Mycept-S 180

Indications

• Prevention of organ rejection in kidney transplants
• Prevention of organ rejection in heart transplants
• Prevention of organ rejection in liver transplants

Dosage

Children: For paediatric patients, mycophenolate dosing is based on body surface area and typically starts at 600 mg/m² taken twice daily. Adjustments may be made according to clinical response. For specific paediatric dosing recommendations, refer to BNF for Children.

Adults: The usual initial dose of mycophenolate mofetil for adults is 1 g taken twice daily, which may be adjusted based on clinical response and tolerability. Dosage can vary based on the specific transplant type and patient condition. Refer to BNF for detailed dosing guidelines.

Mechanism of action

Mycophenolate works by inhibiting inosine monophosphate dehydrogenase (IMPDH), which is crucial for the de novo synthesis pathway of purine nucleotides in lymphocytes. This inhibition selectively affects lymphocytes, as they rely on this pathway for proliferation more than other cell types, leading to reduced lymphocyte counts and a suppressed immune response.

Pharmacodynamics

The pharmacodynamics of mycophenolate involve its selective inhibition of lymphocyte activation and proliferation, which is critical in preventing acute rejection in organ transplantation. By decreasing the number of activated T and B lymphocytes, mycophenolate effectively reduces the likelihood of graft rejection while maintaining some degree of immune function to protect against infections.

Pharmacokinetics

Mycophenolate is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours. It undergoes extensive first-pass metabolism in the liver, resulting in the active metabolite mycophenolic acid. The drug is primarily eliminated via glucuronidation and is excreted in urine. Its plasma half-life is approximately 16-18 hours, although this can vary based on individual patient factors and concurrent medications.

Contra-indications

• Hypersensitivity to mycophenolate or any of its components
• Pregnancy (except in specific cases where benefits outweigh risks)

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Increased risk of infections
• Hematological toxicity (such as leukopenia, anemia, thrombocytopenia)
• Headache
• Hypertension
• Elevated liver enzymes

Interactions

• rifampicin+mycophenolate: Moderate (decreases concentration)
• mycophenolate+aciclovir: Unknown (increases risk of haematological toxicity)
• isavuconazole+mycophenolate: Unknown (increases exposure)
• mycophenolate+ganciclovir: Unknown (increases risk of haematological toxicity)
• live vaccines+mycophenolate: Unknown (increases risk of generalised infection, possibly life-threatening)
• mycophenolate+valaciclovir: Unknown (increases risk of haematological toxicity)
• mycophenolate+valganciclovir: Unknown (increases risk of haematological toxicity)

Precautions

• Monitor for signs of infection due to immunosuppression
• Regular blood count monitoring to detect hematological toxicity
• Use with caution in patients with renal impairment
• Assess risk of malignancy and cardiovascular disease in long-term use

Pregnancy

Use in pregnancy should be avoided unless the potential benefits justify the risks to the fetus.

Breast-feeding

It is not known whether mycophenolate is excreted in human milk. Caution is advised when administered to nursing women.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Mycophenolate mofetil capsules
• Mycophenolate mofetil tablets
• Mycophenolate mofetil oral suspension

Indications

• Prophylaxis of organ rejection in kidney transplantation
• Prophylaxis of organ rejection in heart transplantation
• Prophylaxis of organ rejection in liver transplantation
• Treatment of systemic lupus erythematosus
• Treatment of rheumatoid arthritis

Dosage

Children: Refer to BNF for Children for specific dosing guidelines.

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Mycophenolic acid exerts its effects primarily by inhibiting inosine monophosphate dehydrogenase (IMPDH), which is crucial in the de novo pathway of purine synthesis. This leads to decreased lymphocyte proliferation, particularly affecting T and B lymphocytes, which rely heavily on this pathway for their proliferation and function.

Pharmacodynamics

The inhibition of IMPDH results in reduced synthesis of purines, which are essential for the proliferation of lymphocytes. This immunosuppressive action helps to prevent graft rejection in transplant patients and controls autoimmune conditions. Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid, is often used due to its enhanced bioavailability and safety profile.

Pharmacokinetics

Mycophenolic acid is rapidly absorbed after oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. It is extensively metabolized in the liver, primarily to its active form, mycophenolic acid. The drug has a half-life of approximately 16 to 18 hours, and its elimination is predominantly via the renal route. Dosing adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to mycophenolate mofetil or any component of the formulation
• Pregnant women, due to the risk of teratogenicity
• Active infections, particularly viral infections such as cytomegalovirus (CMV)

Adverse effects

• Gastrointestinal disturbances such as nausea, vomiting, and diarrhea
• Increased risk of infections due to immunosuppression
• Bone marrow suppression leading to leukopenia and thrombocytopenia
• Elevated liver enzymes
• Renal impairment

Interactions

• Antacids and cholestyramine may reduce absorption of mycophenolate
• Concomitant use with other immunosuppressants increases the risk of infections and malignancies
• Certain antibiotics, such as rifampicin, may affect mycophenolate metabolism

Precautions

• Monitor white blood cell counts regularly due to the risk of leukopenia
• Assess for signs of infection, especially in patients on long-term therapy
• Use caution in patients with a history of gastrointestinal disorders
• Avoid pregnancy during treatment and provide effective contraception

Pregnancy

Mycophenolate is contraindicated in pregnancy due to significant risks of fetal malformations and pregnancy loss. Women of childbearing potential must use effective contraception during treatment.

Breast-feeding

Mycophenolate is excreted in breast milk; caution is recommended when administering to breastfeeding mothers as potential adverse effects on the infant are possible.

Storage

Store at room temperature, away from moisture and light. Keep out of reach of children.

Formulations

• Mycophenolate mofetil capsules
• Mycophenolate mofetil tablets
• Mycophenolate mofetil oral suspension