What are the potential side effects of mycophenolate (Cellcept) sodium in patients taking this immunosuppressant medication?

Side Effects of Mycophenolate Sodium

Mycophenolate sodium causes gastrointestinal toxicity (diarrhea, nausea, vomiting), hematologic abnormalities (leukopenia, anemia, thrombocytopenia), and increased risk of serious infections as its most common and clinically significant adverse effects. 1, 2

Major Side Effect Categories

Gastrointestinal Effects (Most Common)

• Diarrhea, nausea, vomiting, abdominal pain, dyspepsia, anorexia, and constipation are the most frequently reported adverse effects 3, 1, 2
• Serious gastrointestinal complications include mouth, esophageal, gastric, duodenal, and intestinal ulcers often complicated by hemorrhage, as well as hematemesis, melena, and hemorrhagic forms of gastritis and colitis 2
• Isolated cases of intestinal villous atrophy have been documented on endoscopic investigation in patients with mycophenolate-related diarrhea 2, 4
• Crohn's disease-like changes, erosive enterocolitis, and graft-versus-host disease-like colonic changes have been reported 5
• The enteric-coated formulation (mycophenolate sodium) may reduce upper GI symptoms compared to mycophenolate mofetil, though overall GI adverse effect rates remain similar 6, 7, 8

Hematologic Effects

• Leukopenia is the most common hematologic effect, followed by anemia and thrombocytopenia 3, 1, 2
• Severe neutropenia (ANC < 0.5 x 10³/μL) develops in up to 2% of kidney transplant patients, 2.8% of heart transplant patients, and 3.6% of liver transplant patients receiving 3 g daily 2
• Pancytopenia and rare cases of pure red cell aplasia (PRCA) have been reported 2
• Bone marrow failure has been documented in postmarketing surveillance 2

Infectious Complications

• Patients face increased risk of bacterial, fungal, protozoal, and viral infections (both new and reactivated) due to immunosuppression 1, 2
• The most common opportunistic infections are mucocutaneous candida, CMV viremia/syndrome (13.5% of patients), and herpes simplex 2
• Fatal infection/sepsis occurs in approximately 2% of kidney and heart patients and 5% of liver transplant patients 2
• Serious viral infections include polyomavirus-associated nephropathy (PVAN, especially BK virus), JC virus-associated progressive multifocal leukoencephalopathy (PML), tuberculosis, and atypical mycobacterial infections 1, 2
• Viral reactivation of hepatitis B and hepatitis C has been reported 2
• Meningitis and infectious endocarditis are documented postmarketing complications 2

Genitourinary Effects

• Urinary tract infections, hematuria, urinary frequency, burning on urination, tubular necrosis, kidney stones, and vaginal burning and bleeding are common 1, 6
• Sterile pyuria and urgency have been reported 3

Cardiovascular Effects

• Systemic hypertension, peripheral edema, and tachycardia occur frequently 1, 6
• Venous thrombosis has been reported with intravenous administration 2

Metabolic and Endocrine Effects

• Hyperglycemia, hypercholesterolemia, hypophosphatemia, hyperkalemia, and hypokalemia are documented 3, 1, 6
• Cushingoid changes and hirsutism may occur 1

Neurologic Effects

• Headache, tremor, insomnia, dizziness, anxiety, paresthesia, somnolence, and hypertonia are reported 1, 2
• Confusion may occur, particularly in elderly patients 2

Dermatologic Effects

• Rash and increased risk of skin neoplasms (particularly squamous cell carcinoma) are significant concerns 3, 1
• Skin benign neoplasms and skin carcinomas have been documented 2

Respiratory Effects

• Increased cough, dyspnea, respiratory infections, risk of pneumonitis, and fibrosis are reported 1
• Pulmonary edema may occur, particularly in elderly patients 2

Musculoskeletal Effects

• Bone pain, leg cramps, myalgias, hand cramps, arthralgia, and myasthenia have been documented 1, 2

Malignancy Risk

• Post-transplant lymphoproliferative disorder (PTLD) develops in 0.4% to 1% of patients, with the majority related to Epstein-Barr Virus (EBV) infection 2
• The risk is greatest in EBV-seronegative individuals, including many young children 2
• Lymphomas and other malignancies, particularly skin cancers, occur with increased frequency related to intensity and duration of immunosuppression 2

Critical Pregnancy and Teratogenic Risks

• FDA black box warning: Mycophenolate is absolutely contraindicated in pregnancy due to severe teratogenic and embryocidal effects 1, 6, 2
• The miscarriage rate is 49% and structural anomaly rate is 23% in live births 6
• Congenital malformations include facial abnormalities (cleft lip/palate, micrognathia, hypertelorism), ear and eye abnormalities (abnormally formed or absent external/middle ear, coloboma, microphthalmos), finger malformations (polydactyly, syndactyly, brachydactyly), cardiac defects (atrial and ventricular septal defects), esophageal atresia, and nervous system malformations (spina bifida) 2
• Patients require two reliable forms of contraception and a 12-week washout period before attempting pregnancy 6
• Pregnancy and breast-feeding must be avoided during treatment, and both male and female patients must use adequate contraceptive precautions 3

Drug Interactions

• Absorption is inhibited by activated charcoal, aluminum/magnesium antacids, cholestyramine, colesevelam, colestipol, iron supplements, and calcium 3, 1, 6
• Coadministration with azathioprine increases purine metabolism inhibition and must be avoided 1, 6, 9
• Increases plasma concentration of acyclovir, ganciclovir, and valganciclovir, especially with renal impairment 3, 1
• May decrease effectiveness of hormonal contraceptives 1
• Live attenuated virus vaccines must be avoided during treatment 3, 1, 6
• Antibiotics including cephalosporins, fluoroquinolones, macrolides, penems, penicillins, and sulfonamides inhibit enterohepatic recirculation and decrease mycophenolate levels 3
• High-dose salicylates, phenytoin, xanthine bronchodilators, and probenecid may interact 3

Special Population Considerations

Pediatric Patients

• Abdominal pain, fever, infection, pain, sepsis, diarrhea, vomiting, pharyngitis, respiratory tract infection, hypertension, leukopenia, and anemia occur at higher proportions in pediatric patients compared to adults 2

Geriatric Patients (≥65 years)

• Elderly patients are at increased risk of certain infections (including CMV tissue invasive disease), gastrointestinal hemorrhage, and pulmonary edema compared to younger individuals 2

Renal Impairment

• The glucuronide metabolite (MPAG) accumulates approximately five times normal levels in end-stage renal disease, potentially increasing susceptibility to various adverse effects including metabolic disturbances 1

Common Pitfalls to Avoid

• Do not assume all diarrhea is benign; colonoscopy may reveal serious pathology including villous atrophy, erosive enterocolitis, or Crohn's disease-like changes 5, 4
• Do not overlook the need for intensive hematologic monitoring, particularly during the first 6 months when neutropenia risk is highest 2
• Do not underestimate infection risk; maintain high clinical suspicion for opportunistic infections including PML, PVAN, and CMV disease 2
• Do not forget that mycophenolate reduces effectiveness of hormonal contraceptives; additional contraceptive methods are mandatory 1
• Do not administer live vaccines during treatment 1, 6