What is the recommended dosage and usage of Candesartan (Angiotensin II receptor antagonist) for adult patients, including geriatric individuals, with hypertension or heart failure, particularly those with a history of cardiovascular disease?

Candesartan Dosing and Clinical Use

Recommended Dosing for Hypertension

For hypertension, initiate candesartan at 16 mg once daily, with titration to 32 mg once daily if blood pressure remains uncontrolled, as doses larger than 32 mg do not provide additional blood pressure lowering benefit. 1

• The usual starting dose is 16 mg once daily when used as monotherapy in patients who are not volume depleted 1
• Candesartan can be administered once or twice daily with total daily doses ranging from 8-32 mg 1
• Patients requiring further blood pressure reduction should be titrated to 32 mg once daily 1
• The maximal antihypertensive effect of any dose can be expected within 4 weeks of initiating that dose 1
• In isolated systolic hypertension, candesartan 16-32 mg once daily produced dose-related decreases in systolic blood pressure (16.5 mm Hg reduction overall), with 49% of patients achieving control 2

Recommended Dosing for Heart Failure

For heart failure patients, start candesartan at 4 mg once daily and gradually titrate to the target dose of 32 mg daily to maximize mortality and morbidity benefits. 3

• Initial dose should be 4 mg once daily in heart failure patients 3
• Gradual titration is essential: increase to 8 mg, then 16 mg, and eventually to the target dose of 32 mg daily 3
• The daily dose range of 4-32 mg has been documented to reduce mortality and morbidity in heart failure patients 3
• Higher doses provide greater benefits than lower doses in heart failure 3
• In the CHARM program, candesartan significantly reduced the composite endpoint of cardiovascular death and heart failure hospitalization compared to placebo in patients intolerant to ACE inhibitors 4

Special Populations and Dose Adjustments

Geriatric Patients

• No initial dosage adjustment is necessary for elderly patients, though plasma concentrations are approximately 50% higher for Cmax and 80% higher for AUC compared to younger subjects 1
• The pharmacokinetics remain linear in elderly patients, and candesartan does not accumulate with repeated once-daily dosing 1

Renal Impairment

• No dose adjustment required for mild (CrCl 60-90 mL/min) or moderate (CrCl 30-60 mL/min) renal impairment 1
• Dosing recommendations cannot be provided for patients with severe renal impairment (CrCl <30 mL/min) 1
• In severe renal impairment, AUC and Cmax are approximately doubled compared to patients with normal kidney function 1
• Candesartan cannot be removed by hemodialysis 1

Hepatic Impairment

• No dose adjustment needed for mild hepatic impairment (Child-Pugh A) 1
• For moderate hepatic impairment (Child-Pugh B), candesartan is not recommended for initiation because the appropriate starting dose of 8 mg cannot be given 1
• In moderate hepatic impairment, AUC increases by 145% and Cmax by 73% 1

Critical Monitoring Parameters

Monitor for hypotension, renal impairment, and hyperkalemia, especially when initiating therapy or increasing doses. 3

Heart Failure Monitoring Protocol

• Check serum potassium and creatinine before initiating therapy 3
• Recheck serum potassium and creatinine 4-6 days after starting treatment 3
• If serum potassium reaches 5-5.5 mmol/L, reduce dose by 50% 3
• Discontinue if serum potassium exceeds 5.5 mmol/L 3

Combination Therapy Considerations

Avoid combining candesartan with ACE inhibitors and aldosterone antagonists routinely, as the triple combination increases risks of renal dysfunction and hyperkalemia. 3

• In the CHARM-Added trial, patients with stable left ventricular dysfunction benefited from combining an ACE inhibitor with candesartan 4
• However, in VALIANT, the combination of valsartan and captopril showed no increased benefit over captopril alone and had higher discontinuation rates due to adverse effects 4
• The difference in outcomes relates to timing: aggressive simultaneous titration in early post-MI period (VALIANT) caused more side effects, while adding an ARB to established ACE inhibitor therapy in stable heart failure (CHARM) was well tolerated 4
• Hydrochlorothiazide 12.5-50 mg once daily can be added for additional blood pressure control 1

Comparative Efficacy

Clinical evidence confirms that candesartan provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. 5

• Candesartan 8-16 mg daily was at least as effective as therapeutic dosages of losartan or other ARBs 6
• At dosages up to 32 mg daily, candesartan demonstrated greater antihypertensive efficacy than losartan 50 or 100 mg daily 6
• Candesartan showed similar or greater efficacy compared with enalapril or hydrochlorothiazide, and equivalent efficacy to amlodipine 6

Tolerability Profile

• Candesartan has a tolerability profile similar to placebo 5, 7, 6
• Most common adverse events are headache, upper respiratory tract infection, back pain, and dizziness 7
• The incidence of cough is similar to placebo, unlike ACE inhibitors 7, 6
• Adverse events are not dose-related and are generally mild to moderate in severity 7, 6
• Angioedema can occur with ARBs, though much less frequently than with ACE inhibitors 3