VESTAR Trimetazidine 35mg Modified-Release Tablet 1's

The physician should be consulted immediately in the event of trimetazidine overdosage.

 

 

Use in pregnancy: Trimetazidine should be avoided particularly during the 1st trimester of pregnancy except when absolutely required. Nevertheless, none of the animal studies have shown any embryotoxicity or teratogenicity.
Use in lactation: In the absence of data on excretion of trimetazidine in breast milk, breastfeeding is not recommended during treatment. A decision should be made whether to stop breastfeeding or discontinue Vestar.

 

Store at temperatures not exceeding 30°C.
Shelf-Life: 24 months.

Pharmacology: Pharmacodynamics: Findings from in vitro and ex vivo studies of myocardial ischemia have demonstrated that trimetazidine limits intracellular acidosis, limits sodium and calcium accumulation, maintains intracellular ATP levels and reduces creatinine phosphokinase release, preserves mitochondrial function, reduces myocardial fatty acid metabolism and increases myocardial glucose metabolism, protects against oxygen-free radical-induced membrane damage and inhibits neutrophil infiltration.
By inhibiting fatty acid metabolism and secondarily stimulating glucose metabolism, trimetazidine optimizes cardiac metabolism and thus protects the heart against the harmful effects of ischemia. However, the definitive mechanism of action of trimetazidine has yet to be determined.
Pharmacokinetics: Trimetazidine is rapidly absorbed from the intestinal mucosa after oral administration. In 13 healthy volunteers, the mean peak plasma trimetazidine concentration (C_max; 53.6 mcg/L) was reached 1.8 hrs after a single 20 mg (immediate-release) oral dose. After twice-daily administration of trimetazidine 20 mg for 15 days, C_max (84.8 mcg/L) was reached in 1.7 hrs. The area under the plasma trimetazidine concentration-time curve (AUC) was 508.9 mcg/L·hr after a single 20-mg dose and 831.4 mcg/L·hr after repeated administration. Steady-state levels were reached within 24 hrs and remained stable for the study duration.
Trimetazidine is only weakly protein bound in plasma (-16%) and therefore is widely distributed throughout the body. In 11 healthy volunteers, the volume of distribution (Vd) of trimetazidine was 318.6 L after a 40-mg IV dose.
In a study by Genissel et al, the pharmacokinetics of immediate-release (IR) and modified-release (MR) trimetazidine in dogs and pigs, have been compared under single dose conditions, then predicted at steady-state under conditions mimicking an actual human pharmacokinetic study.
In both animal species, the MR tablet demonstrated sustained-release properties, as assessed by delayed time to peak and increased mean absorption times compared to the IR format. Multiple-dose simulations in dogs revealed delayed time to peak (3 vs 1 hr), a decrease in peak plasma concentration (544 vs 659 mcg/L), an increase in trough concentrations (115 vs 63 mcg/L), a decrease in peak-trough fluctuation (141 vs 193%) and an increase in plateau time (5.5 vs 4.9 hrs).
Qualitatively similar changes were simulated in pigs. These properties have been verified in humans where a trimetazidine MR 35 mg twice-daily regimen did provide similar total exposure, increased plateau time (11 vs 4 hrs), decreased peak-trough fluctuation (86 vs 121%), a 31% increase in trough concentrations and no increase in interindividual variability compared to a trimetazidine IR 20-mg thrice-daily regimen.
Furthermore, the trimetazidine MR 35-mg twice-daily regimen is likely to result in improved patient compliance and better patient anti-ischemic protection in the early morning.