Usual Adult Dose for Organ Transplant - Rejection Prophylaxis

• RENAL TRANSPLANTATION: 1 g orally or IV 2 times a day (2 gm per day); [in clinical trials, 1.5 g orally or IV 2 times a day (3 gm per day) was used effectively, however, the safety profile for 3 gm a day was lower]
• CARDIAC TRANSPLANTATION: 1.5 g orally or IV 2 times a day (3 gm per day)
• HEPATIC TRANSPLANTATION: 1.5 gm orally or 1 gm IV 2 times a day (3 gm per day orally or 2 gm per day IV)

Comments:

• This drug should be used concomitantly with cyclosporine and corticosteroids.
• The IV formulation should be administered over no less than 2 hours.
• IV administration is recommended in patients unable to take oral medication; oral administration should be initiated as soon as possible.

Usual Geriatric Dose for Organ Transplant - Rejection Prophylaxis

• RENAL TRANSPLANTATION: 1 g orally or IV 2 times a day (2 gm per day)
• CARDIAC TRANSPLANTATION: 1.5 g orally or IV 2 times a day (3 gm per day)
• HEPATIC TRANSPLANTATION: 1.5 gm orally or 1 gm IV 2 times a day (3 gm per day orally or 2 gm per day IV)

Comments:

• This drug should be used concomitantly with cyclosporine and corticosteroids.
• The IV formulation should be administered over no less than 2 hours.
• IV administration is recommended in patients unable to take oral medication; oral administration should be initiated as soon as possible.

Usual Pediatric Dose for Organ Transplant - Rejection Prophylaxis

• RENAL TRANSPLANTATION:

3 months to 18 years of age:
Oral Suspension: 600 mg/m2 orally 2 times a day up to a maximum of 2 grams per day

• Pediatric patients with a body surface area of 1.25 to 1.5 m2 may be dosed with the oral capsules at 750 mg orally 2 times a day (1.5 g per day)
• Pediatric patients with a body surface area greater than 1.5 m2 may be dosed with the oral capsules at 1 g orally 2 times a day (2 g per day)

Comments:

• This drug should be used concomitantly with cyclosporine and corticosteroids.
• The IV formulation should be administered over no less than 2 hours.-IV administration is recommended in patients unable to take oral medication; oral administration should be initiated as soon as possible.

Renal Dose Adjustments

CrCl less than 25 mL/min: Doses greater than 1 gm 2 times a day should be avoided

Liver Dose Adjustments

Data not available

Dose Adjustments

• If a patient develops neutropenia (absolute neutrophil count less than 1300/mm³), dosing should be stopped or the dose reduced, and the patient should be managed appropriately.
• Close clinical monitoring is recommended if this drug is used in patients with liver disease.
• Doses greater than 2 g/day (especially in renal dysfunction) are not recommended.
• Higher doses may lead to more severe gastrointestinal adverse reactions and enhanced immunosuppression.

Precautions

US BOXED WARNINGS:

• Use of this drug during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations. Avoid if safer treatment options are available. Females of reproductive potential should be counseled regarding pregnancy prevention and planning.
• Increased risk of development of lymphoma and other malignancies, particularly of the skin.
• Increased susceptibility to infections, including opportunistic infections and severe infections with fatal outcomes

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for mycophenolate. It includes a medication guide and elements to assure safe use. For additional information: www.fda.gov/REMS.

CONTRAINDICATIONS:

• Hypersensitivity to the active component, mycophenolic acid, or any of the ingredients
• Intravenous formulation in patients who are allergic to Polysorbate 80 (TWEEN)

Safety and efficacy have not been established in patients younger than 3 months.

Consult WARNINGS section for additional precautions.

Dialysis

Mycophenolic acid (the active metabolite) and the inactive glucuronide metabolite are not removed in significant amounts by hemodialysis.

Other Comments

Administration advice:

• The IV formulation should be administered within 24 hours following transplantation. The IV formulation can be administered for up to 14 days.
• Patients should be switched to the oral formulation as soon as they can tolerate oral medication.
• The IV formulation should only be administered by a slow IV infusion over at least 2 hours. It should never be administered by rapid or bolus IV injection.
• The IV formulation incompatible with 0.9% normal saline, Ringers and lactated Ringers solutions, and should not be mixed or given via the same catheter with other IV drugs or admixtures.
• The oral tablets should not be crushed or chewed.
• The oral capsules should not be opened.
• Doses may be taken with or without food.
• Take a missed dose as soon as possible, except if it is closer than 2 hours to the next scheduled dose.

Storage requirements:

• Oral Tablets/Capsules: Store at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).
• Oral Suspension: Store constituted suspension at 25C (77F); excursions permitted to 15C to 30C (59F to 86F) for up to 60 days. Storage in a refrigerator at 2C to 8C (36F to 46F) is acceptable. Do not freeze.
• IV: Store powder and reconstituted infusion solution at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).

Reconstitution/preparation techniques:

• The manufacturer product information should be consulted.

Monitoring:

• Advise patients that this drug can affect the ability to drive or operate machines and if possible to avoid driving or operating machines if they experience somnolence, confusion, dizziness, tremor or hypotension during treatment.
• Advise men that they should not donate semen during therapy and for 90 days after treatment.
• Advise patients that they should not donate blood during therapy and for at least 6 weeks following discontinuation.
• Patients should be monitored for the development of neutropenia.

Advise patients to contact their healthcare provider if they develop any signs and symptoms of infections.

• Advise patients to limit exposure to sunlight and ultraviolet light by wearing protective clothing and use of broad-spectrum sunscreen with high protection factor.
• Advise the patient to contact their healthcare provider if they have symptoms of gastrointestinal bleeding, or sudden onset or persistent abdominal pain.
• Inform patients to discuss first with their physician before seeking vaccines.
• Advise patients to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, or bleeding, or any other manifestation of bone marrow suppression
• Advise patients to avoid inhalation or contact of the skin or mucous membranes with the powder contained in the capsules and the oral suspension and to wash the area with soap and water in case of contact.
• CBCs should be performed weekly during the first month, then twice a month during the second and third month, and then monthly for the remainder of the first year of treatment.