Dosing and uses of CellCept, Myfortic (mycophenolate)
Adult dosage forms and strengths
capsule
- 250mg
tablet
- 500mg
oral suspension
- 200mg/mL
powder for injection
- 500mg/vial
tablet, delayed release
- 180mg
- 360mg
Kidney Transplant
Prophylaxis of organ rejection in patients receiving allogeneic renal transplants; use concomitantly with cyclosporine and corticosteroids
Mycophenolate mofetil (MMF): 1 g PO/IV q12hr, infused over ≥2 hours
Mycophenolic acid (MPA): 720 mg PO q12hr
Heart Transplant
Prophylaxis of organ rejection in patients receiving allogeneic cardiac transplants; use concomitantly with cyclosporine and corticosteroids
MMF: 1.5 g PO/IV q12hr, infused over ≥2 hours
Liver Transplant
Prophylaxis of organ rejection in patients receiving allogeneic hepatic transplants; use concomitantly with cyclosporine and corticosteroids
MMF (IV): 1 g q12hr; infused over ≥2 hours
MMF (PO): 1.5 g q12hr
Dosing Modifications
Renal impairment
- MMF: In severe renal impairment (glomerular filtration rate [GFR] <25 mL/min/1.73 m²), not to exceed 1 g q12hr
- No dosage adjustment needed in renal transplant patients experiencing delayed graft function postoperatively
Lupus Nephritis (Off-label)
Induction therapy for lupus nephritis (MMF)
Induction: 1 g PO q12hr with a glucocorticoid or 2-3 g for 6 months with glucocorticoids
Maintenance: 0.5-3 g/day or 1 g PO q12hr or 1-2 g daily
Administer with initial IV corticosteroid pulse for 3 days, then prednisone 0.5-1 mg/kg/day PO; not to exceed 10 mg/day; after a few weeks, prednisone may be tapered to lowest effective dose
Pediatric dosage forms and strengths
capsule
- 250mg
tablet
- 500mg
oral suspension
- 200mg/mL
tablet, extended release
- 180mg
- 360mg
Kidney Transplant
<3 months
- Safety and efficacy not established
>3 months
- Prophylaxis of organ rejection in patients receiving allogeneic renal transplants
- MMF (suspension): 600 mg/m² PO q12hr; not to exceed 2 g/day
- MMF: BSA 1.25-1.5 m²: 750 mg capsule PO q12hr
- MMF: BSA >1.5 m²: 1 g capsule/tablet PO q12hr
- Extended-release MPA: 400 mg/m² PO q12hr; not to exceed 720 mg q12hr
CellCept, Myfortic (mycophenolate) adverse (side) effects
>10%
Hyperglycemia (44%)
Hypercholesterolemia (41%)
Hypomagnesemia (39%)
Dyspnea (37%)
Back pain (35%)
Increased blood urea nitrogen (BUN) (35%)
Leukopenia (34%)
Pleural effusion (34%)
Urinary tract infection (34%)
Increasing frequency of cough (31%)
Hypocalcemia (30%)
Hypertension (28%)
Abdominal pain (27%)
Peripheral edema (27%)
Anemia (26%)
Fever (23%)
Nausea (23%)
Hyperkalemia (22%)
Diarrhea (21%)
Infection (21%)
Headache (16%)
1-10%
Melanoma (1.6-4.2%)
Other malignancies (0.7-2.1%)
Lymphoma (0.4-1%)
Opportunistic infection (including herpes)
Neutropenia
GI bleeding
Pulmonary fibrosis
Progressive multifocal leukoencephalopathy
Postmarketing Reports
BK virus-associated nephropathy
Congenital malformations, including ear, facial, cardiac and nervous system malformations and an increased incidence of first trimester pregnancy
Colitis (sometimes caused by cytomegalovirus), pancreatitis, isolated cases of intestinal villous atrophy
Cases of pure red cell aplasia (PRCA) and hypogammaglobulinemia reported when administered in combination with other immunosuppressive agents
Warnings
Black box warnings
Increased susceptibility to infection as consequence of immunosuppression
Drug should be prescribed only by healthcare providers experienced in immunosuppressive therapy and management of renal, cardiac, or hepatic transplant patients
Patients receiving drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources
Drug increases risk of developing lymphoma and risk of skin malignancy
Myfortic and CellCept dosage form absorbed differently; not for use interchangeably
Healthcare provider responsible for maintenance therapy should have all information required for follow-up
Risk of first-trimester miscarriage and congenital malformations; after negative pregnancy test and follow-up, women of child-bearing age should use 2 forms of reliable contraception (hormone plus barrier) during entire course of mycophenolate therapy and continue until 6 weeks after drug discontinuance
Contraindications
Hypersensitivity
IV formulation (CellCept) in patients allergic to polysorbate 80
Cautions
Pure red-cell aplasia reported in patients treated with MMF or MPA in combination with other immunosuppressive agents
Avoid use in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency (Lesch-Nyhan, Kelley-Seegmiller syndrome)
Risk of miscarriage and 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 Black box warnings)
MMF PO suspension contains aspartame
MPA not indicated for hepatic or cardiac transplants
Use may be rarely associated with gastric or duodenal ulcers, GI bleeding and/or perforation
Safety and effectiveness of MPA for de novo pediatric renal transplant not established
Neutropenia may occur (may require dose reduction)
Must not be administered by rapid or bolus IV injection
Toxicity may increase in renal impairment; use caution
Serious infections and viral reactivation
- Increased risk of developing bacterial, fungal, protozoal, and new or reactivated viral infections, including opportunistic infections
- Because of danger of oversuppression of immune system, which can increase susceptibility to infection, combination immunosuppressant therapy should be used with caution
- May increase risk of new or reactivated viral infections, including polyomavirus-associated nephropathy (PVAN), JC virus-associated progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV) infections, and reactivation of hepatitis B or C
- PVAN, especially when due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss
- PML, which is sometimes fatal, typically presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia
Pregnancy and lactation
Pregnancy category: d
Can cause fetal harm when administered to pregnant female; use of MMF during pregnancy is associated with increased risk of first trimester pregnancy loss and increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of distal limbs, heart, esophagus, kidney and nervous system
Lactation: Unknown whether drug is excreted in breast milk; avoid using, or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of CellCept, Myfortic (mycophenolate)
Mechanism of action
Inhibits T- and B-cell proliferation, as well as antibody production
Acts as noncompetitive, selective, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH)
Absorption
Bioavailability: 94% (CellCept); 72% (Myfortic)
Peak plasma time: 1.5 hr
Distribution
Protein bound: 82-97%
Vd (MMF): IV, 3.6 L/kg; PO, 4.0 L/kg
Vd (MPA): Steady state, 54 L; elimination phase, 112 L
Metabolism
Metabolized via enterohepatic recirculation
Metabolites: MPA (active form; MMF is prodrug)
Elimination
Half-life (MMF): PO, 18 hr; IV, 17 hr
Half-life (MPA): PO, 8-16 hr; MPA glucuronide (MPAG), 13-17 hr
Excretion as metabolites: Urine; feces
Administration
Drug is taken on empty stomach 1 hour before or 2 hours after meals
Once dosage is stabilized, MMF can be taken with food after kidney transplant
Solid PO forms should be swallowed whole and not chewed, crushed, or split; capsules must not be opened
IV Preparation
Does not contain antibacterial preservative; therefore, reconstitution and dilution must be done aseptically in vertical laminar flow hood, with same precautions as for antineoplastic agents
Step 1
- To prepare 1-g dose, use 2 vials; to prepare 1.5-g dose, use 3 vials
- Reconstitute contents of each vial by injecting 14 mL D5W, then gently shake to dissolve
- Before diluting further, inspect resulting slightly yellow solution for particulate matter and discoloration; discard if either is observed
Step 2
- To prepare 1-g dose, further dilute contents of 2 reconstituted vials into 140 mL D5W; to prepare 1.5-g dose, further dilute contents of 3 reconstituted vials into 210 mL D5W; final concentration of both solutions is 6 mg/mL
- Inspect infusion solution for particulate matter and discoloration; discard if either is observed
IV Administration
Infuse over ≥2 hours
Do not administer via rapid or bolus injection
Storage
Infusion solution is stable for 4 hours after reconstitution and dilution
Store solution at 15-30°C (59-86°F)
