mycophenolate mofetil

Absorption: Following oral and IV administration, mycophenolate mofetil is rapidly hydrolyzed to mycophenolic acid (MPA), the active metabolite. Absorption of enteric-coated mycophenolic acid (Myfortic) is delayed compared with mycophenolate mofetil (CellCept).

Distribution: Cross the placenta and enter breast milk.

Protein Binding: MPA: 97%.

Metabolism/Excretion: MPA is extensively metabolized; <1% excreted unchanged in urine. Some enterohepatic recirculation of MPA occurs.

Half-Life: MPA: 8–18 hr.

Time/Action Profile ⬆ ⬇

(blood levels of MPA)

ROUTE	ONSET	PEAK	DURATION
mycophenolate mofetil-PO	rapid	0.25–1.25 hr	N/A
mycophenolic acid	rapid	1.5–2.75 hr	N/A

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Hypersensitivity to polysorbate 80 (for IV mycophenolate mofetil);
OB: Pregnancy ( risk of congenital anomalies or spontaneous abortion).

Use Cautiously in:

Active serious pathology of the GI tract (including history of ulcer disease or GI bleeding);
Phenylketonuria (oral suspension contains aspartame);
Severe chronic renal impairment (dose not to exceed 1 g twice daily [CellCept] if CCr <25 mL/min/1.73 m²); careful monitoring recommended;
Delayed graft function following transplantation (observe for ↑ toxicity);
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children 3 mo (mycophenolate mofetil) or 5 yr (mycophenolic acid);
Geri: risk of adverse reactions related to immunosuppression in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, hypertension, hypotension, tachycardia

Derm: rash

Endo: hyperglycemia

F and E: hyperkalemia, hypocalcemia, hypokalemia, hypomagnesemia

GI: anorexia, constipation, diarrhea, nausea, vomiting, abdominal pain, GI BLEEDING

GU: renal impairment

Hemat: leukocytosis, leukopenia, thrombocytopenia, anemia, pure red cell aplasia

Metab: hypercholesterolemia

Neuro: anxiety, confusion, dizziness, headache, insomnia, paresthesia, sedation, tremor, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

Resp: cough, dyspnea

Misc: fever, infection (including activation of latent viral infections such as Polyomavirus-associated nephropathy or Hepatitis B/C), acute inflammatory syndrome, MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

Combined use with azathioprine is not recommended (effects unknown).
Acyclovir and ganciclovir compete with MPA for renal excretion and, in patients with renal dysfunction, may ↑ each other’s toxicity.
Magnesium and aluminum hydroxide antacids ↓ the absorption of MPA (avoid simultaneous administration).
Proton pump inhibitors, including dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole may ↓ levels
Cholestyramine and colestipol↓ the absorption of MPA (avoid concurrent use).
May ↓ the effectiveness of oral contraceptives (additional contraceptive method should be used).
May ↓ the antibody response to and ↑ risk of adverse reactions from live attenuated vaccines.
Amoxicillin/clavulanic acid or ciprofloxacin may ↓ MPA trough levels.
Cyclosporine may ↓ levels; use caution when discontinuing cyclosporine (may ↑ mycophenolate levels) or when switching from cyclosporine to another immunosuppressant, such as tacrolimus or belatacept
Telmisartan may ↓ levels

Route/Dosage ⬆ ⬇

Mycophenolate Mofetil

Kidney Transplantation
PO IV (Adults ): 1 g twice daily; IV should be started ≤24 hr after transplantation and switched to PO as soon as possible (IV not recommended for ≥14 days).
PO (Children ≥3 mo): 600 mg/m² twice daily (not to exceed 2 g/day).
Liver Transplantation
PO IV (Adults ): 1 g twice daily IV, or 1.5 g twice daily PO. IV should be started ≤24 hr after transplantation and switched to PO as soon as possible (IV not recommended for ≥14 days).
PO (Children ≥3 mo): 600 mg/m² twice daily; if well tolerated, can ↑ to 900 mg/m² twice daily (not to exceed 3 g/day).
Heart Transplantation
PO IV (Adults ): 1.5 g twice daily; IV should be started ≤24 hr after transplantation and switched to PO as soon as possible (IV not recommended for ≥14 days).
PO (Children ≥3 mo): 600 mg/m² twice daily; if well tolerated, can ↑ to 900 mg/m² twice daily (not to exceed 3 g/day).

Renal Impairment

PO IV (Adults ): CCr <25 mL/min: daily dose should not exceed 2 g.

Mycophenolic Acid

Mycophenolate mofetil and mycophenolic acid should not be used interchangeably without the advice of a health care professional.
Kidney Transplantation
PO (Adults ): 720 mg twice daily.
PO (Children 5–16 yr and ≥1.19 m²): 400–450 mg/m² twice daily (not to exceed 720 mg twice daily).

Availability ⬆ ⬇

(Generic available)

Mycophenolate Mofetil

Tablets: 500 mg
Capsules: 250 mg
Oral suspensionfruit flavor: 200 mg/mL
Powder for injection : 500 mg/vial

Mycophenolic Acid

Delayed-release tablets: 180 mg; 360 mg

Assessment ⬆ ⬇

Assess for symptoms of organ rejection throughout therapy.
Assess for signs of PML (hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia) periodically during therapy.
Monitor for symptoms and laboratory parameters of Acute Inflammatory Syndrome when starting treatment with mycophenolate products or when increasing the dose. Discontinue treatment and consider other treatment alternatives based on risk and benefit for the patient.

Lab Test Considerations:

Verify negative urine pregnancy test with a specificity of 25 mIU/mL immediately prior to beginning therapy and again 8–10 days later. Repeat pregnancy tests should be preformed during routine follow-up visits.
- Monitor CBC with differential weekly during the 1st mo, twice monthly for the 2nd and 3rd mo of therapy, and then monthly during the 1st yr. Neutropenia occurs most frequently from 31–180 days post-transplant. If ANC is <1000/mm³, dose should be reduced or discontinued.
- Monitor hepatic and renal status and electrolytes periodically during therapy. May cause ↑ alkaline phosphatase, AST, ALT, LDH, BUN, and serum creatinine. May also cause hyperkalemia, hypokalemia, hypocalcemia, hypomagnesemia, hyperglycemia, and hyperlipidemia.

Implementation ⬆ ⬇

The initial dose of mycophenolate should be given within 24 hr of transplant.
- Mycophenolate mofetil (Cellcept) and mycophenolic acid (Myfortic) are not interchangeable; rate of absorption is different.
Mycophenolate is administered under REMS requirements. Prescribers are encouraged to complete Prescriber Training program and patients are encouraged to complete the Information for Patients to mitigate the risk of embryofetal toxicity associated with the use of mycophenolate during pregnancy.
PO: Administer on an empty stomach, 1 hr before or 2 hr after meals. DNC: Swallow capsules and delayed-release tablets whole; do not open, crush, or chew. Mycophenolate may be teratogenic; wear gloves and avoid contact with skin or mucous membranes or inhalation of contents of capsules or oral suspension powder. Oral suspension can be administered by nasogastric tube (minimum size of 8 French). Oral solution is stable for 60 days if refrigerated.
- Do not administer mycophenolate concurrently with antacids containing magnesium or aluminum.

IV Administration:

IV: IV route should only be used for patients unable to take oral medication and should be switched to oral dose form as soon as patient can tolerate capsules or tablets.
Intermittent Infusion: Diluent: Reconstitute each vial with 14 mL of D5W. Shake gently to dissolve. Solution is slightly yellow; discard if solution is discolored or contains particulate matter. Dilute contents of 2 vials (1-g dose) further with 140 mL of D5W or 3 vials (1.5-g dose) with 210 mL of D5W.Concentration: 6 mg/mL. Solution is stable for 4 hr.
Rate: Administer via slow IV infusion over at least 2 hr. Do not administer as a bolus or via rapid infusion; increases risk of phlebitis and thrombosis.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed, at the same time each day. Take missed dose as soon as remembered, but not if within 2 hrs before next dose. Do not skip or double up on missed doses. Do not discontinue without consulting health care professional. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
Explain REMS program to patient.
Reinforce the need for lifelong therapy to prevent transplant rejection. Review symptoms of rejection for the transplanted organ, and stress need to notify health care professional immediately if signs of rejection or infection occur.
May cause somnolence, confusion, dizziness, tremor, or hypotension. Caution patient to avoid driving and other activities requiring alertness until response from medication is known.
Instruct patient to notify health care professional immediately if signs and symptoms of infection (temperature ≥100.5°F, cold symptoms [runny nose, sore throat], flu symptoms [upset stomach, stomach pain, vomiting, diarrhea], earache or headache, pain during urination, frequent urination, white patches in mouth or throat, unexpected bruising or bleeding, cuts, scrapes, or incisions that are red, warm, and oozing pus) or PML.
Advise patient to avoid contact with persons with contagious diseases.
Advise patient to avoid vaccinations with live attenuated virus during therapy.
Inform patient of the increased risk of lymphoma and other malignancies. Advise patient to use sunscreen and wear protective clothing to decrease risk of skin cancer.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Instruct patient to avoid donating blood during and for at least 6 wk after discontinuation of therapy.
Rep: May cause fetal harm. Inform females of reproductive potential of the potential for pregnancy loss and fetal harm. Discuss importance of simultaneously using two reliable nonhormonal forms of contraception, unless abstinence is the chosen method, prior to beginning, during, and for 6 wk following discontinuation of therapy and to avoid breastfeeding. Discuss acceptable forms of contraception with health care professional. Mycophenolate may decrease effectiveness of hormonal contraceptives. Encourage patients who become pregnant during or within 6 wk after therapy to enroll in the Pregnancy Registry by calling 1-800-617-8191 or www.mycophenolateREMS.com to monitor pregnancy outcomes in women exposed to mycophenolate during pregnancy. Instruct male patients with female partners of reproductive potential to use effective contraception during and for at least 90 days after discontinuing therapy. Advise male patients to avoid semen donation during and for at least 90 days after discontinuing therapy.
Emphasize the importance of routine follow-up laboratory tests.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇