Pravastatin: uses, appearance and warnings

Pravastatin sodium tablets are indicated: To reduce the risk of myocardial infarction, myocardial revascularization procedures, and cardiovascular mortality in adults with elevated low-density lipoprotein cholesterol (LDL-C) without clinically evident coronary heart disease (CHD). To reduce the risk of coronary death, myocardial infarction, myocardial revascularization procedures, stroke or transient ischemic attack, and slow the progression of coronary atherosclerosis in adults with clinically evident CHD. As an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia. As an adjunct to diet to reduce LDL-C in pediatric patients ages 8 years and older with heterozygous familial hypercholesterolemia (HeFH). As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia. Hypertriglyceridemia. Pravastatin sodium tablets are an HMG-CoA reductase inhibitor (statin) indicated: • To reduce the risk of myocardial infarction, myocardial revascularization procedures, and cardiovascular mortality in adults with elevated low-density lipoprotein cholesterol (LDL-C) without clinically evident coronary heart disease (CHD). • To reduce the risk of coronary death, myocardial infarction, myocardial revascularization procedures, stroke or transient ischemic attack, and slow the progression of coronary atherosclerosis in adults with clinically evident CHD. • As an adjunct to diet to reduce LDL-C in adults with primary hyperlipidemia. • As an adjunct to diet to reduce LDL-C in pediatric patients ages 8 years and older with heterozygous familial hypercholesterolemia (HeFH). As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia. Hypertriglyceridemia.

Pravastatin Sodium Tablets, USP are supplied as: 20 mg tablets: Off-white to light yellow, round, unscored tablets, imprinted “APO” on one side and “PRA” over “20” on the other side. 40 mg tablets: Light green, round, unscored tablets, imprinted “APO” on one side and “PRA” over “40” on the other side. 80 mg tablets: Off-white to light yellow, round, unscored tablets, imprinted “APO” on one side and “PRA” over “80” on the other side. Tablets: 20 mg, 40 mg, 80 mg. ( 3 )

16.1 How Supplied Pravastatin Sodium Tablets, USP 20 mg are available for oral administration as off-white to light yellow, round, unscored tablets, imprinted “APO” on one side and “PRA” over “20” on the other side. They are supplied as follows: Bottles of 1,000 (NDC 82009-006-10) Pravastatin Sodium Tablets, USP 40 mg are available for oral administration as light green, round, unscored tablets, imprinted “APO” on one side and “PRA” over “40” on the other side. They are supplied as follows: Bottles of 90 (NDC 82009-007-90) Bottles of 1,000 (NDC 82009-007-10) Pravastatin Sodium Tablets, USP 80 mg are available for oral administration as off-white to light yellow, round, unscored tablets, imprinted "APO" on one side and "PRA" over "80" on the other side. They are supplied as follows: Bottles of 500 (NDC 82009-008-05) Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container [see USP]. Protect from light and moisture. 16.1 How Supplied Pravastatin Sodium Tablets, USP 20 mg are available for oral administration as off-white to light yellow, round, unscored tablets, imprinted “APO” on one side and “PRA” over “20” on the other side. They are supplied as follows: Bottles of 1,000 (NDC 82009-006-10) Pravastatin Sodium Tablets, USP 40 mg are available for oral administration as light green, round, unscored tablets, imprinted “APO” on one side and “PRA” over “40” on the other side. They are supplied as follows: Bottles of 90 (NDC 82009-007-90) Bottles of 1,000 (NDC 82009-007-10) Pravastatin Sodium Tablets, USP 80 mg are available for oral administration as off-white to light yellow, round, unscored tablets, imprinted "APO" on one side and "PRA" over "80" on the other side. They are supplied as follows: Bottles of 500 (NDC 82009-008-05) Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container [see USP]. Protect from light and moisture.

Acute liver failure or decompensated cirrhosis [see Warnings and Precautions ( 5.3 )]. Hypersensitivity to any pravastatin or any excipients in pravastatin sodium tablets. Hypersensitivity to pravastatin or any excipient in pravastatin sodium tablets ( 4 ) Acute liver failure or decompensated cirrhosis ( 4 , 5.3 )

Myopathy and Rhabdomyolysis: Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher pravastatin dosage. Discontinue pravastatin if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Temporarily discontinue pravastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing pravastatin dosage. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. ( 5.1 , 7.1 , 8.5 , 8.6 ) Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported. Discontinue pravastatin if IMNM is suspected ( 5.2 ). Hepatic Dysfunction: Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzymes before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue ( 5.3 ). 5.1 Myopathy and Rhabdomyolysis Pravastatin may cause myopathy and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including pravastatin. Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CK) to greater than 10 times the upper limit of normal (ULN), occurred <0.1% in pravastatin-treated patients in clinical trials. Risk Factors for Myopathy Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher pravastatin dosage [see Drug Interactions ( 7.1 )]. Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis Pravastatin is not recommended in patients taking gemfibrozil [see Drug Interactions ( 7 )] . There are pravastatin dosage restrictions for patients taking cyclosporin and select macrolide antibiotics [see Dosage and Administration ( 2.5 )] . The following drugs when used concomitantly with pravastatin may also increase the risk of myopathy and rhabdomyolysis: niacin, fibrates, and colchicine [see Drug Interactions ( 7 )] . Discontinue pravastatin if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Muscle symptoms and CK increases may resolve if pravastatin is discontinued. Temporarily discontinue pravastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis, e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the pravastatin dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. 5.2 Immune-Mediated Necrotizing Myopathy There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Discontinue pravastatin if IMNM is suspected. 5.3 Hepatic Dysfunction Increases in serum transaminases have been reported with use of pravastatin [see Adverse Reactions ( 6.1 )] . In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. Persistent increases to more than three times the ULN in serum transaminases have occurred in approximately 1% of patients receiving either pravastatin or placebo in clinical studies. Marked persistent increases of hepatic transaminases have also occurred with pravastatin. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pravastatin. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Consider liver enzyme testing before pravastatin initiation and when clinically indicated thereafter. Pravastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications ( 4 )] . If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue pravastatin. 5.4 Increases in HbA1c and Fasting Serum Glucose Levels Increases in HbA1c and fasting serum glucose levels have been reported with statins, including pravastatin. Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices.

The following important adverse reactions are described below and elsewhere in the labeling: Myopathy and Rhabdomyolysis [see Warnings and Precautions ( 5.1 )] Immune-Mediated Necrotizing Myopathy [see Warnings and Precautions ( 5.2 )] Hepatic Dysfunction [see Warnings and Precautions ( 5.3 )] Increases in HbA1c and Fasting Serum Glucose Levels [see Warnings and Precautions ( 5.4 )] In short-term clinical trials, the most commonly reported adverse reactions (≥2% and greater than placebo) were: musculoskeletal pain, nausea/vomiting, upper respiratory infection, diarrhea, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Quallent, at 1-877-605-7243 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

See full prescribing information for details regarding concomitant use of pravastatin sodium tablets with other drugs that increase the risk of myopathy and rhabdomyolysis. ( 2.5 , 7.1 ) Bile Acid Sequestrants: in patients taking a bile acid sequestrant, administer pravastatin sodium tablets at least 1 hour before or at least 4 hours after the bile acid sequestrant ( 7.2 ) 7.1 Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Pravastatin Pravastatin is a substrate of the transport protein OATP1B1. Pravastatin plasma levels can be significantly increased with concomitant administration of inhibitors of OATP1B1. Table 3 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when used concomitantly with pravastatin and instructions for preventing or managing them [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology (12.3)]. …