Candesartan Cilexetil + Hydrochlorothiazide

• Hypertension:
  Indicated for the treatment of high blood pressure in patients for whom monotherapy with either candesartan cilexetil or hydrochlorothiazide is inadequate.
• Resistant Hypertension:
  Used as combination therapy to achieve better blood pressure control in patients with resistant or difficult-to-control hypertension.
• Off-label Uses:
  Occasionally used in patients with edema associated with heart failure, hepatic cirrhosis, or nephrotic syndrome in combination with other agents.

• Adults:
  Typical initial dose: One tablet once daily containing 16 mg candesartan cilexetil and 12.5 mg hydrochlorothiazide.
  Dosage can be adjusted based on response; maximum dose is usually 32 mg candesartan/25 mg hydrochlorothiazide once daily.
• Elderly:
  No specific dose adjustment required; monitor renal function and electrolyte balance closely.
• Renal Impairment:
  Use cautiously; hydrochlorothiazide is ineffective in severe renal impairment (eGFR <30 mL/min).
  Candesartan dose adjustments may be necessary in severe renal dysfunction.
• Hepatic Impairment:
  Use with caution, particularly in patients with biliary obstruction or severe hepatic impairment.
• Pediatrics:
  Safety and efficacy not established.
• Administration:
  Oral, once daily, with or without food, preferably at the same time each day.

Candesartan cilexetil is a prodrug converted to candesartan, a selective angiotensin II receptor type 1 (AT1) antagonist. It blocks the vasoconstrictive and aldosterone-secreting effects of angiotensin II, leading to vasodilation, reduced aldosterone release, decreased sodium and water retention, and blood pressure lowering. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubules of the kidneys, increasing diuresis and reducing plasma volume. The combined effect of vascular relaxation (candesartan) and diuresis (hydrochlorothiazide) provides enhanced antihypertensive efficacy.

• Absorption:
  Both drugs are rapidly absorbed orally; peak plasma levels of candesartan occur 3–4 hours post-dose, hydrochlorothiazide peaks within 1.5–2 hours.
• Bioavailability:
  Candesartan ~15%; hydrochlorothiazide ~70%.
• Distribution:
  Candesartan is >99% protein bound; hydrochlorothiazide has moderate protein binding (~40%).
• Metabolism:
  Candesartan is minimally metabolized; hydrochlorothiazide is not metabolized.
• Half-life:
  Candesartan: approximately 9 hours; hydrochlorothiazide: 6–15 hours.
• Elimination:
  Candesartan is excreted mainly unchanged via feces and urine; hydrochlorothiazide is primarily eliminated unchanged by the kidneys.

• Pregnancy:
  Contraindicated, especially in the second and third trimesters, due to risk of fetal toxicity including renal impairment and death.
• Lactation:
  Both drugs may be excreted in breast milk; breastfeeding is generally not recommended during treatment.

• Primary: Antihypertensive
• Subclasses:
• Candesartan: Angiotensin II Receptor Blocker (ARB)
• Hydrochlorothiazide: Thiazide Diuretic

• Hypersensitivity to candesartan, hydrochlorothiazide, sulfonamides, or excipients.
• Anuria or severe renal impairment (especially for hydrochlorothiazide).
• Pregnancy and breastfeeding.
• History of angioedema related to previous ACE inhibitor or ARB therapy.
• Concomitant use with aliskiren in diabetic or renal impaired patients.

• Monitor for hypotension and electrolyte imbalances (hypokalemia, hyponatremia, hyperkalemia).
• Risk of acute kidney injury, especially in volume-depleted or renally impaired patients.
• Caution in patients with hepatic impairment or biliary obstruction.
• Increased risk of photosensitivity reactions due to hydrochlorothiazide.
• Watch for signs of angioedema and discontinue immediately if observed.
• Periodic monitoring of renal function, electrolytes, and blood pressure is recommended.

Common:

• Dizziness, headache
• Fatigue
• Hypotension
• Electrolyte disturbances (hypokalemia, hyponatremia)
• Increased urination

Less common:

• Gastrointestinal discomfort
• Rash, photosensitivity reactions
• Hyperkalemia (primarily from candesartan)

Rare but serious:

• Angioedema
• Acute renal failure
• Severe electrolyte imbalance
• Pancreatitis

• Potassium supplements, potassium-sparing diuretics, or other drugs that increase potassium may cause hyperkalemia.
• NSAIDs may reduce antihypertensive efficacy and increase renal risk.
• Other antihypertensives may potentiate hypotension.
• Lithium toxicity risk may increase when used concurrently.
• CYP450 interactions minimal, but monitor combined use with drugs affecting renal function.

• Clinical guidelines recommend combination therapy with ARBs and thiazide diuretics for patients inadequately controlled on monotherapy.
• Updated warnings emphasize monitoring for renal function and potassium disturbances.
• FDA alerts highlight rare cases of angioedema and advise caution.

• 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.