Tonact-FN Special Precautions

Tonact-FN must be preferably avoided in those with any evidence of hepatic disease, or those consuming substantial quantities of alcohol. Fenofibrate (in Tonact-FN) is to be given with care in the presence of pancreatitis.
Tonact-FN should be discontinued, or temporarily withheld, in any patient with an acute, serious condition suggestive of myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures). Myopathy should be considered in any patients with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of creatine phosphokinase.
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 (eg 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 Tonact-FN is recommended. Tonact-FN 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 Tonact-FN 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 cyclosporin, erythromycin, 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 Tonact-FN therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed.
Tonact-FN therapy should be temporarily withheld or discontinued in any patient with 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 Tonact-FN is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone and cimetidine.
Cholelithiasis: Fenofibrate may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Tonact-FN therapy should be discontinued if gallstones are found.
Pancreatitis: Pancreatitis has been reported in patient taking fenofibrate. 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.
Renal Impairment: Renal disease has no influence on the plasma concentrations or lipid effects of atorvastatin. However, fenofibric acid is known to be substantially excreted by the kidney and the risk of adverse reactions may be greater in patients with impaired renal function. Tonact-FN is not recommended for use in patients with severe renal impairment.
Hepatic impairment: In patients with chronic alcoholic liver disease, the therapeutic response to atorvastatin is unaffected but exposure to the drug is greatly increased. Therefore, caution should be exercised in patients who consume substantial quantities of alcohol and/or have a history of liver disease. As atorvastatin is contraindicated, Tonact-FN cannot be used in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels.
Pediatric Use: Safety and efficacy of atorvastatin-fenofibrate combination in pediatric patients have not been established.