Usage
Mycophenolate sodium is an immunosuppressant, specifically an antimetabolite. It’s prescribed to prevent organ rejection after kidney, heart, and liver transplants. It’s used in combination with other immunosuppressants like cyclosporine and corticosteroids. It works by inhibiting inosine monophosphate dehydrogenase (IMPDH), which is crucial for the synthesis of guanine nucleotides in lymphocytes. This suppression of guanine nucleotide synthesis selectively inhibits lymphocyte proliferation, reducing the body’s immune response and thus preventing organ rejection.
Alternate Names
Mycophenolate sodium is also known as mycophenolic acid sodium. A common brand name is Myfortic®.
How It Works
Pharmacodynamics: Mycophenolate sodium suppresses the immune system by inhibiting IMPDH, specifically the type II isoform, which is rate-limiting in the de novo synthesis of guanine nucleotides. Unlike other cell types, lymphocytes rely heavily on the de novo pathway for DNA synthesis. Therefore, this drug selectively targets lymphocytes, inhibiting their proliferation and reducing the risk of organ rejection.
Pharmacokinetics: Mycophenolate sodium is an enteric-coated formulation designed for delayed release in the small intestine to reduce gastrointestinal side effects. After absorption, mycophenolate sodium is rapidly converted to mycophenolic acid (MPA), its active metabolite. MPA is extensively metabolized in the liver, primarily via glucuronidation, forming the inactive mycophenolic acid glucuronide (MPAG). Elimination occurs mainly through renal excretion, with a small portion excreted in bile.
Mode of Action: Mycophenolate sodium, through its active form, MPA, reversibly inhibits IMPDH type II, the rate-limiting enzyme in de novo purine synthesis. This blocks the formation of guanosine monophosphate (GMP), a crucial precursor for DNA. The reduction in GMP levels hinders DNA synthesis and cellular replication, especially in rapidly dividing cells like lymphocytes. This targeted action on lymphocytes makes MPA effective in suppressing immune responses involved in organ rejection.
Dosage
Standard Dosage
Adults:
- Kidney Transplant: 720 mg twice daily (1440 mg total daily dose).
- Heart or Liver Transplant: 1.5g twice daily (3g total daily dose) orally. It may be administered intravenously for the first 4 days post-transplant.
Children (≥ 3 months):
Dosing is based on body surface area (BSA): 600 mg/m² twice daily. Not to exceed specific limits based on organ transplanted.
For Myfortic® (delayed release tablets): For children aged 5 and above (at least 6 months after the transplant), the dose is 400 mg/m² twice daily, not exceeding 720 mg twice daily.
Special Cases:
- Elderly Patients: The standard adult dose is typically appropriate, but careful monitoring is recommended due to potential age-related decline in organ function.
- Patients with Renal Impairment: Dose reduction may be necessary in patients with severe chronic renal impairment.
- Patients with Hepatic Dysfunction: Caution is advised, and dose adjustment may be required.
- Patients with Comorbid Conditions: Careful monitoring and dose adjustments are crucial, particularly in patients with diabetes, cardiovascular disease, or infections.
Clinical Use Cases
Mycophenolate sodium is primarily used for prophylaxis of organ rejection following transplantation. Dosing recommendations for other scenarios outside organ transplant are not explicitly specified in current guidelines.
Dosage Adjustments
Dose modifications may be needed for various factors, including renal/hepatic impairment, myelosuppression, and concomitant medications. Specific adjustments should be determined through therapeutic drug monitoring and clinical evaluation.
Side Effects
Common Side Effects:
Constipation, nausea, vomiting, diarrhea, abdominal pain, headache, insomnia, tremor, dizziness, leukopenia, anemia, infections.
Rare but Serious Side Effects:
Progressive multifocal leukoencephalopathy (PML), sepsis, severe infections, pure red cell aplasia, lymphoma, other malignancies (especially skin cancer), gastrointestinal perforation, severe neutropenia.
Long-Term Effects:
Increased risk of infections, lymphoma, skin cancer, and other malignancies.
Adverse Drug Reactions (ADR):
PML, sepsis, anaphylaxis, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Contraindications
Hypersensitivity to mycophenolate, pregnancy, breastfeeding, women of childbearing potential not using effective contraception.
Drug Interactions
Acyclovir, valacyclovir, ganciclovir, valganciclovir, antacids containing magnesium and aluminum hydroxide, cholestyramine, probenecid, live vaccines. Interactions with many other drugs exist; thorough medication reconciliation is essential.
Pregnancy and Breastfeeding
Mycophenolate sodium is contraindicated during pregnancy (Pregnancy Category D) and breastfeeding due to its teratogenic potential and potential harm to the nursing infant. Women of childbearing potential must use two reliable forms of contraception before, during, and for 6 weeks after treatment. Men should use condoms during treatment and for 90 days afterward.
Drug Profile Summary
- Mechanism of Action: Inhibits IMPDH, blocking de novo purine synthesis, crucial for lymphocyte proliferation.
- Side Effects: Nausea, vomiting, diarrhea, leukopenia, infections, increased risk of malignancy.
- Contraindications: Pregnancy, breastfeeding, hypersensitivity.
- Drug Interactions: Acyclovir, antacids, cholestyramine, live vaccines.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 720mg BID (renal transplant) to 1.5g BID (heart/liver transplant). Pediatric dosing based on BSA.
- Monitoring Parameters: Complete blood count, liver function tests, creatinine, signs of infection.
Popular Combinations
Cyclosporine and corticosteroids are commonly used in combination with mycophenolate sodium for organ transplant rejection prophylaxis.
Precautions
Close monitoring for infections, blood counts, and organ function. Avoid live vaccines. Pre-transplant screening for viral infections is necessary. Patient education on contraception and malignancy risks is vital.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mycophenolate sodium?
A: 720 mg twice daily for kidney transplant and 1.5 g twice daily for heart or liver transplant in adults. Pediatric dosing is based on BSA, usually 600 mg/m² twice daily, not exceeding maximum limits.
Q2: How does Mycophenolate sodium differ from mycophenolate mofetil?
A: Mycophenolate mofetil is a prodrug converted to mycophenolic acid. Mycophenolate sodium is a delayed-release formulation of mycophenolic acid itself, offering better gastrointestinal tolerability. Dosages are not equivalent and should not be substituted without physician guidance.
Q3: What are the most serious side effects of mycophenolate sodium?
A: PML, a rare brain infection, is potentially fatal. Other serious concerns include sepsis, severe infections, and malignancies, including lymphoma and skin cancers.
Q4: Can pregnant women take mycophenolate sodium?
A: No. Mycophenolate sodium is contraindicated in pregnancy due to a high risk of miscarriage and congenital malformations.
Q5: What patient education is important for individuals on mycophenolate sodium?
A: Emphasize strict adherence to prescribed dosage and schedule, importance of regular blood tests, vigilant monitoring for signs of infection, need for reliable contraception, sun protection measures, and reporting any unusual symptoms promptly.
Q6: What are the key drug interactions with Mycophenolate sodium?
A: Drugs that may interact significantly include acyclovir, valacyclovir, antacids containing magnesium and aluminum hydroxide, cholestyramine, and live vaccines.
Q7: How should mycophenolate sodium be administered?
A: Administer orally with or without food, preferably consistently. The intravenous form is used initially in liver transplant patients or those unable to tolerate oral medication.
Q8: What monitoring parameters should be tracked for patients on Mycophenolate sodium?
A: Regular monitoring should include complete blood count (CBC), liver function tests (LFTs), creatinine levels to assess kidney function, and close observation for any signs and symptoms of infection.
Q9: What are the alternatives to mycophenolate sodium for preventing organ rejection?
A: Other immunosuppressants, like tacrolimus, sirolimus, everolimus, and azathioprine, can be used, but the choice depends on the specific organ transplanted and individual patient factors.
