Drug information of Mycophenolate mofetil

Mechanism of effect

Mycophenolate mofetil is hydrolyzed to form mycophenolic acid (MPA), which is the active metabolite. MPA is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways

Pharmacodynamic

Mycophenolate mofetil is a prodrug of mycophenolic acid (MPA), an antibiotic substance derived from Penicillium stoloniferum. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites

Pharmacokinetics

In 12 healthy volunteers, the mean absolute bioavailability of oral Mycophenolate mofetil relative to intravenous Mycophenolate mofetil (based on MPA AUC) was 94% The mean (±SD) apparent volume of distribution of MPA in 12 healthy volunteers is approximately 3.6 (±1.5) and 4.0 (±1.2) L/kg following intravenous and oral administration, respectively. MPA, at clinically relevant concentrations, is 97% bound to plasma albumin. Negligible amount of drug is excreted as MPA (< 1% of dose) in the urine. When orally administered, mycophenolate mofetil was completely recovered with 93% of the dose found in the urine and 6% found in feces. 87% of the administered dose is excreted in the urine as MPAG The mean elimination half-life for mycophenolic acid (the active metabolite) ranges from 8-16 hours Clearance: • mL/min [plasma clearance, MPA, oral administration] 193 • mL/min [plasma clearance, MPA, IV administration] 177 • mL/min [renal clearance, MPAG, delayed-release tablet] 15.5

Drug indications

rejection Renal, Cardiac, and Hepatic Transplant , Lupus nephritis

Dosage

Renal Transplantation Adults A dose of 1 g administered orally twice a day (daily dose of 2 g) is recommended for use in renal transplant patients. Although a dose of 1.5 g administered twice daily (daily dose of 3 g) was used in clinical trials and was shown to be safe and effective, no efficacy advantage could be established for renal transplant patients. Patients receiving 2 g/day of Mycophenolate mofetil demonstrated an overall better safety profile than did patients receiving 3 g/day of Mycophenolate mofetil. Pediatrics (3 months to 18 years of age) The recommended dose of Mycophenolate mofetil oral suspension is 600 mg/m2 administered twice daily (up to a maximum daily dose of 2 g/10 mL oral suspension). Patients with a body surface area of 1.25 m2 to 1.5 m2 may be dosed with Mycophenolate mofetil capsules at a dose of 750 mg twice daily (1.5 g daily dose). Patients with a body surface area >1.5 m2 may be dosed with Mycophenolate mofetil capsules or tablets at a dose of 1 g twice daily (2 g daily dose). Cardiac Transplantation Adults A dose of 1.5 g bid oral (daily dose of 3 g) is recommended for use in adult cardiac transplant patients. Hepatic Transplantation Adults A dose of 1.5 g bid oral (daily dose of 3 g) is recommended for use in adult hepatic transplant patients

Drug contraindications

hypersensitivity to drug or its components. , allergic to Polysorbate 80 (TWEEN , HGPRT deficiency

Side effects

nausea , Headache , insomnia , chest pain , constipation , Tachycardia , abdominal pain , dizziness , vomiting , Hepatic dysfunction , rash , Diarrhea , Dyspnea , asthenia , Hypertension , hypotension , thrombocytopenia , leukopenia , anemia , paresthesia , dyspepsia , Urinary tract infection , edema , Peripheral edema , Cough , sinusitis , respiratory tract infection , fever , anxiety , Hypomagnesemia , Infections , anorexia , back pain , Pain , Sepsis , Cardiovascular disorder , Tremor , Kidney function abnormal , Hyper-cholesteremia , Hyperkalemia , Hypokalemia , Hyperglycemia , Hypocalcemia , Creatinine increased

Interactions

ampicillin , Esomeprazole , Busulfan , Trastuzumab , Deferiprone , Sirolimus , Acyclovir , MG , Aluminium MG+simeticone , Aluminium MGS , Pantoprazole , Ciprofloxacin , Contraceptive HD , Contraceptive LD , Co -amoxiclav , Magnesium hydroxide , Cyclosporine , valganciclovir , Lansoprazole , Human papillomma virus vaccine , Contraceptive , Contraceptive DE , Cloxacillin , Ganciclovir , Bisoprolol , Influenza vaccine , carbonyl iron , Canakinumab , Basiliximab , Alefacept , Adenovirus types 4 and 7 live, oral , Delafloxacin , Dexlansoprazole , tedizolid , dicloxacillin , Cefamandole , Hepatitis B Vaccine , Triphasic , FARMENTIN , Biolectra Magnesium , Iron Dextran Complex , Typhoid vaccine (live), oral , Meningococcal conjugate vaccine , Rabies Vaccine , Bacampicillin , bacillus coagulans and inulin , famciclovir , Aminohippurate Sodium , Efalizumab

Alerts

EMBRYOFETAL TOXICITY, MALIGNANCIES AND SERIOUS INFECTIONS Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations. Females of reproductive potential (FRP) must be counseled regarding pregnancy prevention and planning (see WARNINGS and PRECAUTIONS). Immunosuppression may lead to increased susceptibility to infection and possible development of lymphoma. Only physicians experienced in immunosuppressive therapy and management of renal, cardiac or hepatic transplant patients should prescribe Mycophenolate mofetil. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources

Points of recommendation

Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning To prevent unplanned exposure during pregnancy, 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 mofeti Females of reproductive potential taking Mycophenolate mofetil must receive contraceptive counseling and use acceptable contraception During treatment with Mycophenolate mofetil, the use of live attenuated vaccines should be avoided and patients should be advised that vaccinations may be less effective Mycophenolate mofetil oral suspension contains aspartame, a source of phenylalanine (0.56 mg phenylalanine/mL suspension). Therefore, care should be taken if Mycophenolate mofetil oral suspension is administered to patients with phenylketonuria

Pregnancy level

D

Related drugs

Eculizumab