MOFILET 500

Indications

• Organ transplantation (kidney, heart, liver)
• Autoimmune diseases (lupus nephritis, rheumatoid arthritis)

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Mofetil acts primarily by inhibiting the enzyme inosine monophosphate dehydrogenase (IMPDH), which is crucial in the de novo synthesis of purines. This action selectively affects lymphocytes, as they are reliant on this pathway for proliferation. By reducing the availability of purines, mofetil hinders the proliferation of T and B lymphocytes, thereby exerting its immunosuppressive effects.

Pharmacodynamics

The immunosuppressive effects of mofetil are dose-dependent. The reduction of lymphocyte proliferation leads to decreased antibody production and a lower risk of acute rejection in transplant patients. Mofetil also has anti-inflammatory properties, which can be beneficial in autoimmune disorders, helping to mitigate tissue damage caused by an overactive immune response.

Pharmacokinetics

Mofetil is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a bioavailability of approximately 94% under fasting conditions. The drug is extensively metabolized in the liver, primarily by UDP-glucuronosyltransferases, leading to the formation of mycophenolic acid. The elimination half-life of mofetil is about 16 to 18 hours. It is excreted mainly via urine, with approximately 90% of the dose eliminated as metabolites.

Contra-indications

• Hypersensitivity to mofetil or any component of the formulation
• Pregnancy
• Active infections

Adverse effects

• Gastrointestinal disturbances such as nausea, vomiting, and diarrhea
• Increased risk of infections due to immunosuppression
• Hematological effects including leukopenia and thrombocytopenia
• Liver enzyme elevations
• Headache
• Hypertension

Interactions

• Increased risk of infections when combined with other immunosuppressants
• May interact with drugs that are metabolized by the liver, particularly cytochrome P450 enzymes
• Avoid concomitant use with live vaccines due to immunosuppressive effects

Precautions

• Monitor for signs of infection due to immunosuppressive effects
• Liver function tests should be performed regularly
• Use with caution in patients with pre-existing hepatic or renal impairment
• Consider potential for drug interactions

Pregnancy

Mofetil is contraindicated in pregnancy due to potential teratogenic effects.

Breast-feeding

Mofetil is excreted in breast milk; caution is advised if used during breastfeeding.

Storage

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

Formulations

• Oral tablets
• Oral suspension
• Injection

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