Immunosuppressant (IMPDH inhibitor)
Mycophenolate is an immunosuppressant medicine used to prevent rejection after kidney, heart or liver transplantation, in combination with other immunosuppressants. It reduces the activity of the immune system.
Also known as: Micofenolato, Micofenolato de mofetilo, CellCept
Mycophenolate + cholestyramine: cholestyramine binds mycophenolate in the gut and reduces its absorption, potentially decreasing drug exposure — separate doses.
DailyMed (CellCept) documents interaction studies with cholestyramine, and QUADRO 2 of the Prontuário (Bile acids — sequestering resins) lists mycophenolate among drugs whose absorption can be reduced by the resins. Cholestyramine binds mycophenolate in the gut lumen and interferes with the enterohepatic recirculation of mycophenolic acid, reducing systemic exposure.
Watch immunosuppressive efficacy (MPA levels when available; signs of rejection) during the combination.
Signs of graft rejection or MPA levels below target with simultaneous intake.
Give mycophenolate at least 1-2 hours before or 4 hours after cholestyramine; ideally space the two doses as far apart as possible.
DailyMed/FDA (NIH/NLM) — approved CellCept label (Genentech), section 7.1: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40 ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, Table 2 (Bile acids — sequestering resins)
Mycophenolate + iron: iron reduces oral mycophenolate absorption, potentially decreasing exposure — separate doses by at least 2 hours.
QUADRO 2 of the Prontuário (Iron) lists mycophenolate among drugs whose absorption is reduced with iron ("Drugs whose absorption is reduced with iron: ... Mycophenolate"). Chelation in the gut lumen with iron salts reduces the oral bioavailability of mycophenolate.
Watch immunosuppressive efficacy during iron supplementation.
Signs of rejection or MPA levels below target with simultaneous iron intake.
Give mycophenolate and iron at least 2 hours apart; ideally take iron at a different time of day from mycophenolate.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, Table 2 (Iron) ; DailyMed/FDA (NIH/NLM) — approved CellCept label (Genentech): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40
Mycophenolate + probenecid: probenecid inhibits renal tubular secretion of the MPAG metabolite, raising its plasma concentrations — watch for toxicity.
DailyMed (CellCept) documents that coadministration of probenecid, a known inhibitor of tubular secretion, with mycophenolate mofetil raises plasma AUC of MPAG by 3-fold in animal studies. Other drugs undergoing renal tubular secretion may behave similarly.
Monitor blood counts and gastrointestinal symptoms during co-administration.
Leucopenia, severe diarrhoea or vomiting with the combination.
Watch tolerance (haematological and gastrointestinal) during the combination; consider MPA level monitoring if available.
DailyMed/FDA (NIH/NLM) — approved CellCept label (Genentech), section 7.1 (Probenecid): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40
Mycophenolate + rifampicin: rifampicin induces glucuronidation and reduces systemic exposure to mycophenolic acid — risk of losing immunosuppressive efficacy.
DailyMed (CellCept) records that "concomitant use with drugs inducing glucuronidation decreases MPA systemic exposure, potentially reducing CELLCEPT efficacy" (section 7.1). Rifampicin is a potent enzyme inducer that accelerates mycophenolic acid glucuronidation, reducing active concentrations.
Watch for signs of rejection and, when available, MPA levels during rifampicin.
Signs of graft rejection during rifampicin treatment.
Avoid the combination when possible; if unavoidable, closely monitor immunosuppressive efficacy and consider dose adjustment or MPA level monitoring.
DailyMed/FDA (NIH/NLM) — approved CellCept label (Genentech), section 7.1 (Glucuronidation inducers): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40
The CellCept label recommends: "It is recommended that CELLCEPT be administered on an empty stomach". Administration with food lowers mycophenolic acid Cmax (up to 40%), although total AUC remains similar.
Prefer empty-stomach administration; if gastrointestinal intolerance requires it, it may be taken with food provided this is consistent.
DailyMed/FDA (NIH/NLM) — approved CellCept (mycophenolate mofetil) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40
CELLCEPT label (5.1): use in pregnancy is associated with increased risk of first-trimester loss and multiple congenital malformations — avoid in pregnancy if safer alternatives exist.
Avoid in pregnancy; effective contraception and pregnancy testing are mandatory (REMS).
DailyMed/FDA (NIH/NLM) — Mycophenolate (CELLCEPT), 5.1: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40
CELLCEPT label (5.1/8.1): use of MMF during pregnancy is associated with an increased risk of first-trimester pregnancy loss and of multiple congenital malformations (external ear and other facial abnormalities, cleft lip/palate, distal limbs, heart, oesophagus, kidney and nervous system). Women of reproductive potential must be counselled regarding pregnancy prevention and planning.
Avoid in pregnancy if safer alternatives exist; increased risk of first-trimester loss and multiple malformations (5.1).
No specific breastfeeding data in the label; assess risk/benefit (literature data suggest excretion).
Effective contraception and pregnancy testing are mandatory before and during treatment in women of reproductive potential (REMS — 5.1).
DailyMed/FDA (NIH/NLM) — approved Mycophenolate label (CELLCEPT), sections 5.1/8.1: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40 ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 2, Drugs and Breastfeeding: Contraindicated. Exclude a pregnancy before starting treatment and wait 6 months after stopping the drug before becoming pregnant or breastfeeding.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Immunosuppressant: MMF is hydrolysed to MPA (active metabolite), a selective IMPDH inhibitor — blocks de novo guanosine synthesis and lymphocyte proliferation (CELLCEPT label 12.1).
Selective uncompetitive inhibition of IMPDH (types I and II) — blockade of the de novo pathway of guanine nucleotide synthesis and DNA synthesis.
Oral absorption: mean absolute bioavailability of oral MMF of 94% (relative to IV) (12.3); antacids with Mg/Al and PPIs reduce MPA exposure (7.1).
Metabolism: complete conversion of MMF to MPA (active metabolite); hepatic metabolism of MPA (glucuronidation) and renal excretion of the glucuronide.
Half-life of MPA of approximately 11-18 hours (section 12.3 data).
