Pravastatin Sodium (pravastatin sodium)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Pravastatin sodium, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin), is an antilipemic agent.
Pravastatin is a competitive and reversible inhibitor of 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase (i.e., statin), an enzyme that catalyzes the conversion of HMG-CoA to mevalonate (an early and rate-limiting step in cholesterol biosynthesis). Pravastatin is pharmacologically related to other statins (e.g., atorvastatin, lovastatin, fluvastatin, simvastatin, pitavastatin, rosuvastatin). Pravastatin is structurally related to lovastatin and simvastatin but differs from these agents by the substitution of a hydroxyl group for the methyl group on the hexahydronaphthalene ring.
This structural modification increases the hydrophilicity of pravastatin, making it approximately 100-fold more soluble in water than lovastatin or simvastatin. Unlike the lactone prodrugs lovastatin and simvastatin, pravastatin exists as an active hydroxy acid and does not require hydrolysis in vivo. Pravastatin is similar structurally to HMG-CoA and competes with this compound for interaction with HMG-CoA reductase.
Pravastatin reduces elevated low-density lipotrotein (LDL)-cholesterol concentrations. The mechanism of the LDL-lowering effect of pravastatin may involve both reduction of very low-density lipoprotein (VLDL) concentration, and induction of the LDL receptor, leading to reduced production and/or increased catabolism of LDL-cholesterol. Triglyceride and apolipoprotein B may decrease and high-density lipoptotein (HDL)-cholesterol concentration may increase during treatment with pravastatin.
Other favorable effects of statins (pleitropic effects) include an antiproliferative influence on smooth muscle cells, reconstruction of endothelial activity, antioxidant, antithrombotic, anticancer, and anti-inflammatory effects.
Pravastatin is hydrophilic, average oral absorption is 34%, and absolute bioavailability is 17%. Bioavailability is reduced 60% when administered at bedtime compared to morning administration, however the drug is marginally more effective (not statistically significant) when administered at bedtime. Peak plasma pravastatin concentrations occur within 1-1.5 hours following oral administration.
Administration with food will reduce the AUC and peak plasma concentration 31 and 49%, respectively, however the lipid-lowering effects are similar whether taken with or 1 hour prior to meals. Pravastatin plasma concentrations, AUC and time to steady state are directly proportional to administered dose. Therapeutic response, maximum LDL-cholesterol reduction, is expected within 4 weeks.
Pravastatin is 50% bound to plasma proteins and present in breast milk.
Pravastatin undergoes extensive first-pass extraction in the liver and is metabolized via isomerization and hydroxylation. One isomeric metabolite has 1/10th-1/40th the HMG-CoA reductase inhibitory activity of the parent compound. Pravastatin does not undergo cytochrome P450 isoenzyme metabolism.
Pravastatin is excreted in the feces and urine approximately 70 and 20%, respectively. Following single dose oral administration of radiolabeled pravastatin, the radioactive elimination half-life for pravastatin is 1.8 hours and the elimination half-life for total radioactivity (pravastatin plus metabolites) is 77 hours.
In patients with severe renal impairment, the mean AUC and peak plasma concentrations were 69 and 37% higher, respectively, compared to healthy subjects with normal renal function. No pharmacokinetic differences were observed among other patients with varying degrees of renal impairment. The mean AUC and peak concentrations varied 18- and 47-fold, respectively, in patients with biopsy-confirmed cirrhosis compared to 5- and 6-fold, respectively, in healthy subjects.
Data from a pharmacokinetic study indicate that meanAUC of pravastatin is 25-50% higher in geriatric individuals compared with younger adults. However, because mean peak plasma concentration, time to peak plasma concentration, and half-life are similar between geriatric and younger individuals, substantial accumulation of pravastatin would not be expected in geriatric patients. Patients with certain solute carrier organic anion transporter (SLCO) 1B1 phenotypes (i.e., decreased, possible decreased, or poor function) will have increased pravastatin exposure compared to those with normal function.
USES: Pravastatin is used along with a proper diet to help lower "bad" cholesterol and fats (such as LDL, triglycerides) and raise "good" cholesterol (HDL) in the blood. It belongs to a group of drugs known as "statins." It works by reducing the amount of cholesterol made by the liver. Lowering "bad" cholesterol and triglycerides and raising "good" cholesterol decreases the risk of heart disease and helps prevent strokes and heart attacks.
In addition to eating a proper diet (such as a low-cholesterol/low-fat diet), other lifestyle changes that may help this medication work better include exercising, losing weight if overweight, and stopping smoking. Consult your doctor for more details.
Generic name: pravastatin sodium
Pronunciation: (PRAV-uh-stat-in)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Pravastatin Sodium
Indications
The following indications are listed for Pravastatin Sodium:
- Atherosclerotic Cardiovascular Disease
- Heterozygous Familial Hypercholesterolemia
- Hypercholesterolemia
- Hyperlipidemia
- Hypertriglyceridemia
- Mixed Hyperlipidemia
- Myocardial Infarction Prevention
- Prevention Of Cerebrovascular Accident
- Prevention Of Transient Ischemic Attack
- Primary Dysbetalipoproteinemia
- Primary Prevention Of Coronary Heart Disease
- Treatment To Slow Progression Of Coronary Artery Disease
Also known as: Abnormally Increased Triglycerides In The Blood, Acute Mi Prophylaxis, Acute Myocardial Infarction Prophylaxis, Ami Prophylaxis, Atherosclerosis, Atherosclerotic Vascular Disease, Cardiac Infarct Prophylaxis, Cardiac Infarction Prophylaxis, Cardiovascular Disease Related To Atherosclerosis, Combined Hypercholesterolemia And Hypertriglyceridemia, Coronary Heart Disease Primary Prophylaxis, Cva Prophylaxis, Elevated Blood Cholesterol Level, Elevated Triglyceride Level, Familial Heterozygous Hypercholesterolemia, Familial Type 3 Hyperlipoproteinemia, Fredrickson Type Iii Hyperlipoproteinemia, Heterozygous Familial Elevated Blood Cholesterol, Hyperlipoidemia, Increased Triglyceride Levels, Lipemia, Lipidemia, Lipoidemia, Mi Prophylaxis, Mixed Dyslipidemia, Myocardial Infarct Prophylaxis, Myocardial Infarction Prophylaxis, Primary Prevention Of Cardiac Ischemia, Primary Prevention Of Ischemic Heart Disease, Primary Prevention Of Myocardial Infarct, Stroke Prophylaxis, Tia Prophylaxis, Tias Prophylaxis, Transient Ischemic Attack Prophylaxis, Treatment To Slow Progression Of Cad, Type Iii Hyperlipoproteinemia.
Dosing
Patients receiving cyclosporine concomitantly with pravastatin should receive an initial pravastatin sodium dosage of 10 mg once daily;. the manufacturer states the pravastatin sodium dosage should not exceed 20 mg once daily.
In patients receiving concomitant clarithromycin or erythromycin, the maximum recommended dosage of pravastatin sodium is 40 mg once daily.
Pravastatin sodium is administered orally. The drug may be taken without regard to meals or time of day.
Pravastatin sodium tablets should be stored in well-closed, light-resistant containers at 20-25degreesC; the tablets should be protected from moisture.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Pravastatin does not undergo cytochrome P450 isoenzyme metabolism. Pravastatin is a substrate of organic anion transporter protein (OATP) 1B1, 1B3, and 2B1.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Hypersensitivity to pravastatin or any component of the formulation.
*Acute liver failure or decompensated cirrhosis.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in >=2% of patients, and greater than placebo, receiving pravastatin include musculoskeletal pain, nausea/vomiting, upper respiratory infection, diarrhea, and headache.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and effectiveness of pravastatin as an adjunct to diet to reduce LDL-cholesterol in pediatric patients 8 years of age and older with heterozygous familial hypercholesterolemia (HeFH) have been established in a double-blind, placebo-controlled study. Dosages greater than 40 mg daily have not been studied in this population.
Safety and efficacy of pravastatin have not been evaluated inpediatric patients with other types of hyperlipidemia.
All statins were previously contraindicated in pregnant women because the fetal risk with these drugs was thought to outweigh any possible benefit. This determination was based on several factors including safety signals from animal data. No evidence of fetal malformations was seen in pregnant rats or rabbits orally administered pravastatin during the period of organogenesis at doses that resulted in 10 and 120 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 80 mg/day, based on body surface area (mg/m2). An imbalance in some fetal skeletal variations, increased offspring mortality, and developmental delays occurred when pregnant rats were exposed to 10-12 times the MRHD during organogenesis to parturition.
In addition, congenital anomalies including severe CNS defects and unilateral limb deficiencies were reported in a case series of pregnant women who were exposed to a lipophilic statin (pravastatin is a hydrophilic statin) during the first trimester. Because statins decrease synthesis of cholesterol and possibly other products of the cholesterol biosynthetic pathway, there was also a concern that these drugs could potentially cause fetal harm. More recent data from case series and observational cohort studies have not shown evidence of an increased risk of major birth defects with statin use during pregnancy, and this was observed after controlling for potential confounders such as maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use. The overall evidence from animal studies suggests limited potential for statins to cause malformations or other adverse fetal effects. While an increased risk of miscarriage has been reported in pregnant women exposed to statins, it is not clear whether this effect is related to the drugs or to other confounding factors.
FDA conducted a comprehensive review of all available clinical and nonclinical data related to statin use in pregnant women and concluded that the totality of evidence suggests that there is limited potential for statins to cause malformations and other adverse embryofetal effects. Because statins may prevent serious or potentially fatal cardiovascular events in certain high-risk patients who are pregnant, FDA has requested that the contraindication in pregnant women be removed from the prescribing information for all statins. While FDA still advises that most pregnant patients discontinue statins because of the possibility of fetal harm, there may be some patients (e.g., those with homozygous familial hypercholesterolemia or established cardiovascular disease) in whom continued therapy may be beneficial; therefore, decisions should be individualized based on the patient's risks versus benefits. Patients who become pregnant or suspect that they are pregnant while receiving a statin should notify their clinician who can advise them on the appropriate course of action.
Pravastatin is distributed into human milk. Effects of the drug on breast-fed infants or milk production are not known. Because of the potential for serious adverse reactions from pravastatin in nursing infants, the drug is not recommended in nursing women; women who require pravastatin therapy should not breast-feed their infants. Many patients can stop statin therapy temporarily until breast-feeding is complete; patients who require ongoing statin treatment should not breast-feed and should use alternatives such as infant formula.
The manufacturers make no specific dosage recommendations for geriatric patients. Dose selection in geriatric patients (>=65 years of age) should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy.
In clinical studies, 4,797 (36.4%) pravastatin-treated patients were >=65 years of age, and 110 (0.8%) were >=75 years of age. No overall differences in efficacy or safety were observed between geriatric and younger patients. Data from a pharmacokinetic study indicate that mean AUC of pravastatin is 25-50% higher in geriatric individuals compared with younger adults. However, because mean peak plasma concentration, time to peak plasma concentration, and half-life are similar between geriatric and younger individuals, substantial accumulation of pravastatin would not be expected in geriatric patients.
Because patients >75 years of age may have a higher risk of adverse effects and lower adherence to therapy, the expected benefits versus adverse effects should be considered before initiating statin therapy in this population.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.