Mycophenolate

Renal Allotransplantation

Prevention of rejection of renal allografts.1 3 4 5 6 12 27

Cardiac Allotransplantation

Prevention of rejection of cardiac allografts.1 7

Hepatic Allotransplantation

Prevention of rejection of liver allografts.1 9

Crohn’s Disease

Has been used in the management of Crohn’s Disease†.13 14 15 16 18 20 21 22 23 24 25 Not a first-line agent; reserved for patients who are refractory to or intolerant of other agents (e.g., azathioprine, mercaptopurine, methotrexate, infliximab).14 23

Absorption

Bioavailability

Mycophenolate mofetil: Rapidly absorbed following oral administration; bioavailability is 94%.1

Following oral and IV administration, mycophenolate mofetil undergoes rapid and complete metabolism to mycophenolic acid, the active metabolite.1

Mycophenolate sodium: Following oral administration of the delayed-release tablets, mycophenolic acid is released in the small intestine; bioavailability is 72%.27

Mycophenolate mofetil tablets, capsules, and oral suspension are bioequivalent.1 12

Mycophenolate sodium delayed-release tablets cannot be used interchangeably with mycophenolate mofetil tablets, capsules, or oral suspension without clinician supervision.27 Single oral doses of mycophenolate sodium delayed-release tablets (mycophenolic acid 720 mg) and mycophenolate mofetil 1 g result in bioequivalent mycophenolic acid exposure.28

Food

Food decreases peak plasma concentrations of mycophenolic acid (by 33–40%); no effect on the mycophenolic acid AUC.1 27

Special Populations

Plasma concentrations of free (unbound) mycophenolic acid and total mycophenolic acid glucuronide have increased in nontransplant individuals with severe chronic renal impairment (GFR <25 mL/minute per 1.73 m2).1 Plasma mycophenolic acid concentrations in patients with delayed graft function similar to values in patients not experiencing delayed graft function.1

Pharmacokinetic parameters, including AUC, in children 1–18 years of age receiving mycophenolate mofetil 600 mg/m2 (oral suspension) twice daily following renal transplantation similar to values in adult renal transplant recipients receiving 1 g twice daily.1

Peak plasma concentrations and AUC of mycophenolic acid in stable pediatric renal transplant patients 5–16 years of age receiving a single dose of mycophenolate sodium (mycophenolic acid 450 mg/m2) increased (33 and 18%, respectively) relative to adults receiving the same dose based on body surface area.27 Clinical importance not determined.27

Distribution

Plasma Protein Binding

Mycophenolic acid: ≥97–98% (mainly albumin).1 27

Elimination

Metabolism

Mycophenolate mofetil undergoes complete metabolism to mycophenolic acid; metabolism occurs presystemically following oral administration.1 Mycophenolic acid is metabolized by glucuronyl transferase to the phenolic glucuronide of mycophenolic acid.1 27 The phenolic glucuronide is converted to mycophenolic acid via enterohepatic recirculation.1 27

Elimination Route

Mycophenolate mofetil: Excreted in urine (93%) as the phenolic glucuronide of mycophenolic acid (87%) and in feces (6%).1

Mycophenolate sodium: Excreted principally in urine as phenolic glucuronide of mycophenolic acid (>60%) and as unchanged mycophenolic acid (3%).27

Half-life

Mycophenolic acid: 8–17.9 hours.1 27

Special Populations

Plasma concentrations of mycophenolic acid glucuronide higher in nontransplant subjects with severe renal impairment than in those with mild impairment or normal renal function.1 27

Plasma concentrations of mycophenolic acid glucuronide higher in transplant patients with delayed renal graft function than in patients not experiencing delayed graft function.1

Dialysis does not remove mycophenolic acid.1 27

Pharmacokinetic studies in patients with alcoholic cirrhosis indicate that hepatic mycophenolic acid glucuronidation is not affected by hepatic parenchymal disease; hepatic disease with other etiologies (e.g., biliary cirrhosis) may show a different effect.1

Renal, Cardiac, and Hepatic Transplant

Mycophenolate mofetil capsules USP and Mycophenolate mofetil tablets USP are indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants. Mycophenolate mofetil, USP should be used concomitantly with cyclosporine and corticosteroids.

(See boxed WARNING.)

Embryofetal Toxicity

Mycophenolate mofetil (MMF) can cause fetal harm when administered to a pregnant female. 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 (see PRECAUTIONS, Pregnancy).

Pregnancy Exposure Prevention and Planning

Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning. For recommended pregnancy testing and contraception methods (see PRECAUTIONS, Pregnancy Exposure Prevention and Planning).

Lymphoma and Malignancy

Patients receiving immunosuppressive regimens involving combinations of drugs, including Mycophenolate mofetil, as part of an immunosuppressive regimen are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see ADVERSE REACTIONS). The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent.

As usual for patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.

Lymphoproliferative disease or lymphoma 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 renal, cardiac, and hepatic transplant patients (see ADVERSE REACTIONS).

In pediatric patients, no other malignancies besides lymphoproliferative disorder (2/148 patients) have been observed (see ADVERSE REACTIONS).

Combination With Other Immunosuppressive Agents

Mycophenolate mofetil has been administered in combination with the following agents in clinical trials: antithymocyte globulin (ATGAM®), OKT3 (Orthoclone OKT® 3), cyclosporine (Sandimmune®, Neoral®) and corticosteroids. The efficacy and safety of the use of Mycophenolate mofetil in combination with other immunosuppressive agents have not been determined.

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. These infections may lead to serious, including fatal outcomes. Because of the danger of oversuppression of the immune system which can increase susceptibility to infection, combination immunosuppressant therapy should be used with caution (see ADVERSE REACTIONS).

New or Reactivated Viral Infections

Polyomavirus associated nephropathy (PVAN), JC virus associated progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV) infections, reactivation of hepatitis B (HBV) or hepatitis C (HCV) have been reported in patients treated with immunosuppressants, including Mycophenolate mofetil. Reduction in immunosuppression should be considered for patients who develop evidence of new or reactivated viral infections. Physicians should also consider 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, Postmarketing Experience). 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. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function (see ADVERSE REACTIONS, Postmarketing Experience). In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms and consultation with a neurologist should be considered as clinically indicated.

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.

Neutropenia

Severe neutropenia [absolute neutrophil count (ANC) < 0.5 x 103/µL] developed in up to 2.0% of renal, up to 2.8% of cardiac, and up to 3.6% of hepatic transplant patients receiving Mycophenolate mofetil 3 g daily (see ADVERSE REACTIONS). Patients receiving Mycophenolate mofetil should be monitored for neutropenia (see PRECAUTIONS, Laboratory Tests). The development of neutropenia may be related to Mycophenolate mofetil itself, concomitant medications, viral infections, or some combination of these causes. If neutropenia develops (ANC < 1.3 x 103/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). Neutropenia has been observed most frequently in the period from 31 to 180 days posttransplant in patients treated for prevention of renal, cardiac, and hepatic rejection.

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.

Pure Red Cell Aplasia (PRCA)

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with Mycophenolate mofetil in combination with other immunosuppressive agents. The mechanism for Mycophenolate mofetil induced PRCA is unknown; the relative contribution of other immunosuppressants and their combinations in an immunosuppression regimen are also unknown. In some cases, PRCA was found to be reversible with dose reduction or cessation of Mycophenolate mofetil therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk.

Renal Transplantation

A dose of 1 g administered orally twice a day (daily dose of 2 g) is recommended for use in renal transplant patients. Although a dose of 1.5 g administered twice daily (daily dose of 3 g) was used in clinical trials and was shown to be safe and effective, no efficacy advantage could be established for renal transplant patients. Patients receiving 2 g/day of Mycophenolate mofetil demonstrated an overall better safety profile than did patients receiving 3 g/day of Mycophenolate mofetil.

The recommended dose of Mycophenolate mofetil oral suspension is 600 mg/m2 administered twice daily (up to a maximum daily dose of 2 g/10 mL oral suspension). Patients with a body surface area of 1.25 m2 to 1.5 m2 may be dosed with Mycophenolate mofetil capsules at a dose of 750 mg twice daily (1.5 g daily dose). Patients with a body surface area > 1.5 m2 may be dosed with Mycophenolate mofetil capsules or tablets at a dose of 1 g twice daily (2 g daily dose).

Cardiac Transplantation

A dose of 1.5 g bid oral (daily dose of 3 g) is recommended for use in adult cardiac transplant patients.

Hepatic Transplantation

A dose of 1.5 g bid oral (daily dose of 3 g) is recommended for use in adult hepatic transplant patients.

Mycophenolate Mofetil Capsules and Tablets

The initial oral dose of Mycophenolate mofetil capsules or Mycophenolate mofetil tablets should be given as soon as possible following renal, cardiac or hepatic transplantation. Food had no effect on MPA AUC, but has been shown to decrease MPA Cmax by 40%. Therefore, it is recommended that Mycophenolate mofetil capsules and Mycophenolate mofetil tablets be administered on an empty stomach. However, in stable renal transplant patients, Mycophenolate mofetil capsules and Mycophenolate mofetil tablets may be administered with food if necessary.

Patients should be instructed to take a missed dose as soon as they remember, except if it is near the next scheduled dose, and then continue to take Mycophenolate mofetil at the usual times.

Note:

If required, Mycophenolate mofetil oral suspension can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter).

No dose adjustments are recommended for renal patients with severe hepatic parenchymal disease. However, it is not known whether dose adjustments are needed for hepatic disease with other etiologies (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

No data are available for cardiac transplant patients with severe hepatic parenchymal disease.

The recommended oral dose of 1 g bid for renal transplant patients, 1.5 g bid for cardiac transplant patients, and 1.5 g bid administered orally in hepatic transplant patients is appropriate for elderly patients (see PRECAUTIONS, Geriatric Use).

Dosage Adjustments

In renal transplant patients with severe chronic renal impairment (GFR < 25 mL/min/1.73 m2) outside the immediate posttransplant period, doses of Mycophenolate mofetil capsules or Mycophenolate mofetil tablets greater than 1 g administered twice a day should be avoided. These patients should also be carefully observed. No dose adjustments are needed in renal transplant patients experiencing delayed graft function postoperatively (see CLINICAL PHARMACOLOGY, Pharmacokinetics and PRECAUTIONS, Patients With Renal Impairment).

No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment. Mycophenolate mofetil capsules and Mycophenolate mofetil tablets may be used for cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.

If neutropenia develops (ANC < 1.3 x 103/µL), dosing with Mycophenolate mofetil capsules and Mycophenolate mofetil tablets should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately (see WARNINGS, Neutropenia; ADVERSE REACTIONS; and PRECAUTIONS, Laboratory Tests).

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as mofetil:

CellCept: 250 mg [contains fd&c blue #2 (indigotine)]

Generic: 250 mg

Solution Reconstituted, Intravenous, as mofetil hydrochloride:

CellCept Intravenous: 500 mg (1 ea) [contains polysorbate 80]

Generic: 500 mg (1 ea)

Suspension Reconstituted, Oral, as mofetil:

CellCept: 200 mg/mL (160 mL) [contains aspartame, methylparaben, soybean lecithin; mixed fruit flavor]

Generic: 200 mg/mL (160 mL)

Tablet, Oral, as mofetil:

CellCept: 500 mg [contains fd&c blue #2 aluminum lake]

Generic: 500 mg

Tablet Delayed Release, Oral, as mycophenolic acid:

Myfortic: 180 mg [contains fd&c blue #2 (indigotine)]

Myfortic: 360 mg

Generic: 180 mg, 360 mg

• Immunosuppressant Agent

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

Time to Peak

Plasma: Oral: MPA:

CellCept: 1 to 1.5 hours

Myfortic: 1.5 to 2.75 hours

Half-Life Elimination

CellCept: MPA: Oral: 18 hours; IV: 17 hours

Myfortic: MPA: Oral: 8 to16 hours; MPAG: 13 to 17 hours

Protein Binding

MPA: >97%, MPAG 82%

Oral dosage formulations (tablet, capsule, suspension) should be administered on an empty stomach (1 hour before or 2 hours after meals) to avoid variability in MPA absorption. The oral solution may be administered via a nasogastric tube (minimum 8 French, 1.7 mm interior diameter); oral suspension should not be mixed with other medications. Delayed release tablets should not be crushed, cut, or chewed. Cellcept may be administered with food in stable renal transplant patients when necessary. If a dose is missed, administer as soon as it is remembered. If it is close to the next scheduled dose, skip the missed dose and resume at next regularly scheduled time; do not double a dose to make up for a missed dose.

Intravenous solutions should be administered over at least 2 hours (either peripheral or central vein); do not administer intravenous solution by rapid or bolus injection.

Acyclovir-Valacyclovir: May increase the serum concentration of Mycophenolate. Mycophenolate may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy

Antacids: May decrease the absorption of Mycophenolate. Management: Separate doses of mycophenolate and antacids by at least 2 hours. Monitor for reduced effects of mycophenolate if taken concomitant with antacids. Exceptions: Sodium Bicarbonate. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bile Acid Sequestrants: May decrease the serum concentration of Mycophenolate. Avoid combination

Cholestyramine Resin: May decrease the serum concentration of Mycophenolate. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Contraceptives (Estrogens): Mycophenolate may decrease the serum concentration of Contraceptives (Estrogens). Average AUC values were unchanged, but there was evidence of substantial patient-to-patient variability in response to this combination. Management: Women of childbearing potential who are receiving mycophenolate mofetil should consider using an alternative and/or additional form of contraception. Consider therapy modification

Contraceptives (Progestins): Mycophenolate may decrease the serum concentration of Contraceptives (Progestins). Management: Use of an additional or alternative (nonhormonal) method of contraception should be considered. Consider therapy modification

CycloSPORINE (Systemic): May decrease the serum concentration of Mycophenolate. Specifically, cyclosporine may decrease concentrations of the active metabolite mycophenolic acid. Management: Mycophenolate requirements may be greater in patients receiving cyclosporine. Monitor mycophenolate dosing and response to therapy particularly closely when adjusting concurrent cyclosporine (starting, stopping, or changing dose). Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Ganciclovir-Valganciclovir: Mycophenolate may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Mycophenolate. Monitor therapy

Isavuconazonium Sulfate: May increase the serum concentration of Mycophenolate. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Magnesium Salts: May decrease the serum concentration of Mycophenolate. Management: Separate doses of mycophenolate and oral magnesium salts. Monitor for reduced effects of mycophenolate if taken concomitant with oral magnesium salts. Consider therapy modification

MetroNIDAZOLE (Systemic): May decrease the serum concentration of Mycophenolate. Specifically, metronidazole may decrease concentrations of the active metabolite of mycophenolate. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Penicillins: May decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Probenecid: May increase the serum concentration of Mycophenolate. Monitor therapy

Proton Pump Inhibitors: May decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Monitor therapy

Quinolone Antibiotics: May decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Mycophenolate. Specifically, rifamycin derivatives may decrease the concentration of the active metabolite mycophenolic acid. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sevelamer: May decrease the serum concentration of Mycophenolate. Management: Administer mycophenolate at least 2 hours prior to sevelamer administration. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Teriflunomide: May increase the serum concentration of OAT3 Substrates. Monitor therapy

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

[US Boxed Warning]: Mycophenolate is associated with an increased risk of congenital malformations and first trimester pregnancy loss when used by pregnant women. Females of reproductive potential must be counseled about pregnancy prevention and planning. Alternative agents with less potential for embryofetal toxicity should be considered for women planning a pregnancy. The following congenital malformations have been reported following exposure during pregnancy: External ear abnormalities, cleft lip and palate, anomalies of the distal limbs, heart, esophagus, kidney, and nervous system. The combination of ear, eye, and lip/palate abnormalities has been identified as mycophenolate embryopathy (Perez-Aytes 2017). Spontaneous abortions have also been noted.

Females of reproductive potential (girls who have entered puberty and women with a uterus who have not passed through clinically confirmed menopause) should have a negative pregnancy test with a sensitivity of ≥25 milliunits/mL immediately before mycophenolate therapy and the test should be repeated 8 to 10 days later. Pregnancy tests should then be repeated during routine follow-up visits. Acceptable forms of contraception should be used during treatment and for 6 weeks after therapy is discontinued. The effectiveness of hormonal contraceptive agents may be affected by mycophenolate.

Current guidelines recommend that pregnancy be delayed following a kidney transplant until 1 year has passed without an acute rejection; this time period may be adjusted as clinically appropriate. Women planning a pregnancy and who are already taking mycophenolate following a kidney transplant should be switched to a different medication and mycophenolate should be discontinued for at least 6 weeks before pregnancy is attempted (KDIGO 2009). Mycophenolate is not recommended for the treatment of psoriasis in pregnant women (Menter 2009). Mycophenolate should not be used during pregnancy in women with lupus nephritis; women who become pregnant during mycophenolate therapy should be switched to a different medication (KDIGO 2012). For women with lupus nephritis taking mycophenolate and who are planning a pregnancy, mycophenolate should be discontinued at least 6 weeks prior to trying to conceive (Hahn 2012).

Health care providers should report female exposures to mycophenolate during pregnancy or within 6 weeks of discontinuing therapy to the Mycophenolate Pregnancy Registry (800-617-8191).

The National Transplantation Pregnancy Registry (NTPR) is a registry which follows pregnancies which occur in maternal transplant recipients or those fathered by male transplant recipients. The NTPR encourages reporting of pregnancies following solid organ transplant by contacting them at 877-955-6877 or NTPR@giftoflifeinstitute.org.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site irritation, nausea, vomiting, back pain, constipation, diarrhea, lack of appetite, joint pain, flatulence, tremors, or insomnia. Have patient report immediately to prescriber, signs of infection, signs of skin infection, signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of progressive multifocal leukoencephalopathy (confusion, depression, memory impairment, behavioral changes, change in strength on one side is greater than the other, difficulty speaking, change in balance, or vision changes), signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), angina, tachycardia, bradycardia, abnormal heartbeat, severe headache, edema, excessive weight loss, severe loss of strength and energy, burning or numbness feeling, muscle cramps, mole changes, skin growths, severe dizziness, passing out, vision changes, night sweats, severe abdominal pain, enlarged lymph nodes, pale skin, thrush, vaginitis, or jaundice (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

-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.