mycophenolate

Mycophenolate is an immunosuppressant medication used to prevent rejection of transplant organs, in particular, heart, kidney, and liver. Mycophenolate is administered as intravenous (IV) infusion or oral tablets/capsules, typically in combination with cyclosporine and corticosteroids. Mycophenolate suppresses the recipient’s immune system, preventing it from attacking the transplanted organ and leading to graft rejection.

Mycophenolate is a prodrug that is converted into its active form mycophenolic acid (MPA) in the body. Mycophenolic acid suppresses inflammatory responses from the immune system by inhibiting the proliferation of T-cells and B-cells, and the production of antibodies by the B-cells. Mycophenolic acid inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme that is crucial for purine biosynthesis, and consequently, the DNA and RNA synthesis required for the proliferation of T-cells and B-cells.

MPA also prevents the adhesion of lymphocytes and monocytes to the endothelial cells that form the inner lining of blood vessels, which is a normal part of inflammatory activity, by inhibiting the glycosylation of proteins. Glycosylation is a process that is part of protein processing into glycoproteins required for lymphocytes and monocytes to adhere to the endothelial cells. MPA also inhibits the migration of leukocytes into the sites of inflammation and prevents graft rejection.

• Do not use in patients with hypersensitivity to mycophenolate, mycophenolic acid or any of the components in the formulation.
• Do not use mycophenolate intravenous formulation in patients who are allergic to polysorbate 80.
• Mycophenolate should be prescribed/administered only by physicians well experienced in immunosuppressive therapy and management of renal, cardiac or hepatic transplant patients, and the necessary follow-up of the patient.
• Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources.
• Do not use different brands of mycophenolate interchangeably.
• Administer mycophenolate IV solution as infusion for at least 2 hours and never by rapid or bolus IV injection, it can increase the risk for blood clot (thrombosis) and vein inflammation (phlebitis).
• Immunosuppression can increase the susceptibility to infections, including opportunistic infections, fatal infections and sepsis.
• Mycophenolate increases the risk for the development of skin cancers and lymphoma, cancer of the lymphatic system.
• Mycophenolate can cause pregnancy loss and fetal malformations.
  • Screen women of child-bearing age for pregnancy prior to therapy.
  • Advise women of pregnancy potential to use effective contraception for 4 weeks prior to and for 6 weeks after completion of mycophenolate therapy.
  • If pregnancy occurs during therapy, apprise the patients of the risks to the fetus.
• Mycophenolate therapy has been associated with progressive multifocal leukoencephalopathy, a viral disease of the brain’s white matter that can sometimes be fatal. Monitor patients for neurological symptoms and consider reducing dosage.
• Pure red cell aplasia has been reported in some patients treated with mycophenolate in combination with other immunosuppressants. The condition was found to be reversible with discontinuation or dose reduction of mycophenolate.
• Mycophenolate may cause neutrophil count to drop severely. Monitor patients for neutropenia and bone marrow depression, interrupt the therapy or reduce dosage, and treat appropriately.
• Use mycophenolate with caution in patients with active gastrointestinal orders. There have been reports of gastrointestinal bleeding and rare cases of gastrointestinal perforations with mycophenolate therapy.
• Avoid using mycophenolate in patients with the rare hereditary deficiency of hypoxanthine-guanine phosphoribosyltransferase, such as Lesch-Nyhan or Kelley-Seegmiller syndrome.
• Use mycophenolate with caution in patients with impaired kidney function as toxicity may be increased. Adjust dosage as required in severe renal impairment.
• Advise patients to avoid receiving live attenuated vaccines while on mycophenolate therapy.
• Advise patients to avoid donating blood or blood products during treatment and for at least 6 weeks after the last dose.
• Mycophenolate may cause central nervous system depression and impair mental and physical abilities required for hazardous tasks. Caution patients appropriately.
• Some formulations of mycophenolate contain phenylalanine. Use such formulations with caution in patients with phenylketonuria, an inherited disorder with inability to break down phenylalanine.
• There have been reports of acute inflammatory syndrome. Monitor patients for symptoms and consider alternate treatment if symptoms develop.
• Abrupt discontinuation of immunosuppressants, including mycophenolate, can rapidly worsen symptoms in patients with myasthenia gravis, exercise caution.

Common side effects of mycophenolate include:

• High or low blood pressure (hypertension or hypotension)
• Exacerbation of hypertension
• Rapid heart rate (tachycardia)
• Swelling (edema)
• Lower extremity edema
• Peripheral edema
• Blood clot formation (thrombosis)
• Inflammation of the vein (phlebitis)
• High blood sugar (hyperglycemia)
• Diabetes mellitus
• High cholesterol level in the blood (hypercholesterolemia)
• High level of blood fats (hyperlipidemia)
• High uric acid level in the blood (hyperuricemia)
• High or low blood potassium levels (hyperkalemia/hypokalemia)
• Low calcium in the blood (hypocalcemia)
• Low magnesium in the blood (hypomagnesemia)
• Low phosphates in the blood (hypophosphatemia)
• Increase in lactate dehydrogenase enzyme
• Excessive acidity of body fluids (acidosis)
• Weight loss
• Abdominal pain
• Constipation
• Diarrhea
• Indigestion (dyspepsia)
• Nausea
• Vomiting
• Gas (flatulence)
• Abdominal distension
• Gastroesophageal reflux disease (GERD)
• Reduced appetite
• Inflammation of esophagus (esophagitis)
• Oral inflammation (stomatitis)
• Oral Candida infection (candidiasis)
• Gum overgrowth (gingival hyperplasia)
• Gastritis
• Gastric ulcer
• Gastrointestinal hemorrhage
• Hernia of abdominal cavity
• Intestinal obstruction
• Urinary tract infection
• Blood in the urine (hematuria)
• Urinary retention
• Increased creatinine
• Increased blood urea nitrogen (BUN)
• Kidney insufficiency
• Destruction of kidney tubules (renal tubular necrosis)
• Elevated liver enzymes
• Increase in serum alkaline phosphatase levels
• Liver inflammation (hepatitis)
• Abnormal liver function tests
• Cough
• Shortness of breath (dyspnea)
• Dyspnea on exertion
• Fluid around lungs (pleural effusion)
• Pneumonia
• Upper respiratory tract infection
• Nose and throat inflammation (nasopharyngitis)
• Sinus inflammation (sinusitis)
• Skin rash
• Cellulitis
• Discoloration of skin from bleeding underneath (ecchymosis)
• Itching (pruritus)
• Acne vulgaris
• Abnormal tissue growth (neoplasm)
• Malignant neoplasm
• Benign skin neoplasm
• Skin carcinoma
• Blood disorders including:
  • Low red blood cell count (anemia)
  • Abnormally high or low leukocyte count (leukocytosis or leukopenia)
  • Low platelet count (thrombocytopenia)
  • Severely low count of neutrophils (neutropenia)
  • Disorder of hemostatic components of blood
  • Low count of all types of blood cells (pancytopenia)
• Atypical collection of lymphatic fluid (lymphocele)
• Uncontrolled production of lymphocytes (lymphoproliferative disorder)
• Lymphoma
• Bacterial infection
• Cytomegalovirus disease
• Fungal infection
• Viral infection (including COVID-19)
• Herpes simplex infection
• Herpes zoster infection
• Wound infection
• Sepsis
• Influenza
• Fever
• Chills
• Headache
• Dizziness
• Drowsiness
• Feeling unwell (malaise)
• Weakness (asthenia)
• Fatigue
• Pain
• Peripheral pain
• Back pain
• Joint pain (arthralgia)
• Muscle weakness (myasthenia)
• High muscle tone (hypertonia)
• Muscle cramp
• Muscle pain (myalgia)
• Tremor
• Numbness and tingling (paresthesia)
• Insomnia
• Confusion
• Depression
• Anxiety
• Blurred vision

Less common side effects of mycophenolate include:

• Loss of appetite (anorexia)
• Colon inflammation (colitis)
• Hemorrhagic colitis
• Hemorrhagic gastritis
• Inflammation of the pancreas (pancreatitis)
• Inflammation of the abdominal lining (peritonitis)
• Gastrointestinal perforation
• Duodenal ulcer
• Esophageal ulcer
• Oral ulcer
• Dry mouth (xerostomia)
• Skin and mucous membrane (mucocutaneous) candidiasis
• Fluid collection in the abdomen (ascites)
• Inflammation of the heart’s inner lining (endocarditis)
• Blood clot block in the vein (venous thrombosis)
• Throat inflammation (pharyngitis)
• Wheezing
• Thickening of bronchial tubes (bronchiectasis)
• Interstitial pulmonary disease
• Pulmonary fibrosis
• Pulmonary edema
• Tuberculosis
• Protozoal infection
• Atypical mycobacterial infection
• BK virus infection
• Hepatitis C
• Reactivation of hepatitis B virus
• Polyomavirus infection
• Hypersensitivity reaction
• Hair loss (alopecia)
• Bone marrow failure
• Lack of red cell production (pure red cell aplasia)
• Severely low granulocyte immune cells (agranulocytosis)
• Low lymphocyte count (lymphocytopenia)
• Lymph node swelling (lymphadenopathy)
• Low antibody levels (hypogammaglobulinemia)
• Kapasi sarcoma, a cancer of the lining of blood and lymph vessels
• Inflammation of brain membranes (meningitis)
• Progressive multifocal leukoencephalopathy, a viral disease of the brain’s white matter
• Bone infection (osteomyelitis)
• Acute inflammatory syndrome

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Capsule

• 250 mg (generic; MMF)

Tablet

• 500 mg (generic, CellCept; MMF)

Oral Suspension

• 200 mg/mL (generic, CellCept; MMF)

Powder for Injection

• 500 mg/vial (generic, CellCept; MMF)

Tablet, Delayed Release (generic, Myfortic, MPA)

• 180 mg
• 360 mg

Adult:

Kidney Transplant

• Prophylaxis of organ rejection in patients receiving allogeneic renal transplants; use concomitantly with cyclosporine and corticosteroids
• Mycophenolate mofetil (MMF): 1 g orally or intravenously (IV) every 12 hours, infused over 2 hours or longer
• Mycophenolic acid (MPA): 720 mg orally every 12 hours

Heart Transplant

• Prophylaxis of organ rejection in patients receiving allogeneic cardiac transplants; use concomitantly with cyclosporine and corticosteroids
• MMF: 1.5 g oral/IV every 12 hours, infused over 2 hours or longer

Liver Transplant

• Prophylaxis of organ rejection in patients receiving allogeneic hepatic transplants; use concomitantly with cyclosporine and corticosteroids
• MMF (IV): 1 g every 12 hours; infused over 2 hours or longer
• MMF (PO): 1.5 g every 12 hours

Dosing Modifications

Renal impairment

• MMF: In severe renal impairment (glomerular filtration rate [GFR] below 25 mL/min/1.73 m²), not to exceed 1 g every 12 hours
• No dosage adjustment needed in renal transplant patients experiencing delayed graft function postoperatively

Lupus Nephritis (Off-label)

• Induction therapy for lupus nephritis (MMF)
• Induction: 1 g orally every 12 hours with a glucocorticoid or 2-3 g for 6 months with glucocorticoids
• Maintenance: 0.5-3 g/day or 1 g orally every 12 hours or 1-2 g daily
• Administer with initial IV corticosteroid pulse for 3 days, then prednisone 0.5-1 mg/kg/day orally; not to exceed 10 mg/day; after a few weeks, prednisone may be tapered to lowest effective dose

Pediatric:

Kidney Transplant

• Indicated for prophylaxis of organ rejection in combination with other immunosuppressive agents in patients receiving allogeneic kidney transplants

Mycoophenolate mofetil (MMR; CellCept)

• Children below 3 months: Safety and efficacy not established
• Children 3 months and above
  • Suspension: 600 mg/m2 orally every 12 hours; not to exceed 2 g/day  
  • Capsules; body surface area (BSA) 1.25-1.5 m2: 750 mg capsule orally every 12 hours
  • Capsules or tablets; BSA 1.5 m2 or above: 1 g capsule/tablet orally every 12 hours

Mycophenolic acid (MPA; Myfortic)

• Children below 5 years: Safety and efficacy not established
• Aged 5 years or above who are at least 6 months post-kidney transplant
  • Extended-release tablets: 400 mg/m2 orally every 12 hours; not to exceed 720 mg every 12 hours

Heart Transplant

CellCept only

• Indicated for prophylaxis of organ rejection in combination with other immunosuppressive drugs in children 3 months or above receiving allogeneic heart transplants
• Suspension: 600 mg/m2 orally every 12 hours; if tolerated, may increase the dose to the maintenance of 900 mg/m2 twice daily (not to exceed 3 g/day)
• Capsules; BSA 1.25 to 1.5 m2: 750 mg capsule orally every 12 hours initially; may increase maintenance dose, not to exceed 3 g/day
• Capsules or tablets; BSA 1.5 m2 or above: 1 g capsule/tablet orally every 12 hours initially; may increase maintenance dose, not to exceed 3 g/day

Liver Transplant

CellCept only

• Indicated for prophylaxis of organ rejection in combination with other immunosuppressive drugs in children 3 months or above receiving allogeneic liver transplants
• Suspension: 600 mg/m2 orally every 12 hours; if tolerated, may increase the dose to the maintenance of 900 mg/m2 twice daily (not to exceed 3 g/day)
• Capsules; BSA 1.25 to 1.5 m2: 750 mg capsule orally every 12 hours initially; may increase maintenance dose, not to exceed 3 g/day
• Capsules or tablets; BSA 1.5 m2 or above: 1 g capsule/tablet orally every 12 hours initially; may increase maintenance dose, not to exceed 3 g/day

Overdose

• There is limited experience with mycophenolate overdose in humans.
• Overdose may cause gastrointestinal symptoms such as nausea, vomiting, and diarrhea.
• Mycophenolate overdose treatment may include discontinuation of the drug and removal of undigested drug with the administration of bile acid sequestrant medications such as cholestyramine.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe Interactions of mycophenolate include:
  • cholestyramine
  • colestipol
• Mycophenolate has serious interactions with at least 86 different drugs.
• Mycophenolate has moderate interactions with at least 107 different drugs.
• Mild interactions of mycophenolate include:
  • bazedoxifene/conjugated estrogens
  • conjugated estrogens
  • conjugated estrogens, vaginal
  • estradiol
  • estrogens conjugated synthetic
  • estrogens esterified
  • estropipate
  • mestranol
  • nirmatrelvir/ritonavir
  • phenytoin

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Mycophenolate can cause fetal harm and should not be used in pregnant women. Use of mycophenolate during pregnancy can increase the risk for pregnancy loss or fetal malformations.
• Women of pregnancy potential and sexually active men with women partners should use two methods of effective contraception during, for 4 weeks prior to and for 6 weeks after completion of mycophenolate therapy. Mycophenolate may reduce the effect of birth control pills.
• There is no information on the presence of mycophenolate in human breast milk, however, it is present in animal milk. Based on the importance of the drug to the mother, decision should be made to discontinue the drug or nursing because of potential risks of severe adverse reactions in the breastfed infant.
• Women exposed to mycophenolate during pregnancy or within 6 weeks of discontinuing therapy should be encouraged to report to the Mycophenolate Pregnancy Registry (800-617-8191) or visit www.mycophenolateREMS.com.

• Take mycophenolate exactly as prescribed.
• You will need periodic lab tests while on therapy, follow up with your physician and do not miss your scheduled appointments.
• Do not donate blood while on mycophenolate treatment and for at least 6 weeks after the last dose.
• Do not receive live attenuated vaccines during mycophenolate therapy.
• Limit exposure to sunlight and ultraviolet (UV) light during treatment by using sunscreen and wearing suitable clothes.
• Mycophenolate can impair physical and mental abilities. Avoid hazardous tasks such as driving and operating heavy machinery while on treatment.
• Notify your healthcare provider immediately if you:
  • Develop any signs and symptoms of infection
  • Experience neurological symptoms such as muscle weakness, confusion, apathy, or difficulty with balance, coordination and speech.
  • Have unusual bleeding or bruising
• Store mycophenolate safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.