What is the recommended dosage and treatment protocol for Valsartan (Angiotensin II receptor antagonist) in patients with hypertension and heart failure?

Valsartan Dosing for Hypertension and Heart Failure

Hypertension Dosing

For hypertension, start valsartan at 80-160 mg once daily and titrate up to a maximum of 320 mg once daily as needed, with the antihypertensive effect substantially present within 2 weeks and maximal reduction generally attained after 4 weeks. 1

• The FDA-approved starting dose is 80 mg or 160 mg once daily when used as monotherapy in patients who are not volume-depleted 1
• Patients requiring greater blood pressure reductions may be started at the higher 160 mg dose 1
• If additional antihypertensive effect is required beyond the starting dose, increase to a maximum of 320 mg daily or add a diuretic 1
• Addition of a diuretic has a greater effect than dose increases beyond 80 mg 1
• The antihypertensive efficacy of the 80 mg dose is enhanced by doubling it to 160 mg, with tolerability remaining comparable to placebo 2

Heart Failure Dosing

For heart failure, start valsartan at 40 mg twice daily and uptitrate to 80 mg twice daily, then to the target dose of 160 mg twice daily (320 mg total daily dose), or to the highest dose tolerated by the patient. 1, 3

Titration Protocol

• Begin at 40 mg twice daily 1
• Uptitrate to 80 mg twice daily, then to 160 mg twice daily 1
• Adjust doses no more frequently than every 2 weeks 3, 4
• The maximum daily dose studied in clinical trials is 320 mg in divided doses 1
• Consider reducing the dose of concomitant diuretics when initiating valsartan 1

Target Dose Importance

At least 50% of the target dose (160 mg daily total) is recommended as the minimum effective dose to achieve adequate treatment effect. 3, 4

• Higher doses provide greater benefits than lower doses in clinical trials 3
• The 160 mg twice daily dose reduced the combined endpoint of mortality and morbidity by 13.2% compared with placebo in the Val-HeFT trial 3, 5
• There is little evidence that subtarget doses yield survival benefits comparable to target doses 3
• Many physicians use doses that are too low, which may not provide optimal benefits 4

Post-Myocardial Infarction Dosing

For post-MI patients, start valsartan at 20 mg twice daily as early as 12 hours after myocardial infarction, uptitrate within 7 days to 40 mg twice daily, then to a target maintenance dose of 160 mg twice daily as tolerated. 1

• If symptomatic hypotension or renal dysfunction occurs, consider dosage reduction 1
• Valsartan may be given with other standard post-MI treatments including thrombolytics, aspirin, beta-blockers, and statins 1
• The VALIANT trial found valsartan to be noninferior to captopril in post-MI patients 3

Special Populations

Pediatric Hypertension (Ages 1-16 Years)

• Start at 1 mg/kg once daily (up to 40 mg total) 1
• A higher starting dose of 2 mg/kg may be considered when greater blood pressure reduction is needed 1
• Titrate up to a maximum of 4 mg/kg once daily (maximum daily dose 160 mg) 1
• Use of valsartan is not recommended in children less than 1 year of age 1

Renal Impairment

• For severe renal impairment (eGFR <30 mL/min/1.73 m²), start sacubitril/valsartan at 24/26 mg twice daily 6
• No data are available in pediatric patients undergoing dialysis or with GFR <30 mL/min/1.73 m² 1

Elderly Patients (≥75 Years)

• Start sacubitril/valsartan at 24/26 mg twice daily in elderly patients 6

Hepatic Impairment

• For moderate hepatic impairment (Child-Pugh Class B), start sacubitril/valsartan at 24/26 mg twice daily 6

Monitoring During Titration

Monitor blood pressure, renal function, and electrolytes during dose titration, with consideration of dosage reduction if symptomatic hypotension or renal dysfunction occurs. 3

• Watch for hypotension, renal impairment, and hyperkalemia, especially when initiating therapy or increasing doses 4
• Temporary dose reductions may be necessary, but efforts should be made to restore target doses when possible to ensure optimal outcomes 3, 4
• Patients with initial contraindications should be reevaluated to determine subsequent eligibility for therapy 3

Important Formulation Considerations

• Valsartan tablets and oral suspension are not substitutable on a milligram-per-milligram basis 1
• The systemic exposure (AUC) is 60% higher with the suspension compared to tablets 1
• Do not combine two dosage forms to achieve the total dose 1
• When switching between suspension and tablets, the dose may need to be adjusted 1

Alternative to ACE Inhibitors

For patients intolerant of ACE inhibitors, valsartan is a recommended alternative according to American Heart Association guidelines. 3

• Valsartan has a more favorable tolerability profile than ACE inhibitors, with significantly lower incidence of cough and only rare reports of angioedema 7
• Among patients not receiving an ACE inhibitor, valsartan reduced the risk of mortality and the combined endpoint by 33.1% and 44% compared with placebo 5