- Myopathy manifested as muscle pain, tenderness or weakness with creatine kinase above 10 x ULN, sometimes resulting into rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities, have been reported with ezetimibe/atorvastatin. Risk of myopathy is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, niacin or azole anti-fungals. Advise patients to report promptly any symptoms such as muscle pain, tenderness or weakness, malaise or fever
- The risk of myopathy/rhabdomyolysis is dose related, discontinue the treatment immediately if myopathy is diagnosed or suspected. Monitor creatine kinase prior to starting therapy or when dose is increased
- Discontinue therapy in patients with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis such as severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures
- Asymptomatic elevations (
3 x ULN) in serum transaminases have been reported with atorvastatin/ezetimibe therapy, monitor LFTs before the initiation of treatment and periodically thereafter. Discontinue the therapy with atorvastatin/ezetimibe if persistent increase in AST or ALT of 3 X ULN or greater - Therapy has been associated with fatal and non-fatal hepatic failure in patients taking statins, including atorvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, promptly interrupt therapy.
- Use cautiously in patients who consume substantial quantities of alcohol and/or have a history of liver disease
- HMG-CoA reductase inhibitors interfere with cholesterol synthesis and might impair adrenal and/or gonadal steroid production. Use cautiously in patients undergoing therapy with drugs that may decrease the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone and cimetidine
- Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including atorvastatin
- Coadministration of ezetimibe with fibrates other than fenofibrate may increase cholesterol excretion into the bile, leading to cholelithiasis. Concomitant use is not recommended. If cholelithiasis is suspected, gallbladder studies and alternative lipid-lowering therapy are recommended
- Concomitant administration with inhibitors of cytochrome P450 3A4 such as clarithromycin and erythromycin can lead to increases in plasma concentrations of atorvastatin, and its administration with inducers of cytochrome P450 3A4 such as efavirenz and rifampin can lead to variable reductions in plasma concentrations of atorvastatin
- Coadministration of atorvastatin with digoxin increases plasma digoxin concentration. Closely monitor patients
Cautions: Use cautiously in
- Renal impairment
- Hepatic impairment
- Hx of liver disease
- Alcohol abuse
