MycophenolateRx

Trade Names: CellCept

Synonyms: Mycophenolate mofetil

Drug Class: Immunosuppressant

Preparations
Tablet: 500 mg
Capsule: 250 mg

Dose: In lupus nephritis usually started at 500 mg twice daily for a week and, if tolerated, increased to 1 g twice daily for a week and then increased to a target of 1.5 g twice daily.  For maintenance therapy after remission lower doses (2 g/day) are used.

Indications:  Treatment of SLE, vasculitis, inflammatory muscle disease

Mechanism of Action: Inosine monophosphate dehydrogenase inhibitor, inhibits guanine and de novo purine synthesis, inhibits T and B lymphocyte proliferation

Contraindications: Hypersensitivity to mycophenolate or mycophenolic acid, pregnancy, avoid live virus vaccines

Precautions: The patient must understand the risks and benefits of treatment and the requirement for monitoring. Pregnant women must not receive mycophenolate. Contraceptive methods should be reviewed and be in place before starting therapy. Because mycophenolate may affect the efficacy of estrogen contraceptives, two methods of contraception are recommended. Avoid live virus vaccines.

Monitoring
CBC, platelets, LFTs, creatinine at baseline; check CBC every 2 weeks till stable and and once stable CBC and LFTs every 4–8 weeks.

Pregnancy Risk: D; increased congenital malformations

Adverse Effects
Common: Nausea, GI cramps, diarrhea, headache
Less common: Vomiting, leukopenia, neutropenia, pure red cell aplasia, elevated liver enzymes, hypertension,edema, rash, hyperglycemia, tremor, increased risk of infection, skin cancer, herpes zoster, lymphoma, reactivation of hepatitis B or C, gastrointestinal perforation or bleeding

Drug Interactions
Antacids and cholestyramine: Decreased serum concentrations
Azathioprine: Increased toxicity, avoid this combination
Rifampin: Decreased serum concentrations
Oral contraceptives: Decreased contraceptive efficacy

Patient Instructions: Never increase the dose by yourself. Do not become pregnant. Protect skin from the sun.

Comments: Appears to be as effective as cyclophosphamide  for induction therapy and more effective than azathioprine for maintenance therapy of lupus nephritis with a better side effect profile. In ANCA-associated vasculitis less effective than azathioprine in maintaining remission.

Clinical Pharmacology: Rapidly and completely absorbed, rapidly de-esterified to mycophenolic acid, the active drug, which is glucuronidated and excreted in the urine. Plasma half-life of mycophenolic acid is 16 hours.

Cost: $$$$$

BIBLIOGRAPHY

Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 2012;64:797-808. PMID: 22556106

Dooley MA, Jayne D, Ginzler EM, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N EnglJ Med 2011;365:1886-95. PMID: 22087680.

Henderson LK, Masson P, Craig JC, et al Induction and maintenance treatment of proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis 2013;61:74-87. PMID:23182601.

Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA 2010;304:2381-8. PMID: 21060104.