Usage
Mycophenolate mofetil is an immunosuppressant, specifically an antimetabolite. It’s prescribed to prevent organ rejection in patients who have undergone kidney, heart, or liver transplants. It’s used in conjunction with other immunosuppressants. It is also used in the treatment of some autoimmune diseases.
It works by inhibiting the proliferation of lymphocytes, a type of white blood cell crucial for immune responses. By suppressing lymphocyte activity, mycophenolate mofetil reduces the risk of the body attacking the transplanted organ.
Alternate Names
The active metabolite of mycophenolate mofetil is mycophenolic acid (MPA). Mycophenolate mofetil is also marketed under various brand names, including CellCept and Myhibbin. Mycophenolate sodium (Myfortic) is another medication containing MPA.
How It Works
Pharmacodynamics: Mycophenolate mofetil is rapidly converted to mycophenolic acid (MPA), its active form. MPA is a non-competitive, selective, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo pathway of guanine nucleotide synthesis. Unlike other cell types that can utilize salvage pathways, lymphocytes rely heavily on the de novo pathway for proliferation. Consequently, MPA selectively inhibits lymphocyte proliferation and function, mitigating the immune response that can lead to organ rejection.
Pharmacokinetics:
- Absorption: Mycophenolate mofetil is well-absorbed orally and rapidly hydrolyzed to MPA.
- Metabolism: MPA undergoes enterohepatic recirculation, converting to an inactive glucuronide metabolite (MPAG), which is then converted back to MPA in the gut.
- Elimination: Primarily renal excretion as MPAG.
Dosage
Standard Dosage
Adults:
- Kidney Transplant: 1 g twice daily (2 g total daily dose).
- Heart Transplant: 1.5 g twice daily (3 g total daily dose).
- Liver Transplant: 1.5 g twice daily (3 g total daily dose).
Children (3 months and older):
- Dosing is based on body surface area (BSA), not to exceed 2g daily.
- Generally, the initial dose is 600 mg/m² twice daily. It can be adjusted based on BSA and tolerance up to a maximum of 900 mg/m2 twice daily (3 g). Use in children younger than 3 months is not recommended due to limited safety and efficacy data.
Special Cases:
- Elderly Patients: The standard adult dose is generally appropriate, but close monitoring is recommended.
- Patients with Renal Impairment: Dose reduction may be necessary in severe renal impairment (GFR <25 mL/min/1.73 m²).
- Patients with Hepatic Dysfunction: Close monitoring is essential, but formal dose adjustments are not usually required.
- Patients with Comorbid Conditions: Individualized dosing may be needed for patients with comorbidities such as diabetes, cardiovascular disease, or active gastrointestinal disease.
Clinical Use Cases
Mycophenolate mofetil’s primary clinical use is in organ transplantation. It’s not typically indicated for conditions like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations outside of the context of organ transplantation.
Dosage Adjustments
Dose adjustments might be necessary based on patient-specific factors such as renal or hepatic dysfunction, other medical conditions, other medications, or adverse effects like neutropenia. Therapeutic drug monitoring may be used to optimize MPA exposure.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, constipation, abdominal pain, headache, insomnia, tremor, leukopenia, anemia, hypertension, hypercholesterolemia, hyperglycemia.
Rare but Serious Side Effects:
Increased risk of infections (including opportunistic infections), malignancies (lymphoma, skin cancer), pure red cell aplasia, gastrointestinal perforation, severe neutropenia.
Long-Term Effects:
Increased cancer risk, potential for chronic kidney disease.
Adverse Drug Reactions (ADR):
Severe infections, anaphylaxis, progressive multifocal leukoencephalopathy (PML).
Contraindications
Absolute contraindications include hypersensitivity to mycophenolate mofetil, mycophenolic acid, or any component of the formulation, pregnancy, breastfeeding, women of childbearing potential unless using highly effective contraception.
Drug Interactions
Mycophenolate mofetil can interact with numerous medications, including:
- Acyclovir/Valacyclovir: Increased risk of adverse effects.
- Antacids: Reduced absorption of mycophenolate mofetil.
- Azathioprine: Increased risk of myelosuppression.
- Cholestyramine: Reduced absorption of mycophenolate mofetil.
- Ciclosporin: Increased MPA levels.
- Live Vaccines: Reduced vaccine effectiveness, increased infection risk.
- Oral Contraceptives: Potential reduction in contraceptive efficacy.
- Rifampicin: Reduced MPA levels.
Pregnancy and Breastfeeding
Mycophenolate mofetil is contraindicated in pregnancy and breastfeeding due to its teratogenic effects and potential excretion into breast milk. It can cause miscarriage and birth defects (e.g., craniofacial abnormalities, cardiac defects). Women of childbearing potential must use highly effective contraception before, during, and for 6 weeks after treatment. Men should use condoms during treatment and for 90 days after.
Drug Profile Summary
- Mechanism of Action: Inhibits IMPDH, suppressing lymphocyte proliferation.
- Side Effects: Nausea, vomiting, diarrhea, infections, increased malignancy risk.
- Contraindications: Pregnancy, breastfeeding, hypersensitivity.
- Drug Interactions: Numerous, including acyclovir, antacids, azathioprine.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies based on organ transplanted and patient factors (See dosages section).
- Monitoring Parameters: Complete blood count (CBC), liver function tests, renal function tests, blood pressure, glucose, and lipids.
Popular Combinations
Commonly used in combination with calcineurin inhibitors (e.g., tacrolimus, cyclosporine) and corticosteroids.
Precautions
- Monitor for infections and signs of malignancy.
- Ensure patients understand the importance of contraception.
- Monitor blood counts, liver and kidney function.
- Avoid live vaccines.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mycophenolate mofetil?
A: The recommended dose is transplant and patient specific. (See Dosage section for details).
Q2: What are the major side effects of Mycophenolate mofetil?
A: Common side effects include gastrointestinal issues (nausea, vomiting, diarrhea), increased risk of infections, and increased risk of certain malignancies.
Q3: Can Mycophenolate mofetil be used during pregnancy?
A: No, mycophenolate mofetil is contraindicated during pregnancy due to the risk of birth defects and miscarriage.
Q4: How does Mycophenolate mofetil interact with other immunosuppressants?
A: Interactions with other immunosuppressants can increase the risk of infections and other adverse effects. For example, combining with azathioprine can enhance myelosuppression.
Q5: What is the mechanism of action of Mycophenolate mofetil?
A: It inhibits IMPDH, an enzyme crucial for lymphocyte proliferation, thus suppressing the immune response.
Q6: What monitoring parameters are important for patients taking Mycophenolate mofetil?
A: Regular monitoring of complete blood count, liver and kidney function tests are necessary. Blood pressure, glucose, and lipid levels should also be monitored.
Q7: Is there a risk of cancer with Mycophenolate mofetil?
A: Yes, there is an increased risk of certain cancers, including lymphoma and skin cancer.
Q8: What are the key contraindications for Mycophenolate mofetil?
A: Pregnancy, breastfeeding, hypersensitivity to the drug or its components. Women of childbearing potential must use highly effective contraception while taking this medication.
Q9: What precautions should be taken in elderly patients on mycophenolate mofetil?
A: Close monitoring for adverse effects, especially infections and myelosuppression is important due to age-related decline in immune and renal function. Dose adjustments may be necessary based on renal function.
Q10: What should patients be counseled about regarding lifestyle while on mycophenolate mofetil?
A: Patients should be counseled on minimizing exposure to sunlight and UV radiation due to the increased risk of skin cancer. They should also be advised on strict adherence to infection control measures and pregnancy prevention. Avoiding contact with individuals who have infectious illnesses is also advised.
