What is the recommended dosing for valsartan (angiotensin II receptor antagonist) in a patient with hypertension or heart failure, considering factors such as age, kidney function, and potential drug interactions?

Valsartan Dosing

For hypertension, start valsartan at 80-160 mg once daily and titrate up to 320 mg once daily as needed; for heart failure, start at 40 mg twice daily and uptitrate to the target dose of 160 mg twice daily (320 mg total daily dose). 1

Hypertension Dosing

Starting and Maintenance Doses:

• Initial dose: 80 mg or 160 mg once daily for patients who are not volume-depleted 1
• Patients requiring greater blood pressure reductions may start at 160 mg 1
• Dose range: 80-320 mg once daily, with maximal antihypertensive effect typically achieved within 4 weeks 1
• If additional blood pressure reduction is needed beyond 80 mg, adding a diuretic provides greater benefit than dose escalation alone 1

Pediatric Hypertension (Ages 1-16 years):

• Starting dose: 1 mg/kg once daily (maximum 40 mg total), with a higher starting dose of 2 mg/kg considered when greater blood pressure reduction is needed 1
• Titrate up to maximum 4 mg/kg once daily (maximum 160 mg daily) based on blood pressure response and tolerability 1
• Not recommended in children under 1 year of age 1

Heart Failure Dosing

Target Dosing Strategy:

• Starting dose: 40 mg twice daily 1
• Uptitrate to 80 mg twice daily, then to target dose of 160 mg twice daily (320 mg total daily dose), or to the highest dose tolerated 1
• The American College of Cardiology emphasizes that at least 50% of target dose (160 mg daily total) is the minimum effective dose for adequate treatment effect 2
• Adjust doses no more frequently than every 2 weeks to allow adequate assessment of tolerability 2, 3

Critical Dosing Principle:

• Higher doses provide greater benefits than lower doses in heart failure, with sustained AT1-receptor blockade over 24 hours achieved with 160 mg doses 2
• Many physicians underdose valsartan in heart failure—less than 25% of patients are titrated to target doses in clinical practice, which compromises outcomes 2
• The Val-HeFT trial demonstrated a 13.2% reduction in cardiovascular mortality and morbidity with valsartan up to 320 mg/day compared to placebo 2, 4

Temporary Dose Reductions:

• May be necessary for hypotension or renal dysfunction, but efforts should be made to return to target doses when possible 2, 3
• Consider reducing concomitant diuretic doses rather than valsartan when feasible 1

Post-Myocardial Infarction Dosing

Initiation and Titration:

• May be initiated as early as 12 hours after MI 1
• Starting dose: 20 mg twice daily 1
• Uptitrate within 7 days to 40 mg twice daily, then to target maintenance dose of 160 mg twice daily as tolerated 1
• The VALIANT trial demonstrated that valsartan 160 mg twice daily was noninferior to captopril for mortality outcomes in post-MI patients 5, 2, 3

Special Populations and Monitoring

Renal Impairment:

• Monitor renal function and electrolytes 1-2 weeks after initiation and after each dose increase 2
• Exercise caution when creatinine >221 μmol/L (>2.5 mg/dL) or eGFR <30 mL/min/1.73 m² 2
• No data available for pediatric patients on dialysis or with GFR <30 mL/min/1.73 m² 1

Hypotension Management:

• Use caution when systolic blood pressure <90 mmHg 2
• For symptomatic hypotension, reconsider need for nitrates, calcium-channel blockers, and other vasodilators; reduce or stop if possible 2
• If symptomatic hypotension occurs, consider dosage reduction rather than discontinuation 1

Hyperkalemia Monitoring:

• Monitor potassium within 1-2 weeks after initiation or dose increases, then every 3-6 months 2
• Significant hyperkalemia (K+ >5.0 mmol/L) requires caution and specialist advice 2
• Avoid combining valsartan with ACE inhibitors, as this increases risk of hyperkalemia and renal dysfunction 2
• Avoid potassium supplements, potassium-sparing diuretics, and NSAIDs unless essential 2

Formulation Considerations

Tablets vs. Suspension:

• Tablets and oral suspension are NOT interchangeable on a milligram-per-milligram basis—the suspension provides 60% higher systemic exposure (AUC) than tablets 1
• Use suspension for: pediatric patients aged 1-5 years, patients >5 years who cannot swallow tablets, or when calculated dose doesn't correspond to available tablet strengths 1
• When switching between formulations, dose adjustment may be necessary 1

Common Pitfalls to Avoid

• Underdosing in heart failure: Many clinicians use doses that are too low; always aim for target dose of 160 mg twice daily unless contraindicated 2
• Premature discontinuation: Temporary dose reductions are acceptable, but make efforts to return to target doses 2, 3
• Combining with ACE inhibitors: This combination increases adverse effects without additional mortality benefit and should be avoided 2
• Inadequate monitoring: Failure to check renal function and potassium 1-2 weeks after initiation or dose changes can lead to missed complications 2