Mycophenolate Mofetil

Cholestyramine decreases MPA AUC by approximately 40%. Not recommended for concomitant use due to interruption of enterohepatic recirculation.

Increased risk of hematological and renal toxicity. Monitor for toxicity in patients with normal and impaired renal function.

Increased risk of hematological and renal toxicity. Bidirectional interaction with increased concentrations of both drugs. Monitor for toxicity.

Risk of hematological and renal toxicity may be increased. Monitor for ganciclovir and MMF toxicity.

Increased risk of hematological and renal toxicity. Monitor for ganciclovir and MMF toxicity.

Drug Interactions with Mycophenolate Mofetil that Affect Other Drugs Drugs that Undergo Renal Tubular Secretion Clinical Impact When concomitantly used with mycophenolate mofetil, its metabolite MPAG, may compete with drugs eliminated by renal tubular secretion which may increase plasma concentrations and/or adverse reactions associated with these drugs Prevention or Management Monitor for drug-related adverse reactions in patients with renal impairment Examples Acyclovir, ganciclovir, probenecid, valacyclovir, valganciclovir Combination Oral Contraceptives Clinical Impact Concomitant use with mycophenolate mofetil decreased the systemic exposure to levonorgestrel, but did not affect the systemic exposure to ethinylestradiol [see Clinical Pharmacology ( 12.3 )], which may result in reduced combination oral contraceptive effectiveness.

Decreases mycophenolic acid (MPA) systemic exposure, which may reduce mycophenolate mofetil efficacy. Administer at least 2 hours after mycophenolate mofetil.

Decreases mycophenolate mofetil systemic exposure and may reduce efficacy. Administer at least 2 hours after mycophenolate mofetil.

Mycophenolate mofetil added to basiliximab regimen with cyclosporine and corticosteroids; no dose adjustment necessary. Total body clearance of basiliximab reduced by average 51%.

Monitor for need to adjust MMF dosage when switching between cyclosporine and belatacept, as cyclosporine decreases MPA exposure while belatacept does not. May require higher MMF dosage after switching to cyclosporine or lower dosage after switching from cyclosporine to belatacept.

Decrease MPA systemic exposure, which may reduce mycophenolate mofetil efficacy. Monitor patients for alterations in efficacy.

Colestipol may reduce mycophenolic acid exposure and potentially reduce efficacy of mycophenolate mofetil by binding bile acids.

Interferes with enterohepatic recirculation, decreasing mycophenolate mofetil systemic exposure. Monitor for alterations in efficacy.

Dexlansoprazole can reduce the absorption of mycophenolate mofetil due to its effect on gastric pH.

Esomeprazole can reduce mycophenolate mofetil absorption due to effects on gastric acid secretion.

Esomeprazole magnesium may interfere with mycophenolate mofetil bioavailability due to effects on gastric pH.

Esomeprazole magnesium may interfere with mycophenolate mofetil bioavailability due to effects on gastric pH.

Esomeprazole can reduce mycophenolate mofetil absorption due to effects on gastric acid secretion.

Prevention or Management Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil Examples Telmisartan (induces glucuronidation); isavuconazole (inhibits glucuronidation).

Examples Lansoprazole, pantoprazole Drugs that Interfere with Enterohepatic Recirculation Clinical Impact Concomitant use with drugs that directly interfere with enterohepatic recirculation, or indirectly interfere with enterohepatic recirculation by altering the gastrointestinal flora, can decrease MPA systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce mycophenolate mofetil efficacy Prevention or Management Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil.

Antacid with magnesium and aluminum hydroxides decreases MPA absorption by 33% in Cmax and 17% in AUC. Not recommended for simultaneous administration.

Decreases mycophenolate mofetil systemic exposure and may reduce efficacy. Administer at least 2 hours after mycophenolate mofetil.

Omeprazole may interfere with mycophenolate mofetil bioavailability due to effects on gastric pH.

Omeprazole and sodium bicarbonate reduces exposure to mycophenolic acid, the active metabolite of MMF, possibly due to decreased MMF solubility at increased gastric pH.

Mycophenolate mofetil may reduce effectiveness of oral contraceptives. Use of additional barrier contraceptive methods is recommended.

Examples Lansoprazole, pantoprazole Drugs that Interfere with Enterohepatic Recirculation Clinical Impact Concomitant use with drugs that directly interfere with enterohepatic recirculation, or indirectly interfere with enterohepatic recirculation by altering the gastrointestinal flora, can decrease MPA systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce mycophenolate mofetil efficacy Prevention or Management Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil.

Mycophenolate mofetil dependent on gastric pH for absorption may have decreased absorption when used with pantoprazole.

Patiromer binds mycophenolate mofetil, potentially reducing systemic exposure and clinical efficacy. Separate dosing by at least 3 hours.

Prevention or Management Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil Examples Cyclosporine A, trimethoprim / sulfamethoxazole, bile acid sequestrants (cholestyramine), rifampin as well as aminoglycoside, cephalosporin, fluoroquinolone and penicillin classes of antimicrobials Drugs Modulating Glucuronidation Clinical Impact Concomitant use with drugs inducing glucuronidation decreases MPA systemic exposure, potentially reducing mycophenolate mofetil efficacy, while use with drugs inhibiting glucuronidation increases MPA systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of mycophenolate mofetil related adverse reactions.

Rabeprazole may decrease absorption of mycophenolate mofetil due to increased gastric pH.

Interferes with enterohepatic recirculation, decreasing mycophenolate mofetil systemic exposure. Monitor for alterations in efficacy.

Calcium-free phosphate binder that decreases MPA systemic exposure, which may reduce MYHIBBIN efficacy. Administer at least 2 hours after MYHIBBIN.

Sevelamer carbonate has demonstrated interaction with mycophenolate mofetil. Administer at least 2 hours before sevelamer carbonate.

Demonstrated interaction with sevelamer; take at least 2 hours before sevelamer carbonate.

Sevelamer binds mycophenolate mofetil and reduces its bioavailability. Administer mycophenolate mofetil at least 2 hours before sevelamer.

Prevention or Management Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil Examples Cyclosporine A, trimethoprim / sulfamethoxazole, bile acid sequestrants (cholestyramine), rifampin as well as aminoglycoside, cephalosporin, fluoroquinolone and penicillin classes of antimicrobials Drugs Modulating Glucuronidation Clinical Impact Concomitant use with drugs inducing glucuronidation decreases MPA systemic exposure, potentially reducing mycophenolate mofetil efficacy, while use with drugs inhibiting glucuronidation increases MPA systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of mycophenolate mofetil related adverse reactions.

Interferes with enterohepatic recirculation, decreasing mycophenolate mofetil systemic exposure. Monitor for alterations in efficacy.

7 DRUG INTERACTIONS See FPI for drugs that may interfere with systemic exposure and reduce mycophenolate mofetil efficacy: antacids with magnesium or aluminum hydroxide, proton pump inhibitors, drugs that interfere with enterohepatic recirculation, telmisartan, calcium-free phosphate binders. Prevention or Management Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil Examples Telmisartan (induces glucuronidation); isavuconazole (inhibits glucuronidation).

Drug Interactions with Mycophenolate Mofetil that Affect Other Drugs Drugs that Undergo Renal Tubular Secretion Clinical Impact When concomitantly used with mycophenolate mofetil, its metabolite MPAG, may compete with drugs eliminated by renal tubular secretion which may increase plasma concentrations and/or adverse reactions associated with these drugs Prevention or Management Monitor for drug-related adverse reactions in patients with renal impairment Examples Acyclovir, ganciclovir, probenecid, valacyclovir, valganciclovir Combination Oral Contraceptives Clinical Impact Concomitant use with mycophenolate mofetil decreased the systemic exposure to levonorgestrel, but did not affect the systemic exposure to ethinylestradiol [see Clinical Pharmacology ( 12.3 )], which may result in reduced combination oral contraceptive effectiveness.

Co-administration with micafungin did not alter pharmacokinetics of either drug.

Ciprofloxacin and Amoxicillin plus Clavulanic Acid A total of 64 mycophenolate mofetil-treated renal transplant recipients received either oral ciprofloxacin 500 mg bid or amoxicillin plus clavulanic acid 375 mg tid for 7 days or at least 14 days. Approximately 50% reductions in median trough MPA concentrations (pre-dose) from baseline (mycophenolate mofetil alone) were observed in 3 days following commencement of oral ciprofloxacin or amoxicillin plus clavulanic acid.

Ciprofloxacin and Amoxicillin plus Clavulanic Acid A total of 64 mycophenolate mofetil-treated renal transplant recipients received either oral ciprofloxacin 500 mg bid or amoxicillin plus clavulanic acid 375 mg tid for 7 days or at least 14 days. Approximately 50% reductions in median trough MPA concentrations (pre-dose) from baseline (mycophenolate mofetil alone) were observed in 3 days following commencement of oral ciprofloxacin or amoxicillin plus clavulanic acid.

Drug Interactions Drug interaction studies with mycophenolate mofetil have been conducted with acyclovir, antacids, cholestyramine, cyclosporine, ganciclovir, oral contraceptives, sevelamer, trimethoprim/sulfamethoxazole, norfloxacin, and metronidazole. Norfloxacin and Metronidazole Following single-dose administration of mycophenolate mofetil (1 g) to 11 healthy volunteers on day 4 of a 5 day course of a combination of norfloxacin and metronidazole, the mean MPA AUC 0-48h was significantly reduced by 33% compared to the administration of mycophenolate mofetil alone (p< 0.05). Therefore, mycophenolate mofetil is not recommended to be given with the combination of norfloxacin and metronidazole.

Drug Interactions Drug interaction studies with mycophenolate mofetil have been conducted with acyclovir, antacids, cholestyramine, cyclosporine, ganciclovir, oral contraceptives, sevelamer, trimethoprim/sulfamethoxazole, norfloxacin, and metronidazole. Norfloxacin and Metronidazole Following single-dose administration of mycophenolate mofetil (1 g) to 11 healthy volunteers on day 4 of a 5 day course of a combination of norfloxacin and metronidazole, the mean MPA AUC 0-48h was significantly reduced by 33% compared to the administration of mycophenolate mofetil alone (p< 0.05). Therefore, mycophenolate mofetil is not recommended to be given with the combination of norfloxacin and metronidazole.

Mean serum levels of LH, FSH and progesterone were not significantly affected.