Vytorin

Risk reduction of CV events in patients w/ CHD & history of acute coronary syndrome (ACS), either previously treated w/ statin or not. Adjunctive therapy to diet in patients w/ primary (heterozygous familial & non-familial) hypercholesterolaemia or mixed hyperlipidaemia where use of combination product is appropriate in patients not appropriately controlled w/ statin alone or in patients already treated w/ statin & ezetimibe. Adjunctive therapy to diet in patients w/ HoFH.

Hypercholesterolaemia 10/20 or 10/40 mg daily in the evening. Dose range: 10/10 to 10/80 mg daily in the evening. Adjust dose at intervals of not less than 4 wk, if required. CHD & ACS event history Initially 10/40 mg daily in the evening. HoFH Initially 10/40 mg daily in the evening. May be used as adjunct to other lipid-lowering treatments (eg, LDL apheresis). Max of 10/40 mg daily in patients concomitantly taking lomitapide. Co-administration w/ other medicine Vytorin should be dosed either ≥2 hr before or ≥4 hr after administration of bile acid sequestrant. Max of 10/10 mg daily in patients concomitantly taking verapamil or diltiazem. Max of 10/20 mg daily in patients concomitantly taking amiodarone, amlodipine, ranolazine, or products containing elbasvir or grazoprevir; lipid-lowering dose (≥1 g/day) of niacin. Adolescent ≥10 yr (pubertal boy Tanner stage ≥II & pubertal girl at least 1 yr post-menarche) Initially 10/10 mg daily in the evening. Dose range: 10/10 to max of 10/40 mg daily. Patient w/ CKD & eGFR <60 mL/min/1.73 m² 10/20 mg daily in the evening.

May be taken with or without food: Do not split.

Hypersensitivity. Concomitant use w/ strong CYP3A4 inhibitors (eg, itraconazole, ketoconazole, posaconazole, voriconazole, HIV PIs, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, & drugs containing cobicistat), gemfibrozil, ciclosporin & danazol. Concomitant use of Vytorin dose >10/40 mg & lomitapide in patients w/ HoFH. Active liver disease or unexplained persistent elevations in serum transaminases. Pregnancy & lactation.

Risk of myopathy & rhabdomyolysis; myasthenia gravis & ocular myasthenia; transaminase elevations; raised blood glucose; ILD (especially w/ long-term therapy). Use 10/80 mg dose only in patients who have been taking this dose for ≥12 mth w/o evidence of muscle toxicity. Do not start 10/80 mg dose in new patients, including patients already taking lower doses. Measure creatine kinase (CK) level before starting treatment in patients w/ pre-disposing factors for rhabdomyolysis. Do not start treatment if CK levels are significantly elevated at baseline (>5x ULN). Perform LFTs before treatment initiation & thereafter when clinically indicated. Discontinue treatment if transaminase levels show evidence of progression, particularly if they rise to 3x ULN & are persistent. Promptly interrupt therapy if serious liver injury w/ clinical symptoms &/or hyperbilirubinaemia or jaundice occurs during treatment. Caution in patients who consume substantial quantities of alcohol. Monitor patients at risk of DM. Discontinue therapy if ILD is suspected. Caution when combining w/ less potent CYP3A4 inhibitors (eg, fluconazole, verapamil, diltiazem); daptomycin. Avoid concomitant intake w/ grapefruit juice. Do not co-administer w/ systemic fusidic acid or w/in 7 days of stopping fusidic acid treatment. Avoid combined use of Vytorin dose >10/20 mg & niacin (≥1 g/day); amiodarone, amlodipine, or ranolazine; BCRP inhibitors (eg, elbasvir or grazoprevir). Avoid combined use of Vytorin dose >10/10 mg & verapamil or diltiazem. Co-administration w/ fibrates is not recommended. Appropriately monitor INR if Vytorin is added to warfarin, another coumarin anticoagulant, or fluindione. Should not be taken by patients w/ rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Not recommended in patients w/ moderate or severe hepatic impairment. Not recommended in childn <10 yr. Limited experience in pre-pubertal childn.

Myalgia; increased ALT &/or AST, blood CK.

Increased risk of myopathy/rhabdomyolysis w/ potent CYP3A4 inhibitors eg, itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV PIs (eg, nelfinavir), boceprevir, telaprevir, nefazodone, cobicistat; moderate CYP3A4 inhibitors; ciclosporin, danazol, gemfibrozil; other fibrates, fusidic acid; verapamil, diltiazem; amiodarone, amlodipine, ranolazine, niacin (≥1 g/day), elbasvir, grazoprevir; lomitapide; daptomycin; ticagrelor; grapefruit juice. Small increase in mean AUC of niacin & nicotinuric acid. Ezetimibe: Decreased conc w/ cholestyramine. Increased conc w/ ciclosporin, fenofibrate, gemfibrozil. Post-marketing reports of increased INR in patients who had ezetimibe added to warfarin or fluindione. Simvastatin: Increased conc w/ itraconazole, telithromycin, ticagrelor, ciclosporin, gemfibrozil, verapamil, diltiazem, amlodipine, OATP1B1 inhibitors, BCRP inhibitors, grapefruit juice. Decreased conc w/ rifampicin (potent CYP3A4 inducer). Rare cases of rhabdomyolysis associated w/ concomitant administration of simvastatin & fluconazole have been reported. Co-administration of statins & systemic fusidic acid may cause increased plasma conc of both agents. Cases of myopathy, including rhabdomyolysis, have been reported w/ simvastatin co-administered w/ colchicine in patients w/ renal impairment. Modestly potentiated effect of coumarin anticoagulants.

Dyslipidaemic Agents

C10BA02 - simvastatin and ezetimibe ; Belongs to the class of HMG CoA reductase inhibitors in combination with other lipid modifying agents. Used in the treatment of hyperlipidemia.

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