% bound to albumin. In renal impairment or hypoalbuminemia, free fraction increases. |
| Volume of Distribution | Apparent volume of distribution of MPA is approximately 3.6 L/kg (range 1.5-5.0 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability of mycophenolate mofetil is approximately 94% (converted to MPA). Intravenous: 100%. |
| Onset of Action | Oral: immunosuppressive effect detectable within days, but maximal effect requires steady-state (3-5 days). IV: immediate onset of immunosuppression. |
| Duration of Action | Duration of immunosuppressive effect corresponds to drug presence; trough levels maintained at steady-state with twice-daily dosing. Clinical note: continuous therapy required for sustained effect. |
| Action Class | Immunosuppressant- Purine analogs |
| Brand Substitutes | Cellmune 500mg Tablet, Mycept 500 Tablet, Mofetyl 500 Tablet, Immutil Tablet, IPCA MMF 500 Tablet, Mycept 250 Capsule, Keycept 250mg Capsule, Renodapt 250 Capsule, Stricept 250mg Capsule |
Oral: 1-2 g daily in two divided doses. Intravenous: 1-2 g daily in two divided doses as a 2-hour infusion.
| Dosage form | CAPSULE |
| Renal impairment | For GFR 10-50 mL/min: maximum 2 g daily; for GFR <10 mL/min: maximum 1 g daily. |
| Liver impairment | No dosage adjustment required for hepatic impairment. No Child-Pugh based modifications are established. |
| Pediatric use | For ages 3 months to 18 years: 600 mg/m2 orally twice daily; maximum 2 g daily. Intravenous: same oral dose converted to IV. |
| Geriatric use | No specific dose adjustment, but start at lower end of dosing range due to age-related renal impairment. Monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CELLCEPT (CELLCEPT).
| Breastfeeding | M/P ratio is unknown. Mycophenolic acid is excreted into breast milk in small amounts; however, due to potential for serious adverse effects in the nursing infant, including immunosuppression and growth delay, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | First trimester exposure is associated with a high risk of congenital malformations, including craniofacial defects (cleft lip/palate), cardiovascular anomalies, and neural tube defects. Second and third trimester exposure may cause intrauterine growth restriction, preterm delivery, and neonatal immunosuppression. Mycophenolic acid is contraindicated in pregnancy unless no alternative treatment is available. |
■ FDA Black Box Warning
Increased risk of pregnancy loss and congenital malformations; must avoid pregnancy during therapy. Use in women of childbearing potential only if contraception is used and pregnancy is excluded.
| Serious Effects |
Hypersensitivity to mycophenolate mofetil or mycophenolic acid; women who are pregnant or planning pregnancy (unless no alternative); women of childbearing potential not using effective contraception.
| Precautions | Increased susceptibility to infections (e.g., CMV, BK virus), lymphomas, and other malignancies; dose reduction in renal impairment; avoid use with azathioprine; monitor for neutropenia, GI bleeding, and progressive multifocal leukoencephalopathy. |
| Food/Dietary | Avoid taking with food high in fat or protein as it may reduce absorption. Grapefruit juice may decrease mycophenolate absorption; avoid concurrent consumption. No specific dietary restrictions besides maintaining consistent intake with meals. |
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| Fetal Monitoring | Pregancy test prior to initiation and during therapy (negative test required). Monitor complete blood counts (CBC) for anemia, leukopenia, thrombocytopenia. Assess renal function (serum creatinine, BUN) and liver function tests (ALT, AST). Perform regular fetal ultrasound for growth and anatomy. Monitor for maternal infections and signs of malignancy. |
| Fertility Effects | No direct evidence of impaired fertility in humans, but animal studies show ovarian toxicity in females and testicular toxicity in males at high doses. Use with caution in patients planning pregnancy. Contraception should be used during treatment and for 6 weeks after discontinuation. |
| Clinical Pearls | Mycophenolate mofetil (CELLCEPT) is a prodrug of mycophenolic acid, an inosine monophosphate dehydrogenase inhibitor. It is used for prophylaxis of organ rejection in renal, cardiac, and hepatic transplant recipients. Monitor for leukopenia, neutropenia, and infections. Dose adjustment required in renal impairment (GFR <25 mL/min). Avoid use in pregnancy (Pregnancy Category D). Contraindicated in hypersensitivity to mycophenolate. Intravenous administration should be over 2 hours. Monitor for GI bleeding and CMV infection. |
| Patient Advice | Take exactly as prescribed, with or without food. Do not crush or chew capsules. · Avoid sunlight and use sunscreen due to increased risk of skin cancer. · Report any signs of infection (fever, sore throat, unusual bleeding or bruising). · Use effective contraception during treatment and for 6 weeks after stopping if female of childbearing potential. · Do not breastfeed while taking this medication. · Store at room temperature, away from moisture and heat. |