What are the recommendations for pravastatin (HMG-CoA reductase inhibitor) therapy?

Recommendations for Pravastatin Therapy

Pravastatin is recommended for cardiovascular risk reduction with a standard dose of 40 mg daily for most patients, with dose adjustments based on specific patient factors including renal function, drug interactions, and age. 1

Indications for Pravastatin

• Pravastatin is indicated to reduce the risk of myocardial infarction, myocardial revascularization procedures, and cardiovascular mortality in adults with elevated LDL-C without clinically evident coronary heart disease (primary prevention) 1
• Pravastatin reduces the risk of coronary death, myocardial infarction, revascularization procedures, stroke, and slows coronary atherosclerosis progression in adults with clinically evident CHD (secondary prevention) 1
• Pravastatin is indicated as an adjunct to diet for LDL-C reduction in adults with primary hyperlipidemia 1
• Pravastatin can be used for treatment of primary dysbetalipoproteinemia and hypertriglyceridemia 1

Dosing Recommendations

• For adults, the recommended starting dose is 40 mg once daily 1
• Pravastatin can be taken at any time of day, with or without food 1
• In patients with severe renal impairment, start with 10 mg daily with a maximum dose of 40 mg daily 1
• For pediatric patients aged 8-13 years with heterozygous familial hypercholesterolemia, the recommended dose is 20 mg once daily 1
• For pediatric patients aged 14-18 years, the recommended starting dose is 40 mg once daily 1

Efficacy

• Pravastatin 40 mg daily reduces LDL cholesterol by approximately 34% 2, 3
• In older adults (70-82 years), pravastatin 40 mg reduced major coronary events by 19% and CHD mortality by 24% 4, 2
• Pravastatin is classified as a moderate-intensity statin, with less potent LDL-lowering effects compared to high-intensity statins like atorvastatin and rosuvastatin 2, 5
• In the PROVE-IT trial, pravastatin 40 mg achieved a median LDL-C of 95 mg/dL, compared to 62 mg/dL with high-dose atorvastatin (80 mg) 2, 6

Safety Considerations

• Pravastatin has a favorable safety profile with no cases of severe myopathy (rhabdomyolysis) observed in major clinical trials 2, 7
• Pravastatin is well tolerated in elderly patients, with minimal therapy-related adverse effects 7
• Common adverse events include gastrointestinal events, headaches, and musculoskeletal pain 1, 7
• Advanced age (≥65 years) is a risk factor for pravastatin-associated myopathy and rhabdomyolysis, requiring cautious dose selection 1

Drug Interactions

• When used in combination with amiodarone, no dose adjustment of pravastatin is required 4
• For patients taking ranolazine, pravastatin can be used without dose adjustment 4
• Pravastatin can be safely used with warfarin, but INR should be monitored more closely after initiation or dose changes 4
• When used with cyclosporine, tacrolimus, everolimus, or sirolimus, limit pravastatin dose to 40 mg daily 4

Special Populations

Elderly Patients

• Pravastatin is effective and well-tolerated in older adults 4, 7
• In the PROSPER trial, pravastatin 40 mg reduced the composite endpoint of coronary death, nonfatal MI, and fatal/nonfatal stroke by 15% in adults aged 70-82 years 4
• Mean pravastatin AUCs are 25% to 50% higher in elderly subjects, but dose adjustment is generally not required 1

Renal Impairment

• For severe renal impairment, start with 10 mg daily and do not exceed 40 mg daily 1
• Monitor all patients with renal impairment for development of myopathy 1
• No dose adjustment needed for mild to moderate renal impairment 1

Pediatric Patients

• Pravastatin is approved for heterozygous familial hypercholesterolemia in children 8 years and older 1
• Doses greater than 40 mg daily have not been studied in pediatric populations 1

Monitoring Recommendations

• Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating pravastatin, and adjust dosage if necessary 1
• Monitor liver enzymes before initiating therapy and as clinically indicated thereafter 1
• Discontinue pravastatin if markedly elevated CK levels occur or if myopathy is diagnosed or suspected 1

Common Pitfalls to Avoid

• For patients requiring high-intensity statin therapy or unable to achieve their LDL-C goal on pravastatin 80 mg daily, consider alternative LDL-C-lowering treatment 1
• Pravastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis 1
• Temporarily discontinue pravastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis 1
• Be aware that pravastatin has a relatively short half-life but once-daily administration is still effective for cholesterol reduction 3, 8