Generic Name and Formulations:
Niacin ext-rel, simvastatin; 500mg/20mg, 500mg/40mg, 750mg/20mg, 1000mg/20mg, 1000mg/40mg; tabs.
Adjunct to diet in primary hypercholesterolemia, mixed dyslipidemia, and hypertriglyceridemia if monotherapy is inadequate. Limitations of use: no incremental benefit on cardiovascular morbidity/mortality over and above that demonstrated for simvastatin monotherapy and niacin monotherapy has been established. Niacin ext-rel at doses of 1500–2000mg/day, in combination with simvastatin, did not reduce incidence of cardiovascular events more than simvastatin in a randomized controlled trial of patients with cardiovascular disease and mean baseline LDL-C levels of 74mg/dL.
Take once daily at bedtime with low-fat snack. Swallow whole. Naive to or switching from immediate-release niacin: initially 500/20 once daily. Previously on simvastatin 20‒40mg: initially 500/40 once daily. May increase at 4-wk intervals by up to 500mg/day (ext-rel niacin component); maintenance: 1000/20 to 2000/40 once daily. May substitute for previously-titrated ext-rel niacin at equivalent doses. Re-titrate if therapy interrupted ≥7 days. To reduce flushing, pretreat with aspirin. Concomitant amiodarone, amlodipine, ranolazine: max 1000/20 per day. Chinese patients taking niacin ≥1g/day or niacin-containing products: use caution with doses >1000/20 per day. Avoid concomitant alcohol, hot drinks, or spicy foods around time of ingestion.
Nicotinic acid deriv. + HMG-CoA reductase inhibitor.
Active liver or peptic ulcer disease. Unexplained persistent elevated transaminases. Arterial bleeding. Concomitant strong CYP3A4 inhibitors (eg, itraconazole, ketoconazole, posaconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone), gemfibrozil, cyclosporine, danazol, verapamil, diltiazem. Pregnancy (Cat.X). Nursing mothers.
Do not substitute for equivalent doses of immediate-release niacin. Increased risk of myopathy/rhabdomyolysis with simvastatin 80mg doses. Discontinue if myopathy, elevated CPK levels occur; suspend if a predisposition to development of renal failure secondary to rhabdomyolysis develops. Monitor liver function before starting therapy and repeat as clinically indicated. Interrupt therapy if serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs; do not restart if alternate etiology not found. History of liver disease. Substantial alcohol consumption. Severe renal insufficiency. Suspend therapy before surgery and if major medical event occurs. Renal dysfunction. Gout. Monitor blood glucose, PT, platelets.
See Contraindications. Increased risk of myopathy with strong CYP3A4 inhibitors, cyclosporine, danazol, verapamil, diltiazem, gemfibrozil, other fibrates, amiodarone, amlodipine, ranolazine, colchicine, grapefruit juice >1qt/day (avoid). Potentiated by voriconazole; adjust dose of Simcor. Separate dosing of bile acid sequestrants by 4–6hrs. Postural hypotension with ganglionic blockers, vasoactive drugs. Monitor warfarin, digoxin.
Flushing, headache, pruritus, diarrhea, nausea, back pain; elevated ALT/AST, myopathy, rhabdomyolysis with renal failure, increased HbA1c and fasting serum glucose, rare: cognitive impairment, non-fatal hepatic failure, immune-mediated necrotizing myopathy.