Giran

• Hypertension:
  Treatment of high blood pressure to reduce the risk of cardiovascular morbidity and mortality.
• Heart Failure:
  Management of heart failure with reduced ejection fraction (HFrEF) to improve symptoms and reduce hospitalizations.
• Left Ventricular Dysfunction:
  Treatment to reduce the risk of heart failure progression and cardiovascular events in patients with asymptomatic left ventricular dysfunction.
• Off-label Uses:
  Occasionally used off-label for diabetic nephropathy, especially in hypertensive patients.

• Hypertension:
• Adults: Initial dose 8 mg orally once daily.
• Maintenance dose: 8–16 mg once daily; maximum 32 mg daily.
• Dose adjustment based on blood pressure response.
• Heart Failure:
• Initial dose: 4 mg orally once daily.
• Titration: Increase dose every 2 weeks as tolerated, to a target dose of 32 mg once daily.
• Elderly:
• Start with lower doses (4 mg once daily) and titrate cautiously.
• Renal Impairment:
• Use with caution; initial dose reduction may be necessary in severe renal impairment.
• Hepatic Impairment:
• Use cautiously in mild to moderate impairment; avoid in severe hepatic impairment.
• Administration:
• Oral route, with or without food.
• Taken once daily, preferably at the same time each day.

Candesartan cilexetil is a prodrug converted in vivo to candesartan, a selective angiotensin II receptor blocker (ARB). It binds competitively and selectively to the AT1 receptor subtype, inhibiting the vasoconstrictive and aldosterone-secreting effects of angiotensin II. This leads to vasodilation, decreased aldosterone secretion, reduced sodium and water retention, and lowered blood pressure. The reduction in afterload and preload improves cardiac output in heart failure and protects vascular and renal tissues from hypertensive damage.

• Absorption:
  Rapidly absorbed after oral administration; peak plasma concentration reached within 3 to 4 hours.
• Bioavailability:
  Approximately 15% (due to first-pass metabolism).
• Distribution:
  Highly protein bound (>99%).
• Metabolism:
  Minimal hepatic metabolism; primarily converted from prodrug to active candesartan in the gastrointestinal tract.
• Half-life:
  Approximately 9 hours (effective half-life allows once-daily dosing).
• Excretion:
  Eliminated via feces (~33%) and urine (~67%), mostly unchanged.

• Pregnancy:
  Contraindicated in the second and third trimesters due to risk of fetal toxicity including renal impairment, oligohydramnios, and death. Avoid use in pregnancy; discontinue as soon as pregnancy is detected.
• Lactation:
  It is unknown whether candesartan is excreted in human milk. Due to potential risks, breastfeeding is not recommended during treatment.

• Primary Class: Angiotensin II Receptor Blocker (ARB)
• Subclass: Antihypertensive Agent

• Known hypersensitivity to candesartan or any formulation excipients.
• Pregnancy (especially second and third trimesters).
• Severe hepatic impairment or biliary obstruction.
• Concomitant use with aliskiren in patients with diabetes or renal impairment.

• Risk of hypotension, especially in volume- or salt-depleted patients.
• Monitor renal function and potassium levels; risk of hyperkalemia, particularly with other potassium-sparing agents.
• Risk of acute kidney injury in patients with renal artery stenosis.
• Not recommended in patients with bilateral renal artery stenosis.
• Use caution in elderly, those with impaired hepatic or renal function.
• Discontinue if pregnancy is detected.

Common:

• Dizziness
• Headache
• Fatigue
• Hypotension
• Hyperkalemia

Less common:

• Back pain
• Nasopharyngitis
• Gastrointestinal discomfort

Rare but serious:

• Angioedema
• Severe hypotension
• Renal impairment or failure
• Elevated liver enzymes

• Potentiated risk of hyperkalemia with potassium supplements, potassium-sparing diuretics, or ACE inhibitors.
• Increased risk of hypotension with other antihypertensives, diuretics, or NSAIDs.
• Avoid concurrent use with aliskiren in diabetic or renal impaired patients due to risk of adverse effects.
• Minimal CYP450 involvement; unlikely to cause significant drug interactions via this pathway.

• Clinical guidelines (e.g., ADA, ESC) recommend candesartan as a first-line or alternative therapy for hypertension and heart failure.
• Updated warnings emphasize careful use in renal impairment and pregnancy.
• Some guidelines now prefer ARBs over ACE inhibitors due to lower incidence of cough and angioedema.

• Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in tightly closed containers.
• Keep out of reach of children.