Clortha

Approved Indications:

• Hypertension:
  Used alone or in combination with other antihypertensive agents for the management of essential or secondary hypertension. Effective in reducing the risk of stroke, myocardial infarction, and other cardiovascular events.
• Edema:
  Indicated for fluid retention due to:
• Congestive heart failure
• Hepatic cirrhosis
• Nephrotic syndrome
• Chronic renal insufficiency
• Premenstrual tension syndrome

Clinically Accepted Off-Label Uses:

• Nephrolithiasis (Calcium Kidney Stones):
  Used to decrease urinary calcium excretion and prevent recurrence of calcium-containing stones.
• Osteoporosis (Adjunctive Role):
  Utilized to reduce urinary calcium loss, which may help preserve bone density.
• Nephrogenic Diabetes Insipidus:
  May be used to reduce polyuria and polydipsia.
• Resistant Hypertension:
  Often included as part of multidrug regimens due to its potent and long-acting antihypertensive effect.

Route of Administration: Oral
Available Forms: Tablets

Adults:

• Hypertension:
  Initial: 12.5 to 25 mg once daily
  Maintenance: 12.5 to 50 mg once daily
  Maximum: 100 mg/day (doses >50 mg/day rarely provide additional benefit)
• Edema:
  Initial: 50 to 100 mg once daily or on alternate days
  Titration: Up to 200 mg/day if needed (generally not recommended to exceed this)
• Nephrolithiasis (Off-label):
  25 to 50 mg once daily
• Nephrogenic Diabetes Insipidus (Off-label):
  25 to 50 mg once or twice daily

Pediatrics:

• Use is not routinely recommended.
  If used under specialist guidance: 1–2 mg/kg/day orally in single or divided doses (maximum: 50 mg/day)

Geriatrics:

• Start at the lower end of dosing (e.g., 12.5 mg/day)
• Monitor for orthostatic hypotension and electrolyte imbalances

Renal Impairment:

• Mild to Moderate: Use with caution and monitor renal function and electrolytes
• Severe (eGFR <30 mL/min/1.73m²): Not recommended due to reduced efficacy

Hepatic Impairment:

• Use cautiously; electrolyte disturbances may precipitate hepatic encephalopathy

Chlorthalidone is a long-acting thiazide-like diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule of the nephron. It specifically blocks the Na⁺/Cl⁻ symporter, resulting in increased excretion of sodium, chloride, and water, along with potassium and hydrogen ions. The reduction in plasma volume leads to a decrease in cardiac output and, over time, a reduction in peripheral vascular resistance. These combined effects contribute to its antihypertensive action. Chlorthalidone also promotes calcium reabsorption, which is beneficial in patients with calcium kidney stones or osteoporosis.

• Absorption: Well absorbed after oral administration; bioavailability ~60–65%
• Onset of Action: 2–6 hours
• Peak Effect: 6–12 hours
• Duration of Action: Prolonged, up to 48–72 hours
• Protein Binding: Approximately 75%
• Distribution: Extensive tissue binding, particularly in red blood cells
• Metabolism: Not significantly metabolized; largely excreted unchanged
• Elimination: Renal excretion (50–65% as unchanged drug)
• Half-life: 40 to 60 hours

Pregnancy:
Chlorthalidone is not recommended during pregnancy unless clearly needed. It can reduce placental perfusion and may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Its use is generally avoided, especially in the second and third trimesters.

Lactation:
Small amounts of chlorthalidone may be excreted in breast milk. Though adverse effects are unlikely at low doses, high doses may suppress lactation and affect the nursing infant. Use with caution; monitor infant for signs of dehydration or electrolyte imbalance.

• Primary Class: Thiazide-like Diuretic
• Pharmacologic Class: Sulfonamide-derived Diuretic
• Therapeutic Role: Antihypertensive and Antiedema Agent

• Hypersensitivity to chlorthalidone, sulfonamide derivatives, or any formulation component
• Anuria
• Severe renal impairment (eGFR <30 mL/min/1.73m²)
• Hepatic coma or precoma
• Refractory hypokalemia or hyponatremia
• Symptomatic hyperuricemia or gout

• Electrolyte Imbalance: Monitor serum potassium, sodium, calcium, and magnesium; risk of hypokalemia and hyponatremia
• Volume Depletion: May cause orthostatic hypotension, especially in elderly or dehydrated patients
• Gout: May raise uric acid levels; avoid in patients with active gout
• Diabetes Mellitus: Can impair glucose tolerance; monitor blood sugar
• Photosensitivity: May cause skin sensitivity to sunlight; advise sun protection
• Renal Function: Regular monitoring required; may cause renal impairment or acute kidney injury
• Lupus Activation: Use with caution in patients with systemic lupus erythematosus
• Monitoring Parameters: Periodic serum electrolytes, blood glucose, renal function, blood pressure, and uric acid

Common Adverse Effects:

• Metabolic/Electrolyte: Hypokalemia, hyperuricemia, hyponatremia, hyperglycemia
• Gastrointestinal: Nausea, anorexia, vomiting
• Neurologic: Dizziness, headache, fatigue
• Musculoskeletal: Muscle cramps, weakness
• Dermatologic: Rash, photosensitivity

Less Common / Serious Adverse Effects:

• Hematologic: Thrombocytopenia, leukopenia, agranulocytosis (rare)
• Renal: Elevated creatinine, interstitial nephritis (rare)
• Hepatic: Jaundice
• Endocrine: Erectile dysfunction, menstrual irregularities

• Lithium: Decreased clearance; risk of lithium toxicity
• NSAIDs: May attenuate antihypertensive and diuretic effects; increased nephrotoxicity risk
• Insulin/Oral Hypoglycemics: May reduce effectiveness; monitor blood glucose closely
• ACE Inhibitors/ARBs: Risk of hypotension and hyperkalemia
• Digoxin: Increased risk of toxicity due to potassium depletion
• Corticosteroids or ACTH: Enhanced hypokalemic effect
• Alcohol: May enhance orthostatic hypotension
• Bile Acid Sequestrants (e.g., cholestyramine): Reduce absorption; separate administration by 4–6 hours

Enzyme Interactions:
Chlorthalidone is not a substrate, inducer, or inhibitor of CYP450 enzymes; minimal hepatic metabolism.

• Hypertension Treatment Guidelines (AHA/ACC, NICE):
  Chlorthalidone is preferred over hydrochlorothiazide due to its longer half-life, stronger antihypertensive effect, and superior outcome data.
• Clinical Practice Trend:
  Greater emphasis on using chlorthalidone in combination therapy for resistant or high-risk hypertension.
• 2023/2024 Update:
  No major regulatory changes in labeling or safety profile. However, awareness of electrolyte monitoring and dose adjustment is emphasized.

• Temperature: Store below 25°C (77°F)
• Humidity: Protect from moisture; store in a dry place
• Light Protection: Store in a tightly sealed container away from light
• Handling: Do not store in bathroom cabinets; keep out of reach of children
• Reconstitution: Not applicable (solid oral dosage form)