|Composition||Atorvastatin 10mg,20mg and Clopidogrel 75mg Capsules.|
|Indication||Mixed dyslipidaemia; Heterozygous familial; Nonfamilialhypercholesterolaemia|
|Mechanism of Action||
Atorvastatin competitively inhibits HMG-CoA reductase, the enzyme that catalyses the conversion of HMG-CoA to mevalonic acid. HMG-CoA reductase inhibitors increase HDL-C and decrease LDL-C, VLDL-C and plasma triglycerides Clopidogrel selectively inhibits adenosine diphosphate (ADP) from binding to its platelet P2Y12 receptor and subsequent activation of glycoprotein GPIIb/IIIa complex thus reducing platelet aggregation.
Absorption: Readily absorbed from the GI tract. Bioavailability: Approx 12%.
Distribution: Volume of distribution: Approx 381 L. Plasma protein binding: 98%.
Metabolism: Metabolised by CYP3A4 isoenzyme to active ortho- and parahydroxylatedderivates and an inactive β-oxidation product.
Excretion: Via faeces (as metabolites); urine (<2% as unchanged drug). Elimination half-life: Approx 14 hr
Absorption: Rapidly but incompletely absorbed from the GI tract (approx 50%). Time to peak plasma concentration: Approx 30-60 min.
Distribution: Plasma protein binding: 98% (parent drug); 94% (carboxylic acid derivative).
Metabolism: Undergoes extensive hepatic metabolism via esterase-mediated hydrolysis to inactive carboxylic acid derivative and by CYP450-mediated (primarily CYP2C19 isoenzyme) oxidation to active thiol metabolite.
Excretion: Via urine (approx 50%); faeces (approx 46%) both as metabolites and unchanged drug.
Haematoma, epistaxis, diarrhoea, dyspepsia, abdominal pain, bruising, bleeding at puncture site. Rarely, Stevens-Johnson syndrome, erythema multiforme, serum sickness, interstitial pneumonitis, lichen planus, myalgia.
Potentially Fatal: Intracranial bleeding, GI and retroperitoneal haemorrhage, blood dyscrasias, thrombotic thrombocytopenic purpura.
|Drug drug interaction||
Increased risk of bleeding w/ anticoagulants, other antiplatelets, NSAIDs, SSRIs, serotonin norepinephrine reuptake inhibitors. May reduce antiplatelet effect w/ CYP2C19 inhibitor including PPI (e.g. esomeprazole, omeprazole).
Patient at risk of increased bleeding from trauma, surgery or other pathological conditions. Renal and hepatic impairment. Pregnancy and lactation. Monitoring Parameters Monitor for signs of bleeding; Hb and haematocrit periodically.
Prophylaxis of thromboembolic disorders
Adult: 75 mg once daily.
Acute coronary syndrome
Adult: For ST-elevation MI: In combination w/ aspirin: 75 mg once daily. Loading dose: 300 mg for patients 75 yr. Continue treatment for at least 4 wk. For unstable angina, non-ST-elevation MI: In combination w/ aspirin: Initially, 300 mg loading dose, followed by 75 mg once daily for up to 12 mth.