No

Immunosuppressant Agent

Immunosuppressant used with corticosteroids and cyclosporine to prevent organ rejection in patients receiving allogenic renal and cardiac transplants; treatment of rejection in liver transplant patients unable to tolerate tacrolimus or cyclosporine due to neurotoxicity; mild rejection in heart transplant patients; treatment of moderate-severe psoriasis

C

Hypersensitivity to mycophenolate mofetil, mycophenolic acid or any ingredient; intravenous is contraindicated in patients who are allergic to polysorbate 80

Increased risk for infection and development of lymphoproliferative disorders. Patients should be monitored appropriately and given supportive treatment should these conditions occur. Increased toxicity in patients with renal impairment. Should be used with caution in patients with active peptic ulcer disease.

>10% (doses of mycophenolate 2 g/day or 3 g/day):

Body as a Whole

Pain: 33% (2 g/day); 31.2% (3 g/day)

Abdominal pain: 12.1% to 24.7% (2 g/day); 11.9% to 27.6% (3 g/day)

Fever: 20.4% (2 g/day); 23.3% (3 g/day)

Headache: 20.1% (2 g/day); 16.1% (3 g/day)

Infection: 12.7% to 18.2% (2 g/day); 15.6% to 20.9% (3 g/day)

Sepsis: 17.6% to 20.8% (2 g/day); 17.5% to 19.7% (3 g/day)

Asthenia: 13.7% (2 g/day); 16.1% (3 g/day)

Chest pain: 13.4% (2 g/day); 13.3% (3 g/day)

Back pain: 11.6% (2 g/day); 12.1% (3 g/day)

Hypertension: 17.6% to 32.4% (2 g/day); 16.9% to 28.2% (3 g/day)

Central nervous system

Tremor: 11% (2 g/day); 11.8% (3 g/day)

Insomnia: 8.9% (2 g/day); 11.8% (3 g/day)

Dizziness: 5.7% (2 g/day); 11.2% (3 g/day)

Dermatologic

Acne: 10.1% (2 g/day); 9.7% (3 g/day)

Rash: 7.7% (2 g/day); 6.4% (3 g/day)

Gastrointestinal

Diarrhea: 16.4% to 31% (2 g/day); 18.8% to 36.1% (3 g/day)

Constipation: 21.9% (2 g/day); 18.5% (3 g/day)

Nausea: 19.9% (2 g/day); 23.6% (3 g/day)

Dyspepsia: 17.6% (2 g/day); 13.6% (3 g/day)

Vomiting: 12.5% (2 g/day); 13.6% (3 g/day)

Nausea & vomiting: 10.4% (2 g/day); 9.7% (3 g/day)

Oral monoliasis: 10.1% (2 g/day) 12.1% (3 g/day)

Hemic/Lymphatic

Anemia: 25.6% (2 g/day); 25.8% (3 g/day)

Leukopenia: 11.5% to 23.2% (2 g/day); 16.3% to 34.5% (3 g/day)

Thrombocytopenia: 10.1% (2 g/day); 8.2% (3 g/day)

Hypochromic anemia: 7.4% (2 g/day); 11.5% (3 g/day)

Leukocytosis: 7.1% (2 g/day); 10.9% (3 g/day)

Metabolic/Nutritional

Peripheral edema: 28.6% (2 g/day); 27% (3 g/day)

Hypercholesterolemia: 12.8% (2 g/day); 8.5% (3 g/day)

Hypophosphatemia: 12.5% (2 g/day); 15.8% (3 g/day)

Edema: 12.2% (2 g/day); 11.8% (3 g/day)

Hypokalemia: 10.1% (2 g/day); 10% (3 g/day)

Hyperkalemia: 8.9% ( 2 g/day) 10.3% ( 3 g/day)

Hyperglycemia: 8.6% (2 g/day); 12.4% (3 g/day)

Respiratory

Infection: 15.8% to 21% (2 g/day); 13.1% to 23.9% (3 g/day)

Dyspnea:15.5% (2 g/day); 17.3% (3 g/day)

Cough increase: 15.5% (2 g/day); 13.3% (3 g/day)

Pharyngitis: 9.5% (2 g/day); 11.2% (3 g/day)

Bronchitis: 8.5% (2 g/day); 11.9% (3 g/day)

Pneumonia: 3.6% (2 g/day); 10.6% (3 g/day)

Urogenital

UTI: 37.2% to 45.5% (2 g/day); 37% to 44.4% (3 g/day)

Hematuria: 14% (2 g/day); 12.1% (3 g/day)

Kidney tubular necrosis: 6.3% (2 g/day); 10% (3 g/day)

Urinary tract disorder: 6.7% (2 g/day); 10.6% (3 g/day)

1% to 10%: Thrombophlebitis and thrombosis (4%) with intravenous administration

Decreased effect: Antacids decrease C_max and AUC, do not administer together; cholestyramine decreases AUC, do not administer together

Increased toxicity: Acyclovir and ganciclovir levels may increase due to competition for tubular secretion of these drugs; probenecid may increase mycophenolate levels due to inhibition of tubular secretion; salicylates: high doses may increase free fraction of mycophenolic acid

Tablets/capsules should be stored at room temperature (15°C to 39°C/59°F to 86°F). Tablets should also be protected from light. Intact vials of injection should be stored at room temperature (15°C to 30°C/59°F to 86°F).

Preparation procedure:

Step 1:

a. Two vials of mycophenolate injection are used for preparing a 1 g dose, whereas 3 vials are needed for each 1.5 g dose. Reconstitute the contents of each vial by injecting 14 mL of 5% dextrose injection.

b. Gently shake the vial to dissolve the drug

c. Inspect the resulting slightly yellow solution for particulate matter and discoloration prior to further dilution. Discard the vial if particulate matter or discoloration is observed.

Step 2:

a. To prepare a 1 g dose, further dilute the contents of the two reconstituted vials into 140 mL of 5% dextrose in water. To prepare a 1.5 g dose, further dilute the contents of the three reconstituted vials into 210 mL of 5% dextrose in water. The final concentration of both solutions is 6 mg mycophenolate mofetil per mL.

b. Inspect the infusion solution for particulate matter or discoloration. Discard the infusion solution if particulate matter or discoloration is observed.

Stability of the infusion solution: 4 hours from reconstitution and dilution of the product. Store solutions at 15°C to 30°C (59°F to 86°F)

Inhibition of purine synthesis of human lymphocytes and proliferation of human lymphocytes

Absorption: Mycophenolate mofetil is hydrolyzed to mycophenolic acid in the liver and gastrointestinal tract; food does not alter the extent of absorption, but the maximum concentration is decreased

Protein binding: 97%

Metabolism: Mycophenolate mofetil is metabolized to the acid form which is pharmacologically active; mycophenolic acid is glucuronidated to an inactive form; enterohepatic cycling of mycophenolic acid may occur.

Elimination: Mycophenolic acid glucuronide is excreted in the urine and bile. 87% of mycophenolic acid dose has been recovered in urine as inactive glucuronide metabolite.

Half-life: 18 hours

Serum concentrations: Correlation of toxicity or efficacy is still being developed, however, one study indicated that 12-hour AUCs of >40 mcg/mL/hour were correlated with efficacy and decreased episodes of rejection

Oral:

Children: 600 mg/m²/dose twice daily; Note: Limited information regarding mycophenolate use in pediatric patients is currently available in the literature: 32 pediatric patients (14 underwent living donor and 18 receiving cadaveric donor renal transplants) received mycophenolate 8-30 mg/kg/dose orally twice daily with cyclosporine, prednisone, and Atgam® induction; however, pharmacokinetic studies suggest that doses of mycophenolate adjusted to body surface area resulted in AUCs which better approximated those of adults versus doses adjusted for body weight which resulted in lower AUCs in pediatric patients

Adults: 1 g twice daily within 72 hours of transplant (although 3 g daily has been given in some clinical trials, there was decreased tolerability and no efficacy advantage)

Dosing adjustment in renal impairment: Doses >2 g/day are not recommended in these patients because of the possibility for enhanced immunosuppression as well as toxicities

Dosing adjustment in severe chronic renal impairment: Cl_cr <25 mL/minute/1.73 m²: Doses of >1 g administered twice daily should be avoided; patients should also be carefully observed; no dose adjustments are needed in renal transplant patients experiencing delayed graft function postoperatively

Hemodialysis: Not removed; supplemental dose is not necessary

Peritoneal dialysis: Supplemental dose is not necessary

Dosing adjustment for neutropenia: ANC <1.3 x 10³/mL: Dosing should be interrupted or the dose reduced, appropriate diagnostic tests performed and patients managed appropriately

Dizziness and insomnia are common

Leukopenia is common; avoid clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take as directed, preferably 1 hour before or 2 hours after meals. Do not take within 1 hour before or 2 hours after antacids or cholestyramine medications. Do not alter dose and do not discontinue without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) during entire course of therapy. You will be susceptible to infection (avoid crowds and people with infections or contagious diseases). If you are diabetic, monitor glucose levels closely (may alter glucose levels). You may experience dizziness or trembling (use caution until response to medication is known); nausea or vomiting (frequent small meals, frequent mouth care may help); diarrhea (boiled milk, yogurt, or buttermilk may help); sores or white plaques in mouth (frequent rinsing of mouth and frequent mouth care may help); or muscle or back pain (mild analgesics may be recommended). Report chest pain; acute headache or dizziness; symptoms of respiratory infection, cough, or difficulty breathing; unresolved gastrointestinal effects; fatigue, chills, fever unhealed sores, white plaques in mouth; irritation in genital area or unusual discharge; unusual bruising or bleeding; or other unusual effects related to this medication. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Increased risk for infection and development of lymphoproliferative disorders. Patients should be monitored appropriately and given supportive treatment should these conditions occur. Increased toxicity in patients with renal impairment.

Capsule, as mofetil: 250 mg

Injection: 500 mg

Tablet, film coated: 500 mg

Ettenger R, Warshaw B, Menster M, et al, "Mycophenolate Mofetil in Pediatric Renal Transplantation: A Report of the Ped MMF Study Group." Abstract: 1996, Annual Meeting, ASTP.

Lipsky JJ, "Mycophenolate Mofetil," Lancet, 1996, 348(9038):1357-9.

Shaw LM, Sollinger HW, Halloran P, et al, "Mycophenolate Mofetil: A Report of the Consensus Panel," Ther Drug Monit, 1995, 17(6):690-9.

Sollinger HW, "Mycophenolate Mofetil for the Prevention of Acute Rejection in Primary Cadaveric Renal Allograft Recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group," Transplantation, 1995, 60:225-32.