What is the recommended dosing for Valsartan (valsartan) in a patient with hypertension, considering factors such as age, kidney function, and comorbidities?

Valsartan Dosing for Hypertension

For hypertension, start valsartan at 80-160 mg once daily, titrate to a maximum of 320 mg once daily if needed, and strongly consider initial combination therapy with a dihydropyridine calcium channel blocker or thiazide diuretic for most patients with confirmed hypertension (BP ≥140/90 mmHg). 1, 2

Initial Dosing Strategy

• Start with 80 mg once daily for monotherapy in volume-replete patients, or 160 mg once daily if greater blood pressure reduction is required 1
• The antihypertensive effect becomes substantially present within 2 weeks, with maximal reduction generally attained after 4 weeks 1
• For most patients with confirmed hypertension (BP ≥140/90 mmHg), combination therapy is recommended as initial treatment rather than monotherapy, using valsartan with either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic 2, 3

Dose Titration and Targets

• If additional blood pressure lowering is needed beyond the starting dose, increase to a maximum of 320 mg once daily 1
• Adding a diuretic produces greater blood pressure reduction than dose increases beyond 80 mg 1
• Target treated systolic blood pressure to 120-129 mmHg in most adults to reduce cardiovascular risk, provided treatment is well tolerated 2, 3
• For patients who cannot tolerate achieving 120-129 mmHg, target systolic blood pressure "as low as reasonably achievable" 2

Combination Therapy Approach

• Fixed-dose single-pill combinations are strongly recommended to improve adherence 2, 3
• Common effective combinations include valsartan/hydrochlorothiazide 80/12.5 mg or 160/12.5 mg once daily 4
• If blood pressure remains uncontrolled on two-drug combination, escalate to three-drug therapy with valsartan, a dihydropyridine calcium channel blocker, and a thiazide/thiazide-like diuretic, preferably as a single-pill combination 2, 3
• Never combine valsartan with an ACE inhibitor, as this increases risk of hyperkalemia and renal dysfunction 2, 3, 5

Special Population Considerations

Pediatric Patients (1-16 years)

• Ages 1-5 years: Start at 1 mg/kg once daily (maximum 40 mg), may increase to 2 mg/kg in selected cases, titrate to maximum 4 mg/kg once daily (maximum 160 mg daily) 1
• Ages 6-16 years: Use weight-based dosing with 1 mg/kg once daily as starting dose (maximum 40 mg), titrate to maximum 4 mg/kg once daily (maximum 160 mg daily) 1
• Use of oral suspension is recommended for children 1-5 years and those who cannot swallow tablets 1

Elderly and Frail Patients

• Consider monotherapy in patients aged >80 years or those who are frail 2
• Individualize blood pressure targets based on frailty status 2
• Starting dose of 40 mg twice daily may be appropriate in elderly patients with heart failure 6

Patients with Renal Impairment

• Monitor serum potassium and creatinine within 1-2 weeks after initiating or increasing doses, particularly in patients with baseline renal impairment 3, 5
• Exercise caution when creatinine >221 μmol/L (>2.5 mg/dL) or eGFR <30 mL/min/1.73 m² 5
• No data available for pediatric patients with glomerular filtration rate <30 mL/min/1.73 m² 1

Administration and Monitoring

• Take valsartan once daily at the most convenient time to establish a habitual pattern and improve adherence 2, 3
• Follow-up monthly after initiation or dose changes until blood pressure target is reached, then every 3-6 months for patients under control 3
• Monitor blood pressure, renal function, and electrolytes during dose titration 6, 5

Critical Safety Considerations

Hyperkalemia Risk

• Avoid potassium supplements, potassium-sparing diuretics, and "low-salt" substitutes with high potassium content 5
• Monitor potassium within 1-2 weeks after initiation or dose increases, then every 3-6 months 5
• Significant hyperkalemia (K+ >5.0 mmol/L) requires caution and specialist advice 5

Hypotension Management

• Exercise caution when systolic blood pressure <90 mmHg 5
• For symptomatic hypotension, reconsider need for nitrates, calcium channel blockers, and other vasodilators; reduce or stop if possible 5
• If symptomatic hypotension occurs, consider dosage reduction 1

Drug Interactions

• Avoid NSAIDs unless essential, as they may attenuate diuretic effects and cause renal impairment 5
• The triple combination of ACE inhibitor + ARB + mineralocorticoid receptor antagonist increases risk of hyperkalemia and renal dysfunction 5

Dose Optimization Evidence

• Valsartan demonstrates dose-dependent efficacy over the range of 80-320 mg, with blood pressure reductions from placebo of approximately 6-9/3-5 mmHg at 80-160 mg and 9/6 mmHg at 320 mg 1
• The 160 mg dose provides sustained AT1-receptor blockade over 24 hours 5
• Higher doses provide greater benefits than lower doses in clinical outcomes 6, 5
• Combination with hydrochlorothiazide 12.5 mg or 25 mg produces additional blood pressure lowering of approximately 6/3 mmHg and 12/5 mmHg respectively compared to valsartan 80 mg alone 1