Candesartan

Usage

Candesartan is prescribed for:

• Hypertension (high blood pressure) in adults and children 6 to <18 years of age.
• Heart failure in adults with reduced ejection fraction (HFrEF), especially when Angiotensin-Converting Enzyme (ACE) inhibitors are not tolerated or as add-on therapy to ACE inhibitors when symptoms persist and mineralocorticoid receptor antagonists (MRAs) cannot be used.

Pharmacological Classification: Angiotensin II Receptor Blocker (ARB)

Mechanism of Action: Candesartan blocks the action of angiotensin II, a hormone that causes blood vessels to constrict and raises blood pressure. By blocking angiotensin II receptors, candesartan causes vasodilation (widening of blood vessels), leading to lower blood pressure. It also reduces the workload on the heart, making it easier to pump blood.

Alternate Names

Generic Name: Candesartan cilexetil

Brand Names: Atacand, others

How It Works

Pharmacodynamics: Candesartan exerts its antihypertensive effect primarily by selectively blocking angiotensin II at the AT1 receptor subtype. This leads to decreased vasoconstriction and reduced aldosterone secretion, thus reducing blood pressure. In heart failure patients, this translates to improvement of cardiac performance and reduced morbidity and mortality.

Pharmacokinetics:

• Absorption: Well absorbed orally. The bioavailability of candesartan after oral administration is approximately 15%.
• Metabolism: Extensively metabolized in the liver via O-deethylation to the pharmacologically active metabolite candesartan.
• Elimination: Primarily eliminated in the urine and feces (about two thirds and one third of the dose, respectively).

Mode of Action: Candesartan competitively binds to the AT1 receptor, preventing angiotensin II from binding and exerting its vasoconstricting effects. This inhibition at the receptor level leads to vasodilation and a decrease in blood pressure.

Elimination Pathways: Renal and hepatic elimination; less than 5% of the dose is excreted unchanged in the urine.

Dosage

Standard Dosage

Adults:

• Hypertension: Initial dose is 8 mg once daily, adjustable up to 32 mg/day as a single dose or in two divided doses.
• Heart Failure: Initial dose is 4 mg once daily, doubled at intervals of at least two weeks as needed, up to a maximum of 32 mg once daily.

Children (6 to <18 years, Hypertension):

• <50 kg: Initial dose: 4-8 mg/day; maximum: 8 mg/day.
• ≥50 kg: Initial dose: 8-16 mg/day; maximum: 32 mg/day.

Special Cases:

• Elderly Patients: Start with a lower dose, particularly if volume depleted. Careful monitoring of renal function is recommended.
• Patients with Renal Impairment: Initial dose of 4 mg daily; titrate according to response. Limited experience in patients with severe renal impairment (CrCl <15 mL/min).
• Patients with Hepatic Dysfunction: Initial dose 4 mg daily for mild to moderate impairment. Contraindicated in severe hepatic impairment.
• Patients with Comorbid Conditions: Dose adjustment may be needed.

Clinical Use Cases

Candesartan’s primary uses are hypertension and heart failure. The dosage in these settings is addressed under “Standard Dosage” above. Candesartan does not have direct applications for intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations like status epilepticus or cardiac arrest. Its use in these cases is limited to the management of comorbid conditions such as hypertension or heart failure.

Dosage Adjustments

Dose adjustments may be necessary based on patient-specific factors such as renal/hepatic dysfunction, volume depletion, response to therapy, and concomitant medications.

Side Effects

Common Side Effects:

• Back pain
• Dizziness
• Upper respiratory tract infections (URTI)
• Cold- or flu-like symptoms

Rare but Serious Side Effects:

• Angioedema
• Hypotension (low blood pressure), especially in volume-depleted patients
• Renal impairment (worsening of kidney function)
• Hyperkalemia (high potassium levels)

Long-Term Effects:

• Chronic renal impairment may occur with prolonged use, especially in patients with pre-existing kidney disease.

Adverse Drug Reactions (ADR): Angioedema and symptomatic hypotension.

Contraindications

• Hypersensitivity to candesartan
• Pregnancy (especially second and third trimesters)
• Severe hepatic impairment and/or cholestasis
• Bilateral renal artery stenosis
• Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73m²)
• Children <1 year of age

Drug Interactions

• Aliskiren: Avoid concomitant use, especially in patients with diabetes.
• ACE inhibitors: Increased risk of hypotension, renal impairment, and hyperkalemia.
• Potassium-sparing diuretics, potassium supplements: Increased risk of hyperkalemia.
• NSAIDs (e.g., ibuprofen, naproxen): Reduced antihypertensive effect.
• Lithium: Increased lithium levels.

Pregnancy and Breastfeeding

• Pregnancy: Contraindicated. Can cause fetal harm and neonatal morbidity/mortality.
• Breastfeeding: Not recommended. Small amounts are excreted in breast milk. Use only if clinically indicated, and safer alternatives should be considered.

Drug Profile Summary

• Mechanism of Action: ARB; blocks angiotensin II at AT1 receptors, causing vasodilation and lowering blood pressure.
• Side Effects: Back pain, dizziness, URTI, hypotension, renal impairment, hyperkalemia, angioedema.
• Contraindications: Hypersensitivity, pregnancy, severe hepatic impairment/cholestasis, bilateral renal artery stenosis.
• Drug Interactions: Aliskiren, ACE inhibitors, potassium-sparing diuretics, NSAIDs, lithium.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy; not recommended while breastfeeding.
• Dosage: Hypertension: 8-32 mg/day; heart failure: 4-32 mg/day; adjust for renal/hepatic impairment.
• Monitoring Parameters: Blood pressure, renal function (serum creatinine, electrolytes), potassium levels.

Popular Combinations

• Hydrochlorothiazide: Often combined for additive antihypertensive effects.

Precautions

• Monitor renal function, especially in patients with renal impairment or heart failure.
• Monitor potassium levels, especially when used with other drugs that can increase potassium.
• Discontinue if pregnancy occurs.
• Caution in elderly patients and those with hepatic impairment.
• Avoid or limit alcohol consumption as it can exacerbate hypotensive effects.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Candesartan?

A: The standard adult dose for hypertension is 8-32 mg once daily. For heart failure, it is 4-32 mg once daily. Pediatric dosing for hypertension is based on weight: <50 kg, 4-8 mg/day; ≥50 kg, 8-16 mg/day. Elderly patients and those with renal/hepatic impairment may require lower starting doses.

Q2: What are the common side effects of Candesartan?

A: Common side effects include back pain, dizziness, upper respiratory tract infections, and cold- or flu-like symptoms.

Q3: How does Candesartan differ from an ACE inhibitor?

A: Both lower blood pressure by affecting the renin-angiotensin-aldosterone system (RAAS), but Candesartan acts by blocking angiotensin II receptors, while ACE inhibitors prevent the formation of angiotensin II. Candesartan may be better tolerated by patients who develop a cough with ACE inhibitors.

Q4: Can Candesartan be used in pregnancy?

A: No, Candesartan is contraindicated during pregnancy, especially in the second and third trimesters, due to the risk of fetal harm.

Q5: Are there any specific monitoring requirements when prescribing Candesartan?

A: Yes, monitor blood pressure, renal function (serum creatinine and electrolytes, especially potassium), and signs of angioedema or hypotension.

Q6: What is the initial dose of Candesartan in patients with renal impairment?

A: The initial dose in patients with renal impairment, including those on hemodialysis, is 4 mg once daily, with careful titration according to response.

Q7: Can Candesartan be combined with other antihypertensive medications?

A: Yes, candesartan can be combined with other antihypertensive medications such as hydrochlorothiazide for additive effects. However, concomitant use with aliskiren should be avoided.

Q8: What is the mechanism of action of Candesartan in heart failure?

A: In heart failure, Candesartan blocks the deleterious effects of angiotensin II, which can contribute to cardiac remodeling and worsening heart function. By blocking angiotensin II at the AT1 receptor, candesartan reduces vasoconstriction, decreases aldosterone secretion, and improves cardiac output, thereby reducing morbidity and mortality.

Q9: What are the key patient counseling points for Candesartan?

A: Inform patients about potential side effects (dizziness, back pain), the importance of adhering to the prescribed dosage, reporting any signs of angioedema or worsening renal function, and avoiding potassium supplements unless specifically prescribed. Advise female patients of childbearing age about the potential for fetal harm and the need to use reliable contraception.