Drug Monograph
Full clinical overview, indications, dosage references & safety notes.
Available forms4 forms · 8 strengths documentedShow all ↓
Tablet 12.5 mgTablet 25 mgTablet 50 mgCapsule 12.5 mg Microzide
Spironolactone/hydrochlorothiazide 25/25 mg AldactazideSpironolactone/hydrochlorothiazide 50/50 mg AldactazideAmiloride/hydrochlorothiazide 2.5/25 mg Co-amilozide, Moduret, ModureticAmiloride/hydrochlorothiazide 5/50 mg Co-amilozide, Moduret, Moduretic
Overview
Hydrochlorothiazide (HydroDIURIL®, Microzide®) is a thiazide diuretic used in dogs and cats primarily for nephrogenic diabetes insipidus, prevention of recurrent calcium oxalate uroliths, and as adjunctive therapy in advanced congestive heart failure. Although thiazides were once used more broadly as diuretics, loop diuretics have largely replaced them for routine diuretic therapy in veterinary medicine.
In nephrogenic diabetes insipidus, hydrochlorothiazide produces a paradoxical reduction in urine output by promoting sodium loss and extracellular volume contraction, which increases proximal tubular reabsorption of sodium and water and reduces the amount of filtrate reaching the distal nephron.
Mechanism of Action (MOA): Hydrochlorothiazide inhibits sodium ion transport across the renal tubular epithelium, primarily at the cortical diluting segment of the nephron, resulting in increased excretion of sodium, chloride, and water. It also increases the excretion of potassium, magnesium, phosphate, iodide, and bromide, decreases glomerular filtration rate (GFR), increases plasma renin and aldosterone concentrations, enhances bicarbonate excretion with minimal effects on urine pH, decreases uric acid excretion, and reduces calcium excretion during long-term therapy.
Indications
Hydrochlorothiazide is used in dogs and cats for selected renal, urinary, and cardiovascular conditions. In veterinary medicine, it is most commonly used when its specific pharmacologic effects provide advantages beyond routine diuresis.
- Nephrogenic diabetes insipidus: Used to reduce urine output through its paradoxical antidiuretic effect.
- Calcium oxalate urolith prevention: Used to help prevent recurrence of calcium oxalate uroliths in dogs and potentially in cats.
- Advanced congestive heart failure: Used as adjunctive therapy, typically in combination with a loop diuretic, in advanced cases.
- Ascites: May be used as a diuretic in selected cases.
- Hypermagnesemia: May be used to enhance magnesium excretion.
- Systemic hypertension: An alternative to calcium channel blockers or renin-angiotensin-aldosterone system blockers.
- Insulinoma-related hypoglycemia: Used in dogs as an add-on to diazoxide.
Dosage (Reference)
Dog
Hydrochlorothiazide is administered orally in dogs for urinary, cardiovascular, endocrine, and metabolic disorders. Dosage varies according to the clinical indication, and close monitoring of renal function and electrolytes is recommended, particularly when combined with loop diuretics.
| Clinical use | Route | Dose | Frequency / timing | Notes |
|---|---|---|---|---|
| Prevention of recurrent calcium oxalate uroliths | PO | 2–2.2 mg/kg | q12h | Usually added when dietary treatment does not adequately control calcium oxalate crystalluria. |
| Heart failure (adjunctive therapy) | PO | 0.2–0.84 mg/kg | q24h | Alternative regimen: 0.5–4 mg/kg once or twice daily. |
| Ascites associated with liver disease | PO | 0.5–1 mg/kg | q12h | Used as the fixed-dose (1:1) combination with spironolactone; dose is based on the spironolactone content. |
| Systemic hypertension | PO | 2–4 mg/kg | q12–24h | Alternative regimen: 1 mg/kg once to twice daily; may be combined with spironolactone (1–2 mg/kg BID). |
| Nephrogenic diabetes insipidus | PO | 2 mg/kg | q12h | Administer with a low-sodium diet. |
| Nephrogenic diabetes insipidus | PO | 2.5–5 mg/kg | q12h | Alternative dosage regimen. |
| Hypoglycemia secondary to insulinoma | PO | 1–2 mg/kg | q12h | Use in conjunction with diazoxide if diazoxide alone does not adequately increase blood glucose. |
• When combined with loop diuretics, start with low doses and monitor renal values and electrolytes frequently as the dose is escalated according to clinical response.
• The fixed-dose (1:1) spironolactone/hydrochlorothiazide combination (Aldactazide®) may be considered in dogs already receiving spironolactone.
Cat
Hydrochlorothiazide is used orally in cats primarily as adjunctive therapy for heart failure and for selected urinary disorders.
| Clinical use | Route | Dose | Frequency / timing | Notes |
|---|---|---|---|---|
| Heart failure (adjunctive therapy) | PO | 1–2 mg/kg | q12h | Used in combination with furosemide in patients refractory to furosemide alone. |
| Ascites associated with liver disease | PO | 0.5–1 mg/kg | q12h | Used as the fixed-dose (1:1) combination with spironolactone; dose is based on the spironolactone content. |
| Reduce calcium oxalate saturation in urine | PO | 1 mg/kg | q12h | Study performed in healthy cats; effect in cats with naturally occurring calcium oxalate urolithiasis is unknown. |
| Nephrogenic diabetes insipidus | PO | 2.5–5 mg/kg | q12h | – |
| Central diabetes insipidus | PO | 12.5 mg/cat | q12h | Dose is expressed per cat, not mg/kg. |
| Systemic hypertension | PO | 1 mg/kg | q12h | Other agents are preferred for controlling hypertension. |
• When combined with furosemide, begin with low doses and monitor renal values and electrolytes frequently as the dose is adjusted according to clinical response.
• The fixed-dose (1:1) spironolactone/hydrochlorothiazide combination (Aldactazide®) may be considered in cats already receiving spironolactone.
Warnings & Precautions
Hydrochlorothiazide should be used cautiously in patients at risk of renal dysfunction, electrolyte disturbances, or impaired fluid balance. Careful patient selection and periodic monitoring are recommended throughout therapy.
- Contraindications: Contraindicated in patients with anuria or hypersensitivity to hydrochlorothiazide or other thiazide diuretics.
- Renal disease: Use with extreme caution, if at all, in patients with severe renal disease, as azotemia may worsen; renal impairment is listed as a contraindication, as hydrochlorothiazide tends to reduce glomerular filtration rate.
- Electrolyte and water imbalances: Use with extreme caution in patients with pre-existing electrolyte (including hypercalcemia) or fluid imbalances, and monitor closely during treatment; other references list electrolyte disturbances and high serum calcium as contraindications.
- Hepatic impairment: Use with extreme caution in patients with impaired hepatic function, as treatment may precipitate hepatic coma.
- Hyperuricemia: Use with extreme caution in patients with hyperuricemia.
- Systemic lupus erythematosus (SLE): Use with extreme caution in affected patients.
- Diabetes mellitus: Use with extreme caution, as hydrochlorothiazide may cause or exacerbate hyperglycemia.
- Vomiting or diarrhea: Patients with conditions that may lead to electrolyte or fluid loss should be monitored carefully.
- Dogs with absorptive hypercalciuria: Do not use, as hypercalcemia may result.
- Pregnancy: Safety has not been established in animals; use only when the maternal benefits outweigh the potential risks to the offspring.
- Laboratory tests: Thiazides may elevate serum calcium, so discontinuing them before parathyroid function testing is recommended.
Drug Interactions
Hydrochlorothiazide has numerous clinically important drug interactions, primarily related to electrolyte disturbances, altered antihypertensive effects, changes in drug absorption or elimination, and increased risks of nephrotoxicity or other adverse effects. Appropriate monitoring is recommended when these drugs are used concurrently.
- Amphotericin B: Concurrent use may increase the risk of severe hypokalemia.
- Bromides: May increase bromide excretion, potentially affecting seizure control and dosage requirements.
- Calcium-containing products: May exacerbate hypercalcemia.
- Cholestyramine: May reduce hydrochlorothiazide absorption.
- Corticosteroids or corticotropin: Concurrent use may increase the risk of severe hypokalemia.
- Diazoxide: May increase the risk of hyperglycemia, hyperuricemia, and hypotension.
- Digoxin: Thiazide-induced hypokalemia, hypomagnesemia, and/or hypercalcemia may increase the risk of digitalis toxicity.
- Antihypertensive agents (e.g., amlodipine, enalapril, telmisartan): May produce additive hypotensive effects, and an ACE inhibitor increases the risk of azotemia.
- Insulin: Hydrochlorothiazide may increase insulin requirements.
- Loop diuretics (e.g., furosemide, torsemide): May produce additive hypotensive, hypovolemic, and electrolyte effects; concurrent use may be appropriate in advanced heart failure with close monitoring.
- Methenamine: May have reduced effectiveness because thiazides can alkalinize the urine.
- Myelosuppressive agents (e.g., cyclophosphamide, methotrexate): May increase drug exposure and enhance myelosuppression.
- NSAIDs (e.g., carprofen, meloxicam, robenacoxib): May reduce the diuretic effect of hydrochlorothiazide and increase the risk of renal toxicity.
- Neuromuscular blocking agents: May increase the response to or prolong the effects of nondepolarizing neuromuscular blocking agents.
- Probenecid: Blocks thiazide-induced uric acid retention.
- Quinidine: May have a prolonged half-life because thiazides can alkalinize the urine.
- Vitamin D: Concurrent use may exacerbate hypercalcemia.
Side Effects & Overdose
Side Effects
Adverse effects of hydrochlorothiazide are primarily related to electrolyte disturbances, fluid imbalance, and metabolic changes, and prerenal or renal azotemia can occur. Gastrointestinal effects may occur, particularly in susceptible patients.
- Electrolyte disturbances: Hypokalemia, dilutional hyponatremia, and hypomagnesemia may occur.
- Hypochloremic metabolic alkalosis: May develop, particularly in patients with concurrent potassium or chloride losses or those receiving loop diuretics.
- Hyperuricemia: May occur but is usually subclinical.
- Hypercalcemia and hypophosphatemia: Hyperparathyroid-like effects have been reported in humans.
- Gastrointestinal effects: Vomiting and diarrhea may occur and may be more common in animals with mild azotemia.
- Hypersensitivity and dermatologic reactions: May occur in susceptible patients.
- Genitourinary effects: Polyuria may occur.
- Metabolic effects: Hyperglycemia and hyperlipidemia may occur.
- Orthostatic hypotension: May occur during treatment.
Overdose
Acute overdose primarily results in electrolyte and fluid disturbances, with neurologic and gastrointestinal manifestations. Treatment is supportive and directed toward correcting fluid and electrolyte abnormalities.
- Electrolyte and water imbalance: The most important consequence of acute overdose.
- CNS effects: Lethargy, coma, and seizures may occur.
- Gastrointestinal effects: Hypermotility and gastrointestinal distress may develop.
- Renal effects: Transient increases in blood urea nitrogen (BUN) have been reported.
- Management: Initiate gastrointestinal decontamination following recent oral ingestion using standard protocols. Avoid concomitant cathartics, monitor respiratory, neurologic, and cardiovascular status, and correct electrolyte and fluid imbalances with supportive care.
Key Notes
Practical clinical points that support the effective use of hydrochlorothiazide in dogs and cats:
- Limited role as a routine diuretic: Loop diuretics have largely replaced thiazides for general diuretic therapy in veterinary medicine.
- Sequential nephron blockade: Hydrochlorothiazide may improve diuresis when added to loop diuretics in refractory heart failure by acting at a different nephron site.
- Paradoxical antidiuretic effect: Despite being a diuretic, it reduces urine output in patients with nephrogenic diabetes insipidus.
- Administration with food: May be given with or without food; if gastrointestinal upset occurs, administer with food or a small treat.
- Maintain water access: Animals should have free access to fresh water throughout treatment.
- Owner monitoring: Advise owners to seek veterinary attention if excessive thirst, muscle weakness, collapse, fainting, head tilt, lack of urination, or a rapid heartbeat develops.
