What is the recommended dosing for candesartan (Angiotensin II receptor antagonist) in adults with hypertension or heart failure?

Candesartan Dosing

For hypertension, start candesartan at 16 mg once daily and titrate to 32 mg once daily if needed; for heart failure, start at 4 mg once daily and gradually titrate to the target dose of 32 mg daily. 1, 2

Hypertension Dosing

• Initial dose: 16 mg once daily for patients who are not volume depleted 1
• Dose range: 8-32 mg daily, administered once or twice daily 1
• Titration: Increase to 32 mg daily for patients requiring further blood pressure reduction 1
• Maximum dose: 32 mg daily (doses larger than 32 mg do not provide greater blood pressure lowering) 1
• Time to maximal effect: 4 weeks after initiating any dose 1

Clinical Evidence for Hypertension

• The usual maintenance doses are 8 mg and 16 mg once daily, providing clinically relevant blood pressure reduction 3
• Candesartan 16 mg once daily is more effective than losartan 50 mg once daily, with a response rate of 57% versus 46% 4
• Candesartan demonstrates a trough-to-peak ratio of approximately 1.0, indicating smooth 24-hour blood pressure control, compared to 0.7 for losartan 4

Heart Failure Dosing

• Initial dose: 4 mg once daily 2
• Titration schedule: Gradually increase to 8 mg, then 16 mg, and finally to the target dose of 32 mg daily 2
• Target dose: 32 mg daily for maximal benefit 2
• Monitoring intervals: Check serum potassium and creatinine after 4-6 days of initiating therapy or dose changes 2

Dose Adjustments for Hyperkalemia in Heart Failure

• If potassium 5.0-5.5 mmol/L: Reduce dose by 50% 2
• If potassium >5.5 mmol/L: Discontinue candesartan 2

Clinical Evidence for Heart Failure

• The 4-32 mg daily dose range has documented positive effects on mortality and morbidity in heart failure patients 2
• In the CHARM trial, candesartan reduced heart failure hospitalizations by 11% compared to placebo (22% vs 24% for the composite endpoint of cardiovascular death or heart failure hospitalization) 5
• Higher doses provide greater benefits than lower doses in heart failure patients 2

Special Populations

Renal Impairment

• Creatinine clearance <30 mL/min: Dosing recommendations cannot be provided 1
• For patients with severe renal dysfunction, maximum daily dose should not exceed 8 mg to avoid accumulation 6
• No dose adjustment needed for mild to moderate renal impairment 7

Hepatic Impairment

• Moderate to severe hepatic impairment: Do not initiate therapy with combination products, as the appropriate 8 mg starting dose cannot be given 1
• Mild to moderate hepatic impairment: Doses up to 12 mg/day require no precautions 6, 7

Elderly Patients

• No dosage adjustment necessary in elderly patients 3, 7

Combination Therapy

• Candesartan can be combined with hydrochlorothiazide or amlodipine for enhanced blood pressure lowering in patients with inadequate response to monotherapy 3
• May be administered with or without food 1

Common Pitfalls

• Avoid using doses below target in heart failure, as many physicians use doses that are too low to provide optimal benefits 2
• Monitor for hypotension, renal impairment, and hyperkalemia, especially when initiating therapy or increasing doses 2
• Do not combine with ACE inhibitors and aldosterone antagonists routinely, as the triple combination increases risks of renal dysfunction and hyperkalemia 5
• Angioedema can occur with ARBs, though much less frequently than with ACE inhibitors; some patients who developed angioedema to ACE inhibitors later developed it with ARBs 5