Hydrochlorothiazide
6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
Also known as: HydroDIURIL · Microzide · Aldactazide · Hydro-Par · Ezide · Co-amilozide · Moduretic · HCTZ · hidroclorotiazida · hydrochlorothiazidum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of nephrogenic diabetes insipidus | 2 mg/kg PO twice daily with a low sodium diet | PO | twice daily | — | 🌎 NA |
| Treatment of nephrogenic diabetes insipidus | 2.5-5 mg/kg PO twice daily | PO | twice daily | — | 🌎 NA |
| Treatment of systemic hypertension | 1 mg/kg PO q12-24h | PO | q12-24h | — | 🌎 NA |
| Prevention of recurrent calcium oxalate uroliths with renal hypercalcuria | 2 mg/kg q12h PO | PO | q12h | — | 🌎 NA |
| Prevention of recurrent calcium oxalate uroliths with renal hypercalcuria | 2.2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Prevention of recurrent calcium oxalate uroliths with renal hypercalcuria | 2-4 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Diuretic for heart failure (refractory to furosemide alone) | 2-4 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Adjunctive treatment of heart failure | 2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Ascites secondary to right-sided heart failure | 2 mg/kg initially on an every other day bases | PO | every other day | — | 🌎 NA |
| Ascites in patients with liver disease | 0.5-1 mg/kg PO twice daily | PO | twice daily | — | 🌎 NA |
| As a diuretic (general) | 1-4 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Refractory congestive heart failure / Calcium oxalate urolithiasis prevention / Hypertension | 0.5-4 mg/kg | PO | q12-24h | Long-term | 🌍 EU |
- Treatment of nephrogenic diabetes insipidus: Based on a case report
- Treatment of systemic hypertension: As a second choice agent; may combine with spironolactone (1-2 mg/kg PO q12 hours) to reduce potassium loss
- Prevention of recurrent calcium oxalate uroliths with renal hypercalcuria: Usually added when dietary therapy does not adequately control calcium oxalate crystalluria
- Prevention of recurrent calcium oxalate uroliths with renal hypercalcuria: Repeat urinalysis q2-4 weeks and monitor serum electrolytes within several weeks of initial dose and within 2 weeks of dosage adjustment
- Diuretic for heart failure (refractory to furosemide alone): In combination with furosemide
- Adjunctive treatment of heart failure: When a dog requires 4-5 mg/kg PO q8h of furosemide and continues to exhibit clinical signs of congestion, reduce the furosemide dose by 50% and add hydrochlorothiazide
- Ascites secondary to right-sided heart failure: In addition to furosemide, spironolactone, ACE inhibitors, dietary sodium restriction; monitor electrolytes and renal function
- Ascites in patients with liver disease: Using the fixed-dose combination with spironolactone (Aldactazide); dosed empirically based on the spironolactone content
- Refractory congestive heart failure / Calcium oxalate urolithiasis prevention / Hypertension: Start at low dose and titrate upwards every 5-10 days, to effect. Monitor urea, creatinine, electrolytes and blood pressure before increasing dose.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of systemic hypertension | 1 mg/kg PO q12-24h | PO | q12-24h | — | 🌎 NA |
| Treatment of systemic hypertension | 2-4 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Diuretic for heart failure | 1-2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Ascites in patients with liver disease | 0.5-1 mg/kg PO twice daily | PO | twice daily | — | 🌎 NA |
| To reduce calcium oxalate saturation in urine | 1 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Refractory congestive heart failure / Calcium oxalate urolithiasis prevention / Hypertension | 1-2 mg/kg | PO | q12-24h | Long-term | 🌍 EU |
- Treatment of systemic hypertension: As a second choice agent; may combine with spironolactone (1-2 mg/kg PO q12 hours) to reduce potassium loss
- Treatment of systemic hypertension: Not effective as a single agent in cats, and may be contraindicated (e.g., chronic renal failure). Possibly helpful acutely with retinal detachment.
- Diuretic for heart failure: In combination with furosemide in patients who have become refractory to furosemide alone
- Ascites in patients with liver disease: Using the fixed-dose combination with spironolactone (Aldactazide); dosed empirically based on the spironolactone content
- To reduce calcium oxalate saturation in urine: Study done in normal cats, unknown what effect HCTZ will have in cats with spontaneously occurring calcium oxalate urolithiasis
- Refractory congestive heart failure / Calcium oxalate urolithiasis prevention / Hypertension: Start at low dose and titrate upwards cautiously. Monitor urea, creatinine, electrolytes and blood pressure.
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive therapy of hyperkalemic periodic paralysis (HyPP) | 0.5-1 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
- Adjunctive therapy of hyperkalemic periodic paralysis (HyPP): When diet adjustment does not control episodes. Note: ARCI UCGFS Class 4 Drug
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Hydrochlorothiazide (HCTZ) is a moderately efficacious thiazide diuretic that has largely been replaced by loop diuretics (like furosemide) for general edema management in veterinary medicine, but remains highly valuable for specific indications.
Key clinical uses include:
- Calcium Oxalate Urolithiasis: Used to prevent recurrence in dogs (and potentially cats) due to its unique ability to decrease urinary calcium excretion (hypocalciuric effect).
- Systemic Hypertension: Often used as an adjunctive or second-line antihypertensive agent.
- Nephrogenic Diabetes Insipidus (DI): Paradoxically reduces urine output in DI patients and serves as the primary drug therapy for the nephrogenic form.
- Refractory Heart Failure: Used sequentially with loop diuretics to overcome diuretic resistance (sequential nephron blockade).
- Hyperkalemic Periodic Paralysis (HyPP): Used in horses as an alternative to acetazolamide when dietary management is insufficient.
Clinical Pearl: While the monograph highlights "hypoglycemia" in the prescriber highlights, thiazides are actually known to cause or exacerbate hyperglycemia by decreasing insulin release and peripheral glucose utilization. They are occasionally used to manage hyperinsulinemic hypoglycemia (e.g., insulinoma), though diazoxide is more common.
Mechanism of action
Hydrochlorothiazide acts primarily on the distal convoluted tubule (DCT) (cortical diluting segment) of the nephron.
- Diuretic Effect: It competitively antagonizes the Na⁺/Cl⁻ cotransporter (NCC) → inhibits sodium and chloride reabsorption → enhances excretion of Na⁺, Cl⁻, and water.
- Electrolyte Alterations: Increased distal delivery of Na⁺ stimulates the renin-angiotensin-aldosterone system (RAAS) → increased aldosterone → enhanced secretion of K⁺ and H⁺ (leading to hypokalemia and metabolic alkalosis). It also increases excretion of magnesium, phosphate, iodide, and bromide.
- Calcium Sparing: Unlike loop diuretics, thiazides decrease calcium excretion. By depleting intracellular Na⁺ in the DCT, they enhance the activity of the basolateral Na⁺/Ca²⁺ exchanger → increased calcium reabsorption into the blood.
- Paradoxical Effect in Diabetes Insipidus: Mild volume depletion induced by the diuretic → compensatory increase in proximal tubule reabsorption of Na⁺ and water → decreased delivery of water to the distal nephron → overall reduction in polyuria.
Safety & warnings
Contraindications
- Hypersensitivity to thiazides or sulfonamides
- Anuria
- Pregnancy (relative contraindication in otherwise healthy patients with mild edema)
- Dogs with absorptive (intestinal) hypercalciuria (may result in hypercalcemia)
- Renal impairment (due to reduction in GFR)
- Severe electrolyte imbalances (e.g., severe hypokalaemia or hyponatraemia)
Adverse effects
- Hypokalemia (most common)
- Hypochloremic alkalosis
- Dilutional hyponatremia
- Hypomagnesemia
- Hypercalcemia (hyperparathyroid-like effects)
- Hypophosphatemia
- Hyperuricemia
- Gastrointestinal reactions (vomiting, diarrhea)
- Polyuria
- Hyperglycemia
- Hyperlipidemias
- Orthostatic hypotension
- Hypersensitivity/dermatologic reactions
- Hypokalaemia
- Hyponatraemia
- Hypochloraemia
- Hyperglycaemia
- Volume contraction (dehydration)
- Activation of the renin-angiotensin-aldosterone system (RAAS)
Precautions
Extreme Caution/Avoid: Severe renal disease, preexisting electrolyte (including hypercalcemia) or water balance abnormalities, impaired hepatic function (may precipitate hepatic coma), hyperuricemia, systemic lupus erythematosus (SLE), or diabetes mellitus.
Monitoring: Patients with conditions that may lead to electrolyte or water balance abnormalities (e.g., vomiting, diarrhea) should be monitored carefully. Chronic therapy requires monitoring of serum potassium.
Laboratory Test Interferences: May increase serum amylase, decrease renal excretion of cortisol, falsely decrease total urinary estrogen, cause false-negative histamine tests for pheochromocytoma, elevate serum calcium (discontinue prior to parathyroid testing), compete for PSP secretion, cause false-negative phentolamine tests, decrease protein-bound iodine, slightly reduce T3 resin uptake, and cause false-negative tyramine tests.
Drug interactions
Increased risk for severe hypokalemia
Increased risk for severe hypokalemia
Increased risk for hyperglycemia, hyperuricemia, and hypotension
Thiazide-induced hypokalemia, hypomagnesemia, and/or hypercalcemia may increase the likelihood of digitalis toxicity
Thiazides may increase insulin requirements
Thiazides can increase serum lithium concentrations
Thiazides can alkalinize urine and reduce methenamine effectiveness
Thiazides may increase risk for renal toxicity and NSAIDs may reduce diuretic actions of thiazides
Tubocurarine or other nondepolarizing neuromuscular blocking agents response or duration of effect may be increased
Blocks thiazide-induced uric acid retention (used to therapeutic advantage)
Half-life may be prolonged by thiazides (thiazides can alkalinize the urine)
Hypercalcemia may be exacerbated if thiazides are concurrently administered
Increased risk of developing hypokalaemia.
Synergistic diuresis (sequential nephron blockade) but significantly increased risk of hypokalaemia and dehydration.
Concurrent administration may exacerbate hypercalcaemia.
Concurrent administration may exacerbate hypercalcaemia.
Monitoring
- Serum electrolytes (especially potassium, sodium, chloride, calcium, magnesium)
- Renal function (BUN, Creatinine)
- Hydration status and body weight
- Blood pressure (if treating hypertension)
- Urine output and clinical signs of congestion (if treating heart failure)
- Blood Urea Nitrogen (BUN)
- Serum Creatinine
- Serum Electrolytes (Potassium, Sodium, Chloride, Calcium)
Pharmacokinetics
Half-life
Absorption
In humans, hydrochlorothiazide is about 65-75% absorbed after oral administration. Onset of diuretic activity occurs in 2 hours; peaks at 4-6 hours.
Distribution
Not specifically described in domestic animals.
Metabolism
The drug is apparently not metabolized.
Elimination
Excreted unchanged into the urine. In humans, the serum half-life is approximately 5.6-14.8 hours and duration of activity is 6-12 hours.
Overdose
Acute overdosage may cause:
- Electrolyte and water balance problems (hypokalemia, hyponatremia, dehydration)
- CNS effects (ranging from lethargy to coma and seizures)
- GI effects (hypermotility, GI distress)
- Transient increases in BUN
Treatment:
- Empty the gut after recent oral ingestion using standard protocols.
- Avoid concomitant cathartics as they may exacerbate fluid and electrolyte imbalances.
- Monitor and treat electrolyte and water balance abnormalities supportively.
- Monitor respiratory, CNS, and cardiovascular status; treat supportively and symptomatically if required.
Available products
Formulations
- Oral Tablets
- Oral Capsules
- Oral Suspension (Compounded)
- 25 mg hydrochlorothiazide / 2.5 mg amiloride tablets
- 50 mg hydrochlorothiazide / 5 mg amiloride tablets
Veterinary
- None (ARCI Class 4 substance)
Human-labeled
- Hydrochlorothiazide Oral Tablets: 25 mg, 50 mg, & 100 mg (HydroDIURIL, Hydro-Par, Ezide, generic)
- Hydrochlorothiazide Oral Capsules: 12.5 mg (Microzide, generic)
- Spironolactone/Hydrochlorothiazide Oral Tablets: 25 mg/25 mg & 50 mg/50 mg (Aldactazide, generic)
- Co-amilozide tablets (25 mg hydrochlorothiazide / 2.5 mg amiloride)
- Co-amilozide tablets (50 mg hydrochlorothiazide / 5 mg amiloride)
- Moduretic
Regulatory status
Available as human generic (Co-amilozide) or branded products. Used under the cascade.
POM (Prescription Only Medicine). Used under the prescribing cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Capsules and tablets should be stored at room temperature in well-closed containers. Compounded liquid preparations should be protected from light. A compounded suspension with spironolactone in Ora-Plus/Ora-Sweet retains >90% potency for 60 days at 5°C and 25°C.
Client information
Hydrochlorothiazide (HCTZ) is a "water pill" (diuretic) used to treat fluid retention, high blood pressure, certain types of kidney stones (calcium oxalate), and a specific water-balance disorder called diabetes insipidus.
- Increased Urination: Your pet will likely urinate more frequently and in larger amounts. Ensure they always have access to fresh, clean drinking water unless your veterinarian has specifically restricted it.
- Bathroom Breaks: Dogs will need to be let outside more often to prevent indoor accidents. Ensure litter boxes are kept clean for cats.
- Watch for Imbalances: Because this drug removes water and salts from the body, watch for signs of dehydration or low potassium. Contact your veterinarian immediately if you notice:
- Excessive thirst or extreme lethargy/weakness
- Restlessness or confusion
- Vomiting or diarrhea (which can worsen fluid loss)
- A sudden decrease in urination
- Give with Food: If the medication upsets your pet's stomach, try giving it with a small meal or treat.
- Do Not Stop Abruptly: If treating heart failure or high blood pressure, do not stop giving this medication without consulting your veterinarian, as symptoms can rapidly return.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.