Version October 2024
Only health care providers experienced in immunosuppressive therapy and management of organ transplant patients should prescribe mycophenolate. Manage patients receiving the drug in facilities equipped and staffed with adequate laboratory and supportive medical resources. The health care provider responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.
Immunosuppression may lead to increased susceptibility to bacterial, viral, fungal, and protozoal infections, including opportunistic infections and viral reactivation of hepatitis B and C, which may lead to hospitalizations and fatal outcomes.
Immunosuppression may lead to increased risk of development of lymphoma and other malignancies, particularly of the skin.
Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations. Avoid if safer treatment options are available. Women of reproductive potential must be counseled regarding pregnancy prevention and planning.
Dosage guidance:
Dosage form information: Mycophenolate mofetil (CellCept) and enteric-coated (delayed-release) mycophenolate sodium (Myfortic) are not equivalent. Conversion to equimolar doses is necessary. Mycophenolate mofetil 500 mg is considered equivalent to mycophenolate sodium 360 mg (Ref). IV and oral doses of mycophenolate mofetil are equivalent; transition to oral therapy as soon as tolerated.
Usual dosage range:
Mycophenolate mofetil: Oral, IV: 500 mg to 1.5 g twice daily.
Mycophenolate sodium, delayed release: Oral: 360 to 1,080 mg twice daily.
Bullous pemphigoid, adjunctive therapy (alternative agent) (off-label use): Mycophenolate mofetil: Oral: 750 mg to 1 g twice daily (maximum dose: 3 g/day) in combination with a glucocorticoid (Ref).
Dermatomyositis, cutaneous, refractory (off-label use):
Note: Some experts recommend overlapping with preceding therapy to minimize risk for disease flares (Ref).
Mycophenolate mofetil: Oral: Initial: 500 mg twice daily for 2 weeks then 1 g twice daily. Increase dose to 1.5 g twice daily if needed (Ref).
Dermatomyositis/Polymyositis, refractory (alternative agent) (off-label use):
Note: For use in patients who do not respond sufficiently to conventional induction regimens (eg, systemic glucocorticoids plus azathioprine or methotrexate) (Ref).
Mycophenolate mofetil: Oral: 1 g twice daily; may increase dose to 1.5 g twice daily if needed (Ref). Some experts use lower doses initially (eg, 500 mg once or twice daily) to improve GI tolerance (Ref).
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (alternative agent) (off-label use):
Note: May be used as an alternative induction therapy (in combination with glucocorticoids) in patients with nonsevere disease or as maintenance therapy; efficacy data are limited (Ref).
Mycophenolate mofetil: Oral: 750 mg to 1.5 g twice daily (Ref).
Focal segmental glomerulosclerosis, glucocorticoid-dependent or glucocorticoid-resistant (alternative agent) (off-label use):
Note: Some experts reserve use for patients who have either not responded to or should not be exposed to calcineurin inhibitors, or who have had a partial response to calcineurin inhibitors but developed signs of toxicity (Ref).
Mycophenolate mofetil: Oral: 750 mg to 1 g twice daily in combination with low-dose glucocorticoids (Ref).
Mycophenolate sodium, delayed release: Oral: 540 to 720 mg twice daily in combination with low-dose glucocorticoids (Ref).
Graft-versus-host disease in allogeneic hematopoietic cell transplantation (off-label use):
Prophylaxis:
Note: Generally reserved for patients receiving nonmyeloablative or reduced intensity conditioning regimens; may be an alternative antimetabolite for patients receiving myeloablative conditioning (Ref).
Mycophenolate mofetil: Oral, IV: 15 mg/kg twice daily beginning on day 0 (Ref) or 10 to 15 mg/kg 3 times daily beginning on day 0 or day +1 (Ref); usual dose: 1 g 2 to 3 times daily (Ref). Administer in combination with a calcineurin inhibitor and adjust dose based on toxicities. The duration is typically ~1 month for matched-related donation and 2 to 3 months for matched-unrelated donation; individualize duration based on risk of relapse and risk of graft-vs-host disease (Ref).
Treatment, acute or chronic disease, glucocorticoid-resistant (alternative agent): Mycophenolate mofetil: Oral, IV: 1 to 1.5 g twice daily (Ref) or 1 g every 8 hours (Ref) as part of a combination regimen.
Granulomatosis with polyangiitis and microscopic polyangiitis, maintenance therapy (alternative agent) (off-label use):
Note: Efficacy data are limited, with mixed results (Ref).
Mycophenolate mofetil: Oral: 750 mg to 1.5 g twice daily. Continue for a duration of 12 to 24 months after stable remission is induced (Ref).
Hepatitis, autoimmune, refractory (alternative agent) (off-label use): Mycophenolate mofetil: Oral: 1 g twice daily in combination with a glucocorticoid (Ref).
IgA nephropathy, primary, nonvariant (adjunctive agent) (off-label use):
Note: May consider for use as an alternative to glucocorticoids or as a glucocorticoid-sparing agent in selected patients at high risk of chronic kidney disease progression (eg, proteinuria ≥ 0.75 to 1 g/day) despite 3 to 6 months of optimized doses of nonimmunosuppressive therapies (eg, renin-angiotensin system inhibitors) (Ref). The optimal dose has not been established and may vary based on institutional protocols and patient-specific factors.
Mycophenolate mofetil: Oral: 750 mg to 1 g twice daily for 6 to 12 months; may be followed by a lower maintenance dose for an additional 6 months (Ref). Some experts initiate at a lower dose (eg, 500 mg twice daily) and increase as tolerated over several weeks to the recommended maintenance dose, then slowly taper and discontinue after 12 months of therapy. If disease worsens after 4 to 6 months of treatment, consider switching to an alternative agent (Ref).
Interstitial nephritis, acute (alternative agent) (off-label use):
Note: Reserve for use in glucocorticoid-resistant or glucocorticoid-dependent disease; based on limited data (Ref).
Mycophenolate mofetil: Oral: Initial: 500 mg twice daily; titrate up to goal dose of 1 g twice daily as tolerated (Ref).
Interstitial pneumonia (nonspecific)/connective tissue–associated interstitial lung disease (off-label use): Mycophenolate mofetil: Oral: Initial: 500 mg twice daily; increase to goal maintenance dose of 1 to 1.5 g twice daily as tolerated; give as monotherapy or in combination with a glucocorticoid (Ref).
Lupus erythematosus (off-label use):
Discoid lupus and subacute cutaneous lupus, refractory (alternative agent):
Note: Dose not well established.
Mycophenolate mofetil: Oral: 1 to 1.5 g twice daily (Ref).
Mycophenolate sodium, delayed release: Oral: 720 mg twice daily (Ref).
Duration: ~2 to 3 months (Ref).
Lupus nephritis, focal or diffuse:
Note: Give as part of an appropriate combination regimen (Ref).
Initial therapy:
Mycophenolate mofetil: Oral: 1 to 1.5 g twice daily (Ref) or 500 mg twice daily for 1 week, then 1 g twice daily for 1 week, then 1.5 g twice daily (Ref).
Mycophenolate sodium, delayed release: Oral: 720 mg twice daily (Ref).
Duration: Variable, ~6 months (Ref).
Subsequent therapy:
Mycophenolate mofetil: Oral: 1 g twice daily (range: 500 mg to 3 g/day) (Ref). Duration is typically ≥2 years (Ref).
Mycophenolate sodium, delayed release: Oral: 360 mg twice daily (Ref).
Minimal change disease (alternative agent) (off-label use):
Note: Reserve use for patients who are unable to tolerate high-dose glucocorticoid monotherapy or who have frequently relapsing disease (Ref).
Mycophenolate mofetil: Oral: 500 mg twice daily for ~1 week, then 1 g twice daily; give in combination with low-dose glucocorticoids (Ref).
Mycophenolate sodium, delayed release: Oral: 360 mg twice daily for ~1 week, then 720 mg twice daily; give in combination with low-dose glucocorticoids (Ref).
Myasthenia gravis, chronic immunosuppressive therapy (off-label use):
Note: For use as monotherapy or in combination with glucocorticoids in patients with glucocorticoid-resistant or glucocorticoid-dependent disease. Due to delayed onset of clinical response, most often initially given in combination with a glucocorticoid (Ref).
Mycophenolate mofetil: Oral: Initial: 500 mg twice daily; increase after 1 to 4 weeks based on response and tolerability to a maintenance dose of 1 to 1.5 g twice daily (Ref). Onset of clinical response to mycophenolate may take up to 6 to 12 months, with a maximum effect not apparent until 1 to 2 years (Ref).
Solid organ transplantation, maintenance immunosuppressive therapy:
Heart transplantation:
Mycophenolate mofetil: Oral, IV: 1 to 1.5 g twice daily as part of an appropriate combination regimen (Ref).
Mycophenolate sodium, delayed release (off-label use): Oral: 720 to 1,080 mg twice daily as part of an appropriate combination regimen (Ref).
Kidney transplantation:
Mycophenolate mofetil: Oral, IV: 1 g (range: 500 mg to 1 g) twice daily as part of an appropriate combination regimen (Ref).
Mycophenolate sodium, delayed release: Oral: 720 mg (range: 360 to 720 mg) twice daily as part of an appropriate combination regimen (Ref).
Liver transplantation:
Mycophenolate mofetil: Oral, IV: 1 g twice daily as part of an appropriate combination regimen (Ref).
Mycophenolate sodium, delayed release (off-label use): Oral: 720 mg twice daily as part of an appropriate combination regimen (Ref).
Lung transplantation (off-label use):
Mycophenolate mofetil: Oral, IV: 1 to 1.5 g twice daily as part of an appropriate combination regimen (Ref).
Mycophenolate sodium, delayed release: Oral: 720 to 1,080 mg twice daily as part of an appropriate combination regimen (Ref).
Pancreas transplantation (off-label use):
Mycophenolate mofetil: Oral, IV: 1 to 3 g/day in divided doses as part of an appropriate combination regimen (Ref).
Mycophenolate sodium, delayed release: Oral: 720 mg twice daily as part of an appropriate combination regimen (Ref).
Systemic sclerosis (scleroderma) (off-label use):
Note: Used primarily in patients with diffuse skin disease or interstitial lung disease (Ref).
Mycophenolate mofetil: Oral: Initial: 500 mg twice daily; increase up to 1.5 g twice daily as tolerated (Ref).
Mycophenolate sodium, delayed release: Oral: Initial: 360 mg twice daily; increase up to 720 mg twice daily as tolerated (Ref). Based on data with mycophenolate mofetil and equivalency, may consider increasing dose to 1,080 mg twice daily (Ref).
Takayasu arteritis (alternative agent) (off-label use): Mycophenolate mofetil: Oral: 750 mg to 1.5 g twice daily as tolerated in combination with a glucocorticoid (Ref).
Toxicities associated with immune checkpoint inhibitor therapy, treatment (alternative agent) (off-label use):
Note: For treatment of immune-mediated, glucocorticoid-refractory cardiac, hematologic, hepatic, kidney, musculoskeletal, or pulmonary toxicities (Ref).
Mycophenolate mofetil: Oral, IV: 500 mg to 1 g twice daily in combination with glucocorticoids (Ref); doses of up to 1.5 g twice daily have been used for severe pneumonitis (Ref).
Uveitis, noninfectious (off-label use):
Note: Some experts reserve for use in patients with severe or bilateral disease, active inflammation, or glucocorticoid-resistant or glucocorticoid-dependent disease (Ref).
Mycophenolate mofetil: Oral: Initial: 500 mg twice daily for 2 weeks; increase to a maintenance dose of 1 to 1.5 g twice daily as tolerated (Ref).
Mycophenolate sodium, delayed release: Oral: Initial: 360 mg twice daily for 1 week; increase to a maintenance dose of 720 mg twice daily as tolerated (Ref). Based on data with mycophenolate mofetil and equivalency, may consider increasing dose to 1,080 mg twice daily (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Dosing varies by indication, concomitant medications, time post-transplant, genetic factors, and kidney function; interindividual variability is significant (Ref). Mycophenolic acid (MPA) (active metabolite) exposure increases as kidney function decreases (Ref); mycophenolic acid glucuronide (inactive metabolite) accumulates in severe kidney impairment (Ref).
Immediate post-transplant period: No dosage adjustment necessary for any degree of kidney dysfunction. Rapid achievement of adequate immunosuppressive concentrations is necessary to prevent rejection (Ref). Note: Immediate post-transplant period may vary; refer to institution-specific protocols for further details.
Chronic use (including outside the immediate post-transplant period):
Altered kidney function: IV, Oral:
eGFR ≥25 mL/minute/1.73 m2: No dosage adjustment necessary. Therapeutic drug monitoring may be considered for patients with eGFR <60 mL/minute/1.73 m2 when available (Ref).
eGFR <25 mL/minute/1.73 m2: No initial dosage adjustment necessary; use with caution. For nontransplant indications, consider limiting dose to mycophenolate mofetil 1 g twice daily or mycophenolate sodium delayed release 720 mg twice daily, or monitor closely for adverse effects such as leukopenia from increased MPA exposure. Therapeutic drug monitoring is recommended when available (Ref).
Hemodialysis, intermittent (thrice weekly): Not dialyzable (Ref):
IV, Oral: No initial dosage adjustment necessary; use with caution. For nontransplant indications, consider limiting dose to mycophenolate mofetil 1 g twice daily or mycophenolate sodium delayed release 720 mg twice daily, or monitor closely for adverse effects from increased MPA exposure (Ref). Increased incidence of adverse effects (eg, GI symptoms, anemia, leukopenia) requiring dose reduction or discontinuation have been reported in patients with end-stage kidney disease (ESKD) (Ref). Therapeutic drug monitoring is recommended when available (Ref).
Peritoneal dialysis: Not dialyzable (Ref):
IV, Oral: No initial dosage adjustment necessary; use with caution; however, for nontransplant indications, consider limiting dose to mycophenolate mofetil 1 g twice daily or mycophenolate sodium delayed release 720 mg twice daily, or monitor closely for adverse effects from increased MPA exposure. Increased incidence of adverse effects (eg, GI symptoms, anemia, leukopenia) requiring dose reduction or discontinuation have been reported in patients with ESKD (Ref). Therapeutic drug monitoring is recommended when available (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and for adverse effects (eg, GI symptoms, anemia, leukopenia) due to drug accumulation is important. Therapeutic drug monitoring is recommended when available due to alterations in protein binding associated with critical illness, which may increase free mycophenolate concentrations (Ref).
IV, Oral: Dose as in eGFR <25 mL/minute/1.73 m2, as removal by CRRT is expected to be insignificant (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and for adverse effects (eg, GI symptoms, anemia, leukopenia) due to drug accumulation is important. Therapeutic drug monitoring is recommended when available due to alterations in protein binding associated with critical illness, which may increase free mycophenolate concentrations (Ref).
IV, Oral: Dose as in eGFR <25 mL/minute/1.73 m2, as removal by PIRRT is expected to be insignificant (Ref).
No dosage adjustment is recommended for renal patients with severe hepatic parenchymal disease; however, it is not currently known whether dosage adjustments are necessary for hepatic disease with other etiologies. Increased monitoring may be necessary in patients with hyperbilirubinemia and/or hypoalbuminemia; displacement or decreased number of binding sites may occur resulting in an increase concentration of MPA/MPAG free fraction (Ref).
Neutropenia (ANC <1.3 x 103/mcL): Dosing should be interrupted or the dose reduced, appropriate diagnostic tests performed and patients managed appropriately
Dosage is the same as for younger patients; however, dosing should be cautious due to possibility of increased hepatic, renal, or cardiac dysfunction. Patients ≥65 years of age may be at an increased risk of certain infections, GI hemorrhage, and pulmonary edema, as compared to patients <65 years of age.
(For additional information see "Mycophenolate mofetil (Cellcept) and mycophenolate sodium (Myfortic): Pediatric drug information")
Dosage guidance:
Dosage form information: The parenteral formulation for IV administration may be used for up to 14 days; transition to oral therapy as soon as tolerated. Mycophenolate mofetil (CellCept) tablets, capsules, and suspension, and mycophenolate sodium as the delayed-release tablet formulation (Myfortic) are not equivalent on a mg:mg basis due to differences in the rate of absorption. Mycophenolate sodium delayed release 720 mg twice daily was shown to be bioequivalent to mycophenolate mofetil 1,000 mg twice daily. Consult institution-specific protocols.
Heart transplantation, immunosuppressive therapy:
Mycophenolate mofetil (CellCept):
Infants ≥3 months, Children, and Adolescents:
Suspension: Oral: Initial: 600 mg/m2/dose twice daily; if tolerated, may increase to 900 mg/m2/dose twice daily; maximum daily dose: 3,000 mg/day.
Tablets or capsules: For patients with a BSA ≥1.25 m2:
BSA 1.25 to <1.5 m2: Oral: Initial: 750 mg twice daily; if tolerated, may increase dose as appropriate (using twice-daily dosing); maximum daily maintenance dose: 3,000 mg/day.
BSA ≥1.5 m2: Oral: Initial: 1,000 mg twice daily; if tolerated, may increase dose as appropriate (using twice-daily dosing); maximum daily maintenance dose: 3,000 mg/day.
Kidney transplantation, immunosuppressive therapy:
Mycophenolate mofetil (CellCept):
Infants ≥3 months, Children, and Adolescents:
Suspension: Oral: 600 mg/m2/dose twice daily; maximum daily dose: 2,000 mg/day.
Tablets or capsules:
BSA 1.25 to <1.5 m2: Oral: 750 mg twice daily.
BSA ≥1.5 m2: Oral: 1,000 mg twice daily.
Mycophenolate sodium delayed-release tablets (Myfortic):
Children ≥5 years and Adolescents: Oral: 400 mg/m2/dose twice daily; maximum daily dose: 1,440 mg/day; avoid partial tablet doses by rounding doses to nearest whole tablet size as follows:
BSA <1.19 m2: Use of this formulation is not recommended.
BSA 1.19 to 1.58 m2: Oral: 540 mg twice daily.
BSA >1.58 m2: Oral: 720 mg twice daily.
Liver transplantation, immunosuppressive therapy:
Mycophenolate mofetil (Cellcept):
Infants ≥3 months, Children, and Adolescents:
Suspension: Oral: Initial: 600 mg/m2/dose twice daily; if tolerated, may increase to 900 mg/m2/dose twice daily; maximum daily dose: 3,000 mg/day.
Tablets or capsules: For patients with a BSA ≥1.25 m2:
BSA 1.25 to <1.5 m2: Oral: Initial: 750 mg twice daily; if tolerated, may increase dose as appropriate (twice-daily dosing); maximum daily maintenance dose: 3,000 mg/day.
BSA ≥1.5 m2: Oral: Initial: 1,000 mg twice daily; if tolerated, may increase dose as appropriate (twice-daily dosing); maximum daily maintenance dose: 3,000 mg/day.
Lupus nephritis: Limited data available:
Mycophenolate mofetil (CellCept):
Children and Adolescents: Oral:
BSA-based dosing: Induction and Maintenance: 300 to 600 mg/m2/dose twice daily; maximum daily dose: 3,000 mg/day (Ref).
Nephrotic syndrome: Limited data available:
Mycophenolate mofetil (CellCept):
Children and Adolescents: Oral:
Frequently relapsing:
BSA-based dosing: 600 mg/m2/dose twice daily for at least 12 months; maximum daily dose: 2,000 mg/day (Ref).
Weight-based dosing: 12.5 to 18 mg/kg/dose twice daily; maximum daily dose: 2,000 mg/day for 1 to 2 years with a tapering dose of prednisone (Ref).
Steroid-dependent (for steroid sparing effect):
BSA-based dosing: 600 mg/m2/dose twice daily for at least 12 months; maximum daily dose: 2,000 mg/day (Ref).
Weight-based dosing: 12 to 18 mg/kg/dose twice daily; maximum daily dose: 2,000 mg/day (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Hematologic: ANC <1.3 x 103/μL or anemia: Dosing should be interrupted or the dose reduced.
Mycophenolate mofetil (CellCept): Infants ≥3 months, Children, and Adolescents: Note: Dose adjustments are not needed in kidney transplant recipients experiencing delayed graft function postoperatively. There are no pediatric-specific recommendations for liver or heart transplantation.
Kidney transplant with mild to moderate chronic impairment (GFR ≥25 mL/minute/1.73 m2): No adjustment necessary.
Kidney transplant with severe chronic impairment (GFR <25 mL/minute/1.73 m2): Avoid doses >1,000 mg/dose twice daily; monitor carefully.
Mycophenolate delayed-release tablet (Myfortic): Children ≥5 years and Adolescents: No dosage adjustments are provided in the manufacturer's labeling; however, based on experience with other salt forms, it is likely that no dose adjustments are needed in kidney transplant recipients experiencing delayed graft function postoperatively; monitor carefully for potential concentration dependent adverse events.
Dialysis:
Hemodialysis: Not removed; supplemental dose is not necessary.
Peritoneal dialysis: Supplemental dose is not necessary.
Mycophenolate mofetil (CellCept): Infants ≥3 months, Children, and Adolescents: No dosage adjustment is recommended for renal patients with severe hepatic parenchymal disease; however, it is not currently known whether dosage adjustments are necessary for hepatic disease with other etiologies.
Mycophenolate delayed release (Myfortic): Children ≥5 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mycophenolate administration may result in a reversible acute inflammatory syndrome (AIS) which is characterized by fever, arthralgias, arthritis, myalgias, and increased inflammatory markers (eg, C-reactive protein, erythrocyte sedimentation rate) without evidence of infection or disease recurrence. Improvement typically occurs within 24 to 48 hours of discontinuation.
Mechanism: Exact mechanism unknown; AIS is a pro-inflammatory reaction without evidence of infection or disease recurrence.
Onset: Varied; according to the manufacturer, symptoms occur within weeks to months of initiation of treatment or dose increases.
Mycophenolate administration may result in reversible bone marrow suppression, most commonly anemia or leukopenia (Ref). Neutropenia can be severe and may result in an increased risk of infectious complications. Thrombocytopenia may also commonly occur (Ref). In patients being treated for systemic lupus erythematosus (SLE), hematologic disorders may occur less frequently with mycophenolate as compared to other treatment options (Ref). Bone marrow suppression may warrant treatment interruption, dosage adjustment, or discontinuation; the risk of reduced immunosuppression and graft rejection should be considered in transplant recipients.
Mechanism: Exact mechanism unknown; related to pharmacologic action. Mycophenolate is an inhibitor of inosine monophosphate dehydrogenase (IMPDH) which can result in the induction of apoptosis or inhibition of cell proliferation (Ref). While some evidence exists that suggest a relationship between the degree of mycophenolate exposure (eg, dose, total mycophenolate AUC, free mycophenolate AUC, metabolite(s) AUC, trough concentrations) and the manifestation of bone marrow suppression, data are inconclusive to support a consistent relationship (Ref). In addition, the impact of transplantation and/or other disease processes must be considered (Ref).
Onset: Delayed; according to the manufacturer, neutropenia was observed most frequently in the period from 31 to 180 days post-transplant in patients treated for prevention of kidney, heart, and liver rejection. One retrospective trial found the average onset of leukopenia, anemia, and thrombocytopenia to be ~5 to 6 months in patients receiving mycophenolate after kidney transplantation (Ref). Because the degree of mycophenolate exposure may relate to the manifestation of bone marrow suppression, onset may be affected by dose adjustments or pharmacokinetic variability. Genetic factors may impact onset of leukopenia; one trial found that certain single nucleotide polymorphisms (SNPs) in the IMPDH1 gene were associated with an increased time to leukopenia by ~90 days (Ref).
Risk factors:
• Increased mycophenolate exposure; Note: Data are inconclusive to support a consistent relationship (Ref). There is a high amount of inter- and intrapatient variability with mycophenolate pharmacokinetics due to differences in formulations; gastric pH fluctuations; genetics (eg, UGT-glucuronosyltransferases, transporters); renal and hepatic function; enterohepatic recirculation; etc (Ref). Increased risk of bone marrow suppression may be associated with:
- increased trough concentrations, Cmax, or AUC (Ref)
- higher doses (Ref)
- decreased clearance (Ref)
• Concomitant use of other agents known to cause bone marrow suppression
GI effects, including diarrhea, abdominal pain, nausea, and vomiting, are among the most common adverse effects associated with the use of mycophenolate. Additional symptoms may include constipation, decreased appetite, dyspepsia, and flatulence. Use may rarely be associated with gastric or duodenal ulcers, gastrointestinal hemorrhage, and/or perforation. Patients who undergo colonoscopy for GI complaints secondary to mycophenolate have demonstrated endoscopic features of erythema and erosions/ulcers and histological findings including acute colitis-like findings, inflammatory bowel disease-like characteristics, ischemia-like findings, and graft-versus-host disease-like features (Ref). Presence of GI symptoms may result in noncompliance, slower rates of dose titration, dose reduction, treatment interruption, and/or discontinuation (Ref); the risk of reduced immunosuppression and graft rejection should be considered in transplant recipients. Clinicians should note that some GI effects may be the result of an infectious process (Ref).
Mechanism: Exact mechanism is unknown. Existing theories include direct gut toxicity of the mofetil ester or local toxicity of acyl-mycophenolic acid glucuronide in the GI tract; may also be a result of the pharmacologic action (inhibition of inosine monophosphate dehydrogenase [IMPDH] and subsequent inhibition of enterocyte proliferation) (Ref). While some evidence exists that suggest a relationship between the degree of mycophenolate exposure (eg, dose, total mycophenolate AUC, free mycophenolate AUC, metabolite(s) AUC, trough concentrations) and the risk of GI effects, data are inconclusive to support a consistent relationship (Ref). In addition, the impact of other disease processes must be considered (eg, systemic sclerosis, graft-versus-host disease, infectious processes) (Ref).
Onset: Varied; one retrospective study of patients receiving mycophenolate who had undergone an upper GI tract biopsy found that symptoms developed between 1 month and 10 years post-transplantation (Ref).
Risk factors:
• Concomitant use of calcineurin inhibitors (Ref)
• Use of a nonenteric-coated formulation; Note: An enteric-coated formulation (Myfortic) was developed to delay release of mycophenolate until the small intestine with a goal of decreasing GI effects; however, data are conflicting on the impact of the enteric-coated formulation on the risk of GI side effects (Ref). One study showed that conversion to an enteric-coated formulation may be particularly helpful between 6- and 12-months post-transplantation or in patients with indigestion, diabetes, on concomitant corticosteroids (Ref).
• Increased mycophenolate exposure; Note: Data are inconclusive to support a consistent relationship (Ref). There is a high amount of inter- and intrapatient variability with mycophenolate pharmacokinetics due to differences in formulations; gastric pH fluctuations; genetics (eg, UGT-glucuronosyltransferases, transporters); renal and hepatic function; enterohepatic recirculation; etc (Ref).
• Females (Ref)
Mycophenolate is an immunosuppressant; therefore, use may result in bacterial, viral, fungal, and protozoal infections, including opportunistic infections. Infections may be severe and potentially fatal (Ref).
Viral infections reported with the use of mycophenolate include polyomavirus infection (which may result in polyomavirus associated nephropathy [PVAN]), JC virus-associated progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV) disease, COVID-19, and reactivation of hepatitis B (HBV) or hepatitis C (HCV). PVAN, primarily from activation of BK virus, may lead to the deterioration of kidney function and/or kidney graft loss, especially in kidney transplant recipients (Ref). CMV infection may result in GI effects (eg, diarrhea) (Ref).
Mechanism: Exact mechanism unknown; related to pharmacologic action. Mycophenolate is an inhibitor of inosine monophosphate dehydrogenase (IMPDH) which results in decreased production of guanosine nucleotides in both B and T lymphocytes (Ref). While some evidence exists that suggests a relationship between the degree of mycophenolate exposure (eg, dose, total mycophenolate AUC, free mycophenolate AUC, metabolite(s) AUC, trough concentrations) and the risk of infections, data are inconclusive to support a consistent relationship (Ref). In addition, the impact of transplantation and/or other disease processes must be considered (Ref).
Onset: Varied. In general, the onset of infections following solid organ transplant varies greatly; the majority of clinically important infections occur within the first 180 days (Ref).
Risk factors:
• Concomitant use of other immunosuppressive agents or preexisting immune function impairment
• Increased mycophenolate exposure; Note: Data are inconclusive to support a consistent relationship (Ref). There is a high amount of inter- and intrapatient variability with mycophenolate pharmacokinetics due to differences in formulations; gastric pH fluctuations; genetics (eg, UGT-glucuronosyltransferases, transporters); renal and hepatic function; enterohepatic recirculation; etc (Ref).
• CMV infection: Transplant recipients that are CMV seronegative at the time of transplant who receive a graft from a CMV-seropositive donor
In general, use of immunosuppressive agents may result in an increased risk of lymphoproliferative disorders and/or neoplasms (including skin carcinoma) (Ref).
Some data suggest that mycophenolate may not be associated with an increased risk of post-transplant lymphoproliferative disorder (PTLD); one case-control study found that risk for PTLD was similar in kidney transplant recipients treated with triple immunosuppressive therapy with or without mycophenolate (Ref).
Mechanism: Exact mechanism unknown; related to the pharmacologic action. Mycophenolate is an inhibitor of inosine monophosphate dehydrogenase (IMPDH) which results in decreased production of guanosine nucleotides in both B and T lymphocytes; its effect appears to be more selective on T-lymphocytes (Ref).
Onset: Delayed; onset of PTLD generally occurs months to years post-transplant; the incidence may be highest in the first year post-transplant when immunosuppressive therapy is most aggressive (Ref).
Risk factors:
• Intensity of immunosuppression (Ref)
• Concomitant use of other immunosuppressive agents or preexisting immune function impairment
• EBV-seronegative transplant recipients (Ref)
- Note: In general, pediatric transplant recipients are at a higher risk of PTLD as these patients are more likely to be EBV seronegative at transplantation (Ref)
- Note: Clinicians may also consider the role that EBV acute infection and/or reactivation may play in the risk of EBV-associated lymphoma in patients receiving immunosuppressive therapies; risk not well defined (Ref)
• Pretransplant malignancy (Ref)
• Fewer HLA matches (Ref)
• History of at least 1 prior rejection episode (Ref)
• Age <25 years or >60 years (Ref)
• Skin carcinoma: Exposure to sunlight/UV light
Pure red cell aplasia (PRCA), a type of anemia which can range from subclinical to severe, has been reported in patients receiving mycophenolate concomitantly with other immunosuppressive agents (eg, tacrolimus, cyclosporine, corticosteroids) (Ref). Symptoms may include fatigue, lethargy, or pallor. Occurrence of PRCA may warrant treatment interruption, dosage adjustment, or discontinuation (Ref); the risk of reduced immunosuppression and graft rejection should be considered in transplant recipients.
Mechanism: Exact mechanism unknown (Ref); the impact of concurrent disease processes (eg, parvovirus B19 infection) should be considered (Ref).
Onset: Delayed (Ref)
Risk factors:
• Concomitant use of other immunosuppressive agents or preexisting immune function impairment
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults. Incidences include concomitant use with cyclosporine and corticosteroids. In general, lower doses used in renal rejection patients had less adverse effects than higher doses. Rates of adverse effects were similar for each indication, except for those unique to the specific organ involved.
>10%:
Cardiovascular: Edema (17% to 68%), hypertension (18% to 79%), hypotension (34%), lower extremity edema (16%), tachycardia (22% to 23%)
Dermatologic: Cellulitis (3% to 20%), ecchymoses (20%), skin rash (26%)
Endocrine & metabolic: Acidosis (3% to 20%), hypercholesterolemia (46%), hyperglycemia (44% to 48%), hyperkalemia (22%), hyperlipidemia (10% to 12%), hyperuricemia (13%), hypocalcemia (11% to 30%), hypokalemia (9% to 37%), hypomagnesemia (20% to 39%), hypophosphatemia (9% to 11%), increased lactate dehydrogenase (24%), weight loss (3% to 20%)
Gastrointestinal: Abdominal pain (14% to 63%) (table 1), constipation (38% to 44%) (table 2), decreased appetite (25%) (table 3), diarrhea (24% to 53%) (table 4), dyspepsia (19% to 23%) (table 5), esophagitis (3% to 20%), flatulence (10% to 13%), gastric ulcer (3% to 20%), gastritis (3% to 20%), gastrointestinal hemorrhage (3% to 20%), hernia of abdominal cavity (3% to 20%), intestinal obstruction (3% to 20%), nausea (27% to 56%) (table 6), stomatitis (3% to 20%), vomiting (20% to 39%) (table 7)
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|---|
|
42% |
39% |
N/A |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
N/A |
|
22% |
23% |
11% |
2 g/day or 3 g/day |
Immediate release |
Kidney transplant |
991 |
326 |
166 |
|
14% |
N/A |
N/A |
1.44 g/day |
Delayed release |
Kidney transplant |
213 |
N/A |
N/A |
|
14% |
N/A |
N/A |
2 g/day |
Immediate release |
Kidney transplant |
210 |
N/A |
N/A |
|
63% |
51% |
N/A |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
N/A |
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
|---|---|---|---|---|---|---|
|
44% |
39% |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
|
40% |
N/A |
2 g/day |
Immediate release |
Kidney transplant |
210 |
N/A |
|
38% |
N/A |
1.44 g/day |
Delayed release |
Kidney transplant |
213 |
N/A |
|
38% |
38% |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
|---|---|---|---|---|---|---|
|
25% |
17% |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|---|
|
53% |
39% |
N/A |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
N/A |
|
30% |
21% |
14% |
2 g/day or 3 g/day |
Immediate release |
Kidney transplant |
991 |
326 |
166 |
|
25% |
N/A |
N/A |
2 g/day |
Immediate release |
Kidney transplant |
210 |
N/A |
N/A |
|
24% |
N/A |
N/A |
1.44 g/day |
Delayed release |
Kidney transplant |
213 |
N/A |
N/A |
|
51% |
50% |
N/A |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
N/A |
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
|---|---|---|---|---|---|---|
|
22% |
22% |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
|
23% |
N/A |
1.44 g/day |
Delayed release |
Kidney transplant |
213 |
N/A |
|
19% |
N/A |
2 g/day |
Immediate release |
Kidney transplant |
210 |
N/A |
|
22% |
21% |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
|---|---|---|---|---|---|---|
|
56% |
60% |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
|
29% |
N/A |
1.44 g/day |
Delayed release |
Kidney transplant |
213 |
N/A |
|
27% |
N/A |
2 g/day |
Immediate release |
Kidney transplant |
210 |
N/A |
|
55% |
51% |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
|---|---|---|---|---|---|---|
|
39% |
35% |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
|
23% |
N/A |
1.44 g/day |
Delayed release |
Kidney transplant |
213 |
N/A |
|
20% |
N/A |
2 g/day |
Immediate release |
Kidney transplant |
210 |
N/A |
|
33% |
33% |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
Genitourinary: Hematuria (3% to 20%), urinary tract infection (29% to 33%)
Hematologic & oncologic: Anemia (20% to 45%) (table 8), benign skin neoplasm (3% to 20%), disorder of hemostatic components of blood (3% to 20%), leukocytosis (22% to 43%), leukopenia (19% to 46%) (table 9), neoplasm (3% to 20%), pancytopenia (3% to 20%), skin carcinoma (3% to 20%; non-melanoma: 1% to 12%), thrombocytopenia (24% to 38%) (table 10)
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|---|
|
45% |
47% |
N/A |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
N/A |
|
22% |
N/A |
N/A |
1.44 g/day |
Delayed release |
Kidney transplant |
213 |
N/A |
N/A |
|
22% |
N/A |
N/A |
2 g/day |
Immediate release |
Kidney transplant |
210 |
N/A |
N/A |
|
20% |
24% |
2% |
2 g/day or 3 g/day |
Immediate release |
Kidney transplant |
991 |
326 |
166 |
|
43% |
53% |
N/A |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
N/A |
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|---|
|
34% |
43% |
N/A |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
N/A |
|
29% |
25% |
4% |
2 g/day or 3 g/day |
Immediate release |
Kidney transplant |
991 |
326 |
166 |
|
21% |
N/A |
N/A |
2 g/day |
Immediate release |
Kidney transplant |
210 |
N/A |
N/A |
|
19% |
N/A |
N/A |
1.44 g/day |
Delayed release |
Kidney transplant |
213 |
N/A |
N/A |
|
46% |
39% |
N/A |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
N/A |
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
|---|---|---|---|---|---|---|
|
24% |
28% |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
|
38% |
42% |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
Hepatic: Hepatitis (3% to 20%), increased liver enzymes (25%), increased serum alkaline phosphatase (3% to 20%)
Infection: Bacterial infection (27% to 40%) (table 11), cytomegalovirus disease (4% to 22%), fungal infection (11% to 12%), viral infection (31%; including COVID-19) (table 12)
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|---|
|
40% |
34% |
37% |
2 g/day or 3 g/day |
Immediate release |
Kidney transplant |
991 |
326 |
166 |
|
27% |
27% |
N/A |
3 g/day |
Immediate release |
Liver transplant |
277 |
287 |
N/A |
|
Drug (Mycophenolate) |
Comparator (Azathioprine) |
Dose |
Dosage Form |
Indication |
Number of Patients (Mycophenolate) |
Number of Patients (Azathioprine) |
|---|---|---|---|---|---|---|
|
31% |
25% |
3 g/day |
Immediate release |
Heart transplant |
289 |
289 |
Nervous system: Chills (3% to 20%), confusion (3% to 20%), depression (20%), dizziness (34%), drowsiness (3% to 20%), headache (11% to 59%), hypertonia (3% to 20%), insomnia (24% to 52%), malaise (3% to 20%), myasthenia (3% to 20%), pain (25% to 79%), paresthesia (3% to 20%)
Neuromuscular & skeletal: Arthralgia (7% to 11%), asthenia (35% to 49%), back pain (6% to 12%), tremor (12% to 34%)
Renal: Increased blood urea nitrogen (37%), increased serum creatinine (10% to 42%)
Respiratory: Cough (41%), dyspnea (31% to 44%), pleural effusion (34%)
Miscellaneous: Fever (13% to 56%)
1% to 10%:
Cardiovascular: Exacerbation of hypertension (<10%), peripheral edema (<10%), phlebitis (4%), thrombosis (4%)
Dermatologic: Acne vulgaris (<10%), pruritus (<10%)
Endocrine & metabolic: Diabetes mellitus (<10%)
Gastrointestinal: Abdominal distension (<10%), gastroesophageal reflux disease (<10%), gingival hyperplasia (<10%), oral candidiasis (<10%)
Genitourinary: Urinary retention (<10%)
Hematologic & oncologic: Lymphocele (<10%), lymphoproliferative disorder (≤1%), malignant lymphoma (1%), malignant neoplasm (≤2%), severe neutropenia (2% to 4%)
Hepatic: Abnormal hepatic function tests (<10%)
Infection: Herpes simplex infection (6% to 8%), herpes zoster infection (4% to 5%), infection (<10%; implant), influenza (<10%), sepsis (2% to 5%), wound infection (<10%)
Nervous system: Anxiety (<10%), fatigue (<10%), peripheral pain (<10%)
Neuromuscular & skeletal: Muscle cramps (<10%), myalgia (<10%)
Ophthalmic: Blurred vision (<10%)
Renal: Renal insufficiency (<10%), renal tubular necrosis (<10%)
Respiratory: Dyspnea on exertion (<10%), nasopharyngitis (<10%), pneumonia (<10%), sinusitis (<10%), upper respiratory tract infection (<10%)
Frequency not defined:
Gastrointestinal: Hemorrhagic colitis, hemorrhagic gastritis, mucocutaneous candidiasis
Infection: Protozoal infection
Respiratory: Pharyngitis, respiratory tract infection
Postmarketing:
Cardiovascular: Endocarditis (Kurnicka 2017), venous thrombosis (Cherney 2001)
Dermatologic: Alopecia (Tunnicliffe 2018)
Gastrointestinal: Anorexia, colitis (Calmet 2015), duodenal ulcer (Chen 2004), esophageal ulcer (Parfitt 2008), gastrointestinal perforation (Karagun 2018), oral mucosa ulcer (Asare 2020), pancreatitis (Einollahi 2015), peritonitis, xerostomia
Hematologic & oncologic: Agranulocytosis (Matsui 2010), bone marrow failure, hypogammaglobulinemia (Boddana 2011; Keven 2003; Robertson 2009), Kaposi's sarcoma (Berti 2015), lymphadenopathy (Caillard 2006; Funch 2005), lymphocytopenia (Lima 2020), pure red cell aplasia (Arbeiter 2000)
Hepatic: Ascites (Weber 2017)
Hypersensitivity: Hypersensitivity reaction (Szyper-Kravitz 2005)
Infection: Atypical mycobacterial infection, BK virus (Accott 2012), hepatitis C (reactivation) (Husain 2002), polyomavirus infection (Accott 2012), reactivation of HBV (Husain 2002)
Nervous system: Meningitis (Kapitsinou 2004; Kluger 2009), progressive multifocal leukoencephalopathy (Neff 2008)
Neuromuscular & skeletal: Osteomyelitis
Respiratory: Bronchiectasis (Boddana 2011; Rook 2006), interstitial pulmonary disease (Tull 2016), pulmonary edema, pulmonary fibrosis (Takahashi 2017), tuberculosis (Macauley 2018), wheezing
Miscellaneous: Inflammation (acute inflammatory syndrome) (Hochegger 2006, Konon 2008)
Hypersensitivity to mycophenolate mofetil, mycophenolic acid, mycophenolate sodium, or any component of the formulation.
Mycophenolate mofetil (CellCept): IV formulation is also contraindicated in patients who are allergic to polysorbate 80 (Tween).
Canadian labeling: Additional contraindications (not in the US labeling): Pregnancy; women of childbearing potential and not using highly effective contraceptive methods; women of childbearing potential not providing a pregnancy test result; breastfeeding.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).
Disease-related concerns:
• Gastrointestinal disorders: Use caution in patients with active serious digestive system disease; patients with active peptic ulcers were not included in clinical studies.
• Hypoxanthine-guanine phosphoribosyltransferase deficiency: Theoretically, use should be avoided in patients with the rare hereditary deficiency of hypoxanthine-guanine phosphoribosyltransferase (such as Lesch-Nyhan or Kelley-Seegmiller syndrome).
• Renal impairment: Use with caution in patients with renal impairment as toxicity may be increased; may require dosage adjustment in severe impairment.
Special populations:
• Patients with systemic lupus erythematosus (SLE) undergoing hip or knee replacement surgery: Patients with severe SLE (referring to patients with severe organ manifestations such as nephritis) should not interrupt therapy when undergoing hip or knee replacement surgery. For patients with SLE without severe disease, hold mycophenolate for at least 1 week prior to surgery to reduce infection risk; therapy can be restarted once surgical wound shows evidence of healing (eg, no swelling, erythema, or drainage), sutures/staples are removed, and no ongoing nonsurgical site infections (typically ~14 days to reduce infection risk) (ACR/AAHKS [Goodman 2022]).
Dosage form specific issues:
• Non-interchangeability of dosage forms: Mycophenolate sodium and mycophenolate mofetil should not be used interchangeably without health care provider supervision because the rate of absorption following the administration of these two products is not equivalent. Single dose pharmacokinetic studies in adult renal transplant recipients suggest that bioavailability is similar between oral mycophenolate mofetil (1 g) and delayed-release mycophenolic acid (720 mg) (Arns 2005). In clinical trials, comparative efficacy and safety profiles have been observed in adult renal transplant recipients randomized to either oral mycophenolate mofetil (1 g twice daily) or delayed-release mycophenolic acid (720 mg twice daily) (Budde 2004b; Salvadori 2004).
• Phenylalanine: Some dosage forms may contain phenylalanine.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Blood donations: Patients should not donate blood or blood products during treatment and for at least 6 weeks after the last dose.
• Discontinuation of therapy: Myasthenia gravis: Abrupt cessation of this or any immunosuppressant, especially in clinically unstable individuals, may result in rapid deterioration of myasthenic symptoms and possibly myasthenic crisis (Melzer 2016).
• Immunizations: Live attenuated vaccines should be avoided during use; vaccinations may be less effective during therapy.
• IV administration: IV solutions should be given over at least 2 hours; never administer IV solution by rapid or bolus injection.
Myhibbin (mycophenolate mofetil oral suspension): FDA approved May 2024; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Consult the prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as mofetil:
CellCept: 250 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 250 mg
Solution Reconstituted, Intravenous, as mofetil hydrochloride:
CellCept Intravenous: 500 mg (1 ea) [contains polysorbate 80]
Generic: 500 mg (1 ea)
Solution Reconstituted, Intravenous, as mofetil hydrochloride [preservative free]:
Generic: 500 mg (1 ea)
Suspension Reconstituted, Oral, as mofetil:
CellCept: 200 mg/mL (160 mL) [contains aspartame, methylparaben, sorbitol, soybean lecithin; mixed fruit flavor]
Generic: 200 mg/mL (160 mL, 170 mL)
Tablet, Oral, as mofetil:
CellCept: 500 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: 500 mg
Tablet Delayed Release, Oral, as mycophenolic acid:
Myfortic: 180 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Myfortic: 360 mg
Generic: 180 mg, 360 mg
Yes
Capsules (CellCept Oral)
250 mg (per each): $10.80
Capsules (Mycophenolate Mofetil Oral)
250 mg (per each): $0.32 - $3.99
Solution (reconstituted) (CellCept Intravenous Intravenous)
500 mg (per each): $129.57
Solution (reconstituted) (Mycophenolate Mofetil HCl Intravenous)
500 mg (per each): $22.61 - $87.00
Suspension (reconstituted) (CellCept Oral)
200 mg/mL (per mL): $10.36
Suspension (reconstituted) (Mycophenolate Mofetil Oral)
200 mg/mL (per mL): $9.06
Tablet, EC (Mycophenolate Sodium Oral)
180 mg (per each): $4.39 - $4.57
360 mg (per each): $9.13 - $9.14
Tablet, EC (Myfortic Oral)
180 mg (per each): $8.14
360 mg (per each): $16.29
Tablets (CellCept Oral)
500 mg (per each): $21.59
Tablets (Mycophenolate Mofetil Oral)
500 mg (per each): $1.14 - $20.51
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as mofetil:
CellCept: 250 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 250 mg
Solution Reconstituted, Intravenous, as mofetil hydrochloride:
CellCept IV: 500 mg (1 ea)
Generic: 500 mg (1 ea)
Suspension Reconstituted, Oral, as mofetil:
CellCept: 200 mg/mL (175 mL) [contains aspartame, methylparaben, soybean lecithin]
Generic: 200 mg/mL (165 mL)
Tablet, Oral, as mofetil:
CellCept: 500 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 500 mg
Tablet Delayed Release, Oral, as mycophenolic acid:
Myfortic: 180 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Myfortic: 360 mg
Generic: 180 mg, 360 mg
Oral: May be administered with or without food as effects of food on bioavailability are minor (Ref). Oral suspension may be administered via a nasogastric tube (minimum 8 French, 1.7 mm interior diameter); do not mix oral suspension with other medications. Delayed-release mycophenolate sodium tablets (Myfortic) should be swallowed whole and should not be crushed, cut, or chewed. If a dose is missed, administer as soon as it is remembered. If it is close to the next scheduled dose, skip the missed dose and resume at next regularly scheduled time; do not double a dose to make up for a missed dose.
Bariatric surgery: Tablet, delayed release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. The release of mycophenolate sodium from the enteric coating occurs in the neutral pH of the intestine. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, clinicians should be vigilant in efficacy/side effect monitoring and consider therapeutic drug monitoring before and after surgery given that interpatient variability of mycophenolate absorption has been observed after gastric bypass (Ref).
IV: IV solutions should be administered over at least 2 hours (either peripheral or central vein); do not administer IV solution by rapid or bolus injection.
Oral:
Mycophenolate mofetil (CellCept): Capsule, tablet, suspension: Administer on an empty stomach to avoid variability in absorption; may be administered with food in stable patients when necessary.
Oral suspension: Shake suspension well before use; may be administered via a nasogastric tube (minimum: 8 French, 1.7 mm interior diameter); oral suspension should not be mixed with other medications or liquids.
Capsules and tablets: Swallow whole; do not crush or open.
Missed dose: If a dose is missed, administer as soon as it is remembered. If it is close to the next scheduled dose (within 2 hours), skip the missed dose and resume at next regularly scheduled time; do not double a dose to make up for a missed dose.
Mycophenolate sodium (Myfortic): Delayed-release tablet: Administer on an empty stomach 1 hour before or 2 hours after food to avoid variability in absorption. Swallow whole; do not crush, chew, or cut.
IV: Do not administer IV push or by rapid IV bolus injection; administer by slow IV infusion over a period of no less than 2 hours.
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Myfortic: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/050791s035lbl.pdf#page=23
Organ transplantation: Prophylaxis of organ rejection in patients receiving allogeneic renal (mycophenolate mofetil [CellCept], mycophenolate sodium, delayed release [Myfortic]), cardiac (mycophenolate mofetil), or liver (mycophenolate mofetil) transplants, in combination with other immunosuppressants.
Note: While traditionally used in combination with cyclosporine, mycophenolate is now used primarily in combination with tacrolimus and, to a lesser extent, with a mammalian target of rapamycin inhibitor (everolimus or sirolimus) for prophylaxis of rejection in renal, cardiac, and hepatic transplants (AASLD/AST [Lucey 2013]; Aliabadi 2012; Eisen 2013; Groetzner 2009; Guethoff 2013; ISHLT [Costanzo 2010]; KDIGO [Chapman 2010]).
Bullous pemphigoid; Dermatomyositis, cutaneous, refractory; Dermatomyositis/Polymyositis, refractory; Discoid lupus and subacute cutaneous lupus, refractory; Eosinophilic granulomatosis with polyangiitis (Churg-Strauss); Focal segmental glomerulosclerosis, glucocorticoid-dependent or glucocorticoid-resistant; Graft-vs-host disease in allogeneic hematopoietic cell transplantation; Granulomatosis with polyangiitis and microscopic polyangiitis; Heart transplantation, maintenance immunosuppressive therapy; Hepatitis, autoimmune, refractory; IgA nephropathy, primary, nonvariant; Interstitial nephritis, acute; Interstitial pneumonia (nonspecific)/connective tissue–associated interstitial lung disease; Liver transplantation, maintenance immunosuppressive therapy; Lung transplantation, maintenance immunosuppressive therapy; Lupus nephritis, focal or diffuse; Minimal change disease; Myasthenia gravis, chronic immunosuppressive therapy; Pancreas transplantation, maintenance immunosuppressive therapy; Pemphigus vulgaris and pemphigus foliaceus; Systemic sclerosis (scleroderma); Takayasu arteritis; Toxicities associated with immune checkpoint inhibitor therapy, treatment; Uveitis, noninfectious
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (immunosuppressant agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care and Long-Term Care Settings).
Substrate of OAT1/3, OATP1B1/1B3 (SLCO1B1/1B3), UGT1A10, UGT1A8, UGT1A9, UGT2B7
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Acyclovir-Valacyclovir: May increase the serum concentration of Mycophenolate. Mycophenolate may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor therapy
Aluminum Hydroxide: May decrease the serum concentration of Mycophenolate. Management: Simultaneous administration of aluminum hydroxide antacids with the Myfortic brand of mycophenolic acid is not recommended. Administrater aluminum hydroxide at least 2 hours after a dose of the Cellcept brand of mycophenolate mofetil. Risk D: Consider therapy modification
Antibiotics: May decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Antithyroid Agents: Myelosuppressive Agents may enhance the neutropenic effect of Antithyroid Agents. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Bile Acid Sequestrants: May decrease the serum concentration of Mycophenolate. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cholestyramine Resin: May decrease the serum concentration of Mycophenolate. Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccines: Mycophenolate may diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding mycophenolate for 1 to 2 weeks after each vaccine dose as permitted by the underlying disease. This recommendation is specific to patients using mycophenolate for rheumatic and musculoskeletal diseases. Risk D: Consider therapy modification
CycloSPORINE (Systemic): May decrease the serum concentration of Mycophenolate. Specifically, cyclosporine may decrease concentrations of the active metabolite mycophenolic acid. Management: Mycophenolate requirements may be greater in patients receiving cyclosporine. Monitor mycophenolate dosing and response to therapy particularly closely when adjusting concurrent cyclosporine (starting, stopping, or changing dose). Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Ganciclovir-Valganciclovir: Mycophenolate may enhance the adverse/toxic effect of Ganciclovir-Valganciclovir. Specifically, the risk for leukopenia or neutropenia may be increased with this combination. Mycophenolate may increase the serum concentration of Ganciclovir-Valganciclovir. Risk C: Monitor therapy
Hormonal Contraceptives: Mycophenolate may decrease the serum concentration of Hormonal Contraceptives. Management: Patients of childbearing potential who are taking hormonal contraceptives should use an additional form of barrier contraception during treatment with mycophenolate and for 6 weeks after mycophenolate discontinuation. Risk D: Consider therapy modification
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Mycophenolate. Specifically, concentrations of the active mycophenolic acid may be reduced. Risk C: Monitor therapy
Isavuconazonium Sulfate: May increase the serum concentration of Mycophenolate. Risk C: Monitor therapy
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Linezolid: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Magnesium Hydroxide: May decrease the serum concentration of Mycophenolate. Management: Simultaneous administration of magnesium hydroxide antacids with the Myfortic brand of mycophenolic acid is specifically not recommended. Administer magnesium hydroxide at least 2 hours after a dose of the Cellcept brand of mycophenolate mofetil. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Patiromer: May decrease the serum concentration of Mycophenolate. Management: Administer mycophenolate at least 3 hours before or 3 hours after patiromer. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Probenecid: May increase the serum concentration of Mycophenolate. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
RifAMPin: May decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be decreased. Management: Avoid concurrent use of rifampin and mycophenolate when possible. If used together, closely monitor mycophenolic acid levels and clinical response. Mycophenolate doses may need to be increased. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sevelamer: May decrease the serum concentration of Mycophenolate. Management: Administer mycophenolate at least 2 hours prior to sevelamer administration. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Food decreases Cmax of MPA by 40% following mycophenolate mofetil (CellCept) administration and 33% following mycophenolate sodium (Myfortic) use; the extent of absorption is not changed. Management: Take mycophenolate mofetil or mycophenolate sodium on an empty stomach to decrease variability; however, mycophenolate mofetil may be taken with food if necessary in stable renal transplant recipients.
[US Boxed Warning]: Females of reproductive potential must be counseled regarding pregnancy prevention and planning. Pregnancy testing, prevention, and planning must be discussed with all females of reproductive potential and male patients with female partners of reproductive potential. Alternative agents should be used whenever possible in patients planning a pregnancy.
Females of reproductive potential (girls who have entered puberty and women with a uterus who have not passed through clinically confirmed menopause) should have a negative pregnancy test with a sensitivity of ≥25 milliunits/mL immediately before mycophenolate therapy and the test should be repeated 8 to 10 days later. Pregnancy tests should then be repeated during routine follow-up visits. Acceptable forms of contraception should be used during treatment and for 6 weeks after therapy is discontinued. An intrauterine device, tubal sterilization, or vasectomy of the female patient's partner are acceptable contraceptive methods that can be used alone. If a hormonal contraceptive is used (eg, combination oral contraceptive pills, transdermal patches, vaginal rings, or progestin only products), then one barrier method must also be used (eg, diaphragm or cervical cap with spermicide, contraceptive sponge, male or female condom). Alternatively, the use of 2 barrier methods is also acceptable (eg, diaphragm or cervical cap with spermicide, or contraceptive sponge PLUS male or female condom). Refer to manufacturer's labeling for full details. The effectiveness of hormonal contraceptive agents may be affected by mycophenolate.
Mycophenolate has been used as an immunosuppressant in patients undergoing uterine transplant (limited data); mycophenolate is discontinued and changed to a different agent prior to embryo transfer (Jones 2019).
Mycophenolate should be discontinued, and therapy changed to an appropriate immunosuppressant prior to conception in kidney, liver, and heart transplant recipients who are planning a pregnancy (AASLD [Lucey 2013]); EBPG 2002; ISHLT [Costanzo 2010]; KDIGO 2009; López 2014). Mycophenolate should also be discontinued prior to conception in females treated for other indications who are planning a pregnancy. The Risk Evaluation and Mitigation Strategy (REMS) program recommends discontinuing mycophenolate in females at least 6 weeks before pregnancy is attempted. However, due to the potential for disease flare following discontinuation, women treated for rheumatic and musculoskeletal diseases should consider discontinuing mycophenolate 3 to 6 months prior to attempted pregnancy to allow for disease monitoring and potential change to another immunosuppressant (ACR [Sammaritano 2020]). Women taking mycophenolate for myasthenia gravis are recommended to discontinue therapy at least 4 months prior to planning a pregnancy (Sanders 2016).
When mycophenolate is used for the treatment of rheumatic and musculoskeletal diseases in women undergoing ovarian stimulation for oocyte retrieval or embryo cryopreservation, mycophenolate may be continued in patients whose condition is stable and discontinuation of treatment may lead to uncontrolled disease (ACR [Sammaritano 2020]).
Information related to the mycophenolate and male fertility or pregnancy outcomes following paternal use is limited; however, available data have not suggested safety concerns (Bermas 2019; Mouyis 2019). According to the manufacturer, sexually active male patients and/or their female partners should use effective contraception during treatment of the male patient and for at least 90 days after last dose. In addition, males should not donate semen during mycophenolate therapy and for 90 days following the last mycophenolate dose (recommendation based on animal data). However, use of mycophenolate may be considered for males with rheumatic and musculoskeletal diseases who are planning to father a child (recommendation based on limited human data) (ACR [Sammaritano 2020]; Midtvedt 2017).
[US Boxed Warning]: Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations. Avoid if safer treatment options are available.
Congenital malformations have been reported in 23% to 27% of live births following exposure to mycophenolate during pregnancy. Birth defects include facial malformations (cleft lip, cleft palate, micrognathia, hypertelorism of the orbits); ear and eye abnormalities (abnormally formed or absent external/middle ear, coloboma, microphthalmos); finger malformations (brachydactyly, polydactyly, syndactyly); cardiac abnormalities (atrial and ventricular septal defects); esophageal malformations (esophageal atresia); and CNS malformations (spina bifida). The combination of ear, eye, and lip/palate abnormalities has been identified as mycophenolate embryopathy (Perez-Aytes 2017). The risk of first trimester pregnancy loss may be 45% to 49% following mycophenolate exposure.
Mycophenolate is not an acceptable immunosuppressant for use in patients who become pregnant following a kidney (EBPG 2002; KDIGO 2009; López 2014), liver (AASLD [Lucey 2013]), or heart (ISHLT [Costanzo 2010]) transplant. In addition, mycophenolate should not be used for the treatment of autoimmune hepatitis (AASLD [Mack 2020]), myasthenia gravis (Sanders 2016), or rheumatic and musculoskeletal diseases (ACR [Sammaritano 2020]) during pregnancy.
Data collection to monitor pregnancy and infant outcomes following exposure to mycophenolate is ongoing. Health care providers should report female exposures to mycophenolate during pregnancy or within 6 weeks of discontinuing therapy to the Mycophenolate Pregnancy Registry (800-617-8191).
The Transplant Pregnancy Registry International (TPR) is a registry that follows pregnancies that occur in maternal transplant recipients or those fathered by male transplant recipients. The TPR encourages reporting of pregnancies following solid organ transplant by contacting them at 1-877-955-6877 or https://www.transplantpregnancyregistry.org.
It is not known if mycophenolate is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Adverse events were not observed in 7 infants born between 34 and 40 weeks' gestation and exposed to mycophenolate via breast milk for up to 14 months. However, due to the long half-life and lack of information related to mycophenolate and breastfeeding, breastfeeding is not recommended by some guidelines (ACR [Sammaritano 2020]; Constantinescu 2014; López 2014).
Some products may contain phenylalanine.
Complete blood count (weekly for first month, twice monthly during months 2 and 3, then monthly thereafter through the first year); renal and liver function; signs and symptoms of organ rejection; signs and symptoms of bacterial, fungal, protozoal, new or reactivated viral (including reactivation of HBV or HCV), or opportunistic infections; neurological symptoms (eg, hemiparesis, confusion, cognitive deficiencies, ataxia) suggestive of progressive multifocal leukoencephalopathy; in patients with hepatitis B or hepatitis C, monitor for signs of viral reactivation; monitor for signs/symptoms (eg, fever, arthralgias, arthritis, muscle pain, proinflammatory markers) suggestive of acute inflammatory syndrome; pregnancy test (sensitivity of ≥25 milliunits/mL; immediately prior to initiation and 8 to 10 days later in patients who may become pregnant, followed by repeat tests during therapy); monitor skin (for lesions suspicious of skin cancer); monitor for signs of lymphoma; monitor for signs of pure red cell aplasia or autoimmune hemolytic anemia (Elimelakh 2007; Hodo 2006; Schecter 2007).
Routine monitoring of mycophenolate levels is not recommended (Chapman 2010; ISHLT [Costanzo 2010]). Therapeutic drug monitoring may be beneficial in patients with high risk for rejection or increased adverse effects (Roan 2013; van Gelder 2006; Zuk 2009).
Mycophenolic acid (MPA) trough levels are poorly correlated with AUC and are not recommended (Arns 2006). Two abbreviated AUC0-12 equations have been shown to correlate with a full AUC measurement (Pawinski 2002; Tutor-Crespo 2009). These estimations have only been validated in patients receiving mycophenolate mofetil (CellCept) at steady-state using total MPA (tMPA) concentrations and should not be used for patients receiving mycophenolate sodium (Myfortic). Because MPA is highly protein bound, caution should be used in patients with severe renal impairment, high bilirubin, and low albumin; in this population, free MPA (fMPA) levels may be of more value (van Gelder 2006).
Three sample model equation:
7.75 + 6.49*C0H + 0.76*C0.5H + 2.43*C2H
Where C0H is the concentration tMPA at 0 hours (time dose is administered) and C0.5H, C2H are the tMPA levels 0.5 and 2 hours after the dose, respectively (Pawinski 2002).
Two sample model equation:
11.55 + 7.25*C0H + 3.35*C2H
Where C0H is the tMPA level at 0 hours (time dose is administered) C2H is the tMPA level 2 hours after the dose (Tutor-Crespo 2009).
Goal MPA AUC is ~30 to 60 mcg*hour/mL. Levels <30 have been associated with an increased risk of rejection; however, the upper limit of 60 has not been well defined, nor have MPA AUC been correlated with toxicities or adverse effects (van Gelder 2006).
MPA exhibits a cytostatic and reversible effect on T and B lymphocytes. It is an inhibitor of type I and type II inosine monophosphate dehydrogenase (IMPDH) which inhibits de novo guanosine nucleotide synthesis and blocks DNA synthesis. MPA shifts transcriptional activities in human CD4+ T-lymphocytes by suppressing the Akt/mTOR and STAT5 pathways, causing the T-cells to become less responsive to antigenic stimulation. MPA enhances the expression of negative costimulators such as CD70, PD-1, CTLA-4, and transcription factor FoxP3 as well as decreasing the expression of positive costimulators CD27 and CD28. T and B lymphocytes are dependent on this pathway for proliferation. MPA helps in the production of cytokines from lymphocytes and monocytes such as GM-CSF, IFN-γ, IL-17, and TNF-α. MPA also prevents glycosylation of lymphocyte and monocyte glycoproteins involved in intercellular adhesion to endothelial cells and can inhibit leukocytes into sites of inflammation and graft rejection.
Onset of action: Peak effect: Correlation of toxicity or efficacy is still being developed; however, one study indicated that 12-hour AUCs >40 mcg/mL/hour were correlated with efficacy and decreased episodes of rejection.
Absorption: Rapid and extensive; early post-transplant period mycophenolic acid (MPA) AUC values are lower (~45% to 53%) than later post-transplant period (>3 months) MPA AUC values in both pediatric patients and adults.
Oral: Mycophenolate sodium, delayed release: 93%.
Distribution:
Mycophenolate mofetil: MPA: ~3.6 ± 1.5 L/kg.
Mycophenolate sodium, delayed release: MPA: Oral: 54 L (at steady state); 112 L (elimination phase).
Protein binding: MPA: 97%; glucuronidated MPA (MPAG): 82%.
Metabolism: Hepatic and via GI tract; mycophenolate mofetil is completely hydrolyzed in the liver to mycophenolic acid (MPA; active metabolite); enterohepatic recirculation of MPA may occur; MPA is glucuronidated to MPAG (inactive metabolite).
Bioavailability: Oral: Mycophenolate mofetil: 94% (oral MMF relative to IV MMF); enterohepatic recirculation contributes to MPA concentration (Staatz 2007); two 500 mg tablets have been shown to be bioequivalent to four 250 mg capsules or 1,000 mg of oral suspension; Mycophenolate sodium, delayed release: 72%.
Half-life elimination:
Mycophenolate mofetil: MPA: Oral: 17.9 ± 6.5 hours; IV: 16.6 ± 5.8 hours.
Mycophenolate sodium, delayed release: MPA: Oral: 8 to 16 hours; MPAG: 13 to 17 hours.
Time to peak, plasma: Oral: MPA:
Mycophenolate mofetil: Single dose, healthy volunteers (1 g): 0.8 hours; Steady state, solid organ transplant recipients (1 to 1. 5 g twice daily): 0.9 to 1.8 hours.
Mycophenolate sodium, delayed release: Single dose (720 mg): 2 hours (range: 0.8 to 8 hours); Steady state (720 mg twice daily): 1.5 to 2.5 hours (range: 0 to 8 hours).
Excretion:
Mycophenolate mofetil: MPA: Urine (<1%), feces (6%); MPAG: Urine (87%).
Mycophenolate sodium, delayed release: MPA: Urine (3%), feces; MPAG: Urine (>60%).
Altered kidney function: Mycophenolate mofetil: Mycophenolic acid AUC increased 75%, and mycophenolic acid glucuronide AUC increased 3- to 6-fold in patients with severe renal impairment (glomerular filtration rate [GFR] <25 mL/minute/1.73 m2).
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