on of ezetimibe; simvastatin therapy and repeat as clinically indicated. After extensive data review, the FDA concluded that the risk of serious liver injury is very low and routine periodic monitoring of liver enzymes has not been effective in detection or prevention of serious hepatic injury. Instruct patients to promptly report any symptoms of hepatic injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice) during ezetimibe; simvastatin therapy. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with ezetimibe; simvastatin, therapy should be interrupted. If an alternate etiology is not found, do not restart ezetimibe; simvastatin.
Electrolyte imbalance, endocrine disease, females, hypotension, hypothyroidism, infection, myopathy, organ transplant, renal disease, renal failure, renal impairment, rhabdomyolysis, seizure disorder, surgery, trauma
Discontinue ezetimibe; simvastatin immediately in any patient who develops myopathy, elevations in CPK, or signs of rhabdomyolysis. The risk of myopathy, including rhabdomyolysis, is greater in patients receiving 80 mg/day of simvastatin compared to lower doses or other statin therapies. Therefore, the 10/80 mg dose of ezetimibe; simvastatin is restricted to patients who have taken 10/80 mg/day chronically (e.g. >= 12 months) without evidence of myopathy. The risk is highest during the first year of treatment, and patients >= 65 years, females, and those with uncontrolled hypothyroidism appear to be predisposed to developing myopathy. Ezetimibe; simvastatin is contraindicated in organ transplant patients receiving immunosuppressant therapy such as cyclosporine because of an increased risk of rhabdomyolysis and renal failure. The risk of developing myopathy is increased when ezetimibe; simvastatin is used in combination with CYP3A4 inhibitors or drugs that have an independent risk of myopathy. The manufacturer suggests a lower maximum dosage of ezetimibe; simvastatin when used with some drugs known to increase the risk of myopathy. If a patient who is stabilized on the 10/80 mg/day dose needs to be initiated on an interacting drug that is contraindicated or is associated with a lower maximum simvastatin dose, then that patient should be switched to an alternative statin with less potential for the drug interaction. Chinese patients taking lipid-modifying doses of niacin-containing products (>= 1 g/day niacin) should not receive the 80 mg dose of simvastatin due to an increased risk for myopathy. Simvastatin may be contraindicated in conditions that can cause decreased renal perfusion since renal failure is possible if simvastatin-induced rhabdomyolysis occurs. Predisposing conditions include renal disease or renal insufficiency, hypotension, acute infection, endocrine disease, electrolyte imbalance, uncontrolled seizure disorder, major surgery, and trauma. Although in the SHARP trial there was no significant difference in the incidence of adverse events between ezetimibe 10/20 mg/day PO and placebo in patients with moderate-to-severe renal impairment, higher doses of ezetimibe; simvastatin should be approached with caution and close clinical monitoring because renal impairment is a risk factor for statin-associated myopathy.
Geriatric
Some geriatric patients may be more sensitive to the effects of the usual adult dosage of simvastatin; dosage should be individualized to ac |
