Maximum Dose of Candesartan
The maximum recommended dose of candesartan is 32 mg once daily for both hypertension and heart failure treatment. 1, 2
Dosing Guidelines by Indication
Heart Failure with Reduced Ejection Fraction (HFrEF)
- Starting dose: 4-8 mg once daily 1
- Target/maximum dose: 32 mg once daily 1
- Mean dose achieved in clinical trials: 24 mg/day 1
- Titration schedule: Up-titrate every 2-4 weeks as tolerated, monitoring renal function and potassium levels at 1 and 4 weeks after each dose increase 1
Hypertension
- Starting dose: 16 mg once daily for monotherapy in non-volume depleted patients 2
- Dose range: 8-32 mg once daily (can be given once or twice daily) 2
- Maximum dose: 32 mg once daily 2
- Key point: Doses larger than 32 mg do not appear to provide greater blood pressure lowering effect 2
Evidence-Based Dosing Considerations
Dose-Response Relationship
- Higher doses provide greater benefit: The CHARM trials demonstrated that candesartan 32 mg once daily is the evidence-based target dose for heart failure 1
- Superiority over losartan: Candesartan 16 mg once daily provides greater antihypertensive effect than losartan 50 mg once daily 3
- Dose escalation improves outcomes: In isolated systolic hypertension, escalating from 16 mg to 32 mg provided additional blood pressure reduction of 8.9/3.8 mmHg in patients not controlled on the lower dose 4
Special Populations
Renal Impairment:
- Severe renal dysfunction (CrCl 15-30 mL/min): Maximum 8 mg/day due to prolonged elimination half-life (15.7 hours vs 7.1 hours in normal function) 5
- CrCl <30 mL/min: Dosing recommendations cannot be provided for combination products 2
- Hemodialysis: No significant elimination occurs with dialysis 5
Hepatic Impairment:
- Moderate to severe hepatic impairment: Do not initiate with combination products as the appropriate starting dose of 8 mg cannot be given 2
- Mild to moderate hepatic impairment: Doses up to 12 mg/day do not require precautions 5
Clinical Monitoring Requirements
Before initiation and during titration: 1
- Check renal function and serum electrolytes
- Recheck within 1 week of starting treatment
- Monitor at 1 and 4 weeks after each dose increase
- After achieving maintenance dose: monitor at 1,3, and 6 months, then every 6 months
Do not increase dose if: 1
- Worsening renal function occurs
- Hyperkalemia develops (K+ >5.0 mEq/L)
- Symptomatic hypotension is present
Important Caveats
Combination therapy restrictions: 1
- Routine combined use of ACE inhibitor, ARB, and aldosterone antagonist is potentially harmful (Class III: Harm recommendation)
- ARB addition may be considered only in persistently symptomatic HFrEF patients already on ACE inhibitor and beta blocker when aldosterone antagonist is not indicated or tolerated
Pharmacokinetic considerations: 5
- Terminal elimination half-life is longer than commonly reported (29 hours in hypertensive patients vs 4-9 hours previously stated)
- Trough-to-peak ratio is approximately 1.0, supporting true once-daily dosing 3
- Oral bioavailability is only 40% due to incomplete absorption 5
- Adverse events are not dose-related and are generally mild to moderate
- Tolerability profile similar to placebo across the dose range
- No increased adverse events with 32 mg compared to lower doses