Mycophenolate: uses, appearance and warnings

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 [see Clinical Studies (14.1)] , heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)] , in combination with other immunosuppressants. Mycophenolate mofetil 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. (1)

Mycophenolate mofetil for tablets and capsules are available in the following dosage forms and strengths: Capsules 250 mg mycophenolate mofetil, white to off-white blend of mycophenolate mofetil filled in size "1" hard gelatin capsule with Ivory Cap and Ivory Body, printed "SAL" on cap and "726" on body in black. Tablets 500 mg mycophenolate mofetil, pinkish brown colored, capsule shaped, film coated tablet with "SAL" engraved on one side and engraved "725" on other side. Capsules: 250 mg Tablets: 500 mg

16.1 Handling and Disposal Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)] . Mycophenolate mofetil tablets should not be crushed and mycophenolate mofetil capsules should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in mycophenolate mofetil capsules [see Dosage and Administration (2.6)]. Follow applicable special handling and disposal procedures 1 . 16.2 Mycophenolate Mofetil Capsules, USP 250 mg Capsules White to off-white blend of mycophenolate mofetil filled in size "1" hard gelatin capsule with Ivory Cap and Ivory Body, printed "SAL" on cap and "726" on body in black. Sizes Bottles of 100 ……………. NDC 42543-988-06 Bottles of 500 ……………. NDC 42543-988-07 Storage • Store at 20° to 25°C (68° to 77°F), [See USP controlled room temperature]. Dispense in light-resistant containers, such as the manufacturer's original containers. 16.3 Mycophenolate Mofetil Tablets, USP 500 mg Tablets Pinkish brown colored, capsule shaped, film coated tablet with "SAL" engraved on one side and engraved "725" on other side. Sizes Bottle of 100……………………………… NDC 42543-989-06 Bottle of 500……………………………… NDC 42543-989-07 Storage: • Store at 20° to 25°C (68° to 77°F). [See USP controlled room temperature]. Dispense in light-resistant containers, such as the manufacturer's original containers.

Allergic reactions to mycophenolate mofetil have been observed; therefore, mycophenolate mofetil is contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product. Hypersensitivity to mycophenolate mofetil, mycophenolic acid or any component of the drug product (4)

Blood Dyscrasias (Neutropenia, Red Blood Cell Aplasia): Monitor with blood tests; consider treatment interruption or dose reduction. (5.4) Gastrointestinal Complications: Monitor for complications such as bleeding, ulceration and perforations, particularly in patients with underlying gastrointestinal disorders. (5.5) Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency: Avoid use of mycophenolate mofetil. (5.6) Acute Inflammatory Syndrome Associated with Mycophenolate Products: Monitor for this paradoxical inflammatory reaction. (5.7) Immunizations: Avoid live attenuated vaccines. (5.8) Blood Donation: Avoid during therapy and for 6 weeks thereafter. (5.11) Semen Donation: Avoid during therapy and for 90 days thereafter. (5.12) Potential Impairment on Driving and Use of Machinery: Mycophenolate Mofetil may affect ability to drive or operate machinery. (5.14) 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 [see Use in Specific Populations (8.1, 8.3)]. 5.2 Lymphoma and Other Malignancies Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions (6.1)]. 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 mycophenolate mofetil (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients [see Adverse Reactions (6.1)]. 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 [see Adverse Reactions (6.1)]. 5.3 Serious Infections Patients receiving immunosuppressants, including mycophenolate mofetil, 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 [see Adverse Reactions (6.1, 6.2)]. 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 mycophenolate mofetil 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 [see Adverse Reactions (6.2)]. 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 [see Adverse Reactions (6.2)] . 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. 5.4 Blood Dyscrasias: Neutropenia and Pure Red Cell Aplasia (PRCA) Severe neutropenia [absolute neutrophil count (ANC) <0.5 x 10 3 /μL] developed in transplant patients receiving mycophenolate mofetil 3 g daily [see Adverse Reactions (6.1)]. Patients receiving mycophenolate mofetil 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 mycophenolate mofetil itself, concomitant medications, viral infections, or a combination of these causes. If neutropenia develops (ANC <1.3 x 10 3 /μL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Dosage and Administration (2.5)]. Patients receiving mycophenolate mofetil should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression. …

The following adverse reactions are discussed in greater detail in other sections of the label: Embryofetal Toxicity [see Warnings and Precautions (5.1)] Lymphomas and Other Malignancies [see Warnings and Precautions (5.2)] Serious Infections [see Warnings and Precautions (5.3)] Blood Dyscrasias: Neutropenia, Pure Red Cell Aplasia [see Warnings and Precautions (5.4)] Gastrointestinal Complications [see Warnings and Precautions (5.5)] Acute Inflammatory Syndrome Associated with Mycophenolate Products [see Warnings and Precautions (5.7)] The most common adverse reactions in clinical trials (20 % or greater) include diarrhea, leukopenia, infection, vomiting, and there is evidence of a higher frequency of certain types of infections e.g., opportunistic infection. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Strides Pharma Inc. …

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. (7.1) Mycophenolate mofetil may reduce effectiveness of oral contraceptives. Use of additional barrier contraceptive methods is recommended. (7.2) See FPI for other important drug interactions. (7) 7.1 Effect of Other Drugs on Mycophenolate Mofetil Table 7 Drug Interactions with Mycophenolate Mofetil 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 [see Clinical Pharmacology (12.3)] , which may reduce mycophenolate mofetil efficacy. …