CELLCEPT (mycophenolate mofetil) is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor. The chemical name for mycophenolate mofetil (MMF) is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. It has an empirical formula of C 23 H 31 NO 7 , a molecular weight of 433.50, and the following structural formula: MMF is a white to off-white crystalline powder. It is slightly soluble in water (43 µg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol, and sparingly soluble in ethanol. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for MMF are 5.6 for the morpholino group and 8.5 for the phenolic group. MMF hydrochloride has a solubility of 65.8 mg/mL in 5% Dextrose Injection USP (D5W). The pH of the reconstituted solution is 2.4 to 4.1. CELLCEPT is available for oral administration as capsules containing 250 mg of MMF, tablets containing 500 mg of MMF, and as a powder for oral suspension which, when reconstituted, contains 200 mg/mL of MMF. Inactive ingredients in CELLCEPT 250 mg capsules include croscarmellose sodium, magnesium stearate, povidone (K-90) and pregelatinized starch. The capsule shells contain black iron oxide, FD&C blue #2, gelatin, red iron oxide, silicon dioxide, sodium lauryl sulfate, titanium dioxide, and yellow iron oxide. Inactive ingredients in CELLCEPT 500 mg tablets include croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone (K-90), and Opadry ® lavender Y-5R-10272-A (hydroxypropyl methylcellulose, hydroxypropyl cellulose, titanium dioxide, polyethylene glycol 400, FD&C Blue No. 2 aluminum lake [indigo carmine aluminum lake], and red iron oxide). Inactive ingredients in CELLCEPT Oral Suspension include aspartame, citric acid anhydrous, colloidal silicon dioxide, methylparaben, mixed fruit flavor, sodium citrate dihydrate, sorbitol, soybean lecithin, and xanthan gum. CELLCEPT Intravenous is the hydrochloride salt of MMF. The chemical name for the hydrochloride salt of MMF is 2-morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate hydrochloride. It has an empirical formula of C 23 H 31 NO 7 HCl and a molecular weight of 469.96. CELLCEPT Intravenous is available as a sterile white to off-white lyophilized powder in single-dose vials containing MMF hydrochloride for administration by intravenous infusion only. Each vial contains 500 mg of mycophenolate mofetil equivalent to 542 mg of mycophenolate mofetil hydrochloride. The inactive ingredients are polysorbate 80, 25 mg, and citric acid, 5 mg. Sodium hydroxide or hydrochloric acid may have been used in the manufacture of CELLCEPT Intravenous to adjust the pH. Reconstitution and dilution with 5% Dextrose Injection USP yields a slightly yellow solution of MMF, 6 mg/mL . Chemical Structure

CELLCEPT [mycophenolate mofetil (MMF)] is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney , heart or liver transplants , in combination with other immunosuppressants. CELLCEPT is an antimetabolite immunosuppressant indicated for the prophylaxis of organ rejection in adult and pediatric recipients 3 months of age and older of allogeneic kidney, heart or liver transplants, in combination with other immunosuppressants.

CELLCEPT is available in the following dosage forms and strengths: Capsules 250 mg mycophenolate mofetil, two-piece hard gelatin capsules, blue-brown, "CELLCEPT 250" printed in black on the blue cap and "Roche" on the brown body Tablets 500 mg mycophenolate mofetil, lavender-colored, caplet-shaped, film-coated tablets engraved with "CELLCEPT 500" on one side and "Roche" on the other For oral suspension 35 g mycophenolate mofetil white to off-white powder for reconstitution (200 mg/mL upon reconstitution) For injection 500 mg mycophenolate mofetil white to off-white lyophilized powder, in a single-dose vial for reconstitution Capsules: 250 mg Tablets: 500 mg For Oral Suspension: 35 g mycophenolate mofetil, powder for reconstitution (200 mg/mL upon reconstitution) For Injection: 500 mg mycophenolate mofetil in a single-dose vial for reconstitution.

ADULTS DOSAGE Kidney Transplant 1 g twice daily, orally or intravenously (IV) over no less than 2 h Heart Transplant 1.5 g twice daily orally or IV, over no less than 2 h Liver Transplant 1.5 g twice daily orally or 1g twice daily IV over no less than 2 h PEDIATRICS Kidney Transplant 600 mg/m 2 orally twice daily, up to maximum of 2 g daily Heart Transplant 600 mg/m 2 orally twice daily (starting dose) up to a maximum of 900 mg/m 2 twice daily (3 g or 15 mL of oral suspension) Liver Transplant 600 mg/m 2 orally twice daily (starting dose) up to a maximum of 900 mg/m 2 twice daily (3 g or 15 mL of oral suspension) CELLCEPT Intravenous is an alternative when patients cannot tolerate oral medication. Administer within 24 hours following transplantation, until patients can tolerate oral medication, up to 14 days. Reduce or interrupt dosing in the event of neutropenia. See full prescribing information (FPI) for: adjustments for renal impairment and neutropenia, preparation of oral suspension and IV solution

Important Administration Instructions CELLCEPT should not be used without the supervision of a physician with experience in immunosuppressive therapy. CELLCEPT Capsules, Tablets and Oral Suspension CELLCEPT oral dosage forms (capsules, tablets or oral suspension) should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy because the rates of absorption following the administration of CELLCEPT oral dosage forms and mycophenolic acid delayed-release tablets are not equivalent. CELLCEPT tablets should not be crushed and CELLCEPT capsules should not be opened or crushed. Patients should avoid inhalation or contact of the skin or mucous membranes with the powder contained in CELLCEPT capsules and oral suspension. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water. The initial oral dose of CELLCEPT should be given as soon as possible following kidney, heart or liver transplant. It is recommended that CELLCEPT be administered on an empty stomach. In stable transplant patients, however, CELLCEPT may be administered with food if necessary . Once reconstituted, CELLCEPT Oral Suspension must not be mixed with any liquids prior to dose administration. If needed, CELLCEPT Oral Suspension can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter). Patients should be instructed to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case, they should continue to take CELLCEPT at the usual times. CELLCEPT Intravenous CELLCEPT Intravenous is recommended for patients unable to take oral CELLCEPT. CELLCEPT Intravenous should be administered within 24 hours following transplant. CELLCEPT Intravenous can be administered for up to 14 days; however, patients should be switched to oral CELLCEPT as soon as they can tolerate oral medication. CELLCEPT Intravenous must be reconstituted before use . CELLCEPT Intravenous is incompatible with other intravenous infusion solutions and should not be mixed or administered concurrently via the same infusion catheter with other intravenous drugs or infusion admixtures. CELLCEPT Intravenous must not be administered as a bolus. Following reconstitution, CELLCEPT Intravenous must be administered by slow intravenous infusion over a period of no less than 2 hours by either peripheral or central vein, as rapid infusion increases the risk of local adverse reactions such as phlebitis and thrombosis

Dosage Recommendations for Kidney Transplant Patients Adults The recommended dosage for adult kidney transplant patients is 1 g orally or intravenously infused over no less than 2 hours, twice daily (total daily dose of 2 g). Pediatrics (3 months and older) Pediatric dosing is based on body surface area (BSA). The recommended dosage of CELLCEPT oral suspension for pediatric kidney transplant patients 3 months and older is 600 mg/m 2 , administered twice daily (maximum total daily dose of 2 g or 10 mL of the oral suspension). Pediatric patients with BSA ≥ 1.25 m 2 may be dosed with capsules or tablets as follows: Table 1 Pediatric Kidney Transplant: Dosage Using Capsules or Tablets Body Surface Area Dosage 1.25 m 2 to <1.5 m 2 CELLCEPT capsule 750 mg twice daily (1.5 g total daily dose) ≥ 1.5 m 2 CELLCEPT capsules or tablets 1 g twice daily (2 g total daily dose) 2.3 Dosage Recommendations for Heart Transplant Patients Adults The recommended dosage of CELLCEPT for adult heart transplant patients is 1.5 g orally or intravenously infused over no less than 2 hours administered twice daily (total daily dose of 3 g). Pediatrics (3 months and older) The recommended starting dosage of CELLCEPT oral suspension for pediatric heart transplant patients 3 months and older is 600 mg/m 2 , administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m 2 twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment. Pediatric patients with BSA ≥1.25 m 2 may be started on therapy with capsules or tablets as follows: Table 2 Pediatric Heart Transplant: Pediatric Starting Dosage Using Capsules or Tablets Body Surface Area Starting Dosage Maximum maintenance dose: 3 g total daily

m 2 to <1.5 m 2 CELLCEPT capsule 750 mg twice daily (1.5 g total daily dose) ≥ 1.5 m 2 CELLCEPT capsules or tablets 1 g twice daily (2 g total daily dose) 2.4 Dosage Recommendations for Liver Transplant Patients Adults The recommended dosage of CELLCEPT for adult liver transplant patients is 1.5 g administered orally twice daily (total daily dose of 3 g) or 1 g infused intravenously over no less than 2 hours, twice daily (total daily dose of 2 g). Pediatrics (3 months and older) The recommended starting dosage of CELLCEPT oral suspension for pediatric liver transplant patients 3 months of age and older is 600 mg/m 2 , administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m 2 twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment. Pediatric patients with BSA ≥1.25 m 2 may be started on therapy with capsules or tablets as follows: Table 3 Pediatric Liver Transplant: Pediatric Starting Dosage Using Capsules or Tablets Body Surface Area Starting Dosage Maximum maintenance dose: 3 g total daily

m 2 to <1.5 m 2 CELLCEPT capsule 750 mg twice daily (1.5 g total daily dose) ≥ 1.5 m 2 CELLCEPT capsules or tablets 1 g twice daily (2 g total daily dose) 2.5 Dosage Modifications: Patients with Renal Impairment, Neutropenia Renal Impairment No dosage modifications are needed in kidney transplant patients with delayed graft function postoperatively . In kidney transplant patients with severe chronic impairment of the graft (GFR <25 mL/min/1.73 m 2 ), do not administer doses of CELLCEPT greater than 1 g twice a day. These patients should be carefully monitored . Neutropenia If neutropenia develops (ANC <1.3 × 10 3 /µL), dosing with CELLCEPT should be interrupted or reduced, appropriate diagnostic tests performed, and the patient managed appropriately

Preparation Instructions of Oral Suspension and Intravenous for Pharmacists General Preparation Instructions Before Handling the Formulations Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans. Follow applicable special handling and disposal procedures 1 . Care should be taken to avoid inhalation or direct contact with skin or mucous membranes of the dry powder or the constituted suspension because MMF has demonstrated teratogenic effects in humans . Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the bottle/cap and the table surface after reconstitution. If such contact occurs, wash hands thoroughly with soap and water; rinse eyes with water. Alert patients that they and others should also avoid inhalation or contact of the skin or mucous membranes with the oral suspension. Advise them to wash the area thoroughly with soap and water if such contact occurs; if ocular contact occurs, rinse eyes with plain water. CELLCEPT Oral Suspension CELLCEPT Oral Suspension must be reconstituted by the pharmacist prior to dispensing to the patient. CELLCEPT Oral Suspension should not be mixed with any other medication. After reconstitution, the oral suspension contains 200 mg/mL MMF. Before proceeding with the reconstitution steps read the general preparation instructions above . The following are the steps for reconstitution: Tap the closed bottle several times to loosen the powder. Measure 94 mL of water in a graduated cylinder. Add approximately half the total amount of water for reconstitution to the bottle and shake the closed bottle well for about 1 minute. Add the remainder of water and shake the closed bottle well for about 1 minute. Remove the child-resistant cap and push bottle adapter into neck of bottle. Close bottle with child-resistant cap tightly. This will assure the proper seating of the bottle adapter in the bottle and child-resistant status of the cap. Write the date of expiration of the constituted suspension on the bottle label. (The shelf-life of the constituted suspension is 60 days.) Dispense with the "Instruction for Use" and oral dispensers. Alert patients to read the important handling information described in the instructions for use. Store reconstituted suspension at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Storage in a refrigerator at 2°C to 8°C (36°F to 46°F) is acceptable. Do not freeze. Discard any unused portion 60 days after constitution. CELLCEPT Intravenous Before proceeding with the preparation steps for CELLCEPT Intravenous read the general preparation instructions and note the following: CELLCEPT Intravenous does not contain an antibacterial preservative; therefore, reconstitution and dilution of the product must be performed under aseptic conditions. This product is sealed under vacuum and should retain a vacuum throughout its shelf life. If a lack of vacuum in the vial is noted while adding the diluent, the vial should not be used. CELLCEPT Intravenous must be reconstituted and further diluted. A detailed description of the preparation is given below. Table 4 Preparation Instructions of CELLCEPT Intravenous for Pharmacists Preparation of the 1g dose Reconstitute two vials of CELLCEPT Intravenous by injecting 14 mL of 5% Dextrose Injection USP into each vial. Gently shake the vial to dissolve the drug. Inspect the resulting slightly yellow solution for particulate matter and discoloration prior to further dilution. Discard the vials if particulate matter or discoloration is observed. Dilute the contents of the two reconstituted vials (approximately 2 × 15 mL) into 140 mL of 5% Dextrose Injection USP. Inspect the resulting infusion solution and discard if particulate matter or discoloration is observed. Preparation of the 1.5 g dose Reconstitute three vials of CELLCEPT Intravenous by injecting 14 mL of 5% Dextrose Injection USP into each vial. Gently shake the vial to dissolve the drug. Inspect the resulting slightly yellow solution for particulate matter and discoloration prior to further dilution. Discard the vials if particulate matter or discoloration is observed. Dilute the contents of the three reconstituted vials (approximately 3 × 15 mL) into 210 mL of 5% Dextrose Injection USP. Inspect the resulting infusion solution and discard if particulate matter or discoloration is observed. The administration of the infusion should be initiated within 4 hours of reconstitution and dilution of the drug product. Keep solutions at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Discard unused portion of the reconstituted solutions. CELLCEPT Injection should not be mixed or administered concurrently via the same infusion catheter with other intravenous drugs or infusion admixtures.

Blood Dyscrasias (Neutropenia, Red Blood Cell Aplasia): Monitor with blood tests; consider treatment interruption or dose reduction. Gastrointestinal Complications: Monitor for complications such as bleeding, ulceration and perforations, particularly in patients with underlying gastrointestinal disorders. Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency: Avoid use of CELLCEPT. Acute Inflammatory Syndrome Associated with Mycophenolate Products: Monitor for this paradoxical inflammatory reaction. Hypersensitivity Reactions: Discontinue CELLCEPT; treat and monitor until signs and symptoms resolve. Immunizations: Avoid live attenuated vaccines. Local Reactions with Rapid Intravenous Administration: CELLCEPT Intravenous must not be administered by rapid or bolus intravenous injection. Phenylketonurics: Oral suspension contains aspartame. Blood Donation: Avoid during therapy and for 6 weeks thereafter. Semen Donation: Avoid during therapy and for 90 days thereafter. Potential Impairment on Driving and Use of Machinery: CELLCEPT may affect ability to drive or operate machinery. 5.1 Embryofetal Toxicity Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system. Females of reproductive potential must be made aware of these risks and must be counseled regarding pregnancy prevention and planning. Avoid use of MMF during pregnancy if safer treatment options are available

Lymphoma and Other Malignancies Patients receiving immunosuppressants, including CELLCEPT, are at increased risk of developing lymphomas and other malignancies, particularly of the skin . The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. For patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor. Post-transplant lymphoproliferative disorder (PTLD) developed in 0.4% to 1% of patients receiving CELLCEPT (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients . The majority of PTLD cases appear to be related to Epstein Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children. In pediatric patients, no other malignancies besides PTLD were observed in clinical trials

Serious Infections Patients receiving immunosuppressants, including CELLCEPT, are at increased risk of developing bacterial, fungal, protozoal and new or reactivated viral infections, including opportunistic infections. The risk increases with the total immunosuppressive load. These infections may lead to serious outcomes, including hospitalizations and death . Serious viral infections reported include: Polyomavirus-associated nephropathy (PVAN), especially due to BK virus infection JC virus-associated progressive multifocal leukoencephalopathy (PML), and Cytomegalovirus (CMV) infections: CMV seronegative transplant patients who receive an organ from a CMV seropositive donor are at highest risk of CMV viremia and CMV disease. Viral reactivation in patients infected with Hepatitis B and C COVID-19 Consider dose reduction or discontinuation of CELLCEPT in patients who develop new infections or reactivate viral infections, weighing the risk that reduced immunosuppression represents to the functioning allograft. PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss . Patient monitoring may help detect patients at risk for PVAN. PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia . In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms. The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease. Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended

Blood Dyscrasias: Neutropenia and Pure Red Cell Aplasia (PRCA) Severe neutropenia [absolute neutrophil count (ANC) <0.5 × 10 3 /µL] developed in transplant patients receiving CELLCEPT 3 g daily . Patients receiving CELLCEPT should be monitored for neutropenia . Neutropenia has been observed most frequently in the period from 31 to 180 days post-transplant in patients treated for prevention of kidney, heart and liver rejection. The development of neutropenia may be related to CELLCEPT itself, concomitant medications, viral infections, or a combination of these causes. If neutropenia develops (ANC <1.3 × 10 3 /µL), dosing with CELLCEPT should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately . Patients receiving CELLCEPT should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression. Consider monitoring with complete blood counts weekly for the first month, twice monthly for the second and third months, and monthly for the remainder of the first year. Cases of pure red cell aplasia (PRCA) have been reported in patients treated with CELLCEPT in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of CELLCEPT therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk

Gastrointestinal Complications Gastrointestinal bleeding requiring hospitalization, ulceration and perforations were observed in clinical trials. Physicians should be aware of these serious adverse effects particularly when administering CELLCEPT to patients with a gastrointestinal disease

Patients with Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency (HGPRT) CELLCEPT is an inosine monophosphate dehydrogenase (IMPDH) inhibitor; therefore it should be avoided in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout such as acute arthritis, tophi, nephrolithiasis or urolithiasis and renal disease including renal failure

Acute Inflammatory Syndrome Associated with Mycophenolate Products Acute inflammatory syndrome (AIS) has been reported with the use of MMF and mycophenolate products, and some cases have resulted in hospitalization. AIS is a paradoxical pro-inflammatory reaction characterized by fever, arthralgias, arthritis, muscle pain and elevated inflammatory markers including, C-reactive protein and erythrocyte sedimentation rate, without evidence of infection or underlying disease recurrence. Symptoms occur within weeks to months of initiation of treatment or a dose increase. After discontinuation, improvement of symptoms and inflammatory markers are usually observed within 24 to 48 hours. Monitor patients for symptoms and laboratory parameters of AIS when starting treatment with mycophenolate products or when increasing the dosage. Discontinue treatment and consider other treatment alternatives based on the risk and benefit for the patient

Hypersensitivity Reactions Postmarketing cases of hypersensitivity reactions, including angioedema and anaphylaxis, have been reported with CELLCEPT. These reactions generally occurred within hours to the next day after initiating CELLCEPT. If signs or symptoms of hypersensitivity reaction occur, discontinue CELLCEPT; treat and monitor until symptoms resolve

Immunizations During treatment with CELLCEPT, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) and patients should be advised that vaccinations may be less effective. Advise patients to discuss with the physician before seeking any immunizations

Local Reactions with Rapid Intravenous Administration CELLCEPT Intravenous solution must not be administered by rapid or bolus intravenous injection as rapid infusion increases the risk of local adverse reactions such as phlebitis and thrombosis

Risks in Patients with Phenylketonuria Phenylalanine can be harmful to patients with phenylketonuria (PKU). CELLCEPT Oral Suspension contains aspartame, a source of phenylalanine (0.56 mg phenylalanine/mL suspension). Before prescribing CELLCEPT Oral Suspension to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including CELLCEPT

Blood Donation Patients should not donate blood during therapy and for at least 6 weeks following discontinuation of CELLCEPT because their blood or blood products might be administered to a female of reproductive potential or a pregnant woman

Semen Donation Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of CELLCEPT

Effect of Concomitant Medications on Mycophenolic Acid Concentrations A variety of drugs have potential to alter systemic MPA exposure when co-administered with CELLCEPT. Therefore, determination of MPA concentrations in plasma before and after making any changes to immunosuppressive therapy, or when adding or discontinuing concomitant medications, may be appropriate to ensure MPA concentrations remain stable

Potential Impairment of Ability to Drive or Operate Machinery CELLCEPT may impact the ability to drive and use machines. Patients should avoid driving or using machines if they experience somnolence, confusion, dizziness, tremor, or hypotension during treatment with CELLCEPT .

See FPI for drugs that may interfere with systemic exposure and reduce CELLCEPT efficacy: antacids with magnesium or aluminum hydroxide, proton pump inhibitors, drugs that interfere with enterohepatic recirculation, telmisartan, calcium-free phosphate binders. CELLCEPT may reduce effectiveness of oral contraceptives. Use of additional barrier contraceptive methods is recommended. See FPI for other important drug interactions

Effect of Other Drugs on CELLCEPT Table 7 Drug Interactions with CELLCEPT that Affect Mycophenolic Acid (MPA) Exposure Antacids with Magnesium or Aluminum Hydroxide Clinical Impact Concomitant use with an antacid containing magnesium or aluminum hydroxide decreases MPA systemic exposure , which may reduce CELLCEPT efficacy. Prevention or Management Administer magnesium or aluminum hydroxide containing antacids at least 2h after CELLCEPT administration. Proton Pump Inhibitors (PPIs) Clinical Impact Concomitant use with PPIs decreases MPA systemic exposure , which may reduce CELLCEPT efficacy. Prevention or Management Monitor patients for alterations in efficacy when PPIs are co-administered with CELLCEPT. 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 , which may reduce CELLCEPT efficacy. Prevention or Management Monitor patients for alterations in efficacy or CELLCEPT related adverse reactions when these drugs are co-administered with CELLCEPT. 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 CELLCEPT efficacy, while use with drugs inhibiting glucuronidation increases MPA systemic exposure , which may increase the risk of CELLCEPT related adverse reactions. Prevention or Management Monitor patients for alterations in efficacy or CELLCEPT related adverse reactions when these drugs are co-administered with CELLCEPT. Examples Telmisartan (induces glucuronidation); isavuconazole (inhibits glucuronidation). Calcium Free Phosphate Binders Clinical Impact Concomitant use with calcium free phosphate binders decrease MPA systemic exposure , which may reduce CELLCEPT efficacy. Prevention or Management Administer calcium free phosphate binders at least 2 hours after CELLCEPT. Examples Sevelamer 7.2 Effect of CELLCEPT on Other Drugs Table 8 Drug Interactions with CELLCEPT that Affect Other Drugs Drugs that Undergo Renal Tubular Secretion Clinical Impact When concomitantly used with CELLCEPT, 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 CELLCEPT decreased the systemic exposure to levonorgestrel, but did not affect the systemic exposure to ethinylestradiol , which may result in reduced combination oral contraceptive effectiveness. Prevention or Management Use additional barrier contraceptive methods.