What is the recommended candesartan dosing regimen for an adult with hypertension or heart failure, including adjustments for elderly patients and those with moderate (creatinine clearance 30‑50 mL/min) or severe (<30 mL/min) renal impairment or on dialysis?

Candesartan Dosing for Hypertension and Heart Failure

For hypertension, initiate candesartan at 16 mg once daily and titrate to 32 mg once daily if blood pressure remains ≥140/90 mmHg after 4 weeks; for heart failure with reduced ejection fraction, start at 4 mg once daily and titrate gradually to the target dose of 32 mg once daily. 1

Standard Dosing for Hypertension

• Begin with 16 mg once daily as the usual recommended starting dose in patients who are not volume depleted. 1
• Candesartan can be administered once or twice daily with total daily doses ranging from 8 mg to 32 mg. 1
• Titrate to 32 mg once daily for patients requiring further blood pressure reduction; doses larger than 32 mg do not provide greater antihypertensive effect. 1
• The maximal antihypertensive effect of any dose can be expected within 4 weeks of initiating that dose. 1
• Target blood pressure is <130/80 mmHg for most adults with hypertension to reduce cardiovascular risk. 2

Heart Failure Dosing

• Start at 4 mg once daily for heart failure patients, which is lower than the hypertension starting dose to minimize hypotension risk. 3
• Titrate gradually through 8 mg, then 16 mg, and eventually to the target dose of 32 mg once daily. 3
• Adjust therapy no more frequently than every 2 weeks to allow adequate time to assess tolerability at each dose level. 3
• The 32 mg daily dose has been documented to reduce heart failure hospitalizations and cardiovascular mortality in clinical trials. 3

Renal Impairment Adjustments

Mild to Moderate Renal Impairment (CrCl 30–90 mL/min)

• No dose adjustment is required for patients with mild (CrCl 60–90 mL/min) or moderate (CrCl 30–60 mL/min) renal impairment. 1
• After repeated dosing, AUC and Cmax are approximately doubled in patients with severe renal impairment (CrCl <30 mL/min) compared to those with normal kidney function. 1

Severe Renal Impairment (CrCl <30 mL/min) and Dialysis

• Dosing recommendations cannot be provided for patients with creatinine clearance <30 mL/min because safety and effectiveness have not been established in this population. 1
• A lower starting dose may be appropriate in patients with severe renal impairment, including those requiring dialysis. 4
• The pharmacokinetics of candesartan in hypertensive patients undergoing hemodialysis are similar to those in patients with severe renal impairment, and candesartan cannot be removed by hemodialysis. 1
• In patients with severe renal dysfunction, the elimination half-life increases to 15.7 hours at 8 mg/day, and an accumulation factor of 1.71 was found at 12 mg/day; thus, a maximum daily dose of up to 8 mg appears suitable in patients with severe renal dysfunction. 5

Elderly Patients (≥65 Years)

• No initial dosage adjustment is necessary for elderly patients. 1
• Plasma concentrations of candesartan are higher in the elderly (Cmax approximately 50% higher, AUC approximately 80% higher) compared to younger subjects, but the pharmacokinetics remain linear and candesartan does not accumulate upon repeated once-daily administration. 1
• For elderly or frail patients, particularly those ≥85 years, space dose increments every 2–4 weeks rather than every 2 weeks to improve tolerability. 3
• Measure blood pressure in both seated and standing positions (after 5 minutes seated, then at 1 minute and 3 minutes after standing) to detect orthostatic hypotension before initiating or intensifying therapy. 3

Hepatic Impairment

Mild Hepatic Impairment (Child-Pugh A)

• No dose adjustment is recommended for patients with mild hepatic impairment. 1
• The AUC for candesartan increased 30% and Cmax increased 56% in patients with mild hepatic impairment. 1

Moderate to Severe Hepatic Impairment (Child-Pugh B or C)

• Candesartan is not recommended for initiation in patients with moderate hepatic impairment because the appropriate starting dose of 8 mg cannot be given with available formulations. 1
• In patients with moderate hepatic impairment, the AUC increased 145% and Cmax increased 73%. 1
• The pharmacokinetics of candesartan in severe hepatic impairment have not been studied. 1

Monitoring Requirements

Heart Failure Patients

• Check serum potassium and creatinine before initiating therapy and again after 4–6 days of starting treatment. 3
• If serum potassium reaches 5.0–5.5 mmol/L, reduce the dose by 50%; discontinue if serum potassium exceeds 5.5 mmol/L. 3
• Monitor for hypotension, renal impairment, and hyperkalemia, especially when initiating therapy or increasing doses. 3

All Patients

• Reassess blood pressure every 2–4 weeks during titration, aiming to reach target within 3 months of therapy initiation. 2
• Asymptomatic hypotension does not require treatment changes; only symptomatic hypotension warrants dose adjustment or reconsideration of concomitant vasodilators. 3

Combination Therapy

• If blood pressure is not controlled on candesartan 32 mg alone, add hydrochlorothiazide 12.5–25 mg once daily for additive blood pressure-lowering effects. 1
• For patients with stage 2 hypertension (≥160/100 mmHg), consider initiating two antihypertensive agents from different classes at the outset. 2
• Do not combine candesartan with ACE inhibitors or direct renin inhibitors (e.g., aliskiren); dual renin-angiotensin system blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without added cardiovascular benefit. 3

Critical Safety Considerations

• Candesartan is absolutely contraindicated throughout pregnancy because of serious fetal toxicity (renal dysfunction, oligohydramnios, skull hypoplasia, fetal death). 3
• Upon pregnancy detection, discontinue candesartan immediately and switch to pregnancy-compatible antihypertensives such as methyldopa, labetalol, or extended-release nifedipine. 3
• The most common adverse events are headache, upper respiratory tract infection, back pain, and dizziness, with an incidence similar to placebo. 6
• Tolerability of candesartan is not significantly different from placebo and does not differ with age or gender. 6

Comparative Efficacy

• Clinical evidence confirms that candesartan provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. 7
• Candesartan 16 mg is more effective than losartan 50 mg as once-daily monotherapy. 8
• The trough-to-peak ratio for blood pressure reduction with candesartan is 80–100%, confirming a smooth 24-hour blood pressure-lowering profile. 8