What is the next dose up from pravastatin (pravastatin) 20 mg for an adult patient with hypercholesterolemia (high cholesterol) who is not responding adequately to the current dose?

Pravastatin Dose Escalation from 20 mg

The next dose up from pravastatin 20 mg is pravastatin 40 mg, which provides an additional 3-9% reduction in LDL-C beyond the 20 mg dose, though pravastatin remains a moderate-intensity statin at all doses and cannot achieve the ≥50% LDL-C reductions needed for high-risk patients. 1

FDA-Approved Dosing Ladder

The FDA label establishes the following pravastatin dosing sequence 1:

• Starting dose: 40-80 mg once daily for adults
• Pediatric dose (ages 8-13): 20 mg once daily
• Pediatric dose (ages 14-18): 40 mg once daily
• Maximum dose: 80 mg once daily

For patients currently on 20 mg who need dose escalation, the next step is pravastatin 40 mg once daily 1.

Expected LDL-C Reduction by Dose

The dose-response relationship for pravastatin shows diminishing returns 1, 2, 3:

• 10 mg twice daily (20 mg/day): 28-31% LDL-C reduction 3
• 20 mg twice daily (40 mg/day): 31-34% LDL-C reduction 4, 2, 3
• 40 mg twice daily (80 mg/day): 37-38% LDL-C reduction 1, 4

Critical point: Doubling the dose from 20 mg to 40 mg provides only an additional 3-6% LDL-C reduction, and escalating to 80 mg adds merely another 3-7% beyond 40 mg 1, 4, 2.

When Pravastatin Dose Escalation Is Insufficient

The FDA label explicitly states: "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." 1

This is critical because pravastatin at any dose remains a moderate-intensity statin and cannot achieve the ≥50% LDL-C reductions that define high-intensity therapy 5, 6. The American College of Cardiology defines high-intensity statins as atorvastatin 40-80 mg or rosuvastatin 20-40 mg, which achieve ≥50% LDL-C reduction 6.

Clinical Decision Algorithm

Step 1: Assess Patient Risk Category

• High-risk patients (established ASCVD, diabetes with risk factors, LDL-C ≥190 mg/dL) require high-intensity statin therapy achieving ≥50% LDL-C reduction 6
• Moderate-risk patients may be appropriate for moderate-intensity therapy (30-49% LDL-C reduction) 7

Step 2: Choose Appropriate Action

For high-risk patients on pravastatin 20 mg:

• Do not escalate to pravastatin 40 mg or 80 mg — switch to atorvastatin 40-80 mg or rosuvastatin 20-40 mg instead 6, 1
• Even pravastatin 80 mg achieves only ~37% LDL-C reduction, insufficient for high-risk patients 1, 4

For moderate-risk patients on pravastatin 20 mg:

• Escalate to pravastatin 40 mg once daily 1
• Reassess LDL-C at 4-6 weeks, as maximal lipid-lowering effects are achieved by this time 8, 1
• If still inadequate, consider pravastatin 80 mg (maximum dose) or switching to a more potent statin 1

Evidence from Major Trials

The landmark cardiovascular outcomes trials used pravastatin 40 mg as the standard dose 5, 1:

• CARE trial: Pravastatin 40 mg reduced CHD death or nonfatal MI by 24% (p=0.003) in post-MI patients 1
• LIPID trial: Pravastatin 40 mg reduced CHD mortality by 24% (p=0.0004) in patients with prior MI or unstable angina 1
• PROVE-IT trial: Allowed dose reduction from pravastatin 80 mg to 40 mg for adverse events, indicating 40 mg is a clinically meaningful dose 5

Notably, these trials allowed uptitration from pravastatin 40 mg to 80 mg if LDL-C exceeded 125 mg/dL, but the primary efficacy was demonstrated at the 40 mg dose 5.

Common Pitfalls to Avoid

Pitfall #1: Continuing to escalate pravastatin doses in high-risk patients who need ≥50% LDL-C reduction 6, 1

• Solution: Switch to atorvastatin 40-80 mg or rosuvastatin 20-40 mg for high-intensity therapy 6

Pitfall #2: Assuming linear dose-response with pravastatin 4, 2

• Reality: Each doubling of pravastatin dose adds only ~6% additional LDL-C reduction 1, 4, 2

Pitfall #3: Not reassessing lipid levels after dose changes 1

• Solution: Check LDL-C at 4 weeks after any dose adjustment 8, 1

Safety Considerations with Dose Escalation

Pravastatin has a favorable safety profile across all doses 1, 4:

• Myopathy risk <0.1% at recommended doses 1
• Adverse events leading to discontinuation: 2.4% across all doses 9
• Liver enzyme elevations: approximately 1.1% of patients 8

Dose adjustments required for drug interactions 1:

• With cyclosporine: maximum 20 mg daily
• With clarithromycin or erythromycin: maximum 40 mg daily