What is the maximum recommended dose of valsartan (angiotensin II receptor antagonist) for an adult patient with hypertension or heart failure and no significant renal impairment?

Maximum Dose of Valsartan

The maximum recommended dose of valsartan is 320 mg daily for hypertension (given once daily) and 320 mg daily for heart failure (given as 160 mg twice daily). 1

FDA-Approved Maximum Dosing by Indication

Hypertension

• The maximum dose is 320 mg once daily, with a typical dose range of 80-320 mg daily 1
• The starting dose is 80-160 mg once daily, with antihypertensive effects substantially present within 2 weeks and maximal reduction generally attained after 4 weeks 1
• If additional blood pressure reduction is needed beyond 80 mg, adding a diuretic has greater effect than dose increases alone 1

Heart Failure

• The maximum dose is 320 mg daily (160 mg twice daily), which was the highest dose administered in clinical trials 1
• The starting dose is 40 mg twice daily, with uptitration to 80 mg and then 160 mg twice daily as tolerated 1
• The Val-HeFT trial demonstrated a 13.2% reduction in cardiovascular mortality and morbidity with valsartan at doses up to 320 mg/day 2

Post-Myocardial Infarction

• The target maintenance dose is 320 mg daily (160 mg twice daily) 1
• Start at 20 mg twice daily (as early as 12 hours post-MI), uptitrate within 7 days to 40 mg twice daily, then to the target 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 3

Critical Dosing Principles for Optimal Outcomes

Higher doses provide greater clinical benefits than lower doses, and target doses must be achieved for maximal benefit. 2

• For heart failure with reduced ejection fraction, the American College of Cardiology recommends titrating to 160 mg twice daily (320 mg total daily dose) as the target, with at least 50% of target dose (160 mg daily) as the minimum effective dose 2
• Sustained AT1-receptor blockade over 24 hours is achieved with the 160 mg dose 2
• Many physicians use doses that are too low, which may not provide optimal benefits—less than 25% of patients are ever titrated to target doses in clinical practice 2

Doses Beyond 320 mg Daily

• Doses as high as 640 mg/day have been studied in hypertension and found to be efficacious and safe, though this exceeds FDA-approved maximum dosing 4
• The antihypertensive effect of valsartan increases in a predictable fashion over a wide dose range (20-320 mg), with tolerability remaining comparable to placebo 5

Safety Monitoring During Dose Titration

• Monitor blood pressure, renal function (creatinine/eGFR), and potassium within 1-2 weeks after initiation or dose increases 2
• Therapy should be adjusted no more frequently than every 2 weeks to target doses or maximally tolerated doses 2
• Exercise caution when systolic blood pressure <90 mmHg or creatinine >221 μmol/L (>2.5 mg/dL) or eGFR <30 mL/min/1.73 m² 2

Critical Contraindications and Drug Interactions

• Never combine valsartan with ACE inhibitors, as this combination increases the risk of hyperkalemia and renal dysfunction without additional mortality benefit 2
• The VALIANT trial showed that combining valsartan with captopril had no increased benefit over captopril alone and had higher discontinuation rates due to adverse effects 3
• Avoid NSAIDs unless essential, as they may attenuate diuretic effects and cause renal impairment 2
• Avoid potassium supplements, potassium-sparing diuretics, and "low-salt" substitutes with high potassium content 2

Management of Symptomatic Hypotension

• If symptomatic hypotension occurs during uptitration, reconsider the need for nitrates, calcium-channel blockers, and other vasodilators—reduce or stop if possible 2
• Consider reducing the dose of concomitant diuretics 1
• Temporary dose reductions may be necessary, but efforts should be made to return to target doses when possible 2