A-Z Drug Facts > Mycophenolate Mofetil/Mycophenolic Acid

Mycophenolate Mofetil / Mycophenolic Acid

Pronouncation: (my-koe-FEN-oh-late moE-feh-till/MY-koe-fen-AHL-ik)
Class: Immunosuppressive

Trade Names:
CellCept
- Capsules 250 mg
- Tablets 500 mg
- Powder for oral suspension 200 mg/mL (reconstituted)
- Powder for injection 500 mg as hydrochloride

Trade Names:
Myfortic
- Tablets, delayed-release 180 mg
- Tablets, delayed-release 360 mg

CellCept I.V. (Canada)

Pharmacology

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Inhibits immune-mediated inflammatory responses but exact mechanism is not known.

Pharmacokinetics

Absorption

Rapidly absorbed after oral administration. Mean absolute bioavailability is 94%. Food decreases MPA (active metabolite) C _max 40%.

Distribution

Protein binding is 97% (MPA) and 82% (MPAG; inactive metabolite). Mean apparent Vd is 3.6 L/kg (IV) and 4 L/kg (oral).

Metabolism

Metabolism is rapid and complete to MPA. MPA is metabolized to MPAG by glucuronyl transferase. MPAG undergoes enterohepatic recycling where it is converted to MPA.

Elimination

Mycophenolate is excreted in urine (93%, mostly as MPAG) and feces (6%). Mean apparent t _½ and plasma Cl of MPA are 17.9 h and 193 mL/min following oral administration and 16.6 h and 177 mL/min following IV administration, respectively.

Special Populations

Renal Function Impairment

MPA AUC increased 75% and MPAG AUC increased 3- to 6-fold in patients with severe renal impairment (CrCl less than 25 mL/min/1.73 m ² ). Hemodialysis usually does not remove MPA or MPAG.

Indications and Usage

CellCept

In combination with cyclosporine and corticosteroids for prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac, or hepatic transplants.

Myfortic

In combination with cyclosporine and corticosteroids for prophylaxis of organ rejection in patients receiving allogeneic renal transplants.

Contraindications

Hypersensitivity to the drug, mycophenolic acid, or any component of the drug product; people with a sensitivity to polysorbate 80 (Tween) (IV only).

Dosage and Administration

Renal Transplantation
Adults

CellCept : PO/IV 1 g (over no less than 2 h) twice daily (2 g daily dose). Myfortic delayed-release tablets: PO 720 mg twice daily on an empty stomach, 1 h before or 2 h after food ingestion.

Children

CellCept : PO 600 mg/m ² oral suspension twice daily (up to a max daily dose of 2 g per 10 mL). Patients with body surface area of 1.25 to 1.5 m ² may be dosed with CellCept capsules 750 mg twice daily (1.5 g daily dose). Patients with body surface area greater than 1.5 m ² may be dosed with CellCept capsules or tablets 1 g twice daily (2 g daily dose). Myfortic : PO 400 mg/m ² twice daily (up to a max dose of 720 mg twice daily). Patients with a body surface area of 1.19 to 1.58 m ² may be dosed either with 3 Myfortic 180 mg tablets or one 180 mg tablet plus one 360 mg tablet twice daily (1,080 mg daily dose). Patients with BSA of greater than 1.58 m ² may be dosed either with 4 Myfortic 180 mg tablets or 2 Myfortic 360 mg tablets twice daily (1,440 mg daily dose). Pediatric doses for patients with BSA less than 1.19 m ² cannot be accurately administered using currently available formulations of Myfortic tablets.

Cardiac Transplantation
Adults

CellCept : PO/IV 1.5 g (over no less than 2 h) twice daily (3 g daily dose).

Hepatic Transplantation
Adults

CellCept : PO 1.5 g twice daily (3 g daily dose). IV 1 g twice daily (over no less than 2 h).

General Advice

• For use in combination with cyclosporine and corticosteroids.
• Avoid inhalation and direct contact with skin and mucus membranes of the powder contained in the tablets, capsules, oral suspension, and injection (before and after reconstitution). If accidental skin contact occurs, wash thoroughly with soap and water. If mucus membrane contact occurs, flush thoroughly with water. If eye contact occurs, flush eyes using standard irrigation techniques. If a spill occurs, wipe up using paper towels wetted with water to removed spilled powder or suspension.

• Oral
• Two 500 mg tablets are bioequivalent to four 250 mg capsules; 5 mL of 200 mg/mL oral suspension is bioequivalent to four 250 mg capsules.
• Without health care provider supervision, mycophenolate extended-release tablets are not interchangeable with mycophenolate capsules, tablets, or oral suspension because of differences in absorption rates.
• Oral suspension contains aspartame, a source of phenylalanine. Do not administer oral suspension to patient with phenylketonuria without first discussing with health care provider.
• Administer first dose as soon as possible after transplantation.
• Administer prescribed dose twice daily, preferably every 12 h.
• Administer tablets, capsules, or oral suspension on an empty stomach, 1 h before or 2 h after food ingestion. May administer with food if necessary in stable renal transplant patient.
• Administer extended-release tablets on an empty stomach, 1 h before or 2 h after food ingestion. Caution patient to swallow tablets whole and not to crush, chew, or cut tablets.
• Shake suspension well before measuring dose. Measure and administer prescribed dose using supplied oral dispenser. Have patient swallow a glass of water immediately after taking the suspension.
• Do not mix oral suspension with any other medication.
• Oral suspension may be administered via nasogastric tube with a minimum size of 8 French.

• Injection
• Injection is for patient unable to take capsules, tablets, or oral suspension. Switch patients to oral dose form as soon as they can take oral medications.
• For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
• Administer first dose 24 h or less following transplantation.
• Reconstitute each vial of powder for injection with 14 mL of 5% dextrose injection. Gently shake vial to dissolve drug. Solution should be clear and slightly yellow. Discard vial if particulate matter, cloudiness, or discoloration noted.
• For 1 g dose, further dilute contents of 2 reconstituted vials in 140 mL 5% dextrose injection. For 1.5 g dose, further dilute contents of 3 reconstituted vials in 210 mL 5% dextrose injection. Final concentration of both solutions is 6 mg/mL.
• Do not administer if particulate matter, cloudiness or discoloration noted.
• Administer reconstituted solution by slow IV infusion over a period of 2 h or more.
• Discard any unused solution. Do not save for future use.
• Do not mix with other IV substances or additives, or infuse simultaneously through the same IV line. If the same IV line is used for sequential infusion of different medications, flush line with 5% dextrose injection before and after injection of mycophenolate.

Storage/Stability

Store tablets, capsules, and extended-release tablets at room temperature (59° to 86°F). Protect from moisture. Store reconstituted suspension in refrigerator (36° to 46°F) or at room temperature. Protect suspension from freezing. Discard any unused suspension after 60 days.

Store unopened vials of powder for injection at room temperature. Use diluted infusion solution immediately after reconstitution. If not infused immediately after reconstitution, solution may be stored for up to 4 h at room temperature. Discard infusion solution if administration has not been started within 4 h of reconstitution.

Drug Interactions

Acyclovir

Possible increased plasma concentrations of both drugs.

Antacids containing magnesium and aluminum hydroxides

Decreased absorption of mycophenolate; do not administer simultaneously.

Azathioprine

Avoid use because of lack of clinical studies.

Cholestyramine

Decreased mycophenolate plasma concentrations; do not give mycophenolate with cholestyramine or other agents that may interfere with enterohepatic recirculation.

Contraceptives, oral

Because oral contraceptive efficacy may be decreased, use caution and consider additional birth control methods.

Ganciclovir

Possible increased plasma concentrations of both drugs.

Iron salts

Following coadministration, mycophenolate absorption and MPA AUC were significantly decreased.

Live vaccines

Because vaccinations may be less effective, avoid live attenuated vaccines during mycophenolate treatment.

Metronidazole plus norfloxacin

Mycophenolic acid concentrations may be reduced. Metronidazole plus norfloxacin appear to have an additive effect on the AUC of mycophenolic acid and mycophenolic acid glucuronide.

Phenytoin

MPA decreased protein binding of phenytoin and may increase free phenytoin levels.

Probenecid

May increase plasma concentrations of mycophenolate.

Rifamycins (eg, rifampin)

Mycophenolic acid plasma concentrations may be reduced, decreasing the efficacy.

Salicylates

Coadministration increased the free fraction of MPA.

Sirolimus

Mycophenolic acid trough concentrations may be elevated, increasing the risk of side effects.

Theophylline

MPA decreased protein binding of theophylline and may increase free theophylline levels.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

CV disorder, hypertension, hypotension, tachycardia (more than 20%); angina pectoris, arrhythmia, arterial thrombosis. atrial fibrillation, atrial flutter, bradycardia, cardiac arrest, extrasystoles, heart failure, increased venous pressure, pallor, palpitation, pericardial effusion, peripheral vascular disorder, postural hypotension, pulmonary hypertension, supraventricular extrasystoles, syncope, thrombosis, vasodilation, vasospasm, ventricular tachycardia (3% to less than 20%).

CNS

Anxiety, asthenia, dizziness, headache, insomnia, paresthesia, tremor (more than 20%); abnormal thinking, agitation, convulsion, delirium, depression, emotional lability, hallucinations, hypertonia, hypesthesia, nervousness, neuropathy, psychosis, somnolence, vertigo (3% to less than 20%).

Dermatologic

Rash (more than 20%); acne, alopecia, benign skin neoplasm, fungal dermatitis, hemorrhage, hirsutism, pruritus, skin carcinoma, skin hypertrophy, skin ulcer, vesiculobullous rash (3% to less than 20%); nonmelanoma skin carcinoma (2% to 4%).

EENT

Abnormal vision, amblyopia, cataract, conjunctivitis, deafness, ear disorder, ear pain, eye hemorrhage, lacrimation disorder, pharyngitis, tinnitus (3% to less than 20%).

GI

Abdominal pain, anorexia, constipation, diarrhea, dyspepsia, nausea, vomiting (more than 20%); cholangitis, cholestatic jaundice, dry mouth, dysphagia, enlarged abdomen, esophagitis, flatulence, gastritis, gastroenteritis, GI disorder, GI hemorrhage, GI moniliasis, gingivitis, gum hyperplasia, hepatitis, ileus, infection, melena, mouth ulceration, oral moniliasis, rectal disorder, stomach ulcer, stomatitis, thirst (3% to less than 20%); colitis, pancreatitis (postmarketing).

Endocrine

Cushing syndrome, diabetes mellitus, hypothyroidism, parathyroid disorder (3% to less than 20%).

Genitourinary

Abnormal kidney function (more than 20%); acute kidney failure, albuminuria, dysuria, hematuria, hydronephrosis, impotence, kidney failure, kidney tubular necrosis, nocturia, oliguria, pain, prostatic disorder, pyelonephritis, scrotal edema, urinary frequency, urinary incontinence, urinary retention, urinary tract disorder, urine abnormality, UTI (3% to less than 20%).

Hematologic-Lymphatic

Anemia, hypochromic anemia, leukocytosis, leukopenia, thrombocytopenia (more than 20%); coagulation disorder, ecchymosis, hemorrhage, increased prothrombin, increased thromboplastin, pancytopenia, petechiae, polycythemia, thrombosis (with IV) (3% to less than 20%).

Hepatic

Abnormal LFTs (more than 20%); increased ALT, increased AST, jaundice, liver damage (3% to less than 20%).

Metabolic-Nutritional

Edema, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hypokalemia, hypomagnesemia, increased BUN, increased creatinine, increased lactic dehydrogenase, peripheral edema (more than 20%); abnormal healing, acidosis, bilirubinemia, generalized anemia, hyperlipidemia, hyperuricemia, hypoglycemia, hyponatremia, hypophosphatemia, hypoproteinemia, hypovolemia, weight gain (11%); acidosis, alkalosis, dehydration, hypocalcemia, hypochloremia, hypoxia, increased alkaline phosphatase, creatine, and gamma glutamyl transpeptidase, weight loss (3% to less than 20%).

Musculoskeletal

Back pain (more than 20%); arthritis, joint disorder, leg cramps, myalgia, myasthenia, osteoporosis (3% to less than 20%).

Respiratory

Dyspnea, increased cough, infection, lung disorder, pleural effusion, sinusitis (more than 20%); apnea, asthma, atelectasis, bronchitis, epistaxis, hemoptysis, hiccup, hyperventilation, increased sputum, lung edema, neoplasm, pain, pneumonia, pneumothorax, respiratory acidosis, respiratory disorder, respiratory moniliasis, rhinitis, voice alteration (3% to less than 20%); interstitial lung disorder including fatal pulmonary fibrosis (postmarketing).

Miscellaneous

Ascites, chest pain, fever, infection, pain, sepsis (more than 20%); abscess, abnormal healing, accidental injury, cellulitis (with IV), chills, cyst, face edema, flu syndrome, gout, hernia, malaise, neck pain, pelvic pain, peritonitis, phlebitis (3% to less than 20%); life-threatening infections (eg, infectious endocarditis, meningitis), increased frequency of tuberculosis and atypical mycobacterial infection (postmarketing).

Precautions

Warnings Administer under the supervision of a physician experienced in immunosuppressive therapy and management of organ transplantation and in an equipped facility. Increased risk of lymphoma and increased susceptibility to infection may be related to immunosuppression.

Monitor Perform CBCs weekly during the first month, twice monthly during the second and third months, then monthly through the first year. Monitor patient for signs and symptoms of bacterial, viral, or fungal infections, and for signs and symptoms of organ rejection.

Pregnancy

Category C . Ensure women of childbearing potential have a negative pregnancy test within 1 wk prior to beginning therapy. Do not initiate therapy until negative pregnancy test has been documented. Effective contraception must be used before beginning therapy, during therapy, and for 6 wk following discontinuation of therapy, even when there has been a history of infertility, unless caused by hysterectomy. Two reliable forms of contraception must be used simultaneously unless abstinence is the chosen method.

Lactation

Undetermined.

Children

CellCept

Safety and efficacy in cardiac or hepatic transplants not established.

Myfortic

Safety and efficacy not established.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

CellCept

Do not exceed 2 g/day doses in patients with glomerular filtration rate less than 25 mL/min/1.73 m ² ; carefully monitor these patients.

Vaccinations

Vaccinations may be less effective; do not administer live attenuated vaccines.

GI hemorrhage

GI tract hemorrhage, including perforations, has been observed; administer with caution to patients with active serious digestive system disease.

Lymphomas/Malignancies

Patients receiving immunosuppressive regimens involving combinations of drugs are at increased risk of developing lymphomas and other malignancies, particularly of the skin. Risk appears to be related to intensity and duration of immunosuppression rather than to any specific agent.

Neutropenia

Severe neutropenia may occur. If ANC less than 1.3 × 103/mcL develops, interrupt or reduce mycophenolate dose, perform appropriate diagnostic tests, and manage the patient appropriately.

Phenylketonurics

CellCept oral suspension contains aspartame, a source of phenylalanine; use with caution in patient with phenylketonuria.

Overdosage

Symptoms

Diarrhea, nausea, neutropenia, vomiting.

Patient Information

• Explain name, dose, action, and potential side effects of drug, including increased risk of lymphoproliferative disorders and other malignancies.
• Advise patient, family, or caregiver that medication will be used in combination with other agents, including cyclosporine and corticosteroids, to achieve max benefit.
• Instruct patient to continue to take other medications prescribed for preventing organ transplant rejection.
• Instruct patient to notify health care provider immediately if any of the following occur: fever, chills, or other signs of infection; bleeding or unusual bruising; vomiting blood; black tarry stools; persistent or severe diarrhea; difficulty breathing or unexplained shortness of breath.
• Advise patient to contact health care provider if bothersome side effects or any unusual problems occur.
• Instruct patient with increased risk of skin cancer to limit exposure to sunlight and ultraviolet light (eg, tanning beds) by wearing protective clothing and using effective sunscreen.
• Caution patient that drug may cause drowsiness or dizziness and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
• Instruct women of childbearing potential to use 2 effective forms of contraception before starting therapy, during therapy, and for 6 wk following discontinuation of treatment.

• Injection
• Advise patient or caregiver that medication will be prepared and administered by a health care provider until patient can take oral medication.

• Oral
• Caution patient to avoid inhalation and direct contact with skin and mucus membranes of the powder contained in the tablets and capsules. If accidental skin contact occurs, advise patient to wash thoroughly with soap and water. If mucus membrane contact occurs, advise patient to flush thoroughly with water. If eye contact occurs, advise patient to flush eyes thoroughly with water. If capsules are opened or tablets crushed, advise patient to wipe up using paper towels wet with water to removed spilled powder or tablet particles.
• Advise patient to take prescribed dose on an empty stomach, 1 h before or 2 h after food intake. Caution patient using extended-release tablets to swallow tablets whole and not to crush, chew, or cut tablets.
• Advise patient or caregiver using oral suspension to shake suspension well before measuring dose and to use the supplied oral dispenser for measuring and taking dose. Advise patient to follow dose of suspension with a full glass of water to wash all medication into stomach. Caution patient or caregiver not to mix suspension with any other medication.
• Advise patient that if a dose is missed to take it as soon as remembered. If it is almost time for the next dose, advise patient to skip the missed dose and take the next dose at the regularly scheduled time. Caution patient not to double the dose to catch up.
• Advise patient not to change the dose or stop taking unless advised by health care provider.

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