|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(mye koe FEN oh late)
Generic Available (U.S.)
Yes: Capsule, tablet
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Myfortic®: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM172735.pdf
CellCept®: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM170919.pdf
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Prophylaxis of organ rejection concomitantly with cyclosporine and corticosteroids in patients receiving allogeneic renal (CellCept®, Myfortic®), cardiac (CellCept®), or hepatic (CellCept®) transplants
Use: Unlabeled
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; treatment of proliferative lupus nephritis; treatment of myasthenia gravis; prevention and treatment of graft-versus-host disease (GVHD)
Pregnancy Risk Factor
D
Pregnancy Considerations
[U.S. Boxed Warning]: Mycophenolate is associated with an increased risk of congenital malformations and spontaneous abortions when used during pregnancy. Adverse events have been reported in animal studies at doses less than the equivalent recommended human dose. Data from the National Transplantation Pregnancy Registry (NTPR) have observed an increase in structural malformations (including ear malformations) in infants born to mothers taking mycophenolate during pregnancy. Spontaneous abortions have also been noted. Females of childbearing potential should have a negative pregnancy test within 1 week prior to beginning therapy. Two reliable forms of contraception should be used beginning 4 weeks prior to, during, and for 6 weeks after therapy. The effectiveness of hormonal contraceptive agents may be affected by mycophenolate. The National Transplantation Pregnancy Registry (NTPR, Temple University) is a registry for pregnant women taking immunosuppressants following any solid organ transplant. The NTPR encourages reporting of all immunosuppressant exposures during pregnancy in transplant recipients at 877-955-6877.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is unknown if mycophenolate is excreted in human milk. Due to potentially serious adverse reactions, the decision to discontinue the drug or discontinue breast-feeding should be considered. Breast-feeding is not recommended during therapy or for 6 weeks after treatment is complete.
Contraindications
Hypersensitivity to mycophenolate mofetil, mycophenolic acid, mycophenolate sodium, or any component of the formulation; intravenous formulation is contraindicated in patients who are allergic to polysorbate 80
Warnings/Precautions
Boxed warnings:
• Experienced physician: See “Other warnings/precautions” below.
• Infections: See “Concerns related to adverse effects” below.
• Lymphoproliferative disorders: See “Concerns related to adverse effects” below.
• Pregnancy: See “Special populations” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal. Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits, tablets should not be crushed or cut, and capsules should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in the capsules and the powder for oral suspension. Caution should be exercised in the handling and preparation of solutions of intravenous mycophenolate. Avoid skin contact with the intravenous solution and reconstituted suspension. If such contact occurs, wash thoroughly with soap and water, rinse eyes with plain water.
Concerns related to adverse effects:
• Infections: [U.S. Boxed Warning]: Risk for infection is increased. Immunosuppressive therapy may lead to opportunistic infections, sepsis, and/or fatal infections.
• Latent viral infections: Patients receiving immunosuppressive therapy are at an increased risk of activation of latent viral infections, including John Cunningham virus (JCV) and BK virus infection. Activation of JCV may result in progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal condition affecting the CNS. Symptoms of PML include apathy, ataxia, cognitive deficiencies, confusion, and hemiparesis. Activation of BK virus may result in BK virus-associated nephropathy (BKVAN) which may lead to the deterioration of renal function and/or renal graft loss. Risk factors for the development of PML and BKVAN include immunosuppression and treatment with immunosuppressant therapy. The onset of PML or BKVAN may warrant a reduction in immunosuppressive therapy; however, in transplant recipients, the risk of reduced immunosuppression and graft rejection should be considered.
• Lymphoproliferative disorders: [U.S. Boxed Warning]: Risk of development of lymphoma and skin malignancy is increased. Patients should be monitored appropriately, instructed to limit exposure to sunlight/UV light, and given supportive treatment should these conditions occur.
• Neutropenia: Neutropenia (including severe neutropenia) may occur, requiring dose reduction or interruption of treatment (risk greater from day 31-180 post-transplant).
• Pure red cell aplasia (PRCA): PRCA, a type of anemia which can range from subclinical to severe, has been reported in patients receiving mycophenolate concomitantly with other immunosuppressive agents (eg, tacrolimus, cyclosporine, corticosteroids). Symptoms may include fatigue, lethargy, or pallor. Although not precisely known, risk factors for the development of PRCA may include immunosuppression and treatment with immunosuppressant therapy. Dose reduction or discontinuation of immunosuppressive therapy may reverse PRCA; however, in transplant recipients, the risk of reduced immunosuppression and graft rejection should be considered.
Disease-related concerns:
• Hypoxanthine-guanine phosphoribosyltransferase deficiency: Theoretically, use should be avoided in patients with the rare hereditary deficiency of hypoxanthine-guanine phosphoribosyltransferase (such as Lesch-Nyhan or Kelley-Seegmiller syndrome).
• Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease; use may rarely be associated with gastric or duodenal ulcers, GI bleeding and/or perforation.
• Renal impairment: Use with caution in patients with renal impairment as toxicity may be increased; may require dosage adjustment in severe impairment.
Dosage form specific issues:
• Non-interchangeability of forms: Note: CellCept® and Myfortic® dosage forms should not be used interchangeably due to differences in absorption.
• Phenylalanine: Some dosage forms may contain phenylalanine.
Special populations:
• Pregnancy: [U.S. Boxed Warning]: Mycophenolate is associated with an increased risk of congenital malformations and spontaneous abortions when used during pregnancy. Females of childbearing potential should have a negative pregnancy test within 1 week prior to beginning therapy. Two reliable forms of contraception should be used beginning 4 weeks prior to, during, and for 6 weeks after therapy.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of a physician experienced in immunosuppressive therapy.
• I.V. administration: Intravenous solutions should be given over at least 2 hours; never administer intravenous solution by rapid or bolus injection.
Adverse Reactions
Data for incidence >20% as reported in adults following oral dosing of CellCept® alone in renal, cardiac, and hepatic allograft rejection studies. Profile in 3% to <20% range reflects use in combination with cyclosporine and corticosteroids. In general, lower doses used in renal rejection patients had less adverse effects than higher doses. Rates of adverse effects were similar for each indication, except for those unique to the specific organ involved. The type of adverse effects observed in pediatric patients was similar to those seen in adults, with the exception of abdominal pain, anemia, diarrhea, fever, hypertension, infection, pharyngitis, respiratory tract infection, sepsis, and vomiting; lymphoproliferative disorder was the only type of malignancy observed. Percentages of adverse reactions were similar in studies comparing CellCept® to Myfortic® in patients following renal transplant.
>20%:
Cardiovascular: Hypertension (28% to 78%), hypotension (33%), peripheral edema (27% to 64%), edema (27% to 28%), chest pain (26%), tachycardia (20% to 22%)
Central nervous system: Pain (31% to 76%), headache (16% to 54%), insomnia (41% to 52%), fever (21% to 52%), dizziness (29%), anxiety (28%)
Dermatologic: Rash (22%)
Endocrine & metabolic: Hyperglycemia (44% to 47%), hypercholesterolemia (41%), hypomagnesemia (39%), hypokalemia (32% to 37%), hypocalcemia (30%), hyperkalemia (22%)
Gastrointestinal: Abdominal pain (25% to 63%), nausea (20% to 55%), diarrhea (31% to 51%), constipation (19% to 41%), vomiting (33% to 34%), anorexia (25%), dyspepsia (22%)
Genitourinary: Urinary tract infection (37%)
Hematologic: Leukopenia (23% to 46%), anemia (26% to 43%; hypochromic 25%), leukocytosis (22% to 41%), thrombocytopenia (24% to 38%)
Hepatic: Liver function tests abnormal (25%), ascites (24%)
Neuromuscular & skeletal: Back pain (35% to 47%), weakness (35% to 43%), tremor (24% to 34%), paresthesia (21%)
Renal: Creatinine increased (39%), BUN increased (35%), kidney function abnormal (22% to 26%)
Respiratory: Dyspnea (31% to 37%), respiratory tract infection (22% to 37%), pleural effusion (34%), cough (31%), lung disorder (22% to 30%), sinusitis (26%)
Miscellaneous: Infection (18% to 27%), sepsis (27%), lactate dehydrogenase increased (23%), Candida (17% to 22%), herpes simplex (10% to 21%)
3% to <20%:
Cardiovascular: Angina, arrhythmia, arterial thrombosis, atrial fibrillation, atrial flutter, bradycardia, cardiac arrest, cardiac failure, CHF, extrasystole, facial edema, hyper-/hypovolemia, pallor, palpitation, pericardial effusion, peripheral vascular disorder, postural hypotension, supraventricular extrasystoles, supraventricular tachycardia, syncope, thrombosis, vasodilation, vasospasm, venous pressure increased, ventricular extrasystole, ventricular tachycardia
Central nervous system: Agitation, chills with fever, confusion, delirium, depression, emotional lability, hallucinations, hypoesthesia, malaise, nervousness, psychosis, seizure, somnolence, thinking abnormal, vertigo
Dermatologic: Acne, alopecia, bruising, cellulitis, fungal dermatitis, hirsutism, petechia, pruritus, skin carcinoma, skin hypertrophy, skin ulcer, vesiculobullous rash
Endocrine & metabolic: Acidosis, alkalosis, Cushing's syndrome, dehydration, diabetes mellitus, gout, hypercalcemia, hyper-hypophosphatemia, hyperlipemia, hyperuricemia, hypochloremia, hypoglycemia, hyponatremia, hypoproteinemia, hypothyroidism, parathyroid disorder
Gastrointestinal: Abdomen enlarged, dysphagia, esophagitis, flatulence, gastritis, gastroenteritis, gastrointestinal hemorrhage, gastrointestinal moniliasis, gingivitis, gum hyperplasia, ileus, melena, mouth ulceration, oral moniliasis, stomach disorder, stomach ulcer, stomatitis, xerostomia, weight gain/loss
Genitourinary: Impotence, nocturia, pelvic pain, prostatic disorder, scrotal edema, urinary frequency, urinary incontinence, urinary retention, urinary tract disorder
Hematologic: Coagulation disorder, hemorrhage, neutropenia, pancytopenia, polycythemia, prothrombin time increased, thromboplastin time increased
Hepatic: Alkaline phosphatase increased, bilirubinemia, cholangitis, cholestatic jaundice, GGT increased, hepatitis, jaundice, liver damage, transaminases increased
Local: Abscess
Neuromuscular & skeletal: Arthralgia, hypertonia, joint disorder, leg cramps, myalgia, myasthenia, neck pain, neuropathy, osteoporosis
Ocular: Amblyopia, cataract, conjunctivitis, eye hemorrhage, lacrimation disorder, vision abnormal
Otic: Deafness, ear disorder, ear pain, tinnitus
Renal: Albuminuria, creatinine increased, dysuria, hematuria, hydronephrosis, oliguria, pyelonephritis, renal failure, renal tubular necrosis
Respiratory: Apnea, asthma, atelectasis, bronchitis, epistaxis, hemoptysis, hiccup, hyperventilation, hypoxia, respiratory acidosis, pharyngitis, pneumonia, pneumothorax, pulmonary edema, pulmonary hypertension, respiratory moniliasis, rhinitis, sputum increased, voice alteration
Miscellaneous: Candida (mucocutaneous 16% to 18%), CMV viremia/syndrome (12% to 14%), CMV tissue invasive disease (6% to 12%), herpes zoster cutaneous disease (4% to 10%), cyst, diaphoresis, flu-like syndrome, healing abnormal, hernia, ileus infection, neoplasm, peritonitis, thirst
Postmarketing and/or case reports: Atypical mycobacterial infection, BK virus-associated nephropathy, colitis, gastrointestinal perforation, infectious endocarditis, interstitial lung disorder, intestinal villous atrophy, lymphoma, lymphoproliferative disease, malignancy, meningitis, pancreatitis, progressive multifocal leukoencephalopathy (sometimes fatal), pulmonary fibrosis (fatal), pure red cell aplasia, tuberculosis
Metabolism/Transport Effects
None known.
Drug Interactions
Acyclovir-Valacyclovir: Mycophenolate may increase the serum concentration of Acyclovir-Valacyclovir. Acyclovir-Valacyclovir may increase the serum concentration of Mycophenolate. Risk C: 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. Risk D: Consider therapy modification
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Belatacept: May increase serum concentrations of the active metabolite(s) of Mycophenolate. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the serum concentration of Mycophenolate. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification
CycloSPORINE: May decrease the serum concentration of Mycophenolate. Specifically, cyclosporine may decrease concentrations of the active metabolite mycophenolic acid. Risk D: Consider therapy modification
CycloSPORINE (Systemic): May decrease the serum concentration of Mycophenolate. Specifically, cyclosporine may decrease concentrations of the active metabolite mycophenolic acid. Risk D: Consider therapy modification
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Ganciclovir-Valganciclovir: Mycophenolate may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Mycophenolate. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification
MetroNIDAZOLE: May decrease the serum concentration of Mycophenolate. Specifically, metronidazole may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
MetroNIDAZOLE (Systemic): May decrease the serum concentration of Mycophenolate. Specifically, metronidazole may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Penicillins: May decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Probenecid: May increase the serum concentration of Mycophenolate. Risk D: Consider therapy modification
Proton Pump Inhibitors: May decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Risk C: Monitor therapy
Quinolone Antibiotics: May decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Mycophenolate. Specifically, rifamycin derivatives may decrease the concentration of the active metabolite mycophenolic acid. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Sevelamer: May decrease the serum concentration of Mycophenolate. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. 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. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Food: Food decreases Cmax of MPA by 40% following CellCept® administration and 33% following Myfortic® use; the extent of absorption is not changed. Management: May be taken with food if necessary in stable patients; otherwise, take on an empty stomach to decrease variability.
Herb/Nutraceutical: Cat's claw and echinacea have immunostimulant properties. Management: Avoid cat's claw and echinacea.
Storage
Capsules: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Tablets: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture and light.
Oral suspension: Store powder for oral suspension at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Once reconstituted, the oral solution may be stored at room temperature or under refrigeration. Do not freeze. The mixed suspension is stable for 60 days.
Injection: Store intact vials and diluted solutions at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Begin infusion within 4 hours of reconstitution.
Reconstitution
Oral suspension: Should be constituted prior to dispensing to the patient and not mixed with any other medication. Add 47 mL of water to the bottle and shake well for ~1 minute. Add another 47 mL of water to the bottle and shake well for an additional minute. Final concentration is 200 mg/mL of mycophenolate mofetil.
I.V.: Reconstitute the contents of each vial with 14 mL of 5% dextrose injection; dilute the contents of a vial with 5% dextrose in water to a final concentration of 6 mg mycophenolate mofetil per mL. Note: Vial is vacuum-sealed; if a lack of vacuum is noted during preparation, the vial should not be used.
Compatibility
Stable in D5W.
Y-site administration: Compatible: Anidulafungin, caspofungin, cefepime, dopamine, norepinephrine, tacrolimus, vancomycin. Incompatible: Micafungin. Variable (consult detailed reference): Cyclosporine.
Mechanism of Action
MPA exhibits a cytostatic effect on T and B lymphocytes. It is an inhibitor of inosine monophosphate dehydrogenase (IMPDH) which inhibits de novo guanosine nucleotide synthesis. T and B lymphocytes are dependent on this pathway for proliferation.
Pharmacodynamics/Kinetics
Onset of action: 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
Absorption: AUC values for MPA are lower in the early post-transplant period versus later (>3 months) post-transplant period. The extent of absorption in pediatrics is similar to that seen in adults, although there was wide variability reported.
Oral: Myfortic®: 93%
Distribution:
CellCept®: MPA: Oral: 4 L/kg; I.V.: 3.6 L/kg
Myfortic®: MPA: Oral: 54 L (at steady state); 112 L (elimination phase)
Protein binding: MPA: >97%, MPAG 82%
Metabolism: Hepatic and via GI tract; CellCept® is completely hydrolyzed in the liver to mycophenolic acid (MPA; active metabolite); enterohepatic recirculation of MPA may occur; MPA is glucuronidated to MPAG (inactive metabolite)
Bioavailability: Oral: CellCept®: 94%; Myfortic®: 72%
Half-life elimination:
CellCept®: MPA: Oral: 18 hours; I.V.: 17 hours
Myfortic®: MPA: Oral: 8-16 hours; MPAG: 13-17 hours
Time to peak, plasma: Oral: MPA:
CellCept®: 1-1.5 hours
Myfortic®: 1.5-2.75 hours
Excretion:
CellCept®: MPA: Urine (<1%), feces (6%); MPAG: Urine (87%)
Myfortic®: MPA: Urine (3%), feces; MPAG: Urine (>60%)
Dosage
Children: Renal transplant: Oral:
CellCept® suspension: 600 mg/m2/dose twice daily; maximum dose: 1 g twice daily
Alternatively, may use solid dosage forms according to BSA as follows:
BSA 1.25-1.5 m2: 750 mg capsule twice daily
BSA >1.5 m2: 1 g capsule or tablet twice daily
Myfortic®: 400 mg/m2/dose twice daily; maximum dose: 720 mg twice daily
BSA <1.19 m2: Use of this formulation is not recommended
BSA 1.19-1.58 m2: 540 mg twice daily (maximum: 1080 mg/day)
BSA >1.58 m2: 720 mg twice daily (maximum: 1440 mg/day)
Adults: Note: May be used I.V. for up to 14 days; transition to oral therapy as soon as tolerated.
Renal transplant:
CellCept®:
Oral: 1 g twice daily. Doses >2 g/day are not recommended.
I.V.: 1 g twice daily
Myfortic®: Oral: 720 mg twice daily (1440 mg/day)
Cardiac transplantation:
Oral (CellCept®): 1.5 g twice daily
I.V. (CellCept®): 1.5 g twice daily
Hepatic transplantation:
Oral (CellCept®): 1.5 g twice daily
I.V. (CellCept®): 1 g twice daily
Lupus nephritis (unlabeled use): Oral: 0.5-3 g/day (Contreras, 2004; Ong, 2005)
Myasthenia gravis (unlabeled use): Oral (CellCept®): 1 g twice daily (range: 1-3 g/day) (Cahoon, 2006; Ciafaloni, 2001; Merriggioli, 2003)
Psoriasis (unlabeled use): Oral: 2-3 g/day (Menter, 2009)
Elderly: Dosage is the same as younger patients, however, dosing should be cautious due to possibility of increased hepatic, renal or cardiac dysfunction; elderly patients may be at an increased risk of certain infections, gastrointestinal hemorrhage, and pulmonary edema, as compared to younger patients
Dosing adjustment for toxicity (neutropenia): Neutropenia (ANC <1.3 x 103/μL): Dosing should be interrupted or the dose reduced, appropriate diagnostic tests performed and patients managed appropriately
Dosing adjustment in renal impairment:
Renal transplant: GFR <25 mL/minute/1.73 m2 in patients outside the immediate post-transplant period:
CellCept®: 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
Myfortic®: No dose adjustments are needed in renal transplant patients experiencing delayed graft function postoperatively; however, monitor carefully for potential concentration dependent adverse events
Cardiac or liver transplant: No data available; mycophenolate may be used in cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefit outweighs the potential risk
Hemodialysis: Not removed; supplemental dose is not necessary
Peritoneal dialysis: Supplemental dose is not necessary
Dosage adjustment in hepatic impairment: No dosage adjustment is recommended for renal patients with severe hepatic parenchymal disease; however, it is not currently known whether dosage adjustments are necessary for hepatic disease with other etiologies
Administration: Oral
Oral dosage formulations (tablet, capsule, suspension) should be administered on an empty stomach 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.
Administration: I.V.
Intravenous solutions should be given over at least 2 hours. Do not administer intravenous solution by rapid or bolus injection.
Administration: I.V. Detail
Reconstituted solution: pH 2.4-4.1
Monitoring Parameters
Complete blood count (weekly for first month, twice monthly during months 2 and 3, then monthly thereafter through the first year); renal and liver function; signs and symptoms of infection; pregnancy test (prior to initiation in females of childbearing potential)
Dietary Considerations
Oral dosage formulations should be taken on an empty stomach to avoid variability in MPA absorption. However, in stable renal transplant patients, may be administered with food if necessary. Some products may contain phenylalanine.
Patient Education
Take oral formulations as directed, preferably 1 hour before or 2 hours after meals. Do not cut, chew, or crush delayed-release tablets. You will be susceptible to infection. You may be at increased risk for skin cancer. If you have diabetes, monitor glucose levels closely (drug may alter glucose levels). You may experience dizziness or trembling, trouble sleeping, nausea or vomiting, diarrhea, sores or white plaques in mouth, or muscle or back pain. Report chest pain; irregular or rapid heartbeat; acute headache or dizziness; swelling of extremities; unusual weight gain; symptoms of respiratory infection, cough, or respiratory difficulty; abdominal pain or unresolved GI effects; unusual weakness; fatigue, chills, or fever; unhealed sores or white plaques in mouth; irritation in genital area or unusual discharge; change in mental status, memory loss, or loss of coordination or clumsiness; weakness in legs; difficulty speaking or understanding what others say; or unusual bruising or bleeding.
Cardiovascular Considerations
Hypertension may accompany the use of mycophenolate in patients post-transplantation. Furthermore, this drug may also induce increases in cholesterol, increases in serum phosphate, hyperkalemia, and hyperglycemia.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Mouth ulceration, gum hyperplasia, gingivitis, dry mouth, dysphagia, oral moniliasis, and stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness and insomnia are common
Mental Health: Effects on Psychiatric Treatment
Leukopenia is common; avoid clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Monitor blood pressure periodically while receiving this medication. Assess for peripheral edema and other signs of fluid retention. Patients with diabetes should monitor glucose levels closely (this medication may alter glucose levels). Monitor for signs of opportunistic infection. Patient is at risk for lymphoproliferative disease and certain other malignancies; monitor closely.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral, as mofetil: 250 mg
CellCept®: 250 mg
Injection, powder for reconstitution, as mofetil hydrochloride:
CellCept®: 500 mg [contains polysorbate 80]
Powder for suspension, oral, as mofetil:
CellCept®: 200 mg/mL (175 mL) [contains phenylalanine 0.56 mg/mL, soybean lecithin; mixed fruit flavor]
Tablet, oral, as mofetil: 500 mg
CellCept®: 500 mg [contains ethanol (may have trace amounts)]
Tablet, oral, as mycophenolic acid: 500 mg
Tablet, delayed release, oral, as mycophenolic acid:
Myfortic®: 180 mg, 360 mg [formulated as a sodium salt]
Pricing: U.S. (www.drugstore.com)
Capsules (CellCept)
250 mg (30): $166.00
Capsules (Mycophenolate Mofetil)
250 mg (30): $35.99
Suspension (reconstituted) (CellCept)
200 mg/mL (160): $909.96
Tablet, EC (Myfortic)
360 mg (120): $949.00
Tablets (CellCept)
500 mg (100): $951.33
Tablets (Mycophenolate Mofetil)
500 mg (100): $129.99
Extemporaneously Prepared
Hazardous agent: Use appropriate precautions for handling and disposal.
A 50 mg/mL oral suspension may be made with mycophenolate mofetil capsules, Ora-Plus®, and cherry syrup. In a vertical flow hood, empty six 250 mg capsules into a mortar; add 7.5 mL Ora-Plus® and mix to a uniform paste. Mix while adding 15 mL of cherry syrup in incremental proportions; transfer to a calibrated bottle, rinse mortar with cherry syrup, and add sufficient quantity of cherry syrup to make 30 mL. Label "shake well". Stable for 210 days at 5°C, for 28 days at 25°C to 37°C, and for 11 days at 45°C.
Venkataramanan R, McCombs JR, Zuckerman S, et al, "Stability of Mycophenolate Mofetil as an Extemporaneous Suspension," Ann Pharmacother, 1998, 32(7-8):755-7.
References
Bertsias G, Ioannidis JP, Boletis J, et al, “EULAR Recommendations for the Management of Systemic Lupus Erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics,” Ann Rheum Dis, 2008, 67(2):195-205.
Cahoon WD Jr and Kockler DR, “Mycophenolate Mofetil Treatment of Myasthenia Gravis,” Ann Pharmacother, 2006, 40(2):295-8.
Chaudhry V, Cornblath DR, Griffin JW, et al, “Mycophenolate Mofetil: A Safe and Promising Immunosuppressant in Neuromuscular Diseases,” Neurology, 2001, 56(1):94-6.
Ciafaloni E, Massey JM, Tucker-Lipscomb B, et al, “Mycophenolate Mofetil for Myasthenia Gravis: An Open-Label Pilot Study,” Neurology, 2001, 56(1):97-9.
Contreras G, Pardo V, Leclercq B, et al, “Sequential Therapies for Proliferative Lupus Nephritis,” N Engl J Med, 2004, 350(10):971-80.
Dooley MA, Jayne D, Ginzler EM, et al, “Mycophenolate versus Azathioprine as Maintenance Therapy for Lupus Nephritis,” N Engl J Med, 2011, 365(20):1886-95.
Ettenger R, Warshaw B, Menster M, et al, “Mycophenolate Mofetil (MMF) in Pediatric (Ped) Renal Transplantation (Tx): A Report of the Ped MMF Study Group (PMMSG),” 1996:97 [abstract 97 from ASTP Annual Meeting].
Gabardi S, Tran JL, and Clarkson MR, “Enteric-Coated Mycophenolate Sodium,” Ann Pharmacother, 2003, 37(11):1685-93.
Lipsky JJ, “Mycophenolate Mofetil,” Lancet, 1996, 348(9038):1357-9.
Menter A, Korman NJ, Elmets CA, et al, “Guidelines of Care for the Management of Psoriasis and Psoriatic Arthritis: Section 4. Guidelines of Care for the Management and Treatment of Psoriasis With Traditional Systemic Agents,” J Am Acad Dermatol, 2009, 61(3):451-85.
Meriggioli MN, Ciafaloni E, Al-Hayk KA, et al, “Mycophenolate Mofetil for Myasthenia Gravis: An Analysis of Efficacy, Safety, and Tolerability,” Neurology, 2003, 61(10):1438-40.
Ong LM, Hooi LS, Lim TO, et al, “Randomized Controlled Trial of Pulse Intravenous Cyclophosphamide versus Mycophenolate Mofetil in the Induction Therapy of Proliferative Lupus Nephritis,” Nephrology (Carlton), 2005, 10(5):504-10.
Shaw LM, Sollinger HW, Halloran P, et al, “Mycophenolate Mofetil: A Report of the Consensus Panel,” Ther Drug Monit, 1995, 17(6):690-9.
Sifontis NM, Coscia LA, Constantinescu S, et al, “Pregnancy Outcomes in Solid Organ Transplant Recipients With Exposure to Mycophenolate Mofetil or Sirolimus,” Transplantation, 2006, 82(12):1698-702.
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.
Vogelsang GB, and Arai S, “Mycophenolate Mofetil for the Prevention and Treatment of Graft-Versus-Host Disease Following Stem Cell Transplantation: Preliminary Findings,” Bone Marrow Transplant, 2001, 27(12):1255-62.
Zhu B, Chen N, Lin Y, et al, “Mycophenolate Mofetil in Induction and Maintenance Therapy of Severe Lupus Nephritis: A Meta-Analysis of Randomized Controlled Trials,” Nephrol Dial Transplant, 2007, 22(7):1933-42.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
|
