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Sunday, July 27, 2025

Candesartan


Candesartan is a long-acting angiotensin II receptor blocker (ARB) used primarily for the treatment of hypertension, heart failure, and in some cases for renal protection in patients with chronic kidney disease (CKD) or diabetes. It functions by antagonizing the effects of angiotensin II at the AT1 receptor, leading to vasodilation, reduced aldosterone secretion, and decreased blood pressure. Candesartan is known for its high receptor affinity, long half-life, and favorable tolerability profile, making it a first-line antihypertensive in many clinical guidelines.

This document provides a comprehensive pharmacological overview of candesartan, including its mechanism of action, approved indications, dosing, contraindications, adverse effects, precautions, and drug interactions.

Pharmacological Classification

  • Therapeutic class: Antihypertensive

  • Pharmacologic class: Angiotensin II receptor blocker (ARB)

  • ATC code: C09CA06

  • Legal status: Prescription-only medicine (Rx)

Brand Names and Formulations

  • Brand names: Atacand®, Amias®, Blopress®, Candesar®, Candil®

  • Available forms: Oral tablets – 4 mg, 8 mg, 16 mg, and 32 mg

  • Salt form: Candesartan cilexetil (a prodrug converted to active candesartan)

Mechanism of Action

Candesartan is a selective blocker of the angiotensin II type 1 (AT1) receptor, which is responsible for:

  • Vasoconstriction

  • Aldosterone release → sodium and water retention

  • Sympathetic nervous system stimulation

  • Cardiac remodeling and hypertrophy

By inhibiting these actions:

  • It lowers systemic vascular resistance (afterload)

  • Reduces blood pressure

  • Decreases aldosterone-mediated fluid retention

  • Provides cardioprotective and renoprotective effects

Unlike ACE inhibitors, candesartan does not affect bradykinin metabolism, which results in a lower incidence of cough and angioedema.

Indications

Approved therapeutic uses:

  1. Hypertension (essential / primary)

    • First-line monotherapy or in combination

    • Effective in both young and elderly patients

  2. Heart failure (NYHA class II–IV)

    • In patients intolerant to ACE inhibitors or as an alternative

    • Reduces morbidity and mortality when added to standard therapy

  3. Left ventricular systolic dysfunction post-myocardial infarction (off-label in some countries)

  4. Renal protection in diabetic nephropathy (off-label; supported by trials)

  5. Migraine prophylaxis (off-label; supported by studies)

Dosage and Administration

Hypertension

  • Starting dose: 8 mg once daily

  • Maintenance dose: 8–32 mg once daily

  • Maximum dose: 32 mg/day

  • May be used as monotherapy or with a thiazide diuretic (e.g., hydrochlorothiazide)

Heart Failure

  • Initial dose: 4 mg once daily

  • Titration: Double the dose every 2 weeks as tolerated

  • Target dose: 32 mg once daily

Pediatric Use (Hypertension, age ≥6)

  • Based on weight:

    • <50 kg: 4–8 mg daily (max 8 mg/day)

    • ≥50 kg: 4–16 mg daily (max 16 mg/day)

Administration Notes

  • Can be taken with or without food

  • Dose adjustments may be needed in renal or hepatic impairment

Pharmacokinetics

  • Prodrug: Candesartan cilexetil is rapidly converted to active candesartan during GI absorption

  • Bioavailability: ~15%

  • Time to peak: 3–4 hours

  • Protein binding: >99%

  • Half-life: ~9 hours (once-daily dosing effective)

  • Metabolism: Not significantly metabolized by CYP450 enzymes

  • Elimination: Renal (26%) and fecal (56%) as unchanged drug

Contraindications

  • Pregnancy (category D): Teratogenic effects in 2nd and 3rd trimesters

  • Breastfeeding (not recommended)

  • Severe hepatic impairment with cholestasis

  • Bilateral renal artery stenosis or single kidney with artery stenosis

  • **History of hypersensitivity to candesartan or any ARB

  • Use with aliskiren in patients with diabetes (risk of hyperkalemia, renal impairment)

Adverse Effects

Common (≥1%)

  • Dizziness, headache (dose-dependent)

  • Hypotension, particularly in volume-depleted individuals

  • Hyperkalemia

  • Elevated creatinine and BUN

  • Fatigue

  • Back pain

  • Upper respiratory tract infections

Uncommon/Rare

  • Renal impairment or acute kidney injury (especially in elderly or those with dehydration)

  • Angioedema (less frequent than with ACE inhibitors)

  • Hepatitis, hepatic enzyme elevation

  • Anemia, leukopenia (rare)

  • Rash or pruritus

Precautions and Monitoring

Renal Function

  • Monitor creatinine and BUN, especially in patients with:

    • Chronic kidney disease

    • Heart failure

    • On diuretics

    • Elderly population

Potassium Levels

  • Risk of hyperkalemia, especially with:

    • ACE inhibitors

    • Potassium-sparing diuretics (e.g., spironolactone)

    • Potassium supplements

Blood Pressure

  • Monitor regularly, particularly after initiation or dose escalation

Volume Depletion

  • Caution in patients with diuretic use, vomiting, diarrhea, or dehydration

Drug Interactions

  • ACE inhibitors or aliskiren: Increased risk of hyperkalemia, renal impairment, hypotension

  • Potassium-sparing diuretics (e.g., amiloride, spironolactone) or K+ supplements: Hyperkalemia risk

  • NSAIDs: May reduce antihypertensive effect and impair renal function

  • Lithium: Increased lithium levels and toxicity risk

  • Diuretics: May enhance hypotensive effect

  • CYP450 interactions: Minimal (not metabolized by CYP enzymes)

Pregnancy and Lactation

Pregnancy

  • Contraindicated:

    • Use during 2nd and 3rd trimester associated with fetal renal impairment, skull hypoplasia, oligohydramnios, neonatal hypotension, and death

    • Discontinue immediately if pregnancy is detected

Breastfeeding

  • Not recommended: Unknown if candesartan is excreted in human milk

Comparison with Similar Agents (No Tables)

Candesartan vs. Losartan

  • Candesartan has higher AT1 receptor affinity

  • Longer half-life (~9 hours vs. ~6 hours)

  • Non-CYP metabolism (fewer interactions)

Candesartan vs. Valsartan

  • Similar efficacy for BP control

  • Candesartan may offer slightly better BP-lowering potency per mg

  • Both reduce cardiovascular mortality in heart failure

Candesartan vs. ACE inhibitors (e.g., ramipril)

  • Equal in efficacy

  • Lower risk of cough and angioedema

  • Better tolerated in patients intolerant to ACE inhibitors

Clinical Trials and Guidelines

  • CHARM Trials: Demonstrated benefit of candesartan in reducing CV death and hospitalization in heart failure patients

  • SCOPE Study: Showed stroke risk reduction in elderly hypertensives

  • Recommended in ESC, ACC/AHA, and NICE guidelines as a first-line antihypertensive, especially when ACE inhibitors are not tolerated

Patient Counseling Points

  • Take medication daily at the same time

  • Do not stop without physician supervision

  • Inform physician of any dizziness, fainting, swelling, or muscle weakness

  • Avoid salt substitutes or potassium supplements unless directed

  • Report pregnancy immediately

  • Attend all follow-up appointments for blood pressure and blood test monitoring



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