Pravastatin

Increases in HbA1c and fasting blood glucose have been reported with HMG-CoA reductase inhibitors; however, the benefits of statin therapy far outweigh the risk of dysglycemia.

Reduced cholesterol synthesis as a result of therapy could theoretically lead to reduced adrenal or gonadal steroid hormone production; clinical trial data is inconsistent in regards to the effect on basal steroid hormone levels. Patients with signs/symptoms of endocrine dysfunction should be evaluated as clinically indicated; use caution with concomitant medications (eg, spironolactone, cimetidine, ketoconazole) that may reduce steroid hormone levels/activity.

Postmarketing reports of fatal and nonfatal hepatic failure are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy. If an alternate etiology is not identified, do not restart pravastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated; routine periodic monitoring of liver enzymes is not necessary. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption.

IMNM, an autoimmune-mediated myopathy, has been reported (rarely) with HMG-CoA reductase inhibitor therapy. IMNM presents as proximal muscle weakness with elevated CPK levels, which persists despite discontinuation of HMG-CoA reductase inhibitor therapy; additionally, muscle biopsy may show necrotizing myopathy with limited inflammation. Immunosuppressive therapy (eg, corticosteroids, azathioprine) may be used for treatment.

Rhabdomyolysis with acute renal failure secondary to myoglobinuria and/or myopathy have been reported; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of erythromycin, cyclosporine, fibric acid derivatives (eg, gemfibrozil), or niacin (doses ≥1 g/day). Temporarily withhold therapy in patients experiencing conditions predisposing to the development of renal failure secondary to rhabdomyolysis (eg, sepsis, hypotension, major surgery, trauma, uncontrolled epilepsy; severe metabolic, endocrine, or electrolyte disorders). Discontinue therapy in any patient in which CPK levels are markedly elevated (>10 times ULN) or if myopathy is suspected/diagnosed. Use caution in patients with inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine. 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 transaminase elevations.

Use with caution in patients with renal impairment; these patients are predisposed to myopathy. 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 or serious condition predisposing to renal failure (eg, sepsis, hypotension, trauma, uncontrolled seizures). 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. Other warnings/precautions:

Has not been studied in homozygous familial hypercholesterolemia (statins may be less effective due to lack of functional LDL receptors).

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