What is the appropriate starting dose, dosing schedule, contraindications, precautions, and monitoring for pravastatin in an adult with hyperlipidemia?

Pravastatin for Hyperlipidemia in Adults

Starting Dose and Dosing Schedule

The recommended starting dose of pravastatin is 40 mg to 80 mg once daily, taken at any time of day with or without food. 1

• For most adults with hyperlipidemia, initiate pravastatin 40 mg once daily as this represents the moderate-intensity statin dose used in major cardiovascular outcomes trials 2, 3
• The 80 mg dose may be considered for patients requiring more aggressive LDL-C reduction, though pravastatin is classified as a moderate-intensity statin at all doses 2, 4
• Pravastatin can be administered at any time of day (unlike some other statins) because it does not rely on circadian cholesterol synthesis patterns 1
• Assess lipid response at 4-6 weeks after initiation, as maximal lipid-lowering effects are achieved by this timeframe 5, 1

Expected LDL-C Reductions by Dose:

• Pravastatin 40 mg reduces LDL-C by approximately 30-35% 5, 3
• Pravastatin 20 mg reduces LDL-C by approximately 23% 6
• Pravastatin 10 mg reduces LDL-C by approximately 18% 6
• The 80 mg dose provides only modest additional benefit beyond 40 mg 1

Contraindications

Pravastatin is contraindicated in patients with active liver disease, unexplained persistent elevations of serum transaminases, pregnancy, and breastfeeding. 1

• Active hepatic disease or unexplained persistent transaminase elevations are absolute contraindications 1
• Pregnancy (Category X) - statins can cause fetal harm 1
• Breastfeeding - pravastatin is excreted in breast milk 1
• Known hypersensitivity to pravastatin or any component of the formulation 1

Precautions and Drug Interactions

Dose Adjustments Required:

When used with cyclosporine, start pravastatin at 10 mg once daily with a maximum dose of 20 mg daily 1

• With clarithromycin or erythromycin, limit pravastatin to a maximum of 40 mg daily 1
• Administer pravastatin at least 1 hour before or 4 hours after bile acid sequestrants (cholestyramine, colestipol) to avoid binding interactions 1
• With tacrolimus, everolimus, or sirolimus, limit pravastatin dose to 40 mg daily 3

Important Drug Interactions:

• Pravastatin can be safely combined with amiodarone and ranolazine without dose adjustment 3
• When used with warfarin, monitor INR more closely after pravastatin initiation or dose changes 3
• Pravastatin has fewer drug interactions than other statins because it is not metabolized by CYP3A4 7

Renal Impairment:

In patients with severe renal impairment, start pravastatin at 10 mg once daily with a maximum dose of 40 mg daily 1

• No dose adjustment needed for mild to moderate renal impairment 1

Monitoring Requirements

Obtain baseline liver enzymes (ALT) before initiating pravastatin, and monitor during early treatment 5

• Check lipid panel at 4-6 weeks to assess therapeutic response 5, 1
• Liver enzyme monitoring is recommended as pravastatin causes transaminase elevations in approximately 1.1% of patients 5
• Monitor for myopathy symptoms (unexplained muscle pain, tenderness, or weakness), though severe myopathy is rare with pravastatin 5, 3
• No routine creatine kinase monitoring is required unless patient develops muscle symptoms 7
• Repeat lipid panels as clinically appropriate to guide ongoing therapy 1

Clinical Context and Limitations

Pravastatin 40 mg is a moderate-intensity statin that may be insufficient for high-risk patients requiring ≥50% LDL-C reduction 2, 4

• For patients requiring high-intensity statin therapy (≥50% LDL-C reduction), consider atorvastatin 40-80 mg or rosuvastatin 20-40 mg instead 2, 4
• If pravastatin 80 mg fails to achieve LDL-C goals, switch to an alternative high-intensity statin rather than adding combination therapy 1
• Pravastatin has proven cardiovascular outcomes data: it reduces major coronary events by approximately 27% in secondary prevention and 19% in elderly patients 5, 3
• Pravastatin is particularly well-suited for elderly patients (age ≥70 years) and those with multiple drug interactions due to its favorable safety profile and lack of CYP3A4 metabolism 3, 7