Mycophenolate is a pyrimidine synthesis inhibitor immunosuppressive agent. Mycophenolate mofetil (MMF, CellCept), a prodrug for mycophenolic acid (MPA), is indicated for the prevention of organ (kidney, heart, liver) rejection in adult and pediatric patients 3 months of age and older following allogeneic kidney, heart or liver transplantation, in combination with other immunosuppressants. Mycophenolate sodium (Myfortic) is approved for prevention of renal transplant rejection in adults, and for prevention of renal organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant in combination with other immunosuppressants. Mycophenolate sodium may be used in combination with cyclosporine and corticosteroids. Twice daily oral administration of mycophenolate sodium 720 mg and MMF 1,000 mg were found to be therapeutically equivalent in adult renal transplant patients. The incidence of nephrotoxicity appears to be less with MMF than with cyclosporine, and lower doses of cyclosporine can be used when mycophenolate therapy is added, thereby reducing the risk of cyclosporine-induced nephrotoxicity. Mycophenolic acid has been successful in patients with rheumatoid arthritis, including patients resistant to methotrexate. Mycophenolate products may increase the risk of fetal harm (birth defects) and miscarriage in the first trimester of pregnancy; the Mycophenolate REMS program has been established to manage these risks. Females of reproductive potential must receive pregnancy testing before and after starting treatment, and routinely during follow-up visits with the prescriber. More information is available at www.mycophenolaterems.com.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 2
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.
Route-Specific Administration
Oral Administration
-Mycophenolate mofetil (capsules, oral suspension, and tablets) and mycophenolate sodium (delayed-release tablets) are not interchangeable on a mg-per-mg basis.
Oral Solid Formulations
Mycophenolate mofetil oral capsules or tablets
-Administer on an empty stomach. However, in stable transplant patients, mycophenolate mofetil may be administered with food, if necessary.
-Do not crush or open mycophenolate capsules. Do not crush mycophenolate tablets.
-Care should be taken to avoid inhalation or direct contact with skin or mucous membranes of the dry powder from the capsules. If such contact occurs, wash thoroughly with soap and water. If ocular contact occurs, rinse eyes thoroughly with plain water.
-Missed doses: If a dose is missed, take it as soon as possible. If less than 2 hours to next scheduled dose, then skip the missed dose and take the next scheduled dose. Then continue to take mycophenolate mofetil at the usual scheduled times.
Mycophenolate sodium delayed-release tablets
-Administer on an empty stomach, 1 hour before or 2 hours after a meal or food intake.
-Do not crush, chew, or cut delayed-release tablets. Swallow delayed-release tablets whole to maintain the enteric coating.
Oral Liquid Formulations
Oral suspension Administration (mycophenolate mofetil oral suspension)
-Administer on an empty stomach. However, in stable transplant patients mycophenolate mofetil may be administered with food, if necessary.
-Shake well before each use.
-To ensure accurate dosage, administer with the oral dispenser provided with bottle.
-If needed, may be administered through a nasogastric (NG) tube with a minimum size of 8 French (minimum 1.7 millimeter interior diameter).
-Do not mix with other liquids or medications.
-During administration, avoid skin contact with the oral suspension. If contact occurs, wash the exposed area thoroughly with soap and water; if ocular contact occurs, rinse eyes with plain water.
-Missed dose: If a dose is missed, take it as soon as possible. If less than 2 hours to next scheduled dose, then skip the missed dose and take the next scheduled dose. Then continue to take mycophenolate mofetil at the usual scheduled times.
Reconstitution of the oral suspension (Cellcept oral suspension) before dispensing
-Care should be taken to avoid inhalation or direct contact with skin or mucous membranes of the dry powder from the oral suspension. If such contact occurs, wash thoroughly with soap and water. If ocular contact occurs, rinse eyes thoroughly with plain water.
-Wear disposable gloves during reconstitution.
-Measure 94 mL of water. Add approximately half the total amount of water to the bottle and shake well for about 1 minute.
-Add remainder of the water and shake well for another minute.
-The final concentration of the oral suspension is 200 mg/mL.
-Remove the child-resistant cap and push the bottle adapter into the neck of the bottle.
-Close the bottle with the child-resistant cap. This will ensure the proper sealing to the bottle adapter in the bottle and the child-resistant status of the cap.
-Wipe the outer surface of the bottle and cap, as well as the preparation space following reconstitution of the suspension.
-Pharmacists: write the date of expiration of the constituted suspension on the bottle label. The shelf-life of the prepared oral suspension is 60 days.
-Storage of reconstituted suspension: Store the suspension at room temperature at 59 to 86 degrees F (15 to 30 degrees C) or under refrigeration, 36 to 46 degrees F (2 to 8 degrees C). Discard any unused portion 60 days after preparation. Do not freeze.
Injectable Administration
-For intravenous infusion as directed ONLY. Avoid administration by rapid or bolus IV administration. Rapid IV infusion increases the risk of local adverse reactions, including phlebitis and thrombosis.
-Visually inspect the solution for particulate matter or discoloration prior to administering. Discard solution if particulate matter or discoloration is observed.
-Reconstituted mycophenolate mofetil solution is slightly yellow.
Intravenous Administration
-As an alternative to the oral formulation, intravenous mycophenolate mofetil is recommended in patients who are unable to tolerate oral medications.
-The intravenous mycophenolate mofetil may be administered for a duration of up to 14 days. Patients should be switched to an oral formulation as soon as possible.
Reconstitution of Vials and Infusion Preparation:
-Intravenous mycophenolate mofetil does not contain an antibacterial preservative; therefore, it should be prepared under aseptic conditions.
-Avoid direct contact with the prepared solution.
-Mycophenolate mofetil vials are vacuum-sealed and should retain a vacuum throughout its shelf life. Do not use a vial if a lack of a vacuum is noted during diluent addition.
-Intravenous mycophenolate may ONLY be reconstituted and diluted with 5% Dextrose Injection.
-Reconstitute each vial with 14 mL of 5% Dextrose Injection. Gently shake vial to dissolve the drug.
-Once the appropriate number of vials are reconstituted, they must be further diluted as an infusion before administration to the patient.
-Further dilute into 5% Dextrose Injection to prepare the infusion.
--For 1 gram doses, remove the reconstituted solution from 2 vials and dilute in 140 mL 5% Dextrose Injection.
-For 1.5 grams doses, removed the reconstituted solution from 3 vials and dilute in 210 mL 5% Dextrose Injection.
-The final concentration of the infusion is approximately 6 mg/mL.
-Storage of reconstituted/infusion solutions: Store at room temperature range of 59 to 86 degrees F (15 to 30 degrees C). Administration should begin within 4 hours of reconstitution and dilution.
Intravenous infusion Administration
-Administer via slow IV infusion of a period of not less than 2 hours by either a peripheral or central vein. Never administer as a rapid or bolus intravenous injection.
-During Y-site administration, mycophenolate is physically compatible and chemically stable with 0.9% Sodium Chloride injection for up to 4 hours.
-Do not mix mycophenolate mofetil with other medications or infuse concurrently via the same infusion catheter with other medications or infusion admixtures.
The most common side effects associated with mycophenolate mofetil (MMF) and mycophenolate sodium therapies involve the gastrointestinal (GI) tract, especially abdominal pain (24.7 to 62.5%), anorexia (25.3%), constipation (18.5 to 41.2%), diarrhea (21.4 to 51.3%), dyspepsia (19 to 22.5%), nausea (19 to 54.5%), and vomiting (20 to 33.9%). Additional GI and digestive adverse events reported by 3 to 19.9% of patients receiving mycophenolate in combination with cyclosporine and corticosteroids included abdominal distension, cholangitis, dysphagia, esophagitis, flatulence, gastritis, gastroenteritis, gastroesophageal reflux, gingivitis, gingival hyperplasia, ileus, melena, moniliasis (GI and oral), oral ulceration, stomatitis, and throat irritation. Mycophenolate has also been associated with GI bleeding, including hemorrhagic forms of gastritis and colitis, and hematemesis. Among mycophenolate mofetil 3 grams daily recipients, GI bleeding requiring hospitalization was observed in 3% of renal, in 1.7% of cardiac, and in 5.4% of hepatic transplant patients. Five of 148 pediatric renal transplant patients had gastrointestinal bleeding requiring hospitalization. GI bleeding requiring hospitalization occurred in 1% of de novo renal transplant patients and in 1.3% of maintenance patients who received mycophenolate sodium for up to one year. Esophageal ulceration and gastrointestinal ulcerations such as gastric, duodenal, intestinal and peptic ulcer, and GI perforation have been reported. Most patients receiving mycophenolate were also receiving other drugs known to be associated with these complications. Colitis, sometimes caused by cytomegalovirus, ischemic colitis, intestinal perforation, duodenal ulcers, and pancreatitis have been reported during post-marketing use. The contribution of mycophenolate to the development of GI adverse events is uncertain, as most patients received other drugs that are known to cause GI complications (see Drug Interactions). Because of the serious nature of the events and the possible contribution of mycophenolate, mycophenolate should be given cautiously to patients with active serious GI disease (see Contraindications). Patients with active peptic ulcer disease were excluded from enrollment in studies with mycophenolate. The propensity of mycophenolate to cause GI problems appears to be related to the maximum serum concentration. Thus, administration of the daily dose in 3 rather than 2 divided doses may be beneficial.
Adverse events involving the kidneys and urinary tract have been reported by patients receiving treatment with mycophenolate. During clinical trials, abnormal kidney function, including azotemia (34.6%) and increased serum creatinine (39.4%), occurred in 21.8 to 25.6% of mycophenolate mofetil treated patients. Other adverse events experienced by 3 to 19.9% of mycophenolate mofetil recipients included renal failure (unspecified), albuminuria, nocturia, oliguria, prostatic disorders, testicular swelling, increased urinary frequency, and urinary incontinence. Renal tubular necrosis, renal impairment, dysuria, hematuria, hydronephrosis, and bladder spasm or urinary retention occurred in 3 to 19.9% of patients who received either mycophenolate mofetil or mycophenolate sodium during clinical trials. Of note, urinary side effects decrease with continued use.
Mycophenolate may cause immunosuppression; thus, patients receiving treatment with mycophenolate are at risk of developing an opportunistic infection or of reactivating a latent viral infection. Specific infection types reported during clinical use of mycophenolate include viral infections (herpes simplex, 1.3 to 20.8%; herpes zoster, 1.9 to 10.7%; cytomegalovirus (CMV) viremia, 12.4 to 14.1%; invasive CMV infection, 5.8 to 11.5%; any CMV infection, 1.8 to 21.6%; influenza, 3 to 19.9%), fungal infections (candidiasis, 0.6 to 22.4%; aspergillosis; cryptococcosis; Pneumocystis carinii; mucor infection), and bacterial infections (cellulitis, 3 to 19.9%; urinary tract infection, 29.1 to 37.2%; pyelonephritis, 3 to 19.9%; respiratory tract infection, 3 to 37%; pneumonia, 3 to 19.9%; pharyngitis, 3 to 19.9%; sinusitis, 3 to 26%; implant or wound infection, 3 to 19.9%). Fatal infection/sepsis occurred in approximately 2% of renal and cardiac transplant patients and in 5% of hepatic transplant patients who received mycophenolate mofetil (MMF). In cardiac transplant patients, the overall incidence of opportunistic infections was about 10% higher in patients treated with MMF as compared with patients treated with azathioprine. There was an increased incidence of herpes simplex, herpes zoster, and CMV infections in cardiac patients receiving MMF compared to those receiving azathioprine. There was no difference in the incidence of fungal infections. In renal transplant patients, sepsis, generally CMV viremia, was slightly more common in patients treated with MMF compared to azathioprine. Hepatic patients treated with MMF had a higher incidence of herpes simplex infection compared to azathioprine-treated patients. Polyomavirus-associated nephropathy (PVAN), especially due to BK virus infection (BK virus-associated nephropathy), has been observed in patients receiving mycophenolate. In transplant patients, polyomavirus infections may have serious outcomes such as renal function deterioration, renal graft loss, or death. Patient monitoring may help detect patients at risk for polyomavirus-associated nephropathy. Consider reduction in immunosuppression for patients who develop evidence of polyomavirus-associated nephropathy; however, also consider the potential impact of reduced immunosuppression to the functioning allograft. In addition, life-threatening infections such as meningitis and infectious endocarditis have been reported occasionally, and there is evidence of a higher incidence of certain types of serious infections such as tuberculosis and atypical mycobacterium infections. Coronavirus disease 2019 (COVID-19) has been reported during mycophenolate use. Fever, which may be indicative of an infection, occurred in 21.4 to 52.3% of transplant patients who received mycophenolate during clinical trials. Other symptoms potentially associated with infection and experienced by 3 to 19.9% of MMF recipients included chills, increased sputum, flu syndrome, and rhinitis. Tell patients to immediately report any signs or symptoms of an infection.
Treatment with mycophenolate is associated with the development of hematologic and lymphatic adverse events including agranulocytosis, anemia (3 to 43%), coagulopathy (3 to 19.9%), hypochromic anemia (24.6%), leukocytosis (22.4 to 40.5%), leukopenia (3 to 45.8%), lymphocele (3 to 19.9%), neutropenia (2 to 3.6%), pancytopenia (1.8 to 19.9%), polycythemia (3 to 19.9%), and thrombocytopenia (3 to 38.3%). Severe neutropenia develops (absolute neutrophil count less than 500/mm3) in up to 2% of renal transplant patients, 2.8% of cardiac transplant patients, and 3.6% of liver transplant patients. Neutropenia is more common with higher doses of mycophenolate and occurs most commonly 31 to 180 days posttransplant. Anemia and leukopenia also appear to be more common with higher doses. During clinical trials, the incidence of anemia and leukopenia in renal transplant patients receiving 2 grams of mycophenolate mofetil daily was 25.6% and 23.2%, respectively; however, these incidences increased to 42.9 to 43% and 30.4 to 45.8%, respectively, when mycophenolate 3 grams daily was administered to cardiac and hepatic transplant patients. Further, in a 1-year placebo-controlled study of renal transplant recipients who received cyclosporine and corticosteroids, anemia was noted in 2.4% of 166 placebo recipients, in 4.8% of 165 mycophenolate mofetil 2-gram recipients, and in 8.1% of 160 mycophenolate mofetil 3-gram recipients. Leukopenia was noted in 4.2% of 166 placebo recipients, in 12.1% of mycophenolate mofetil 2-gram recipients, and in 16.3% of mycophenolate mofetil 3-gram recipients. Thrombocytopenia occurred in 4.8% of both placebo and mycophenolate mofetil 2-gram recipients and in 4.4% of mycophenolate mofetil 3 gram daily recipients. Pancytopenia occurred in 3 of the 165 patients who received 2 grams daily, and agranulocytosis occurred in 2 of the 160 patients who received 3 grams daily; neither pancytopenia nor agranulocytosis was noted among the 166 placebo recipients. Decreases in hemoglobin occurred in 3 to 19.9%, anemia in 21.6%, and leukopenia in 19.2% of 213 patients who received mycophenolate sodium 1440 mg daily in combination with cyclosporine and corticosteroids. Patients should be monitored for the development of cytopenias. Therapy with mycophenolate should be interrupted or the dose reduced, appropriate diagnostic tests instigated together with suitable patient management if neutropenia (absolute neutrophil count less than 1300/mm3) occurs. In clinical trials, the dose of mycophenolate could be reduced by 50% or stopped if a leukocyte count less than 4000 cells/mm3 or a neutrophil count less than 1500 cells/mm3 developed. Patients should be told to immediately report any unexpected bruising, bleeding, and sign or symptom of infection.
Adverse events due to intravenous administration of mycophenolate mofetil include phlebitis and thrombosis, which occurred in 4% of patients in clinical trials.
A new primary malignancy presenting as lymphoma or as other cancers including skin cancer has been reported. Post-transplant lymphoproliferative disorder (PTLD) occurred in approximately 0.4 to 1% of patients receiving mycophenolate mofetil (MMF) 2-g or 3-g daily with other immunosuppressives for at least 1 year. Of 372 patients who received mycophenolate sodium with other immunosuppressives, 4 developed a lymphoma. The development of other malignancies has also been reported. Non-melanoma skin carcinoma occurred in 1.6 to 4.2% of patients who received MMF and in 0.9 to 1.8% of patients who received mycophenolate sodium. Other malignancies occurred in 0.5 to 2.1% of patients with either formulation. Three-year safety data in renal and cardiac patients did not reveal any unexpected changes in the incidence of malignancy as compared to 1-year data. The risk of malignancy development appears to be related to immunosuppression intensity and duration and not to a specific drug. Patients should be told to protect their skin from the sun.
During clinical trials, treatment with mycophenolate was associated with the development of respiratory adverse events. The most commonly reported events were increased cough (3 to 31.1%), dyspnea (3 to 36.7%), and pleural effusion (3 to 34.3%). Among 289 patients who received mycophenolate mofetil in combination with cyclosporine and corticosteroids for cardiac transplant, 36.7% had dyspnea and 31.1% had increased cough. Similar percentages (36.3% and 25.6%, respectively) of 289 patients who got azathioprine, cyclosporine, and corticosteroids had the events. Cough, dyspnea, and exertional dyspnea occurred in 3 to 19.9% of patients who received mycophenolate sodium in combination with cyclosporine (USP modified) and corticosteroids. Additional respiratory adverse reaction occurring in 3 to 19.9% of mycophenolate recipients included apnea, asthma, atelectasis, bronchitis, dysphonia, epistaxis, hemoptysis, hiccups, hyperventilation, hypoxia, nasal congestion, pulmonary edema, pulmonary neoplasm, and pneumothorax. Interstitial pneumonitis, including fatal pulmonary fibrosis, has been reported rarely. A female with no previous lung problems developed progressive pulmonary fibrosis that only continuously improved after discontinuation of mycophenolate mofetil for renal transplant rejection prophylaxis. She initially received mycophenolate, tacrolimus, and methylprednisolone. Three days after transplantation, she developed a productive cough that progressed to respiratory distress and failure within a week. Improvement in pulmonary infiltrates occurred with mycophenolate mofetil withdrawal and worsened within days of reinstitution. Usual interstitial pneumonitis with patchy fibrosis was discovered by biopsy. Inflammatory changes in the interstitium appeared chronic, and mild and reactive pneumocytes were not seen. The patient finally stabilized with permanent mycophenolate discontinuation. Severe lung restriction, infiltrates, and diffusion abnormalities slowly resolved over several months. Consider interstitial lung disorders in the differential diagnosis of symptoms ranging from dyspnea to respiratory failure in posttransplant patients receiving mycophenolate.
Dermatologic adverse reactions have been associated with the use of mycophenolate during clinical trials. Rash (unspecified) (3 to 22.1%), acne vulgaris (3 to 19.9%), and pruritus (3 to 19.9%) were reported in patients receiving treatment with mycophenolate mofetil and mycophenolate sodium. Adverse events occurring only in mycophenolate mofetil treated patients (3 to 19.9%) included alopecia, bullous rash, sweating, ecchymosis, fungal dermatitis, hemorrhage, petechiae, skin hypertrophy, skin ulcer, and vesicular rash. Contusions were reported in 3 to 19.9% of mycophenolate sodium recipients.
Cardiovascular adverse events have developed following use of mycophenolate during clinical trials. The most commonly reported events included chest pain (unspecified) (3 to 26.3%), hypertension (3 to 77.5%), hypotension (3 to 32.5%), and tachycardia (including sinus tachycardia, supraventricular tachycardia (SVT), and ventricular tachycardia; 3 to 22%). Other adverse reactions affecting the cardiovascular system and reported in 3 to 19.9% of mycophenolate mofetil recipients included angina pectoris, arrhythmia exacerbation, atrial fibrillation, atrial flutter, bradycardia, cardiac arrest, congestive heart failure, extrasystole, increased venous pressure, orthostatic hypotension, pallor, palpitations, pericardial effusion, peripheral vasodilation, pulmonary hypertension, syncope, and vasospasms.
Elevated hepatic enzymes have been reported in 3 to 24.9% of patients that received treatment with mycophenolate during clinical trials. Other hepatic adverse events reported in 3 to 19.9% of mycophenolate mofetil recipients include cholestasis, hepatitis, and jaundice.
Metabolic and nutritional adverse events have occurred following use of mycophenolate. During clinical trials, the most commonly reported metabolic/nutritional adverse events were edema (3 to 28.2%), hyperkalemia (3 to 22%), hypocalcemia (3 to 30%), hypokalemia (3 to 37.2%), and hypomagnesemia (3 to 39%). Other adverse events occurring in 3 to 19.9% of patients included dehydration, hypercalcemia, hypercholesterolemia, hyperlipidemia, hyperphosphatemia, hyperuricemia, hypophosphatemia, peripheral edema, and weight gain. Recipients of mycophenolate mofetil (3 to 19.9%) also experienced impaired wound healing, respiratory and metabolic acidosis, metabolic alkalosis, increased alkaline phosphatase and gamma glutamyl transpeptidase, hyperbilirubinemia, gout, hypervolemia, hypochloremia, hypoglycemia, hyponatremia, hypoproteinemia, hypovolemia, increased lactic dehydrogenase, polydipsia, and weight loss.
Adverse events affecting the musculoskeletal system and the body as a whole have been reported by recipients of mycophenolate. During clinical trials, the most commonly reported adverse events were asthenia (35.4 to 43.3%), headache (3 to 54.3%), back pain (3 to 46.6%), and ascites (24.2%). Other reactions occurring in 3 to 19.9% of patients included arthralgia, drowsiness or fatigue, muscle cramps, and myalgia. Events only experienced by patients treated with mycophenolate mofetil (3 to 19.9%) included hernia, malaise, myasthenia, neck pain, osteoporosis, pelvic pain, and peritonitis. Acute inflammatory syndrome (AIS), a paradoxical pro-inflammatory reaction, has been reported in some patients receiving mycophenolate therapy, including severe cases that required hospitalization. AIS is characterized by fever, arthralgias, arthritis, muscle pain, and elevated inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate, without evidence of infection or underlying disease recurrence. Onset of symptoms occurred within weeks to months mycophenolate initiation or dose increase. Improvement in symptoms and inflammatory markers usually observed within 24 to 48 hours following discontinuation of mycophenolate therapy. Monitor patients for symptoms and laboratory parameters of AIS when starting mycophenolate therapy or increasing the dose. Advise patients to notify their physicain or health care professional if they develop fever, joint stiffness, joint pain, or muscle pain. In patients who develop AIS, discontinue treatment and consider alternative therapy based upon assess risks and benefits to the patient.
Endocrine abnormalities observed in patients receiving mycophenolate during clinical trials include diabetes mellitus (3 to 19.9%), hyperglycemia (3 to 46.7%), Cushing's syndrome (3 to 19.9%), and hirsutism (3 to 19.9%). Impotence (erectile dysfunction), hypothyroidism, and parathyroid disorder were reported by 3 to 19.9% of mycophenolate mofetil recipients. In addition to impotence, other reproductive system abnormalities, in both men and women renal transplant patients, appear to be common. Of 20 men, testosterone was below the normal range in 14 and within the lowest third in 6. The absence of an increase in luteinizing hormone suggested an inhibition of the reproductive axis. Half of the 20 women had menstrual cycle disorders. No relationship was found between female reproductive function and age, graft function or duration of the post-transplant period. Although not well understood, numerous etiologies, such as glucocorticoids are likely for the changes in the hypothalamic-pituitary-gonadal axis function.
The most common neurologic and psychiatric adverse events to be associated with mycophenolate treatment during clinical trials include anxiety (3 to 28.4%), depression (3 to 19.9%), dizziness (3 to 28.7%), insomnia (23.5 to 52.3%), paresthesias (20.8%), and tremor (3 to 33.9%). Other adverse events reported by 3 to 19.9% of mycophenolate mofetil recipients include abnormal thinking, agitation, confusion, convulsions or seizures, delirium, emotional lability, hallucinations, hypertonia, hypesthesia, nervousness, peripheral neuropathy, psychosis, vertigo, and xerostomia.
Mycophenolate may cause pure red cell aplasia. Pure red cell aplasia was diagnosed by bone marrow biopsy in 4 renal transplant patients who received corticosteroids, cyclosporine, and mycophenolate mofetil immediately after transplantation. Other etiologies for the anemia were excluded, and mycophenolate cessation in 3 patients and dose reduction in 1 patient led to hematological improvement in 5 to 9 days. Cases of pure red cell aplasia have been reported in patients treated with mycophenolic acid derivatives in combination with other immunosuppressive agents. According to the manufacturer, in some cases, pure red cell aplasia was reversible with dose reduction or mycophenolic acid derivative cessation. Reduced immunosuppression in patients who have received a transplant may place the graft at risk. The mechanism for mycophenolate mofetil induced pure red cell aplasia is unknown, and the relative contribution of other immunosuppressants and their combinations in an immunosuppression regimen are also unknown. Additionally, hypogammaglobulinema has been observed in patients treated with mycophenolate in combination with other immunosuppressive agents. Monitor patients who are receiving mycophenolate for blood dyscrasias such as neutropenia and anemia. Also, instruct patients to immediately report any evidence of infection, unexpected bruising, bleeding, or any other manifestation of bone marrow suppression. If anemia occurs, interrupt mycophenolate receipt or reduce the dose, perform appropriate diagnostic tests, and appropriately manage the patient.
Mycophenolate is an immunosuppressant, and patients who take it are at an increased risk for opportunistic infections such as polyomavirus infections. An example of a polyomavirus infection is progressive multifocal leukoencephalopathy (PML), which is a progressive, demyelinating disease of the central nervous system that is caused by the reactivation of the JC virus. Progressive multifocal leukoencephalopathy usually leads to death or severe disability. Progressive multifocal leukoencephalopathy has been observed in patients receiving mycophenolic acid derivatives such as mycophenolate mofetil and mycophenolate sodium. Hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia are common presenting symptoms of PML. Risk factors for PML development include immunosuppressant receipt and immune function impairment. Consider the possibility of PML during mycophenolate therapy if a patient presents with neurological symptoms; consider a neurologist consultation. Localized neurologic signs and symptoms such as cognitive problems, visual problems including cortical blindness, or muscle weakness in half of the body in the setting of a suppressed immune system may indicate PML. Consider decreasing total immunosuppression of patients who develop PML; however, also consider the potential impact of reduced immunosuppression to the functioning allograft.
During clinical trials, 3 to 19.9% of patients treated with mycophenolate mofetil reported experiencing ophthalmic and otic adverse events including amblyopia, cataracts, conjunctivitis, lacrimation disorder, ocular hemorrhage, visual impairment, hearing loss or deafness, otalgia, and tinnitus. Blurred vision was reported by 3 to 19.9% of mycophenolate sodium recipients.
According to the National Transplant Pregnancy Registry, of 33 mycophenolate exposed pregnancies, spontaneous fetal abortion occurred in 15 (45%) and teratogenesis was observed in 4 of the 18 (22%) live-born infants. During post-marketing use of mycophenolate from 1995 to 2007, 77 women were exposed to mycophenolate during pregnancy. Of these 77 exposures, 25 resulted in spontaneous abortion and 14 had a malformed infant or fetus. Congenital malformations including ear, facial, cardiac, and nervous system malformations have occurred. Due to the voluntary nature of post-marketing reports, neither an incidence nor a definitive causal relationship with mycophenolate can be established from these reports. Health care providers are advised to conduct urine pregnancy tests within 1 week prior to initiating mycophenolate in women of childbearing age. Further, women of childbearing age are advised to use two methods of contraception, beginning 4 weeks prior to starting mycophenolate. If a patient becomes pregnant during treatment, the patient should be apprised of the potential hazard to the infant. Women exposed to mycophenolate at any time during pregnancy should be enrolled in the National Transplantation Pregnancy Registry.
Allergic reactions to mycophenolate have been observed; therefore, mycophenolate products are contraindicated in patients with a hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product. Mycophenolate mofetil intravenous is contraindicated in patients who exhibit polysorbate 80 hypersensitivity.
Mycophenolate therapy requires an experienced clinician knowledgeable in immunosuppressant therapy and organ transplantation. The clinician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient. A patient receiving mycophenolate requires access to proper medical management facilities, acutely and chronically; facilities should be equipped and staffed with adequate laboratory and supportive medical services.
Patients receiving immunosuppressants are at increased risk for the development of a new primary malignancy, such as lymphoma or skin cancer. The risk of developing a malignancy appears to be related to the intensity and duration of immunosuppression rather than the use of any specific immunosuppressant agent. Patients receiving mycophenolate should limit their sunlight (UV) exposure by wearing protective clothing, including hats, and using a broad-spectrum sunscreen with a high protection factor. Post-transplant lymphoproliferative disorder (PTLD) has been reported in 0.4% to 1% of patients who received combination immunosuppression with mycophenolate mofetil in clinical trials involving kidney, heart, and liver transplant. The majority of these cases were found to be related to Epstein Barr Virus (EBV). The greatest risk of PTLD appears to be in those patients who are EBV seronegative; a population that includes young children. In pediatric patients, no other malignancies besides PTLD were observed in clinical trials.
Immunosuppression from mycophenolate products may lead to increased susceptibility to new or reactivated infections. The risk increases with the total immunosuppressive load. These infections may lead to serious outcomes, including hospitalizations
and death. Bacterial infection, viral infection, protozoal infection, and fungal infection occur commonly during immunosuppressive therapy. Reactivation of a latent viral infection (e.g., hepatitis B, hepatitis C, herpes infection, or varicella) and opportunistic infections can occur with immunosuppressive therapy. Examples of opportunistic infections are JC virus-associated progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy associated with BK virus infection, and severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) infection (COVID-19). Instruct patients to report signs of infection promptly. In patients who develop new infections or reactivation of viral infections, consider a dose reduction or discontinuation of mycophenolate while weighing the risk of reduced immunosuppression on the functioning allograft.
Patients with pre-existing hepatic disease should be approached with caution when receiving mycophenolate. No mycophenolate dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. However, it is not known how hepatic impairment due to other etiologies (e.g., biliary cirrhosis) would affect mycophenolate exposure and dosage needs. No data are available for heart transplant patients with severe hepatic parenchymal disease. Viral reactivation has been reported in patients with hepatitis B or hepatitis C infection (HBV or HCV); some of these cases have been serious. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection or hepatitis B exacerbation or HCV exacerbation is recommended.
Patients receiving mycophenolate should be monitored for neutropenia. Severe neutropenia [i.e., absolute neutrophil count (ANC) less than 500 cells/mcL] has developed in transplant patients receiving mycophenolate 3 g/day. Neutropenia has been observed most frequently in the period from 31 to 180 days post-transplant in patients treated for prevention of kidney, heart and liver rejection. The development of neutropenia may be related to mycophenolate itself, concomitant medications, viral infections, or a combination of these causes. If neutropenia develops (ANC less than 1,300 cells/mcL), dosing with mycophenolate should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately. Instruct patients receiving mycophenolate should be instructed to report immediately any evidence of anemia, unexpected bruising, bleeding, symptoms of infection, or any other manifestation of bone marrow suppression. Consider monitoring a complete blood count (CBC) weekly for the first month, twice monthly for the second and third months, and monthly for the remainder of the first year. Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of mycophenolate.
Gastrointestinal bleeding (GI bleeding) requiring hospitalization, GI ulceration, and GI perforation were observed with mycophenolate use during clinical trials. Physicians should be aware of these serious adverse effects particularly when administering mycophenolate products to patients with a history of significant GI disease.
Avoid use of mycophenolate in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT), such as Lesch-Nyhan syndrome and Kelley-Seegmiller syndrome. Mycophenolate, an inosine monophosphate dehydrogenase (IMPDH) inhibitor, has been reported to cause hyperuricemia and may exacerbate symptoms associated with gout, such as acute arthritis, tophi, nephrolithiasis or urolithiasis, and renal disease including kidney failure.
Acute inflammatory syndrome (AIS) has been reported with the use of mycophenolate products, and some cases have resulted in hospitalization. AIS is a paradoxical pro-inflammatory reaction characterized by fever, inflammation such as arthralgia, arthritis, and muscle pain, and elevated inflammatory markers (i.e., increased C-reactive protein and erythrocyte sedimentation rate), without evidence of infection or underlying disease recurrence. Symptoms occur within weeks to months of initiation of treatment or a dose increase. After discontinuation, improvement of symptoms and inflammatory markers are usually observed within 24 to 48 hours. Monitor patients for symptoms and laboratory parameters of AIS when starting treatment with mycophenolate products or when increasing the dosage. Discontinue treatment and consider other treatment alternatives based on the risk and benefit for the patient.
During treatment with mycophenolate, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) and patients should be advised that vaccination may be less effective. Advise patients to discuss vaccination with their physician before seeking any immunizations.
Mycophenolate mofetil oral suspension contains aspartame, a source of phenylalanine (0.56 mg/mL phenylalanine). Care should be taken if mycophenolate mofetil oral suspension is given to patients with phenylketonuria (PKU). In patients with PKU, consider the combined daily amount of phenylalanine from all sources, including the mycophenolate oral suspension.
Patients should avoid blood donation during therapy and for at least 6 months following discontinuation of mycophenolate due to the potential administration of their blood or blood products to a pregnant woman or female of reproductive potential.
Mycophenolate therapy may be associated with confusion, dizziness, somnolence, tremor, or hypotension and may impair the ability to drive or operate machinery. Patients should be cautioned to avoid driving or operating machinery or doing activities requiring coordination and concentration until they are aware of the effects of the medication.
No dosage adjustments are needed in kidney transplant patients experiencing delayed graft function postoperatively, but these patients should be carefully monitored. In kidney transplant patients with severe chronic renal impairment of the graft (eGFR less than 25 mL/minute/1.73 m2), no dose adjustments are necessary; however, doses greater than 1 g twice daily should be avoided. No data are available for heart or liver transplant patients with severe chronic renal impairment or renal failure. Mycophenolate may be used for heart or liver transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.
Avoid mycophenolate use during pregnancy and use a safe, alternative treatment, if available. For patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity. Use of mycophenolate during pregnancy is associated with an increased risk of first-trimester pregnancy loss (45% to 49% loss rate) and an increased risk of congenital malformations have been reported in 23% to 27% of live births. Documented congenital malformations include external ear and other facial abnormalities including cleft lip and palate and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system. Females of child-bearing potential should have a pregnancy test done immediately before beginning therapy and have a negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL). Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Discuss contraception recommendations with the patient and encourage proactive pregnancy planning. Perform repeat pregnancy tests during routine follow-up visits. In the event of a positive pregnancy test, counsel females about whether the maternal benefits of mycophenolate treatment may outweigh the risks to the fetus in certain situations. Data on 33 mycophenolate-exposed pregnancies in 24 patients are available from the national transplantation pregnancy registry. Of the 33 pregnancies, 15 were spontaneously aborted (45%), and 18 were live births. Four of the 18 neonates had structural malformations. Additional data are available from the voluntary reporting of events. Of 77 women who were exposed to mycophenolate during pregnancy, 25 had spontaneous abortions, and 14 (18%) had a malformed infant or fetus; 6 of the 14 malformed offspring had ear abnormalities. Of note, the background rate for congenital anomalies in the US is about 3%, and data from the national transplantation pregnancy registry show a rate of 4 to 5% among babies born to organ transplant recipients who use other immunosuppressive drugs. Strongly encourage women who are using mycophenolate at any time during pregnancy or who became pregnant within 6 weeks of discontinuing therapy to enroll in the Mycophenolate Pregnancy Registry. The pregnancy exposure registry monitors outcomes in pregnant patients exposed to mycophenolate and those who become pregnant within 6 weeks of discontinuing therapy with mycophenolate; information about the registry can be obtained at www.Mycophenolatepregnancyregistry.com or by calling 1-800-617-8191.
Due to the increased risk of first-trimester pregnancy loss and congenital malformations, females of reproductive potential should be educated on the reproductive risk associated with mycophenolate use and prevention of pregnancy. Females of child-bearing potential should have pregnancy testing done immediately before beginning therapy and have a negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL). Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Additionally, discuss contraception requirements with the patient. Women of child-bearing potential who are sexually active must use effective contraception. Acceptable monotherapy options are IUD, tubal sterilization, or vasectomy of partner. Otherwise, 2 methods must be used such as 1 hormone and 1 barrier or 2 barrier methods, one of which is a male or female condom. Hormone methods include the birth control pill, transdermal patch, vaginal ring, injection, and implant. Mycophenolate may reduce the effectiveness of oral contraceptives. Contraceptive use must continue during mycophenolate receipt and for 6 weeks after stopping the drug unless the patient chooses abstinence (completely avoids heterosexual intercourse). Perform repeat pregnancy tests during routine follow-up visits. Discuss the results of all pregnancy tests with the patient. Based on genotoxic effects observed in animal studies of mycophenolate mofetil at approximately 1.25 times human therapeutic exposures, there is a potential risk of male-mediated teratogenicity. Sexually active male patients with female partners should use effective, reliable contraception during treatment and for at least 90 days after treatment cessation; sperm donation should also be avoided for at least 90 days after treatment cessation.
There are no data describing the presence of mycophenolate in human milk or the effect of the drug on milk production. Studies in rats treated with mycophenolate have shown mycophenolic acid (MPA) to be present in milk. Because available data are limited, it is not possible to exclude potential risks to a breast-feeding infant. No adverse events were reported among 7 babies who were breastfed for up to 14 months while the mother was taking mycophenolate. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for mycophenolate and any potential adverse effects on the breastfed infant from mycophenolate or the underlying maternal condition.
Mycophenolate has demonstrated teratogenic effects in humans. Due to the potential effects, care should be taken by caregivers, health care workers, and patients to avoid accidental exposure via inhalation, skin, mucous membrane or ocular exposure. Mycophenolate tablets and capsules should not be opened or crushed. Use caution when handling and preparing oral formulations or intravenous mycophenolate mofetil. Handle and dispose of the medication properly.
Mycophenolate mofetil is indicated for allogenic kidney, heart, and liver transplant rejection prophylaxis in children and infants at least 3 months of age. Safety and efficacy in younger infants or neonates has not been established. Mycophenolate sodium is indicated for the prophylaxis of kidney organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant.
Geriatric patients (65 years and older), particularly those who are receiving mycophenolate as part of a combination immunosuppressive regimen, may be at increased risk of certain infections (including cytomegalovirus [CMV] tissue invasive disease) and possibly gastrointestinal hemorrhage and pulmonary edema, compared to younger individuals.
Switching between mycophenolate formulations
-Mycophenolate mofetil and mycophenolate sodium: Mycophenolate mofetil capsules, oral suspension, and tablets are not interchangeable on a mg-per-mg basis with mycophenolate sodium delayed-release tablets. However, mycophenolate mofetil 1 g PO twice daily was found to be therapeutically equivalent to mycophenolate sodium 720 mg PO twice daily in renal transplant patients.
-Mycophenolate mofetil oral and IV formulations: Mycophenolate mofetil oral (capsules, oral supension, and tablets) and mycophenolate mofetil IV are interchangeable on a mg-per-mg basis.
For the treatment of refractory acute kidney transplant rejection*:
NOTE: The pharmacokinetic parameters of mycophenolic acid are unchanged in patients who have renal transplant rejection. No dosage change or cessation of mycophenolate is needed.
Oral dosage (mycophenolate mofetil):
Adults: 1.5 g PO twice daily. In patients with refractory acute renal allograft rejection, mycophenolate mofetil was compared to a 5-day course of intravenous methylprednisolone followed by a 5-day course of oral corticosteroids. Both groups also received cyclosporine and oral maintenance corticosteroids. Mycophenolate mofetil was clinically more effective than IV methylprednisolone in preserving renal allografts, however, statistical significance was not demonstrated.
For kidney transplant rejection prophylaxis:
Intravenous dosage:
Adults: 1 g IV infusion over at least 2 hours twice daily in combination with other immunosuppressants. Max: 2 g/day. The initial dose should be administered within 24 hours of transplantation. IV mycophenolate may be continued for up to 14 days; however, patients should be switched to oral therapy as soon as they can tolerate oral medication. According to renal transplant guidelines, mycophenolate is the suggested first-line antiproliferative agent to be used for initial maintenance immunosuppression in combination with other immunosuppressive agents, which may include a calcineurin inhibitor such as tacrolimus, corticosteroids, and induction therapy with basiliximab or anti-thymocyte globulin.
Oral dosage (mycophenolate mofetil capsules and tablets):
NOTE: Mycophenolate mofetil capsules and tablets are not interchangeable on a mg-per-mg basis with mycophenolate sodium delayed-release tablets.
Adults: 1 g PO twice daily is recommended in combination with other immunosuppressants. The initial dose should be administered as soon as possible following transplantation. Max: 2 g/day. According to renal transplant guidelines, mycophenolate is the suggested first-line antiproliferative agent to be used for initial maintenance immunosuppression in combination with other immunosuppressive agents, which may include a calcineurin inhibitor such as tacrolimus, corticosteroids, and induction therapy with basiliximab or anti-thymocyte globulin.
Infants, Children, and Adolescents 3 months and older: Pediatric dosing is based on body surface area (BSA). PATIENTS WITH a BSA of 1.25 m2 to less than 1.5 m2: 750 mg PO twice daily. (total daily dose 1.5 g/day). PATIENTS WITH a BSA of 1.5 m2 or greater: 1 g PO twice daily (total daily dose 2 g/day). PATIENTS WITH a BSA less than 1.25 m2: See oral suspension dosing. The initial oral dose should be administered as soon as possible following transplantation. Mycophenolate is given in combination with other immunosuppressants. According to renal transplant guidelines, mycophenolate is the suggested first-line antiproliferative agent to be used for initial maintenance immunosuppression in combination with other immunosuppressive agents, which may include a calcineurin inhibitor such as tacrolimus, corticosteroids, and induction therapy with basiliximab or anti-thymocyte globulin.
Oral dosage (mycophenolate mofetil oral suspension):
NOTE: Mycophenolate mofetil oral suspension is not interchangeable on a mg-per-mg basis with mycophenolate sodium delayed-release tablets.
Adults: 1 g PO twice daily, given in combination with other immunosuppressants. The initial dose should be administered as soon as possible following transplantation. Max: 2 g/day. According to renal transplant guidelines, mycophenolate is the suggested first-line antiproliferative agent to be used for initial maintenance immunosuppression in combination with other immunosuppressive agents, which may include a calcineurin inhibitor such as tacrolimus, corticosteroids, and induction therapy with basiliximab or anti-thymocyte globulin.
Infants, Children, and Adolescents 3 months and older: Pediatric dosing is based on body surface area (BSA). 600 mg/m2 PO twice daily, up to a maximum of 2 g/day. The initial oral dose should be administered as soon as possible following transplantation. Mycophenolate is given in combination with other immunosuppressants. According to renal transplant guidelines, mycophenolate is the suggested first-line antiproliferative agent to be used for initial maintenance immunosuppression in combination with other immunosuppressive agents, which may include a calcineurin inhibitor such as tacrolimus, corticosteroids, and induction therapy with basiliximab or anti-thymocyte globulin.
Oral dosage (mycophenolate sodium delayed-release tablet):
Adults: 720 mg PO twice daily (total dose 1,440 mg/day) in combination with other immunosuppressants. According to renal transplant guidelines, mycophenolate is the suggested first-line antiproliferative agent to be used for initial maintenance immunosuppression in combination with other immunosuppressive agents, which may include a calcineurin inhibitor such as tacrolimus, corticosteroids, and induction therapy with basiliximab or anti-thymocyte globulin.
Children and Adolescents 5 years and older who are at least 6 months post transplant: Pediatric dosing is based on body surface area (BSA). 400 mg/m2 PO twice daily, up to a maximum of 720 mg PO twice daily. Patients with a BSA of 1.19 m2 to 1.58 m2 may be given three 180 mg tablets, or one 180 mg tablet plus one 360 mg tablet twice daily (1,080 mg/day). Patients with a BSA greater than 1.58 m2 may be dosed with either four 180 mg tablets or two 360 mg tablets twice daily (1,440 mg/day). Due to limited tablet strengths, mycophenolate sodium cannot be used for patients with a BSA less than 1.19 m2.
For heart transplant rejection prophylaxis:
Intravenous dosage (mycophenolate mofetil):
Adults: 1.5 g IV infusion over at least 2 hours twice daily in combination with other immunosuppressants. Max: 3 g/day. Administer the first dose within 24 hours following transplantation. IV mycophenolate may be continued for up to 14 days; however, patients should be switched to oral therapy as soon as they can tolerate oral medication. Guidelines state that mycophenolate or sirolimus, as tolerated, should be included in contemporary immunosuppressive regimens because of a reduced onset and progression of cardiac allograft vasculopathy as assessed by intravascular ultrasound.
Oral dosage (mycophenolate mofetil capsules and tablets):
Adults: 1.5 g PO twice daily in combination with other immunosuppressants. Max: 3 g/day. The initial oral dose should be administered as soon as possible following transplantation. Guidelines state that mycophenolate or sirolimus, as tolerated, should be included in contemporary immunosuppressive regimens because of a reduced onset and progression of cardiac allograft vasculopathy as assessed by intravascular ultrasound.
Infants, Children, and Adolescents 3 months and older: Pediatric dosing is based on body surface area (BSA). PATIENTS WITH a BSA of 1.25 m2 to less than 1.5 m2: Initially, 750 mg PO twice daily (total daily dose 1.5 g/day). PATIENTS WITH a BSA of 1.5 m2 or greater: Initially, 1 g PO twice daily (total daily dose 2 g/day). PATIENTS with a BSA less than 1.25 m2: See oral suspension dosing. The initial oral dose should be administered as soon as possible following transplantation. If tolerated, the dose may be increased and individualized based on clinical assessment. Maximum total daily dose is 3 g/day. Mycophenolate is given in combination with other immunosuppressants.
Oral dosage (mycophenolate mofetil oral suspension):
Adults: 1.5 g PO twice daily in combination with other immunosuppressants. Max: 3 g/day. The initial oral dose should be administered as soon as possible following transplantation. Guidelines state that mycophenolate or sirolimus, as tolerated, should be included in contemporary immunosuppressive regimens because of a reduced onset and progression of cardiac allograft vasculopathy as assessed by intravascular ultrasound.
Infants, Children, Adolescents 3 months and older: Pediatric dosing is based on body surface area (BSA). 600 mg/m2 PO twice daily, initially. The initial oral dose should be administered as soon as possible following transplantation. If well tolerated, the dose may be increased to a maintenance dose of 900 mg/m2 PO twice daily (Max: 3 g/day). Individualize dose based on clinical assessment. Mycophenolate is given with other immunosuppressants.
For liver transplant rejection prophylaxis:
Intravenous dosage (mycophenolate mofetil):
Adults: 1.5 g IV infusion over at least 2 hours twice daily in combination with other immunosuppressants. Max: 3 g/day. Administer the first dose within 24 hours following transplantation. IV mycophenolate may be continued for up to 14 days; however, patients should be switched to oral therapy as soon as they can tolerate oral medication.
Oral dosage (mycophenolate mofetil capsules and tablets):
Adults: 1.5 g PO twice daily in combination with other immunosuppressants. Max: 3 g/day. The initial dose should be administered as soon as possible following transplantation.
Infants, Children, and Adolescents 3 months and older: Pediatric dosing is based on body surface area (BSA). PATIENTS WITH a BSA of 1.25 m2 to less than 1.5 m2: Initially, 750 mg PO twice daily (total daily dose 1.5 g/day). PATIENTS WITH a BSA of 1.5 m2 or greater: Initially, 1 g PO twice daily (total daily dose 2 g/day). PATIENTS WITH a BSA less than 1.25 m2: See oral suspension dosing. The initial oral dose should be administered as soon as possible following transplantation. If tolerated, the dose may be increased and individualized based on clinical assessment. Maximum total daily dose is 3 g/day. Mycophenolate is given in combination with other immunosuppressants.
Oral dosage (mycophenolate mofetil oral suspension):
Adults: 1.5 g PO twice daily in combination with other immunosuppressants. Max: 3 g/day. The initial dose should be administered as soon as possible following transplantation.
Infants, Children and Adolescents 3 months and older: Pediatric dosing is based on body surface area (BSA). 600 mg/m2 PO twice daily, initially. The initial oral dose should be administered as soon as possible following transplantation. If well tolerated, the dose may be increased to a maintenance dose of 900 mg/m2 PO twice daily (Max: 3 g/day). Individualize dose based on clinical assessment. Mycophenolate is given with other immunosuppressants.
For the treatment of rheumatoid arthritis*:
Oral dosage (mycophenolate mofetil):
Adults: Doses ranging from 250 mg to 2 g per day PO have been used in treating rheumatoid arthritis. Improvements in disease markers such as rheumatoid factor titers, immunoglobulin levels, and total number of T cells were all reported during therapy. The dose of 2 g/day was more effective than lower doses and pulse regimens.
For the treatment of graft-versus-host disease (GVHD)*:
Oral dosage (mycophenolate mofetil):
Adults: 250 mg PO 4 times daily or 1 g PO twice daily, initially. May increase the dose by 1 g/day after at least 1 week if inadequate response and based on tolerability. Max: 3 g/day. Guidelines suggest mycophenolate mofetil as a second-line treatment option for steroid-refractory acute GVHD or a second- or third-line treatment option for refractory chronic GVHD.
Children and Adolescents weighing 50 kg or more: 250 mg PO 4 times daily or 1 g PO twice daily, initially. May increase the dose by 1 g/day after at least 1 week if inadequate response and based on tolerability. Max: 3 g/day. Guidelines suggest mycophenolate mofetil as a second-line treatment option for steroid-refractory acute GVHD or a second- or third-line treatment option for refractory chronic GVHD.
Children and Adolescents weighing less than 50 kg: 20 mg/kg/dose PO twice daily, initially. May increase the dose after at least 1 week if inadequate response and based on tolerability. Max: 3 g/day. Guidelines suggest mycophenolate mofetil as a second-line treatment option for steroid-refractory acute GVHD or a second- or third-line treatment option for refractory chronic GVHD.
For the treatment of lupus nephritis*:
Oral dosage:
Adults: 2 to 3 g/day PO plus methylprednisolone 500 to 1000 mg/day IV for 3 days then prednisone 0.5 to 1 mg/kg/day (1 mg/kg/day recommended if crescents seen) tapered after a few weeks to lowest effective dose is recommended for class III/IV disease either for initial induction therapy or for induction therapy after lack of improvement with cyclophosphamide. Mycophenolate mofetil (MMF) and cyclophosphamide are considered equivalent for induction, but MMF is preferred for African Americans and Hispanics and for patients who express a major concern with fertility preservation; high-dose cyclophosphamide can cause permanent infertility in both women and men. For class V disease without proliferative changes but with nephrotic range proteinuria, MMF 2 to 3 g/day PO plus prednisone 0.5 mg/kg/day is recommended. Guidelines recommend that most patients be followed for 6 months after induction initiation before making major treatment changes unless >= 50% worsening of proteinuria or serum creatinine at 3 months exists. MMF and mycophenolic acid (MPA) are likely to be equivalent in inducing improvement with 1440 to 2160 mg total daily dose of MPA roughly equivalent to 2000 to 3000 mg total daily dose of MMF. MMF 1 to 2 g/day PO is a recommended option for maintenance therapy for those who respond to induction therapy. Fewer patients with active class III, IV, or V disease who had a clinical response to induction with either MMF or cyclophosphamide had treatment failure during maintenance therapy with MMF PO 2 g/day (16.4%) as compared with azathioprine 2 mg/kg/day PO recipients (32.4%) (HR, 0.44; 95% CI, 0.25-0.77, p = 0.003). Treatment failure was defined as death, end-stage renal disease, doubling of the serum creatinine concentration, renal flare, or rescue therapy need.
For the treatment of atopic dermatitis*:
Oral dosage (mycophenolate mofetil):
Adults: 1 to 1.5 g PO twice daily.
Adolescents: 600 to 1,200 mg/m2/day PO or 30 to 40 mg/kg/day PO in 2 divided doses. Treatment for up to 24 consecutive months has been reported without harm.
Children: 600 to 1,200 mg/m2/day PO or 40 to 50 mg/kg/day PO in 2 divided doses. Treatment for up to 24 consecutive months has been reported without harm.
For the adjuvant treatment of pemphigus* (pemphigus vulgaris* and pemphigus foliaceus*):
Oral dosage (mycophenolate mofetil):
Adults: 35 to 45 mg/kg/day PO, or alternately, 1 gram PO twice daily. Use adjunctively with corticosteroids. Continue treatment until disease progression ceases and treatment goals are achieved. The timeframe for cessation of disease activity and remission varied widely in clinical trials due to variations in treatment regimens and outcome definitions. Using mycophenolate and corticosteroid regimens, complete lesion healing was reported at an average of 30 +/- 7 days, and complete remission (defined as the absence of lesions for 4 weeks) was reported at median 9 months (range: 1 to 13 months). Mycophenolate may be discontinued using a slow taper. In 1 clinical study, mycophenolate was more effective than azathioprine in inducing disease control. Mycophenolate may have inferior steroid-sparing effects compared to azathioprine and cyclophosphamide.
For the treatment of myasthenia gravis*:
Oral dosage (mycophenolate mofetil):
Adults: Dosage not established. 1 gram PO twice daily has been used with adjunctive corticosteroids or other non-steroidal immunosuppressive medications. Data from randomized, controlled trials do not support use; however, mycophenolate mofetil is widely used for myasthenia gravis. Some experts suggest mycophenolate mofetil use in poorly responsive disease where azathioprine is not tolerated or has failed.
For the treatment of uveitis*:
Oral dosage (mycophenolate mofetil):
Adults: 1 gram PO twice daily for 6 to 41 months has been found to be an effective steroid-sparing agent in the treatment of uveitis; initiating with 500 mg PO twice daily for 1 week may decrease adverse events. Therapy with mycophenolate mofetil (MMF) was introduced in patients intolerant to high-dose steroids (> 20 mg/day) administered over at least 6 months continuously, patients with arterial hypertension and renal impairment on cyclosporine, patients with significant alterations in the differential blood count while receiving methotrexate, or patients with refractory uveitis where prednisolone had been used in combination with cyclosporine or methotrexate or both. In 92 of 106 patients studied with anterior uveitis (n = 26), intermediate uveitis (n = 51), posterior uveitis (n = 23), or panuveitis (n = 6), the number of uveitis recurrences was limited to none or 1 during the treatment period. In 95 patients, MMF was combined with prednisolone 2.5 to 10 mg/day PO. Eight patients were able to use MMF as monotherapy; 3 patients required additional immunosuppression with cyclosporine (dose not reported). Adverse events reported in the study were generally mild with gastrointestinal side effects being the most frequently reported adverse effect.
For the treatment of psoriasis*:
Oral dosage:
Adults: Limited data suggest 1 to 1.5 g PO twice daily may be effective. In an open-label study of 23 patients with moderate to severe psoriasis, administration of mycophenolate mofetil (MMF) in doses of 2 to 3 g/day PO resulted in a 47% reduction in the psoriasis area severity index (PASI) at 12 weeks. Another open-label study of 11 patients with severe stable plaque psoriasis treated with MMF 1 g twice daily PO showed a 40% to 70% reduction in PASI within 3 weeks of initiating therapy.
For the treatment of systemic lupus erythematosus (SLE)*:
Oral dosage:
Adults: Initially, 0.5 gram/day PO (i.e., 250 mg PO twice daily), then titrated as indicated/tolerated, is commonly used. Max: 2 grams/day PO. Consider immunosuppressive agents such as mycophenolate mofetil for patients unresponsive to antimalarials and/or glucocorticoids or for patients unable to reduce steroids below doses acceptable for chronic use.
For the treatment of dermatomyositis* or polymyositis*:
Oral dosage (mycophenolate mofetil):
Adults: 500 mg PO twice daily, initially. May increase the dosage by 500 mg/week up to 1,500 mg twice daily.
Children and Adolescents: 10 mg/kg/dose or 600 mg/m2/dose (Max: 1,500 mg/dose) PO twice daily, whichever is greater.
For the treatment of sarcoidosis*:
Oral dosage (mycophenolate mofetil):
Adults: 500 mg PO twice daily, initially. Increase the dose to 750 to 1,500 mg PO twice daily based on tolerability.
Therapeutic Drug Monitoring:
-Only physicians experienced in the monitoring and management of organ transplant recipients (including the use of immunosuppressant therapy) should prescribe mycophenolate.
-Complete blood count (CBC) assessment is recommended weekly during the first month of therapy, every other week during months 2 and 3, and monthly throughout the first year of treatment.
-To prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL immediately before starting mycophenolate. Another pregnancy test with the same sensitivity should be performed 8 to 10 days later. Repeat pregnancy tests should be performed during routine follow-up visits.
Mycophenolate Drug Concentration Monitoring
Renal Transplant
Guidelines for renal transplant recipients do not recommend mycophenolate drug monitoring for all patients because of limited supportive evidence and, thus, uncertain benefit. Other guidelines suggest drug concentration monitoring after mycophenolate mofetil receipt, but the suggestion is based on very low quality of evidence. The area under the time versus concentration curve (AUC) is widely regarded as the best measure of mycophenolic acid (MPA) exposure. For mycophenolate mofetil combination with cyclosporine, the proposed MPA AUC0-12 is 30 to 60 mcg x hour/mL during the early period after transplantation.
Heart Transplant
According to guidelines for heart transplant recipients, routine MPA concentration monitoring to adjust mycophenolate mofetil doses is not recommended. Measurement of trough MPA concentrations may be used to guide mycophenolate dosing in situations where it is suspected that altered mycophenolate mofetil exposure contributes to heart allograft dysfunction. A MPA concentration less than 1.5 mg/L is considered to be sub-therapeutic. Insufficient data exist to support routine monitoring of MPA concentrations in pediatric recipients, but intermittent monitoring is reasonable when there is ongoing rejection, doubts about dosing adequacy, and to assess medical compliance.
Dosage adjustments for hematologic toxicity (neutropenia):
Absolute neutrophil count (ANC) less than 1,300 cells/mcL: Mycophenolate therapy should be interrupted or the dose reduced, appropriate tests performed, and the patient managed accordingly.
Maximum Dosage Limits:
-Adults
For mycophenolate mofetil tablets, capsules, or intravenous solution: maximum 2 g/day (kidney transplant) or 3 g/day (heart or liver transplant) PO or IV.
For mycophenolate sodium delayed-release tablets: 1,440 mg/day PO.
-Geriatric
For mycophenolate mofetil tablets, capsules, or intravenous solution: maximum 2 g/day (kidney transplant) or 3 g/day (heart or liver transplant) PO or IV.
For mycophenolate sodium delayed-release tablets: 1,440 mg/day PO.
-Adolescents
For the mycophenolate mofetil oral suspension: 1,200 mg/m2/day PO, not to exceed 2 g/day PO, for kidney transplant rejection prophylaxis. Maximum 1,800 mg/m2/day, not to exceed 3 g/day, for heart or liver transplant rejection prophylaxis.
For mycophenolate mofetil capsules and tablets: 1,500 mg/day PO for BSA 1.25 to less than 1.5 m2 for kidney transplant rejection prophylaxis and maximum maintenance dose of 3 g/day for heart or liver transplant rejection prophylaxis. Maximum is 2 g/day PO for BSA of 1.5 m2 or greater for kidney transplant rejection prophylaxis and maximum maintenance dose of 3 g/day for heart or liver transplant rejection prophylaxis.
For mycophenolate sodium delayed-release tablets: 800 mg/m2/day PO (Max: 1,440 mg/day PO) for BSA greater than 1.19 m2 for kidney transplant rejection prophylaxis. Safety and efficacy have not been established for BSA of 1.19 m2 or less.
-Children
Children 5 years and older:
For the mycophenolate mofetil oral suspension: 1,200 mg/m2/day PO, not to exceed 2 g/day PO, for kidney transplant rejection prophylaxis. Maximum 1,800 mg/m2/day, not to exceed 3 g/day, for heart or liver transplant rejection prophylaxis.
For mycophenolate mofetil capsules and tablets: 1,500 mg/day PO for BSA 1.25 to less than 1.5 m2 for kidney transplant rejection prophylaxis and maximum maintenance dose of 3 g/day for heart or liver transplant rejection prophylaxis. Maximum is 2 g/day PO for BSA of 1.5 m2 or greater for kidney transplant rejection prophylaxis and maximum maintenance dose of 3 g/day for heart or liver transplant rejection prophylaxis.
For mycophenolate sodium delayed-release tablets: 800 mg/m2/day PO (Max: 1,440 mg/day PO) for BSA greater than 1.19 m2 for kidney transplant rejection prophylaxis. Safety and efficacy have not been established for BSA of 1.19 m2 or less.
Children 1 to 4 years:
For the mycophenolate mofetil oral suspension: 1,200 mg/m2/day PO, not to exceed 2 g/day PO, for kidney transplant rejection prophylaxis. Maximum 1,800 mg/m2/day, not to exceed 3 g/day, for heart or liver transplant rejection prophylaxis.
For mycophenolate mofetil capsules and tablets: 1,500 mg/day PO for BSA 1.25 to less than 1.5 m2 for kidney transplant rejection prophylaxis and maximum maintenance dose of 3 g/day for heart or liver transplant rejection prophylaxis. Maximum is 2 g/day PO for BSA of 1.5 m2 or greater for kidney transplant rejection prophylaxis and maximum maintenance dose of 3 g/day for heart or liver transplant rejection prophylaxis.
For mycophenolate sodium delayed-release tablets: Safety and efficacy have not been established.
-Infants
3 months and older: For the mycophenolate mofetil oral suspension: 1,200 mg/m2/day PO (not to exceed 2 g/day PO), for kidney transplant rejection prophylaxis. Maximum 1,800 mg/m2/day PO (not to exceed 3 g/day) for heart or liver transplant rejection prophylaxis. The safety and efficacy of other dosage forms has not been established.
Less than 3 months: Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. However, mycophenolic acid (MPA) is highly bound to albumin, and patients with severe hepatic impairment or hepatic encephalopathy may have increased free MPA concentrations.
Patients with Renal Impairment Dosing
CrCl < 25 ml/min: Do not exceed 1 g PO twice daily of mycophenolate mofetil if renal impairment occurs after the initial post-renal transplant period. No dosage adjustments are needed in renal transplant patients that develop delayed graft function postoperatively. There are no quantitative guidelines for mycophenolate sodium dose adjustment in patients with severe chronic renal impairment. Elevated free mycophenolic acid concentrations may be present (see Pharmacokinetics).
*non-FDA-approved indication
Abciximab: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Acetaminophen; Aspirin: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Acyclovir: (Moderate) Coadministration of mycophenolate mofetil and acyclovir to healthy volunteers resulted in no significant change in mycophenolic acid concentrations or AUC. However, the glucuronide metabolite of mycophenolate (MPAG) and acyclovir AUCs were increased 10.6% and 21.9%, respectively. Because MPAG and acyclovir concentrations are increased in the presence of renal impairment, the potential exists for the two drugs to compete for tubular secretion, further increasing the concentration of both drugs in patients renal dysfunction.
Aluminum Hydroxide: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum/magnesium hydroxide antacids decrease the AUC of mycophenolic acid by about 17% when given as mycophenolate mofetil. Decreased absorption of mycophenolate (possible chelation) is the likely etiology for reduced systemic exposure. If antacids and mycophenolate need to be used together, separate administration times are recommended (do not give simultaneously).
Aluminum Hydroxide; Magnesium Carbonate: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum/magnesium hydroxide antacids decrease the AUC of mycophenolic acid by about 17% when given as mycophenolate mofetil. Decreased absorption of mycophenolate (possible chelation) is the likely etiology for reduced systemic exposure. If antacids and mycophenolate need to be used together, separate administration times are recommended (do not give simultaneously).
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum/magnesium hydroxide antacids decrease the AUC of mycophenolic acid by about 17% when given as mycophenolate mofetil. Decreased absorption of mycophenolate (possible chelation) is the likely etiology for reduced systemic exposure. If antacids and mycophenolate need to be used together, separate administration times are recommended (do not give simultaneously).
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum/magnesium hydroxide antacids decrease the AUC of mycophenolic acid by about 17% when given as mycophenolate mofetil. Decreased absorption of mycophenolate (possible chelation) is the likely etiology for reduced systemic exposure. If antacids and mycophenolate need to be used together, separate administration times are recommended (do not give simultaneously).
Aluminum Hydroxide; Magnesium Trisilicate: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum/magnesium hydroxide antacids decrease the AUC of mycophenolic acid by about 17% when given as mycophenolate mofetil. Decreased absorption of mycophenolate (possible chelation) is the likely etiology for reduced systemic exposure. If antacids and mycophenolate need to be used together, separate administration times are recommended (do not give simultaneously).
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Amoxicillin: (Moderate) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Amoxicillin;Clavulanic Acid may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption. The effect of amoxicillin without clavulantic acid on mycophenolate kinetics is unclear.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic). (Moderate) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Amoxicillin;Clavulanic Acid may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption. The effect of amoxicillin without clavulantic acid on mycophenolate kinetics is unclear.
Amoxicillin; Clavulanic Acid: (Moderate) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Amoxicillin;Clavulanic Acid may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption. The effect of amoxicillin without clavulantic acid on mycophenolate kinetics is unclear.
Anagrelide: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Antacids: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum/magnesium hydroxide antacids decrease the AUC of mycophenolic acid by about 17% when given as mycophenolate mofetil. Decreased absorption of mycophenolate (possible chelation) is the likely etiology for reduced systemic exposure. If antacids and mycophenolate need to be used together, separate administration times are recommended (do not give simultaneously).
Anticoagulants: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Antithrombin III: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Apixaban: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Argatroban: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Aspirin, ASA: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Aspirin, ASA; Caffeine: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption. (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Aspirin, ASA; Dipyridamole: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects. (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Aspirin, ASA; Omeprazole: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic). (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Aspirin, ASA; Oxycodone: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Azathioprine: (Major) Concomitant use of mycophenolate and azathioprine is not recommended, as both drugs inhibit purine metabolism. Because azathioprine is an immunosuppressant with myelosuppressive actions, additive affects may be seen with other immunosuppressant agents (e.g., mycophenolate). Also, the drug combination has not been studied clinically.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Basiliximab: (Minor) Because mycophenolate mofetil is an immunosuppressant, additive effects may be seen with other immunosuppressives. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections, malignancies including lymphoma and leukemia, myelodysplastic syndromes, and lymphoproliferative disorders. The risk is related to the intensity and duration of immunosuppression rather than the specific agents.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Betrixaban: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Coadministration of mycophenolate mofetil, norfloxacin, and metronidazole is not recommended. Administration of all 3 drugs significantly reduced the systemic exposure of mycophenolic acid. Specifically, as compared with the value obtained with mycophenolate mofetil monotherapy, the mean mycophenolic acid AUC (0 to 48 h) was decreased by 33% when 1 gram of mycophenolate mofetil was administered to healthy patients who had received 4 days of both norfloxacin and metronidazole. The mycophenolic acid systemic exposure was slightly reduced when mycophenolate mofetil was coadministered with either norfloxacin or metronidazole. The mean (+/-SD) mycophenolic acid AUC (0 to 48 h) was 56.2 (+/-24) mcgh/ml after mycophenolate mofetil monotherapy, 48.3 (+/-24) mcgh/ml after coadministration with norfloxacin, and 42.7 (+/-23) mcgh/ml after coadministration with metronidazole. Addtionally, potential QT prolongation has been reported in limited case reports with metronidazole; therefore, it should be used cautiously when adminstered with norfloxacin, which has a possible risk for QT prolongation and TdP.
Bismuth Subsalicylate: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Coadministration of mycophenolate mofetil, norfloxacin, and metronidazole is not recommended. Administration of all 3 drugs significantly reduced the systemic exposure of mycophenolic acid. Specifically, as compared with the value obtained with mycophenolate mofetil monotherapy, the mean mycophenolic acid AUC (0 to 48 h) was decreased by 33% when 1 gram of mycophenolate mofetil was administered to healthy patients who had received 4 days of both norfloxacin and metronidazole. The mycophenolic acid systemic exposure was slightly reduced when mycophenolate mofetil was coadministered with either norfloxacin or metronidazole. The mean (+/-SD) mycophenolic acid AUC (0 to 48 h) was 56.2 (+/-24) mcgh/ml after mycophenolate mofetil monotherapy, 48.3 (+/-24) mcgh/ml after coadministration with norfloxacin, and 42.7 (+/-23) mcgh/ml after coadministration with metronidazole. Addtionally, potential QT prolongation has been reported in limited case reports with metronidazole; therefore, it should be used cautiously when adminstered with norfloxacin, which has a possible risk for QT prolongation and TdP. (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Bivalirudin: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Calcium Carbonate: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption.
Calcium Carbonate; Magnesium Hydroxide: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption.
Calcium Carbonate; Simethicone: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption.
Calcium; Vitamin D: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption.
Carboplatin: (Contraindicated) Concurrent use of carboplatin with other agents that cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cefuroxime: (Minor) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Cefuroxime may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption.
Charcoal: (Major) Activated charcoal binds bile acids and can interrupt enterohepatic recirculation of mycophenolic acid and thus, reduce mycophenolic acid systemic exposure. Concurrent use of any drug that may interfere with enterohepatic recirculation of MPA such as activated charcoal is not recommended.
Chikungunya Vaccine, Live: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Chlorambucil: (Minor) Chlorambucil is known to cause myelosuppression, which may lead to neutropenia related side effects. Concurrent use of chlorambucil with other agents which cause bone marrow or immune suppression such as immunosuppressives may result in additive effects.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cholestyramine: (Major) Avoid administration of mycophenolate mofetil with cholestyramine. Coadministration of mycophenolate mofetil with cholestyramine decreases the bioavailability of mycophenolate mofetil. Cholestyramine decreases the AUC of mycophenolate by about 40%.
Choline Salicylate; Magnesium Salicylate: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Cilostazol: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Ciprofloxacin: (Moderate) Drugs that alter the gastrointestinal flora such as ciprofloxacin may interact with mycophenolate by disrupting enterohepatic recirculation. Mycophenolic acid (MPA) is converted to an inactive phenolic glucuronide, MPA glucuronide (MPAG), which undergoes enterohepatic recirculation. Bacteria that express beta-glucuronidase cleave the glucuronide conjugate, which results in liberation of MPA. Normally, two peaks of MPA occur after administration. The first peak occurs after absorption of MPA, and the second peak occurs after cleavage of MPAG by beta-glucuronidase producing bacteria. Antibiotics with activity against such bacteria can reduce the second peak in MPA serum concentrations; interference of MPAG hydrolysis may lead to less MPA available for absorption. A reduction in predose MPA concentrations was noted after ciprofloxacin (500 mg PO twice daily) was administered to 24 patients taking mycophenolate mofetil and tacrolimus for renal transplant prophylaxis. The predose concentration was obtained before the morning dose and 12 hours after the evening mycophenolate dose. The mean MPA predose concentration at baseline was 2.3 mg/L. After 3 days of ciprofloxacin, the mean concentration was 1.5 mg/L. With 7 days of ciprofloxacin, the predose concentration was 1.2 mg/L, and 3 days after the 7-day course, the mean concentration was not significantly different from baseline (2.6 mg/L). A reduction in the MPA predose concentration was also noted among 21 patients who took a 14-day course of ciprofloxacin. Interestingly, the predose concentration rose with continued ciprofloxacin use. The mean predose concentration was 2.3 mg/L at baseline, 1.4 mg/L after 3 days of the antibiotic, 1.5 mg/L after 7 days of the antibiotic, and 1.9 mg/L after 14 days of the antibiotic. In addition to a rise in predose concentrations with continued antibiotic use, some patients did not have a large reduction in their predose concentration. Nine of 44 patients who got a 7-day course of ciprofloxacin or another antibiotic, and 7 of 38 patients who got a 14-day course with either ciprofloxacin or another antibiotic had MPA concentrations on day 3 of antibiotics that were greater than 80% of baseline values. Also, the predose MPA concentration may not accurately represent changes in overall MPA exposure. No deaths, graft losses, acute rejection episodes, or gastrointestinal disturbances were noted throughout the study. A mycophenolate dose increase in response to reduced MPA predose concentrations could cause toxicity in some patients. Of note, the impact of an antibiotic that reduces enterohepatic recirculation of MPA on patients also taking cyclosporine needs investigation; cyclosporine also reduces the enterohepatic recirculation of MPA.
Clopidogrel: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Colesevelam: (Major) Bile acid sequestrants can interrupt enterohepatic recirculation and thus, reduce mycophenolic acid systemic exposure. Concurrent use of colesevelaml and mycophenolate mofetil is not recommended.
Colestipol: (Major) Bile acid sequestrants, such as colestipol can interrupt enterohepatic recirculation and thus, reduce mycophenolic acid systemic exposure. The AUC of mycophenolic acid when given as mycophenolate mofetil is decreased by about 40% when take with cholestyramine. Concurrent use of a bile acid sequestrant, such as colestipol, or any drug that may interfere with enterohepatic recirculation of MPA is not recommended.
Cyclosporine: (Moderate) Monitor for alterations in mycophenolate mofetil efficacy when administered concurrently with cyclosporine. The enterohepatic circulation of mycophenolic acid (MPA) is inhibited by cyclosporine; cyclosporine use decreases the mean exposure of MPA by 20% to 50% when compared with other immunosuppressants.
Dabigatran: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Dalteparin: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Daunorubicin: (Major) Concurrent use of daunorubicin with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Desogestrel; Ethinyl Estradiol: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Dexlansoprazole: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Dichlorphenamide: (Moderate) Use dichlorphenamide and mycophenolate together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Dipyridamole: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Doxorubicin Liposomal: (Major) Concurrent use of doxorubicin with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Doxorubicin: (Major) Concurrent use of doxorubicin with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Drospirenone; Ethinyl Estradiol: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Edoxaban: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Enoxaparin: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Eptifibatide: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Esomeprazole: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Ethinyl Estradiol; Norelgestromin: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Ethinyl Estradiol; Norgestrel: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Etonogestrel; Ethinyl Estradiol: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Ferric Maltol: (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
Fondaparinux: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Food: (Minor) Administration of mycophenolate with food can affect absorption of the drug. The extent of absorption is not affected, but the maximum serum concentration is lowered as compared with the fasting state. Patients need to be told to take mycophenolate either 1 hour before or 2 hours after eating.
Fosphenytoin: (Moderate) The pharmacokinetics of mycophenolate mofetil, an immunosuppressive agent, are not affected by phenytoin. However, mycophenolate decreases the protein binding of phenytoin by roughly 3%, which may increase unbound phenytoin concentrations.
Ganciclovir: (Moderate) The systemic concentration of ganciclovir and the glucuronide metabolite of mycophenolate are increased in the presence of renal impairment. Concomitant use may result in competition for tubular secretion, which could further increase the systemic exposures. Thus, adverse effects from increased serum concentrations may be anticipated; blood cell count monitoring is recommended.
Heparin: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Infliximab: (Moderate) Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections. The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.
Intranasal Influenza Vaccine: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Iron Salts: (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
Iron: (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with mycophenolate results in elevated mycophenolate serum concentrations. Patients receiving this drug combination should be closely monitored for mycophenolate-related adverse reactions and toxicities. The mechanism of the interaction is not completely understood, but is expected to be due to UDP-glucosyltransferase (UGT) metabolism; both isavuconazole, the active moiety of isavuconazonium, and mycophenolate are substrates for UGT, and isavuconazole may also inhibit UGT.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Use of both rifampin and mycophenolate mofetil is not recommended unless the benefit outweighs the risk. Concurrent administration to a heart-lung transplant patient led to a a 67% decrease in mycophenolic acid exposure after correction for dose.
Isoniazid, INH; Rifampin: (Major) Use of both rifampin and mycophenolate mofetil is not recommended unless the benefit outweighs the risk. Concurrent administration to a heart-lung transplant patient led to a a 67% decrease in mycophenolic acid exposure after correction for dose.
Lansoprazole: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic). (Moderate) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Amoxicillin;Clavulanic Acid may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption. The effect of amoxicillin without clavulantic acid on mycophenolate kinetics is unclear.
Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like mycophenolate, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered. (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered. (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
Live Vaccines: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Magnesium Hydroxide: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum/magnesium hydroxide antacids decrease the AUC of mycophenolic acid by about 17% when given as mycophenolate mofetil. Decreased absorption of mycophenolate (possible chelation) is the likely etiology for reduced systemic exposure. If antacids and mycophenolate need to be used together, separate administration times are recommended (do not give simultaneously).
Magnesium Salicylate: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Melphalan Flufenamide: (Minor) Bone marrow suppression is the most significant toxicity associated with melphalan in most patients. The bone marrow depressant effects of melphalan can be potentiated by concurrent or sequential administration of other bone marrow depressants and immunosuppressives.
Melphalan: (Minor) Bone marrow suppression is the most significant toxicity associated with melphalan in most patients. The bone marrow depressant effects of melphalan can be potentiated by concurrent or sequential administration of other bone marrow depressants and immunosuppressives.
Methenamine; Sodium Salicylate: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Metronidazole: (Moderate) Coadministration of mycophenolate mofetil, norfloxacin, and metronidazole is not recommended. Administration of all 3 drugs significantly reduced the systemic exposure of mycophenolic acid. Specifically, as compared with the value obtained with mycophenolate mofetil monotherapy, the mean mycophenolic acid AUC (0 to 48 h) was decreased by 33% when 1 gram of mycophenolate mofetil was administered to healthy patients who had received 4 days of both norfloxacin and metronidazole. The mycophenolic acid systemic exposure was slightly reduced when mycophenolate mofetil was coadministered with either norfloxacin or metronidazole. The mean (+/-SD) mycophenolic acid AUC (0 to 48 h) was 56.2 (+/-24) mcgh/ml after mycophenolate mofetil monotherapy, 48.3 (+/-24) mcgh/ml after coadministration with norfloxacin, and 42.7 (+/-23) mcgh/ml after coadministration with metronidazole. Addtionally, potential QT prolongation has been reported in limited case reports with metronidazole; therefore, it should be used cautiously when adminstered with norfloxacin, which has a possible risk for QT prolongation and TdP.
Micafungin: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. In theory, patients who are taking immunosuppressive agents such as mycophenolate concomitantly with micafungin may have additive risks for infection or other side effects. However, the manufacturer has listed no particular precautions for co-use of micafungin with these medications. Concurrent administration of micafungin and mycophenolate mofetil did not alter the pharmacokinetic parameters of micafungin. Furthermore, there was no effect of a single or multiple doses of micafungin on mycophenolate mofetil pharmacokinetic parameters.
Naproxen; Esomeprazole: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Natalizumab: (Major) The concomitant use of natalizumab and immunosuppressives may further increase the risk of infections, including progressive multifocal leukoencephalopathy (PML), over the risk observed with use of natalizumab alone. Prior treatment with an immunosuppressant is also a risk factor for PML. The safety and efficacy of natalizumab in combination with immunosuppressants has not been evaluated. Multiple sclerosis (MS) patients receiving chronic immunosuppressant therapy should not ordinarily be treated with natalizumab. Also, natalizumab for Crohn's disease should not be used in combination with mycophenolate.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered. (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
Norethindrone; Ethinyl Estradiol: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered. (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
Norgestimate; Ethinyl Estradiol: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Omeprazole: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic). (Moderate) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Amoxicillin;Clavulanic Acid may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption. The effect of amoxicillin without clavulantic acid on mycophenolate kinetics is unclear.
Omeprazole; Sodium Bicarbonate: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption. (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Pantoprazole: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Patiromer: (Moderate) Separate the administration of patiromer and oral mycophenolate by at least 3 hours if concomitant use is necessary. Simultaneous oral coadministration may reduce gastrointestinal absorption of mycophenolate and reduce its efficacy. Patiromer has been observed to bind some oral medications when given at the same time and separating administration by at least 3 hours has effectively mitigated this risk.
Pentosan: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Phenytoin: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Administration of mycophenolate mofetil decreased the protein binding of phenytoin by 3%. Monitor patients receiving mycophenolate with highly protein bound drugs, such as phenytoin for changes in clinical status.
Platelet Inhibitors: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Polysaccharide-Iron Complex: (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
Prasugrel: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Probenecid: (Minor) Probenecid is a known inhibitor of renal tubular secretion, and the inactive metabolite, MPAG undergoes tubular secretion. Increased MPAG concentrations can cause increased mycophenolic acid systemic exposure and thus, adverse effects. Patients receiving both drugs should be monitored carefully.
Probenecid; Colchicine: (Minor) Probenecid is a known inhibitor of renal tubular secretion, and the inactive metabolite, MPAG undergoes tubular secretion. Increased MPAG concentrations can cause increased mycophenolic acid systemic exposure and thus, adverse effects. Patients receiving both drugs should be monitored carefully.
Proton pump inhibitors: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Rabeprazole: (Moderate) Concomitant administration of proton pump inhibitors (PPIs) with mycophenolate mofetil (Cellcept) appears to reduce MPA exposure AUC-12h (25.8 +/- 6.4 mg/L x h with omeprazole vs. 33.3 +/- 11.5 mg//L x h without omeprazole); however, the interaction does not appear to exist with mycophenolate sodium delayed-release tablets (Myfortic). Reduced systemic exposure of MPA after mycophenolate mofetil in the presence of a PPI appears to be due to impaired absorption of mycophenolate mofetil which may occur because of incomplete dissolution of mycophenolate mofetil in the stomach at elevated pH. The clinical significance of reduced MPA exposure is unknown; however patients should be evaluated periodically if mycophenolate mofetil is administered with a PPI. Of note, MPA concentrations appear to be reduced in the initial hours after mycophenolate mofetil receipt but increase later in the dosing interval because of enterohepatic recirculation. A second peak in the concentration-time profile of MPA is observed 612 hours after dosing due to enterohepatic recirculation. For example, the 12-hour plasma concentrations of MPA were similar among patients who received mycophenolate mofetil with or without omeprazole. The biphasic plasma concentration-time course of MPA due to extensive enterohepatic circulation hampers therapeutic drug monitoring of MPA. Drug exposure as measured by AUC-12h is the best estimator for the clinical effectiveness of mycophenolate, but measurement of full-dose interval MPA AUC-12h requires collection of multiple samples over a 12-hour period; MPA predose concentrations correlate poorly with MPA AUC-12h. The interaction does not appear to exist with Mycophenolate sodium (Myfortic).
Rifampin: (Major) Use of both rifampin and mycophenolate mofetil is not recommended unless the benefit outweighs the risk. Concurrent administration to a heart-lung transplant patient led to a a 67% decrease in mycophenolic acid exposure after correction for dose.
Rivaroxaban: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Rotavirus Vaccine: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Salicylates: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
Salsalate: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Mycophenolate mofetil may not have any influence on the ovulation suppressing action of ethinyl estradiol. However, it is recommended that hormonal contraceptives be given to women receiving mycophenolate and additional birth control methods be considered.
Sevelamer: (Major) Do not administer sevelamer simultaneously with mycophenolate mofetil. The mean mycophenolic acid Cmax was decreased by 36%, and the mean mycophenolic acid AUC(0-12h) was decreased by 26% when sevelamer and mycophenolate mofetil were coadministered in adult and pediatric patients. If sevelamer and mycophenolate are needed, administer sevelamer 2 hours after mycophenolate mofetil intake in order to minimize the impact on the absorption of mycophenolic acid.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Sodium Bicarbonate: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Separate administration of mycophenolate and iron by at least 4 hours. Iron may decrease the oral bioavailability of mycophenolate. Mycophenolate recovery was reduced by up to 16% under certain pH conditions in drug interaction studies.
Tacrolimus: (Minor) Tacrolimus is a potent inhibitor of UDP-glucuronosyl transferase. As mycophenolic acid is metabolized by UDPGT, increased concentrations of mycophenolic acid would be anticipated.
Telmisartan: (Moderate) Concommitant administration of telmisartan and mycophenolate resulted in a 30% decrease in mycophenolic acid (MPA) concentration. Telmisartan enhances PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which results in enhanced UGT1A9 expression and activity. MPA is primarily metabolized by glucuronyl transferase to the phenolic glucuronide of MPA (MPAG) which is not pharmacologically active. Monitor patients receiving these drugs concurrently for signs or symptoms of organ rejection.
Telmisartan; Amlodipine: (Moderate) Concommitant administration of telmisartan and mycophenolate resulted in a 30% decrease in mycophenolic acid (MPA) concentration. Telmisartan enhances PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which results in enhanced UGT1A9 expression and activity. MPA is primarily metabolized by glucuronyl transferase to the phenolic glucuronide of MPA (MPAG) which is not pharmacologically active. Monitor patients receiving these drugs concurrently for signs or symptoms of organ rejection.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Concommitant administration of telmisartan and mycophenolate resulted in a 30% decrease in mycophenolic acid (MPA) concentration. Telmisartan enhances PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which results in enhanced UGT1A9 expression and activity. MPA is primarily metabolized by glucuronyl transferase to the phenolic glucuronide of MPA (MPAG) which is not pharmacologically active. Monitor patients receiving these drugs concurrently for signs or symptoms of organ rejection.
Temozolomide: (Minor) Concurrent use of temozolomide with other agents that cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Theophylline, Aminophylline: (Minor) Mycophenolic acid is highly protein bound. Administration of mycophenolate mofetil decreases the protein binding of aminophylline. Monitor patients receiving mycophenolate with highly protein bound drugs, such as aminophylline for changes in clinical status. (Minor) Mycophenolic acid is highly protein bound. Administration of mycophenolate mofetil decreases the protein binding of theophylline. Monitor patients receiving mycophenolate with highly protein bound drugs, such as theophylline for changes in clinical status.
Ticagrelor: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Tirofiban: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Tobramycin: (Minor) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Tobramycin may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption.
Typhoid Vaccine: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Valacyclovir: (Moderate) Valacyclovir, a prodrug of acyclovir, when added to a regimen of MMF, cyclosporine, and prednisolone caused neutropenia. The acyclovir trough concentration was 4.5 mg/L, which is in the upper range of the EC(50) for antiviral activity. Cessation of valacyclovir led to immediate recovery of the neutrophil count and an increased concentration of mycophenolic acid (from 0.85 to 1.93 mg/L). Coadministration of mycophenolate mofetil (MMF) and acyclovir to healthy volunteers resulted in no significant change in mycophenolic acid concentrations or AUC. However, the systemic exposure of the glucuronide metabolite of mycophenolate (MPAG) and of acyclovir was increased 10.6% and 21.9%, respectively. Blood cell count monitoring is recommended. The risk of adverse effects (e.g., leukopenia) from concomitant use may be greater in patients with renal impairment, as MPAG and acyclovir concentrations undergo renal tubular secretion. The potential exists for the two drugs to compete for tubular secretion, which could further increase the concentration of both drugs in patients with renal dysfunction.
Valganciclovir: (Moderate) Because the glucuronide metabolite of mycophenolate and ganciclovir concentrations are increased in the presence of renal impairment, the potential exists for the two drugs to compete for tubular secretion, further increasing the concentration of both drugs.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Vonoprazan: (Moderate) Monitor for altered mycophenolate efficacy when coadministered with vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of mycophenolate reducing its efficacy.
Vonoprazan; Amoxicillin: (Moderate) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Amoxicillin;Clavulanic Acid may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption. The effect of amoxicillin without clavulantic acid on mycophenolate kinetics is unclear. (Moderate) Monitor for altered mycophenolate efficacy when coadministered with vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of mycophenolate reducing its efficacy.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Amoxicillin;Clavulanic Acid may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption. The effect of amoxicillin without clavulantic acid on mycophenolate kinetics is unclear. (Moderate) Monitor for altered mycophenolate efficacy when coadministered with vonoprazan. Vonoprazan reduces intragastric acidity, which may decrease the absorption of mycophenolate reducing its efficacy.
Vorapaxar: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
Warfarin: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Yellow Fever Vaccine, Live: (Contraindicated) Do not administer live vaccines to mycophenolate recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving mycophenolate. At least 2 weeks before initiation of mycophenolate therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Mycophenolate recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Mycophenolic acid (MPA) inhibits lymphocyte purine synthesis by reversibly and noncompetitively inhibiting the enzyme, inosine monophosphate dehydrogenase (IMPDH). IMPDH is an important enzyme in the de novo synthesis of purines and is the rate-limiting step in converting inosine monophosphate (IMP) to guanosine monophosphate (GMP), an important intermediate in the synthesis of lymphocyte DNA, RNA, proteins, and glycoproteins. T- and B-lymphocytes, unlike other cells, can not synthesize GMP sufficiently through the salvage pathway. The cytostatic effect on lymphocytes is thus, greater than the effect on other cell types. Mycophenolic acid's inhibition of IMPDH prevents the formation of GMP, which decreases guanosine triphosphate (GTP) and deoxy-GTP that are necessary substrates for DNA, RNA, and protein synthesis. Subsequently, MPA inhibits lymphocyte proliferation and the formation of adhesion molecules in response to antigenic or mitogenic stimulation. Adhesion molecules are usually present on the surface of activated T cells.
In comparison with other immunosuppressive agents, MPA has several potential advantages. First, in vitro studies show that MPA blocks the secondary antibody responses mediated by memory B cells. Secondly, in contrast to azathioprine and methotrexate which have a nonselective effect on DNA synthesis in all cell types, MPA has a selective effect on lymphocyte proliferation. Next, MPA is not incorporated into DNA and does not cause chromosome breaks. Lastly, MPA inhibits the proliferation of human B lymphocyte cell lines transformed by the Epstein-Barr virus (EBV); cyclosporine inhibits T-cell mediated surveillance of EBV-transformed B lymphocytes but does not block B-lymphocyte replication. The overall effects of MPA as revealed by clinical studies show that MPA is at least as potent as azathioprine when used in combination with cyclosporine and corticosteroids for immunosuppression.
Mycophenolate mofetil (MMF) is administered orally or intravenously whereas mycophenolate sodium is only administered orally. After both intravenous and oral administration, MMF is immediately hydrolyzed to form free mycophenolic acid (MPA), the active compound. The principal route of MPA metabolism is glucuronidation via glucoronyl transferase (UGT) to form the primary, inactive metabolite, mycophenolic acid glucuronide (MPAG). The minor acyl glucuronide metabolite has similar pharmacologic activity as compared with MPA. At steady state, the AUC ratio of MPA:MPAG:acyl glucuronide is approximately 1:24:0.28. During enterohepatic recirculation, MPAG is converted to MPA, which results in a secondary peak in plasma MPA concentration 6 to 12 hours post-dose. MPA is 97%, and MPAG is 82% bound to plasma albumin. Patients with kidney impairment or delayed kidney graft function may have higher MPAG concentrations resulting in decreased protein binding and increased free MPA due to competition for binding sites between MPAG and MPA. An increase in free MPA concentrations may occur under conditions of decreased protein binding, such as uremia, hepatic failure, and hypoalbuminemia.
Therapeutic drug monitoring (TDM) for mycophenolate is not currently recommended, as there is an absence of needed data. Data from 1 study suggest the possible utility of TDM. Patients received cyclosporine, prednisone, and MMF to a predefined target MPA AUC concentrations (16.1, 32.2, or 60.6 mcg*hr/mL) for 6 months after renal transplantation. The number of patients with biopsy-proven acute rejection in the low, intermediate, and high target MPA AUC groups was 14 of 51, 7 of 47, and 6 of 52, respectively. The numbers of patients with premature withdrawal from the study due to adverse events in the 3 respective groups were 4 of 51, 11 of 47, and 23 of 52.
Affected Cytochrome P450 enzymes and drug transporters: None known
Mycophenolate is not known to induce or inhibit CYP isoenzymes or drug transporters in a clinically significant way. Drugs that inhibit or induce glucuronidation via UGT, which is the principal route of mycophenolate metabolism, may alter mycophenolate exposure.
-Route-Specific Pharmacokinetics
Oral Route
-Mycophenolate mofetil capsules, tablets, and oral suspension: After oral administration, mycophenolate mofetil is immediately hydrolyzed to form free mycophenolic acid (MPA), the active compound. Mean peak plasma concentrations of MPA were found to occur within approximately 0.5 to 2 hours following single-dose administration to healthy volunteers and after multiple dose administration to kidney, heart, or liver transplant patients. Compared to intravenous MMF, oral MMF had a mean absolute oral bioavailability of 94%. Four 250 mg MMF capsules have been shown to be bioequivalent to two 500 mg MMF tablets. Also, 5 mL of MMF oral suspension (200 mg/mL) is bioequivalent to four 250 mg MMF capsules. The mean MPA AUC was 20% to 41% lower and Cmax was 32% to 44% lower during the early post-transplant period (less than 40 days post-transplant) compared to the late transplant period (i.e., 3 to 6 months post-transplant). Presence of food decreased the MPA Cmax by 40% but did not affect the AUC at doses of 1.5 g twice daily in kidney transplant patients. In healthy volunteers, the mean volume of distribution was 3.6 L/kg. Mean elimination half-life is 17.9 hours. Ninety-three percent of the orally administered dose is excreted in the urine, 87% of which is as MPAG, and 6% in the feces.
-Mycophenolate sodium delayed-release tablets: The release of MPA from enteric-coated mycophenolate sodium does not occur under acidic conditions (pH less than 5) but in the neutral pH conditions of the intestines. Peak plasma concentrations of MPA are attained between 1.5 and 2.75 hours after administration of mycophenolate sodium. Gastrointestinal absorption of MPA following administration to stable renal transplant patients on cyclosporine was 93%, and MPA had an absolute bioavailability of 72%. Myfortic displays linear and dose-proportional pharmacokinetics over a dosage range of 360 mg to 2,160 mg. Mean elimination half-life for MPA is 8 to 16 hours and MPAG is 13 to 17 hours. Approximately 3% of the MPA dose is eliminated unchanged in the urine and over 60% of the dose as MPAG. Although the systemic exposure of MPA is similar when taken with or without food, peak concentrations are decreased by 33% and Tmax delayed by 5 hours.
Intravenous Route
After intravenous administration, mycophenolate mofetil is immediately hydrolyzed to form free mycophenolic acid (MPA), the active compound. During intravenous infusions, the parent drug mycophenolate mofetil can be measured; however, 5 minutes after the infusion is stopped the mycophenolate mofetil concentration is not detectable. The mean elimination half-life of MPA is approximately 16.6 hours following intravenous administration. Compared to oral administration, the mean AUC was 24% higher following intravenous administration of 1 g twice daily for 5 days in kidney transplant patients.
-Special Populations
Hepatic Impairment
Pharmacokinetic data from patients with hepatic disease are limited. In 1 study, the presence of hepatic parenchymal disease did not appear to appreciably affect the glucuronidation of MPA.
Renal Impairment
Greater exposure to MPAG, which can be a source of MPA, is likely in patients with renal impairment. The systemic exposure of MPAG and of free MPA is increased over the first 12 hours after dosing in patients with renal dysfunction. The MPA free fraction is also increased. Data suggest that MPAG may compete with MPA for albumin binding sites. Hemodialysis or peritoneal dialysis does not significantly remove either MPA or MPAG. The pharmacokinetic parameters of MPA appear to be unchanged in patients who have acute renal transplant rejection.
Pediatrics
-Mycophenolate mofetil capsules, tablets, and oral suspension: Following an oral suspension dose of 600 mg/m2 twice daily (up to a maximum of 1 g twice daily) during the early post-transplant period, the mean mycophenolic acid (MPA) AUC values in pediatric patients were similar to those observed in adult kidney transplant patients who received capsules at a dose of 1 g twice daily. There was wide variability in the data. Similar to adult patients, early post-transplant MPA AUC values were about 45% to 53% lower than those observed in the later post-transplant period (greater than 3 months). Across the 1 to 18 year age range, the MPA AUC values were similar in the early and late post-transplant periods. In a dose-normalized comparison (to 600 mg/m2), MPA AUC levels were 23% lower in 7 pediatric liver transplant patients (10 months to 60 months of age) compared to 12 pediatric kidney transplant patients (less than 6 years of age), which is consistent with the need for higher dosing in adult liver transplant patients compared to adult kidney transplant patients. Based on the similarity in MPA exposure between adult kidney and adult heart transplant patients and the similarity between pediatric kidney transplant and adult kidney transplant patients, it is expected that the MPA exposure at the recommended dosage will be similar in pediatric heart transplant and adult heart transplant patients.
-Mycophenolate sodium delayed-release tablets: Systemic exposure to MPA after 450 mg/m2 of mycophenolate sodium was 18% higher and Cmax was 33% higher in children 5 to 16 years of age as compared with adults.
Geriatric
-Mycophenolate mofetil capsules, tablets, and oral suspension: Compared to younger patients, no alterations in the pharmacokinetics of mycophenolate mofetil or its metabolites have been found in geriatric patients.
-Mycophenolate sodium delayed-release tablets: Mycophenolate sodium pharmacokinetics have not been formally studied in geriatric patients.
Gender Differences
Mycophenolate is available as mycophenolate mofetil (MMF) capsules, tablets, and oral suspension and mycophenolic acid (MPA) delayed-release tablets.
-MMF capsules, tablets, and oral suspension: Pooled data from several studies were evaluated for any gender-related differences in mycophenolate mofetil pharmacokinetics; data were adjusted to a 1 g oral dose. Mean MPA AUC0 to 12 h was 32 (+/- 14.5) for male patients (n = 79) and 36.5 (+/- 18.8) for female patients (n = 41); these differences were not deemed to be of clinical significance.
-MPA delayed-release tablets: There were no significant differences in gender pharmacokinetics of mycophenolate sodium.
Ethnic Differences
-Mycophenolate sodium delayed-release tablets: Following a single dose of 720 mg of mycophenolate sodium to healthy Japanese (n = 18) and White (n = 18) patients, the AUCinf values for mycophenolic acid (MPA) and the phenolic glucuronide metabolite of MPA (MPAG) were 15% and 22%, respectively, lower in Japanese patients compared to White patients. Cmax for MPA was 9.6% higher in Japanese patients; there was no difference in the Cmax for MPAG between the two patient populations. These observed pharmacokinetic differences were not deemed to be clinically significant.