Atorsam-F Special Precautions

Liver Function: The two drugs, given individually, have been associated with biochemical abnormalities of liver function. Persistent elevations (>3 times the upper limit of normal [ULN] occurring on two or more occasions) in serum transaminases occurred in 0.7% of patients who received atorvastatin in clinical trials. Specifically, the incidence of these abnormalities was 0.2% for atorvastatin 10 mg. In a pooled analysis of 10 placebo-controlled trials, increases in serum transaminases to >3 ULN occurred in 5.3% of patients taking fenofibrate versus 1.1% of patients treated with placebo.
It is recommended that liver function tests be performed prior to and at 12 weeks following initiation of therapy and periodically thereafter (e.g. semiannually).
Patients who develop increased transaminase levels should be monitored until the abnormalities resolve. Should an increase in ALT or AST of >3 times ULN persist, withdrawal of the fixed dose combination of atorvastatin and fenofibrate is recommended. The fixed dose combination of atorvastatin and fenofibrate should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease.
Skeletal Muscle: The use of the fixed dose combination of atorvastatin and fenofibrate may occasionally be associated with myopathy since the two drugs, individually, have been shown to cause myopathy in a small percentage of patients (<1%) in international trials. Treatment with atorvastatin as well as fenofibrate has been associated on rare occasions with rhabdomyolysis, usually in patients with impaired renal function. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevations of CPK levels. The risk of myopathy during treatment may be increased with concurrent administration of cyclosporine, erythromycin, and niacin or azole anti-fungals. Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. The CPK levels should be assessed in patients reporting these symptoms and the fixed dose combination of atorvastatin and fenofibrate should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed. The fixed dose combination of Atorvastatin and Fenofibrate should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (eg, severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).
Endocrine Function: Statins interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production. Clinical studies have shown that Atorvastatin does not reduce basal plasma cortisol concentration or impair adrenal reserve. The effects of statins on male fertility have not been studied in adequate numbers of patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Caution should be exercised if the fixed dose combination of Atorvastatin and Fenofibrate is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine.
Cholelithiasis: Fenofibrate, like clofibrate and gemfibrozil, may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Fenofibrate therapy should be discontinued if gallstones are found.
Pancreatitis: Pancreatitis has been reported in patients taking Fenofibrate, gemfibrozil, and clofibrate. This occurrence may represent a failure of efficacy in patients with severe hypertriglyceridemia, a direct drug effect, or a secondary phenomenon mediated through biliary tract stone or sludge formation with obstruction of the common bile duct.
Hypersensitivity Reactions: Acute hypersensitivity reactions including severe skin rashes requiring patient hospitalization and treatment with steroids have occurred very rarely during treatment with Fenofibrate, including rare spontaneous reports of Stevens-Johnson syndrome, and toxic epidermal necrolysis. Urticaria was seen in 1.1 vs. 0%, and rash in 1.4 vs. 0.8% of Fenofibrate and placebo patients respectively in controlled trials.
Hematologic Changes: Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in patients following initiation of fenofibrate therapy. However, these levels stabilize during long-term administration. Extremely rare spontaneous reports of thrombocytopenia and agranulocytosis have been received during post-marketing surveillance outside of the U.S. Periodic blood counts are recommended during the first 12 months of fenofibrate administration.