Introduction
Pravastatin is a hydrophilic, competitive HMG-CoA reductase inhibitor belonging to the statin class of lipid-lowering medications. First approved by the FDA in 1991, pravastatin is widely prescribed for the management of dyslipidemia and cardiovascular risk reduction. Unlike some other statins, pravastatin is not extensively metabolized by the cytochrome P450 system, which contributes to its favorable drug interaction profile.
Mechanism of Action
Pravastatin competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis in the liver. This inhibition reduces hepatic cholesterol production, leading to upregulation of LDL receptors on hepatocytes and increased clearance of low-density lipoprotein cholesterol (LDL-C) from the bloodstream. Additionally, pravastatin modestly increases high-density lipoprotein cholesterol (HDL-C) and reduces triglyceride levels.
Indications
- Primary hypercholesterolemia (including heterozygous familial hypercholesterolemia) and mixed dyslipidemia
- Primary prevention of cardiovascular disease in patients without clinically evident coronary heart disease but with multiple risk factors
- Secondary prevention of cardiovascular events in patients with established coronary heart disease
- Pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia
Dosage and Administration
Adults: Initial dose 10-40 mg once daily at bedtime; maximum dose 80 mg daily Geriatric patients: Consider starting at lower end of dosing range Renal impairment: Initial dose 10 mg daily for severe impairment (CrCl <30 mL/min) Hepatic impairment: Use with caution in active liver disease Administration: May be taken without regard to mealsPharmacokinetics
Absorption: Rapid but incomplete (34% oral bioavailability); peak plasma concentrations within 1-1.5 hours Distribution: Volume of distribution ~0.5 L/kg; 50% protein bound Metabolism: Minimal hepatic metabolism via cytochrome P450 system; undergoes extensive first-pass extraction Elimination: Half-life 1.3-2.8 hours; primarily excreted in feces (70%) via biliary elimination; 20% renal excretionContraindications
- Active liver disease or unexplained persistent elevations of serum transaminases
- Pregnancy and breastfeeding
- Hypersensitivity to pravastatin or any component of the formulation
- Concomitant use with cyclosporine
Warnings and Precautions
Hepatotoxicity: Monitor liver enzymes before initiation and periodically thereafter Myopathy/Rhabdomyolysis: Risk increases with higher doses, advanced age, renal impairment, and concomitant interacting medications Renal effects: May cause proteinuria; monitor renal function in patients at risk Diabetes: Statins may increase HbA1c and fasting serum glucose levels Cognitive effects: Rare reports of cognitive impairmentDrug Interactions
Strong inhibitors of OATP1B1: Avoid concomitant use with cyclosporine (contraindicated) Gemfibrozil: Increases pravastatin exposure; avoid combination Other fibrates: Increased risk of myopathy; use with caution Niacin: May increase risk of myopathy Colchicine: Increased risk of myopathy, particularly in elderly patients Warfarin: May potentiate anticoagulant effect; monitor INR closelyAdverse Effects
Common (≥2%): Headache, musculoskeletal pain, nausea/vomiting, diarrhea, rash, fatigue Serious:- Rhabdomyolysis with renal failure
- Hepatotoxicity
- Myopathy
- Immune-mediated necrotizing myopathy
- Increased HbA1c and fasting glucose
- Cognitive impairment (memory loss, confusion)
Monitoring Parameters
- Lipid panel at baseline, 4-12 weeks after initiation or dose change, and periodically thereafter
- Liver enzymes (ALT, AST) at baseline, 12 weeks after initiation, then periodically
- CPK levels if symptoms of myopathy occur
- Renal function in patients with risk factors
- HbA1c in patients with diabetes or prediabetes
- Signs and symptoms of muscle pain, tenderness, or weakness
Patient Education
- Take medication as prescribed, typically at bedtime
- Report unexplained muscle pain, tenderness, weakness, or brown urine immediately
- Avoid excessive alcohol consumption
- Maintain heart-healthy diet and regular exercise
- Inform all healthcare providers about pravastatin use
- Notify physician if planning pregnancy or becoming pregnant
- Be aware of potential interactions with other medications, including over-the-counter products
References
1. Pravastatin Sodium Prescribing Information. FDA Label. 2. Grundy SM, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. J Am Coll Cardiol. 2019;73(24):e285-e350. 3. Mach F, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188. 4. Newman CB, et al. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2019;39(2):e38-e81. 5. Thompson PD, et al. An assessment of statin safety by muscle experts. Am J Cardiol. 2006;97(8A):69C-76C. 6. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2023. Pravastatin.