Mycophenolate Mofetil, the active ingredient of MyceptTM, is chemically 2-morpholinoethyl(E)-6-(1,3-dihydro-4hydroxy-6-methoxy-7methyl-3-oxo-5 isobenzofuranyl)-4-methyl-4-hexenoate. Its emperical formula is C23H31NO7 and has a molecular weight of 433.50.

DESCRIPTION AND COMPOSITION
Mycept - 500
Mycept - 500 is a Lavender coloured, oval shaped, film coated tabletimprinted with "MYT-500" on one side and scored on other side. Each film-coated tablet contains:
Mycophenolate Mofetil................... 500 mg
Colours: Ferric oxide red, Indigo Carmine and Titanium Dioxide



Mycept - 250
Mycept - 250 is a grey / yellow hard gelatin capsule containing off-white powder.
Each hard gelatin capsule contains:
Mycophenolate Mofetil................... 250 mg
Approved colours used in capsule shells

MECHANISM OF ACTION
Mycophenolate Mofetil is a morpholinoethyl ester prodrug of the immunosuppressant mycophenolic acid (MPA), a fermentation product of several Penicillium species. The mechanism of action of MPA is based on interference with purine synthesis . It is a reversible, noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) which is an enzyme that facilitates the conversion of inosine monophosphate (IMP) to xanthosine monophosphate, a precursor of guanine nucleotides. This blocks the de novo synthesis of guanosine nucleotides which are necessary substrates for DNA and RNA synthesis. Unlike other cell types which can use the salvage pathways, B and T lymphocytes are dependent upon the de novo pathway for the generation of guanosine

PRECAUTIONS
Monitoring: Perform complete blood counts weekly during first month of treatment, twice monthly for second and third months, then monthly through the first year.
GI hemorrhage: Since mycophenolate has been associated with an increased incidence of GI adverse events, including infrequent cases of GI tract ulceration, hemorrhage, and perforation, administer with caution in patients with active serious GI disease. Delayed renal graft function post transplant: No dose adjustment is recommended for these patients, however they should be carefully observed.

WARNINGS
Pregnancy : There are no adequate and well controlled studies in pregnant women. Do not use in pregnant women unless the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should have a negative serum of urine pregnancy test with a sensitivity at least 50 mIU/ml ≤ 1 week prior to beginning therapy. Do not initiate mycophenolate therapy until a negative pregnancy test report is obtained.
Effective contraception must be used before beginning mycophenolate therapy, during therapy, and for 6 weeks following discontinuation of therapy, even when there has been a history of infertility, unless due to hysterectomy. Two reliable forms of contraception must be used
simultaneously unless abstinence is the chosen method. If pregnancy does occur during treatment, the physician and patient should discuss the desirability of continuing the pregnancy.

Lactation: Studies in rats treated with mycophenolate have shown mycophenolic acid to be excreted in milk. It is not known whether this drug is excreted in human breast milk. Because of the potential for serious adverse reactions in nursing infants from mycophenolate, decide whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Children: Safety and efficacy have not been established.

Lymphomas / Malignancies: Patients receiving immunosuppressive regimens involving combinations of drugs, including mycophenolate, as part of an immunosuppressive regimen are at increased risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. Oversuppression of the immune system can also increase susceptibility to infection.

Neutropenia: Monitor patients receiving mycophenolate for neutropenia . The development of neutropenia may be related to mycophenolate itself, concomitant medications, viral infections or some combination of these causes.

Renal function impairment: Avoid mycophenolate doses > 1 g twice a day and carefully observe patients.

ADVERSE EFFECTS
The principal adverse reactions associated with mycophenolate include diarrhoea, leukopenia, sepsis, and vomiting, and evidence of a higher frequency of certain types of infections.
Serious life-threatening infections such as meningitis and infectious endocarditis have been reported occasionally, and there is evidence of a higher frequency of certain types of serious infections such as tuberculosis and atypical mycobacterial infection.
Other adverse reactions occurring in ≥ 3% of patients in combination with cyclosporine and corticosteroids, are as follows:

Cardiovascular
Angina pectoris; atrial fibrillation; hypotension; palpitation; peripheral vascular disorder, postural hypotension; tachycardia; thrombosis; vasodilation; ventricular extrasystole; CHF; supraventricular tachycardia; ventricular tachycardia; atrial flutter; pulmonary hypertension; heart arrest; venous pressure increased; syncope; supraventricular extrasystoles; pallor; vasospasm.

CNS
Anxiety; depression; hypertonia; paresthesia; somnolence; emotional lability; neuropathy, convulsion, hallucinations, abnormal thinking, vertigo.

Dermatologic
Alopecia, fungal dermatitis, hirsutism, pruritus, benign skin neoplasm, skin disorder, skin hypertrophy, skin ulcer, sweating, hemorrhage and skin carcinoma.

Endocrine
Diabetes, parathyroid disorder, Cushing's syndrome, hypothyroidism
GI: Anorexia, esophagitis, flatulence, gastritis, gastroenteritis, GI hemorrhage, gingivitis, gum hyperplasia, hepatitis, ileus, infection, mouth ulceration; rectal disorder, GI disorder, liver damage, dysphagia, jaundice, stomatitis, thirst.
GU: Albuminuria, dysuria, hydronephrosis, impotence, pain, pyelonephritis, urinary frequency, nocturia, kidney failure, urine abnormality, hematuria, urinary incontinence, prostatic disorder, urinary retention
Musculoskeletal: Arthralgia, joint disorder, leg cramps myalgia, myasthenia.

Respiratory: Asthma, lung edema, pleural effusion, rhinitis, sinusitis, atelectasis, hiccough, pneumothorax, increased sputum, epistaxis, apnea, voice alteration, pain, hemoptysis, neoplasm, respiratory acidosis.

Special sense: Amblyopia, cataract, conjunctivitis, ear pain, deafness, ear disorder, tinnitus, abnormal vision, lacrimation disorder, eye hemorrhage.

Miscellaneous: Abdomen enlarged, chills/fever, cyst, face edema, flu syndrome, hemorrhage, hernia, malaise, pelvic pain, ecchymosis, polycythemia, neck pain, cellulitis, increased
prothrombin, decreased thromboplastin, petechia, phlebitis, thrombosis, weight gain/loss, abnormal healing dehydration.

Lab test abnormalities: Increased alkaline phosphatase, creatinine, gamma glutamyl transpeptidase, lactic dehydrogenase, AST and ALT, hypercalcemia, hyperlipemia, hyperuricemia, hypervolemia, hypocalcemia, hypoglycemia, hypoproteinemia, acidosis, hypoxia, hypophosphatemia, alkalosis and hypochloremia.


OVERDOSAGE Symptoms: At doses of 4 or 5g/day, there appears to be a higher rate, compared with the use of ≤ 3g/day, of GI intolerance (nausea, vomiting, diarrhea), and occasional hematologic abnormalities, principally neutropenia.

Treatment: MPA and MPAG are usually not removed by hemodialysis. However, at high MPAG plasma concentration (> 100 mcg/ml), small amounts of MPAG are removed . By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine.


STORAGE INSTRUCTIONS
Store at a temperature below 30°C, protect from light and moisture.

PRESENTATION
500mg Tablets Blister strip of 3 x 10 tablets