Pravastatin Sodium
Pravastatin Sodium Prescribing Information
Contraindications, Pregnancy and Lactation Removed (
· Acute liver failure or decompensated cirrhosis [
· Hypersensitivity to any pravastatin or any excipients in Pravastatin sodium tablets.
· Hypersensitivity to pravastatin or any excipient in Pravastatin sodium tablets
· Acute liver failure or decompensated cirrhosis
Warnings and Precautions,
Immune-Mediated Necrotizing Myopathy Updated (
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 sodium tablets if IMNM is suspected.
Pravastatin sodium tablets is 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:
o Primary dysbetalipoproteinemia.
o Hypertriglyceridemia.
· Take orally once daily at any time of the day, with or without food (
· Take Pravastatin sodium tablets orally once daily as a single dose at any time of the day, with or without food.
· For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving Pravastatin sodium tablets 80 mg daily, prescribe alternative LDL-C-lowering treatment.
· Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating Pravastatin sodium tablets, and adjust the dosage if necessary.
· For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving Pravastatin sodium tablets 80 mg daily, prescribe alternative LDL- C-lowering treatment (
· Take Pravastatin sodium tablets orally once daily as a single dose at any time of the day, with or without food.
· For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving Pravastatin sodium tablets 80 mg daily, prescribe alternative LDL-C-lowering treatment.
· Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating Pravastatin sodium tablets, and adjust the dosage if necessary.
· Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating Pravastatin sodium tablets, and adjust the dosage if necessary (
· Take Pravastatin sodium tablets orally once daily as a single dose at any time of the day, with or without food.
· For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving Pravastatin sodium tablets 80 mg daily, prescribe alternative LDL-C-lowering treatment.
· Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating Pravastatin sodium tablets, and adjust the dosage if necessary.
· Adults: recommended starting dosage is Pravastatin sodium tablets 40 mg to 80 mg once daily. (
The recommended starting dosage is Pravastatin sodium tablets 40 mg to 80 mg once daily.
· Pediatric Patients (
· In pediatric patients aged 8 to 13 years, the recommended dosage is Pravastatin sodium tablets 20 mg once daily.
· In pediatric patients aged 14 to 18 years, the recommended starting dosage is Pravastatin sodium tablets 40 mg once daily.
o aged 8 to 13 years, the recommended dosage is 20 mg once daily.
o aged 14 to 18 years, the recommended starting dosage is 40 mg once daily.
· Severe renal impairment: recommended starting dosage is pravastatin sodium 10 mg once daily. Recommended maximum Pravastatin sodium tablets dosage is 40mg once daily. (
· In patients with severe renal impairment, the recommended starting dosage is pravastatin sodium 10 mg once daily. Pravastatin sodium tablets is available in a 10 mg strength. The maximum recommended dosage of Pravastatin sodium tablets in patients with severe renal impairment is 40 mg once daily
· The recommended dosage of Pravastatin sodium tablets for patients with mild or moderate renal impairment is the same as patients with normal renal function.
· See full prescribing information for dosage modifications due to drug interactions (
· In patients taking a bile acid sequestrant, administer Pravastatin sodium tablets at least 1 hour before or 4 hours after the bile acid sequestrant
·
o
In patients taking cyclosporine, the recommended starting dosage is pravastatin sodium 10 mg once daily. Pravastatin sodium tablets is available in a 10 mg strength. The maximum recommended dosage of Pravastatin sodium tablets in patients taking cyclosporine is 20 mg once daily.
o
The maximum recommended dosage is Pravastatin sodium tablets 40 mg once daily.
· See full prescribing information for details regarding concomitant use of Pravastatin sodium tablets with other drugs that increase the risk of myopathy and rhabdomyolysis.
· 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
Pravastatin sodium tablets is a substrate of the transport protein OATP1B1. Pravastatin sodium tablets 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 sodium tabletsand instructions for preventing or managing them
Gemfibrozil | |
Clinical Impact: | There is an increased risk of myopathy/rhabdomyolysis when Pravastatin sodium tablets is administered with gemfibrozil |
Intervention: | Avoid concomitant use of gemfibrozil with Pravastatin sodium tablets. |
Cyclosporine | |
Clinical Impact: | The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine with Pravastatin sodium tablets. |
Intervention: | Initiate with a dosage of pravastatin sodium 10 mg once daily. Pravastatin sodium tablets is available in a 10 mg strength. Do not exceed Pravastatin sodium tablets 20 mg once daily [ see Dosage and Administration(2.5)]. |
Select Macrolide Antibiotics | |
Clinical Impact: | The risk of myopathy and rhabdomyolysis is increased by concomitant use of clarithromycin or erythromycin with Pravastatin sodium tablets. Other macrolides (e.g., azithromycin)have the potential to increase Pravastatin sodium tablets exposures and increase the risk of myopathy and rhabdomyolysis when used concomintantly. |
Intervention: | For patients taking erythromycin or clarithromycin, do not exceed 40mg Pravastatin sodium tablets once daily [ see Dosage and Administration (2.5)]. |
Niacin | |
Clinical Impact: | Cases of myopathy and rhabdomyolysis have been observed with concomitant use of niacin with Pravastatin sodium tablets. |
Intervention: | Consider if the benefit of using niacin concomitantly with Pravastatin sodium tablets outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitorpatientsforsignsandsymptomsofmyopathy,particularlyduringinitiation of therapy and during upward dose titration of either drug. |
Fibrates(other than Gemfibrozil) | |
Clinical Impact: | Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysisisincreasedwithconcomitantuseoffibrateswithPravastatin sodium tablets. |
Intervention: | Consider if the benefit of using fibrates concomitantly with Pravastatin sodium tablets outweighstheincreasedriskofmyopathyandrhabdomyolysis.Ifconcomitantuseis decided,monitorpatientsforsignsandsymptomsofmyopathy,particularlyduring initiation of therapy and during upward dose titration of either drug. |
Colchicine | |
Clinical Impact: | Casesofmyopathyandrhabdomyolysishavebeenreportedwithconcomitantuseof colchicine with Pravastatin sodium tablets. |
Intervention: | Consider if the benefit of using colchicine concomitantly with Pravastatin sodium tablets outweighstheincreasedriskofmyopathyandrhabdomyolysis.Ifconcomitantuseis decided,monitorpatientsforsignsandsymptomsofmyopathy,particularlyduring initiation of therapy and during upward dose titration of either drug. |
Table 4 presents drug interactions that may decrease the efficacy of Pravastatin sodium tablets and instructions for preventing or managing them.
Bile Acid Sequestrants | |
Clinical Impact: | Concomitant cholestyramine or colestipol administration decreased the mean exposure of pravastatin approximately 51% and 47%, respectively [ see Clinical Pharmacology (12.3)]. |
Intervention: | 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 [ see Dosage and Administration (2.5)]. |
· Pregnancy: May cause fetal harm (
Discontinue Pravastatin sodium tablets when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Pravastatin sodium tablets decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, Pravastatin sodium tablets may cause fetal harm when administered to pregnant patients based on the mechanism of action
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
A Medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential cofounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for cofounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births.
Embryofetal and neonatal mortality was observed in rats given pravastatin during the period of organogenesis or during organogenesis continuing through weaning. In pregnant rats given oral gavage doses of 4, 20, 100, 500, and 1000 mg/kg/day from gestation days 7 through 17 (organogenesis) increased mortality of offspring and increased cervical rib skeletal anomalies were observed at ≥100 mg/kg/day systemic exposure, 10 times the human exposure at 80 mg/day MRHD based on body surface area (mg/m2).
In other studies, no teratogenic effects were observed when pravastatin was dosed orally during organogenesis in rabbits (gestation days 6 through 18) up to 50 mg/kg/day or in rats (gestation days 7 through 17) up to 1000 mg/kg/day. Exposures were 10 times (rabbit) or 120 times (rat) the human exposure at 80 mg/day MRHD based on body surface area (mg/m2).
In pregnant rats given oral gavage doses of 10, 100, and 1000 mg/kg/day from gestation day 17 through lactation day 21 (weaning), developmental delays were observed at ≥100 mg/kg/day systemic exposure, corresponding to 12 times the human exposure at 80 mg/day MRHD, based on body surface area (mg/m2).
In pregnant rats, pravastatin crosses the placenta and is found in fetal tissue at 30% of the maternal plasma levels following administration of a single dose of 20 mg/day orally on gestation day 18, which corresponds to exposure 2 times the MRHD of 80 mg daily based on body surface area (mg/m2).
· Lactation: Breastfeeding not recommended during treatment with Pravastatin sodium tablets (
Based on one lactation study in published literature, pravastatin is present in human milk. There is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Statins, including Pravastatin sodium tablets, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant.
Because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with Pravastatin sodium tablets
· Acute liver failure or decompensated cirrhosis [
Increases in serum transaminases have been reported with use of Pravastatin sodium tablets [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 sodium tablets or placebo in clinical studies. Marked persistent increases of hepatic transaminases have also occurred with Pravastatin sodium tablets. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including Pravastatin sodium tablets.
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 sodium tablets initiation and when clinically indicated thereafter. Pravastatin sodium tablets 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 sodium tablets.
· Hypersensitivity to any pravastatin or any excipients in Pravastatin sodium tablets.