Hydrochlorothiazide

Abdelwahab Ward, BS Pharm, PharmD
DIURETICS...
MECHANISM OF ACTION ã…¡ Thiazide diuretic; inhibits sodium reabsorption in distal renal tubules, resulting in increased excretion of water and of sodium, potassium, and hydrogen ions.

  • Prevention of calcium nephrolithiasis.
      • Initial: 25 mg orally once daily; titrate based on tolerance and urinary calcium levels to usual effective dose of 50 to 100 mg/day in 1 to 2 divided doses.
  • Diabetes insipidus, nephrogenic (off-label use).
      • Note: Consider for use in addition to a low-solute diet to help reduce polyuria.
      • 25 mg orally once or twice daily.
  • Edema, refractory (adjunctive to loop diuretic).
      • Note: Reserve for patients without hypokalemia.
      • Initial: 25 to 100 mg orally daily in 1 to 2 divided doses; adjust dose based on response and tolerability; maximum daily dose: 200 mg/day. Some experts favor twice-daily dosing.
  • Hypertension.
      • Note: When a thiazide diuretic is chosen, chlorthalidone or indapamide is preferred. For patients who warrant combination therapy (blood pressure ≥ 20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use in combination with another appropriate agent (e.g. angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, dihydropyridine calcium channel blocker). However, some experts prefer regimens that do not include thiazide diuretics for combination therapy.
      • Initial: 12.5 to 25 mg once daily; titrate as needed based on patient response up to 50 mg once daily; some experts do not recommend doses higher than 25 mg/day because of greater adverse effects without additional antihypertensive effect.
  • Hypersensitivity to sulfonamide-derived drugs. Anuria. Severe renal impairment. 
  • Special Precautions.
      • Patient with electrolyte or fluid disturbances, gout, history or at high risk of skin cancer (e.g. light-coloured-skin, immunosuppression), Addison’s disease, SLE, ascites due to cirrhosis and diabetes.
  • Onset of action: Diuresis, ~2 hr; hypertension, 3-4 days.
  • Peak plasma time: 1-2.5 hr.
  • Peak effect: Diuresis, 4-6 hr.
  • Absorption: Rapidly and well-absorbed from the gastrointestinal tract. Bioavailability: Approx 65-75%. Time to peak plasma concentration: Approx 1-5 hours.
  • Distribution: Crosses the placenta and enters the breast milk. Volume of distribution: 3.6-7.8 L/kg. Plasma protein binding: Approx 40-68%.
  • Excretion: Mainly via urine (≥61% as unchanged drug). Elimination half-life: Approx 5-15 hours.
  • Significant: Photosensitivity, non-melanoma skin cancer (NMSC) (long-term use), SLE, electrolyte imbalance (e.g. hyponatremia, hypokalemia, hypochloremic alkalosis, hypomagnesemia).
  • Metabolism and nutrition disorders: Hyperglycaemia, glycosuria, hyperuricemia.
  • Cardiac disorders: Hypotension, orthostatic hypotension.
Abdelwahab Ward, BS Pharm, PharmD