What are the dosing recommendations, contraindications, monitoring parameters, and alternative therapies for Atacand (candesartan) in adults?

Atacand (Candesartan) Clinical Guidance

Dosing Recommendations

For hypertension, initiate candesartan at 16 mg once daily in volume-replete patients and titrate to 32 mg once daily if blood pressure remains ≥140/90 mmHg after 2–4 weeks; doses above 32 mg provide no additional benefit. 1

Hypertension Dosing

• Start at 16 mg once daily for most patients who are not volume depleted 1
• Titrate to 32 mg once daily for inadequate blood pressure control 1
• Candesartan can be administered once or twice daily with total daily doses of 8–32 mg 1
• Doses larger than 32 mg do not provide greater blood pressure-lowering effect 1
• Target blood pressure goal is <130/80 mmHg for most adults to reduce cardiovascular risk 2
• Reassess blood pressure every 2–4 weeks during titration, aiming to reach target within 3 months 2

Heart Failure Dosing

• Initiate at 4 mg once daily in heart failure patients, with gradual titration to a target of 32 mg daily 3, 2
• Titration schedule: increase from 4 mg → 8 mg → 16 mg → 32 mg at intervals of at least 2 weeks 3, 2
• The 4–32 mg daily range has demonstrated positive effects on mortality and morbidity in heart failure 2
• Higher doses provide greater benefits than lower doses in heart failure patients 2

Special Populations

• Hepatic impairment (moderate to severe): Candesartan is not recommended for initiation because the appropriate starting dose of 8 mg cannot be given with available formulations 1
• Renal impairment (CrCl <30 mL/min): Dosing recommendations cannot be provided; use with extreme caution 1
• Elderly patients: No dosage adjustment necessary 4, 5

Contraindications

Candesartan is absolutely contraindicated in pregnancy (all trimesters) due to serious fetal toxicity including renal dysfunction, oligohydramnios, skull hypoplasia, and fetal death. 1

Absolute Contraindications

• Pregnancy – discontinue immediately when pregnancy is detected 1
• Concurrent use with ACE inhibitors – dual RAAS blockade increases hyperkalemia, syncope, and acute kidney injury 2–3-fold without cardiovascular benefit 3, 2, 6
• Triple combination with ACE inhibitors and aldosterone antagonists – dramatically increases renal dysfunction and hyperkalemia risks 2, 6
• History of angioedema with ARBs – although less common than with ACE inhibitors, cross-reactivity can occur 3, 2

Monitoring Parameters

Check serum creatinine/eGFR and potassium within 1–2 weeks after initiating candesartan or increasing doses, especially in patients with diabetes, chronic kidney disease, or baseline systolic BP <80 mmHg. 3, 2, 6

Initial Monitoring (Within 1–2 Weeks)

• Blood pressure (including orthostatic measurements in elderly) 3, 2
• Serum creatinine and eGFR 3, 2, 6
• Serum potassium 3, 2, 6

Heart Failure-Specific Monitoring

• Check serum potassium and creatinine before initiating therapy 2
• Recheck after 4–6 days of starting treatment 2
• If potassium 5.0–5.5 mmol/L: reduce dose by 50% 2
• If potassium >5.5 mmol/L: discontinue candesartan 2

High-Risk Patients Requiring Closer Surveillance

• Systolic blood pressure <80 mmHg 3, 6
• Low serum sodium 3
• Diabetes mellitus 3, 6
• Pre-existing renal dysfunction (creatinine >250 μmol/L or >2.8 mg/dL) 3, 6
• Volume depletion 3

Ongoing Monitoring

• Blood pressure every 3–6 months once target achieved 2
• Annual renal function and electrolyte assessment during maintenance 2

Alternative Therapies

For patients requiring ARB therapy, candesartan and valsartan have the strongest evidence for reducing hospitalizations and mortality in heart failure patients intolerant to ACE inhibitors. 6

Preferred ARB Alternatives

• Valsartan: 80–320 mg daily (divided twice daily); target dose 160 mg twice daily for heart failure 3, 6
• Losartan: 50–100 mg once daily for hypertension; 100–150 mg daily for heart failure 3, 7
• Telmisartan: 40–80 mg once daily 6
• Olmesartan: 20–40 mg once daily 6

Combination Therapy Options

• Candesartan + hydrochlorothiazide: Provides additive blood pressure-lowering effects 1, 8, 4
• Candesartan + amlodipine: Enhanced blood pressure reduction, well tolerated 8, 4
• For stage 2 hypertension (≥160/100 mmHg), initiate two antihypertensive agents from different classes at outset 2

Comparative Efficacy

• Candesartan 16 mg is more effective than losartan 50 mg 4, 5
• Candesartan 8 mg is as effective as enalapril 10–20 mg, amlodipine 5 mg, or hydrochlorothiazide 25 mg 8, 4, 5
• Candesartan provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan 9

Critical Safety Considerations

Volume Depletion

• Correct volume and/or salt depletion before initiating candesartan 1
• Symptomatic hypotension most likely in patients with prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting 1
• May require temporary dose reduction or volume repletion 1

Renal Function

• Monitor renal function periodically; changes including acute renal failure can occur 1
• Patients with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion are at particular risk 1
• Consider withholding or discontinuing if clinically significant decrease in renal function develops 1

Electrolyte Abnormalities

• When combined with hydrochlorothiazide: risk of both hyperkalemia (from candesartan) and hypokalemia (from HCTZ) 1
• Hypomagnesemia can result in difficult-to-treat hypokalemia 1
• Monitor serum electrolytes periodically 1

Acute Myopia and Angle-Closure Glaucoma

• Hydrochlorothiazide (when combined with candesartan) can cause acute transient myopia and acute angle-closure glaucoma 1
• Symptoms include acute onset of decreased visual acuity or ocular pain, typically within hours to weeks of initiation 1

Common Pitfalls to Avoid

• Do not combine candesartan with ACE inhibitors – this increases adverse events without improving outcomes 3, 2, 6
• Do not use triple RAAS blockade (ARB + ACE inhibitor + aldosterone antagonist) – dramatically increases renal dysfunction and hyperkalemia 2, 6
• Do not exceed 32 mg daily for hypertension – no additional benefit 1
• Do not initiate in patients with potassium >5.0 mmol/L or creatinine >250 μmol/L until corrected 6
• Do not discontinue prematurely for asymptomatic blood pressure reductions during titration in heart failure patients 2