Each film coated tablet contains: Trimetazidine dihydrochloride 20 mg.
Pharmacology: Trimetazidine prevents a decrease in intracellular ATP levels, thereby ensuring the proper functioning of ionic pumps and transmembranous sodium-potassium flow while maintaining cellular homeostasis. In animals, Trimetazidine has been shown to help maintain energy metabolism in the heart during episodes of ischemia and hypoxia, to reduce intracellular acidosis and alterations in transmembranous ion flow caused by ischemia, to decrease the migration and infiltration of polynuclear neutrophils in ischemic and reperfused cardiac tissue, to also reduce the size of experimental infarction and to exert this action in the absence of any direct hemodynamic effect.
In man, controlled studies in anginal patients have shown that Trimetazidine increase coronary flow reserve, thereby delaying the onset of exercise-induced ischemia, starting from the 15th day of treatment; limits rapid swings in blood pressure without any significant variations in heart rate; significantly decreases the frequency of angina attacks; leads to a significant decrease in the use of trinitroglycerin.
Pharmacokinetics: Absorption: Following oral administration of 40 mg of Trimetazidine, the blood level rapidly increases to reach a peak between 2 and 3 hours and then gradually decreases with a terminal half-life of about 6 hours. The bioavailability of orally administered Trimetazidine is approximately 90%.
Metabolism/ Elimination: The major route of elimination is urinary, with about 60% of the administered dose being eliminated in the unchanged form. The rest is metabolized. Little is known of the properites of the metabolites, which are, however, only present in weak concentrations.
Mean Half-life: 6 hours.
Plasma Protein Binding: Approximately 16% is bound to plasma proteins, chiefly, albumin.
Plasma Levels: In one study, plasma levels measured at the end of the treatment period ranged between 70 and 200 mcg/mL. Two of ten subjects did not respond to treatment despite high plasma levels, whereas in the other anginal patients, the plasma level correlated with increase in work.
Volume of distribution: The large volume of distribution of Trimetazidine is supported by the recovery in animal experiments of radioactive Trimetazidine from a large variety of internal organs. The apparent volume of distribution is 4.8L/kg.
Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies.
Usual adult dose: 60 mg daily, equivalent to 3 tablets per day. Tablets should be taken orally in 3 doses with meals.
Hypersensitivity to Trimetazidine.
Hypersensitivity to the active substance or to any excipients of the product.
Parkinsons disease, parkinsonian symptoms, tremors, restless leg syndrome, and other related movement disorders.
Severe renal impairment (creatinine clearance < 30 mL/min).
Trimetazidine can cause or worsen parkinsonian symptoms (tremor, akinesia, hypertonia), which should be regularly investigated, especially in elderly patients. In doubtful cases, patients should be referred to a neurologist for appropriate investigations.
The occurrence of movement disorders such as parkinsonian symptoms, restless leg syndrome, tremors, gait instability should lead to definitive withdrawal of Trimetazidine.
These cases have low incidence and are usually reversible after treatment discontinuation. The majority of the patients recovered within 4 months after Trimetazidine withdrawal. If parkinsonian symptoms persist more than 4 months after drug discontinuation, a neurologist opinion should be sought.
Falls may occur, related to gait instability or hypotension, in particular in patients taking antihypertensive treatment.
Caution should be exercised when prescribing Trimetazidine to patients in whom an increased exposure is expected: Moderate renal impairment; Elderly patients older than 75 years old.
Studies in animal have not demonstrated a teratogenic effect, however in the absence of clinical data and for safety reasons, prescription should be avoided during pregnancy. In the absence of data on excretion in breast milk, breastfeeding is not recommended during treatment.
Unexpected incidence of sedation or drowsiness; Rare cases of gastrointestinal disorders.
Trimetazidine has no significant effects on the kinetics of two commonly used drugs, namely Theophylline and Digoxin. Also Trimetazidine does not alter the rate of metabolism of antipyrine, which is used as an index of a possible effect of Trimetazidine as an inducer or inhibitor of drug hydroxylation reactions. The low plasma protein binding of Trimetazidine suggests that it is not likely to interact with other highly bound drugs such as Warfarin. Trimetazidine should not be co-administered with MAOIs.
Store at temperature not more than 30°C.
C01EB15 - trimetazidine ; Belongs to the class of other cardiac preparations.
FC tab 20 mg x 10 x 10's.