What is the maximum recommended dose of Valsartan (Angiotensin II Receptor Antagonist) and Hydrochlorothiazide (HCTZ) (Thiazide Diuretic)?

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Maximum Dose of Valsartan/HCTZ

The maximum recommended dose of valsartan/hydrochlorothiazide is 320 mg valsartan combined with 25 mg hydrochlorothiazide, administered once daily. 1, 2

Dosing Framework

Standard Maximum Dosing

  • Valsartan component: Maximum 320 mg daily 3, 1
  • HCTZ component: Maximum 25 mg daily when combined with valsartan 1, 2
  • Administration: Once daily dosing is standard for hypertension 3

Available Combination Strengths

The evidence supports the following valsartan/HCTZ combinations, with the highest being the maximum dose 1:

  • 80/12.5 mg
  • 160/12.5 mg
  • 160/25 mg
  • 320/12.5 mg
  • 320/25 mg (maximum dose)

Clinical Context for Maximum Dosing

Efficacy at Maximum Dose

  • The 320/25 mg combination achieves blood pressure control in 84.8% of patients by week 8, compared to 54.2% with valsartan 320 mg alone 1
  • In stage 2 hypertension specifically, 75.8% of patients reach BP goal <140/90 mmHg by week 8 with the maximum dose 1
  • Median time to blood pressure goal is 2.1 weeks with valsartan 320 mg/HCTZ compared to 6.1 weeks with valsartan 320 mg monotherapy 1

Tolerability Profile

  • Discontinuation rates due to adverse events remain low even at maximum doses 1
  • The combination is generally as well-tolerated as placebo across the dose range 4
  • HCTZ-induced hypokalemia is actually less common during combination therapy than with HCTZ alone 4

Important Caveats

Heart Failure Dosing Differs

  • For heart failure with reduced ejection fraction, valsartan is dosed 160 mg twice daily (total 320 mg/day) without HCTZ 5
  • The twice-daily regimen for heart failure is distinct from once-daily hypertension dosing 3
  • HCTZ is not part of guideline-directed medical therapy for heart failure 5

Titration Approach

  • Start with lower combination doses (e.g., 160/12.5 mg) and titrate upward every 2-4 weeks based on blood pressure response 1, 2
  • Initial combination therapy achieves faster blood pressure control than starting with monotherapy and adding the second agent later 2

Monitoring Requirements

  • Check serum potassium and creatinine within 1-2 weeks after initiating or increasing doses, particularly in patients with baseline renal impairment 6
  • Avoid combining with ACE inhibitors due to increased risk of hyperkalemia and renal dysfunction 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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