Hydrochlorothiazide is a widely prescribed thiazide diuretic, recognized for its efficacy in managing hypertension and fluid retention. As a first-line antihypertensive agent, it works by promoting sodium and water excretion, thereby reducing blood volume and peripheral vascular resistance. Its well-established safety profile, cost-effectiveness, and compatibility with other cardiovascular medications make it a cornerstone in clinical practice for both monotherapy and combination regimens.

Features

• Active ingredient: Hydrochlorothiazide
• Drug class: Thiazide diuretic
• Available formulations: Oral tablets (12.5 mg, 25 mg, 50 mg)
• Mechanism: Inhibits sodium-chloride symporter in distal convoluted tubule
• Onset of action: Within 2 hours post-administration
• Duration: 6–12 hours
• Bioavailability: Approximately 50–70%
• Half-life: 5.6–14.8 hours

Benefits

• Significantly reduces systolic and diastolic blood pressure, lowering cardiovascular risk
• Effectively alleviates edema associated with heart failure, hepatic cirrhosis, and renal disorders
• Minimizes calcium excretion, offering potential protective effects against osteoporosis
• Compatible with multiple drug classes (e.g., ACE inhibitors, ARBs) for synergistic hypertension management
• Cost-effective therapy with widespread availability and generics
• Reduces risk of stroke, myocardial infarction, and heart failure in hypertensive patients

Common use

Hydrochlorothiazide is primarily indicated for the management of essential hypertension, either as monotherapy or in combination with other antihypertensive agents. It is also employed in the treatment of edema due to congestive heart failure, hepatic cirrhosis, corticosteroid or estrogen therapy, and renal dysfunction, including nephrotic syndrome. Off-label uses may include prevention of recurrent calcium-containing kidney stones and adjunct treatment in diabetes insipidus.

Dosage and direction

For hypertension, the initial adult dose is typically 12.5–25 mg once daily, which may be titrated to 50 mg daily based on therapeutic response. Edema management usually begins with 25–100 mg daily, administered in single or divided doses, though higher doses are rarely more effective and increase adverse effect risks. Administration in the morning is advised to minimize nocturia. Dosage should be individualized considering renal function, electrolyte balance, and concomitant medications. In elderly patients or those with impaired renal function, lower initial doses are recommended.

Precautions

Regular monitoring of serum electrolytes (particularly potassium, sodium, and magnesium), BUN, creatinine, and uric acid is essential, especially during initial therapy or after dosage adjustments. Use with caution in patients with sulfonamide hypersensitivity due to cross-reactivity risk. Hepatic impairment may precipitate hepatic encephalopathy; discontinue if progressive liver injury is suspected. Photosensitivity reactions may occur—advise sunscreen use and protective clothing. Caution is warranted in patients with history of gout or hyperuricemia, as hydrochlorothiazide may exacerbate these conditions.

Contraindications

Hydrochlorothiazide is contraindicated in patients with anuria or known hypersensitivity to hydrochlorothiazide or other sulfonamide-derived drugs. It should not be used in patients with refractory hypokalemia, hypercalcemia, or Addison’s disease. Concurrent use with lithium is contraindicated due to increased lithium toxicity risk. Avoid in severe renal impairment (eGFR <30 mL/min) due to reduced efficacy and heightened electrolyte disturbance risk.

Possible side effect

Common adverse reactions include hypokalemia, hyperuricemia, hyperglycemia, hyponatremia, hypochloremic alkalosis, and hypercalcemia. Gastrointestinal effects such as nausea, vomiting, diarrhea, or constipation may occur. Dizziness, lightheadedness, and headache are frequently reported, especially during initiation. Photosensitivity, rash, and impotence have been observed. Rare but serious side effects include pancreatitis, jaundice, aplastic anemia, Stevens-Johnson syndrome, and orthostatic hypotension.

Drug interaction

Hydrochlorothiazide may potentiate hypotensive effects of other antihypertensives, alcohol, or barbiturates. It can reduce renal clearance and increase toxicity of lithium—monitor lithium levels closely. Corticosteroids, amphotericin B, and stimulant laxatives may exacerbate hypokalemia. NSAIDs can diminish its antihypertensive and diuretic efficacy. Cholestyramine and colestipol may reduce absorption. It may enhance hyperglycemic effects of diazoxide and hypoglycemic requirements in diabetics.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. If it is near the time for the next dose, skip the missed dose and resume the regular schedule. Do not double the dose to catch up. Consistent daily timing optimizes therapeutic effect and minimizes electrolyte fluctuations.

Overdose

Symptoms of overdose include profound electrolyte depletion (hypokalemia, hyponatremia), dehydration, hypotension, drowsiness, and gastrointestinal disturbances. Hemoconcentration and hemodynamic instability may occur. Management involves gastric lavage if recent ingestion, followed by supportive measures including IV fluids and electrolyte replacement. There is no specific antidote; treatment should focus on symptomatic care and continuous monitoring of vital signs and electrolyte balance.

Storage

Store at controlled room temperature (20–25°C or 68–77°F), in a tightly closed container, protected from light and moisture. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging. Avoid storing in bathrooms or damp areas to prevent degradation.

Disclaimer

This information is intended for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider for personalized recommendations based on individual health status and concurrent medications. Do not initiate, adjust, or discontinue hydrochlorothiazide without medical supervision.

Reviews

Clinical trials and meta-analyses consistently demonstrate hydrochlorothiazide’s efficacy in reducing blood pressure and cardiovascular events. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) affirmed thiazides as first-line therapy. However, some studies note metabolic side effects like hypokalemia and glucose intolerance, underscoring the need for monitoring. Overall, it remains a foundational agent in hypertension guidelines worldwide due to its proven benefits and cost-effectiveness.