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. |
Pharmacokinetic's | Atorvastatin 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 Clopidogrel: 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. |
Side effects | 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). |
Precaution | 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. |
Dosage | Oral Prophylaxis of thromboembolic disorders Adult: 75 mg once daily. Oral 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 |