Mycophenolate Prescribing

Mycophenolate is an inosine monophosphate dehydrogenase inhibitor that blocks lymphocyte purine synthesis. It is used in solid organ transplantation, lupus nephritis, systemic sclerosis lung disease, vasculitis, autoimmune hepatitis and refractory autoimmune disease. It is teratogenic and carries a high risk of miscarriage and congenital malformation.

Formulations. Mycophenolate mofetil 250 mg capsules and 500 mg tablets; enteric-coated mycophenolic acid 180 mg and 360 mg tablets. 720 mg of mycophenolic acid is equivalent to 1000 mg of mycophenolate mofetil; do not swap formulations without a dose conversion.

Contraindications. Pregnancy or inadequate contraception, breastfeeding, hypoxanthine-guanine phosphoribosyl transferase deficiency (Lesch-Nyhan and Kelley-Seegmiller syndromes), active serious infection and severe neutropenia.

Kidney, heart and liver transplant. Mycophenolate mofetil 1 g orally twice daily (kidney); 1.5 g twice daily (heart); 1 to 1.5 g twice daily (liver). With ciclosporin or tacrolimus and corticosteroids.

Lupus nephritis, induction. Mycophenolate mofetil 1 to 1.5 g orally twice daily (2 to 3 g daily), with prednisolone, for 3 to 6 months; maintenance 500 to 1000 mg twice daily for at least 3 years.

Other autoimmune disease. Start 500 mg twice daily and increase by 500 mg every 1 to 2 weeks to 1 to 1.5 g twice daily (systemic sclerosis, vasculitis, myositis, autoimmune hepatitis, refractory skin disease).

Titration. Start low and titrate over 2 to 4 weeks to reduce gastrointestinal effects; split into 3 or 4 doses or switch to enteric-coated mycophenolic acid if gastrointestinal intolerance continues.

Kidney impairment. Maximum 1 g twice daily if eGFR under 25 mL/min outside the early post-transplant period.

Liver impairment. No adjustment in hepatic parenchymal disease, though data are limited.

Neutropenia. Hold or halve the dose if neutrophils fall under 1.3 x 10⁹/L.

Interactions.

• Antacids containing magnesium or aluminium, and colestyramine, reduce absorption; separate by at least 2 hours.
• Proton pump inhibitors lower mycophenolic acid exposure from mofetil.
• Azathioprine: avoid together because of marrow suppression.
• Ciclosporin lowers mycophenolic acid levels; tacrolimus does not.
• Rifampicin lowers exposure. Aciclovir and ganciclovir levels can rise with kidney impairment.
• Live vaccines are contraindicated.

Pregnancy. Exclude pregnancy by test before starting and 8 to 10 days later; use highly effective contraception (two methods unless intrauterine device or sterilisation) during treatment and for 6 weeks after stopping. Male patients and partners: use condoms during treatment and for 90 days after stopping. Exposure in pregnancy: stop, replace with azathioprine and refer to a foetal medicine unit.

Adverse effects. Diarrhoea, nausea, abdominal pain, leucopenia, anaemia, infection (cytomegalovirus, BK virus, herpes zoster), progressive multifocal leukoencephalopathy (rare) and pure red cell aplasia (rare).

Regional. Screen for hepatitis B, hepatitis C, HIV and tuberculosis; give cytomegalovirus and pneumocystis prophylaxis in transplant recipients.

Monitoring. Full blood count weekly for 4 weeks, every 2 weeks for months 2 and 3, then monthly in year 1 and every 3 months after. Creatinine and liver tests with each blood count. Mycophenolic acid area under the curve (target 30 to 60 mg.h/L) is useful in transplantation but not routine.

Withhold. Neutrophils under 1.3 x 10⁹/L, platelets under 100 x 10⁹/L, haemoglobin falling over 2 g/dL, or active infection.

Stop and escalate. Stop for pregnancy, serious infection, severe cytopenia, unexplained neurological change (possible progressive multifocal leukoencephalopathy) or malignancy; refer for urgent specialist review.