Atorvastatin

Increases in HbA1c and fasting blood glucose have been reported.

Persistent elevations in serum transaminases have been reported; upon dose reduction, drug interruption, or discontinuation, transaminase levels returned to or near pretreatment levels. Postmarketing reports of fatal and nonfatal hepatic failure have been reported and are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy promptly. If an alternate etiology is not identified, do not restart atorvastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated and if signs/symptoms of liver injury occur. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption.

Rhabdomyolysis with acute renal failure secondary to myoglobinuria and/or myopathy has been reported; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, protease inhibitors), cyclosporine, fibric acid derivatives (eg, gemfibrozil), or niacin (doses ≥1 g/day); if concurrent use is warranted, consider lower starting and maintenance doses of atorvastatin. Use caution in patients with inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Uncomplicated myalgia immune-mediated necrotizing myopathy (IMNM) associated with HMG-CoA reductase inhibitors use has also been reported. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever. Discontinue therapy if markedly elevated CPK levels occur or myopathy is diagnosed/suspected. Disease-related concerns:

Use with caution in patients who consume large amounts of ethanol or have a history of liver disease; use is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases.

Use with caution in patients with renal impairment; these patients are predisposed to myopathy.

Patients with recent stroke or TIA receiving long-term therapy with high-dose (ie, 80 mg/day) atorvastatin may be at increased risk for hemorrhagic stroke (SPARCL Investigators 2006). A subsequent post-hoc analysis demonstrated that patients with lacunar or hemorrhagic stroke may be at higher risk of hemorrhagic stroke; however, this finding was determined to be hypothesis generating. The overall benefit of treatment with atorvastatin (ie, reduced risk of stroke and cardiovascular events) in this population seems to outweigh the increased risk of hemorrhagic stroke if one truly exists (Goldstein 2008). Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution in patients with advanced age, these patients are predisposed to myopathy.

The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (eg, sepsis, hypotension, trauma, uncontrolled seizures, severe metabolic, endocrine, or electrolyte disorders). Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period for noncardiac and cardiac surgery (ACC/AHA [Fleisher 2014]; ACC/AHA [Hillis 2011]). Perioperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality. Dosage form specific issues:

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Other warnings/precautions:

Secondary causes of hyperlipidemia should be ruled out prior to therapy. Atorvastatin has not been studied when the primary lipid abnormality is chylomicron elevation (Fredrickson types I and V).

Secondary causes of hyperlipidemia should be ruled out prior to therapy.