MPHETAS-500MG

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 transplant rejection
• Treatment of certain autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis

Dosage

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

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Mycophenolate acts as a selective inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme critical in the de novo synthesis pathway of purine nucleotides. By inhibiting this pathway, mycophenolate preferentially targets lymphocytes, which rely on this pathway for proliferation, thus suppressing immune responses.

Pharmacodynamics

Mycophenolate is converted to mycophenolic acid, its active form, which exerts its immunosuppressive effects by inhibiting the proliferation of T and B lymphocytes. This leads to decreased antibody production and a reduced immune response, making it effective in preventing graft rejection and treating autoimmune disorders. The effects can lead to an increased risk of infections and malignancies due to overall immune suppression.

Pharmacokinetics

Mycophenolate is well absorbed after oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. It is extensively metabolized in the liver, primarily by the enzyme UGT1A9, and has a half-life of about 16 to 18 hours. Approximately 95% of mycophenolate is bound to plasma proteins, and it is eliminated mainly through the urine as metabolites. Renal impairment can significantly affect the drug's clearance.

Contra-indications

• Hypersensitivity to mycophenolate mofetil or any component of the formulation
• Pregnancy
• Severe renal impairment
• Active or recurrent infections

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Bone marrow suppression leading to leukopenia, anemia, or thrombocytopenia
• Increased risk of infection due to immunosuppression
• Headache
• Hypertension
• Elevated liver enzymes

Interactions

• Antacids containing magnesium or aluminum may reduce the absorption of mycophenolate
• Cholestyramine may reduce the absorption of mycophenolate
• Concomitant use with other immunosuppressants may increase the risk of adverse effects

Precautions

• Use with caution in patients with a history of gastrointestinal disease
• Monitor blood counts regularly due to the risk of bone marrow suppression
• Consider alternative contraception methods in women of childbearing potential
• Patients should be monitored for signs of infection

Pregnancy

Mycophenolate is contraindicated during pregnancy due to risk of teratogenic effects and potential miscarriage.

Breast-feeding

Mycophenolate is excreted in breast milk; nursing is not recommended while receiving this medication.

Storage

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

Formulations

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