What is Diuril (chlorothiazide), including its indications, typical dosing, contraindications, side effects, and monitoring recommendations?

Diuril (Chlorothiazide): Clinical Overview

What is Diuril?

Diuril is the brand name for chlorothiazide, a thiazide-type diuretic that acts on the distal convoluted tubule of the kidney to promote sodium and water excretion. 1

Primary Indications

Diuril is indicated for managing fluid overload and hypertension, though it is not a first-line agent for hypertension in modern practice. 2, 1

• Heart failure with congestion: Use to relieve breathlessness and edema in patients with symptoms and signs of fluid overload, always combined with an ACE inhibitor (or ARB), beta-blocker, and mineralocorticoid receptor antagonist in patients with reduced ejection fraction 2
• Hypertension: While thiazide diuretics have proven cardiovascular benefit, chlorthalidone and hydrochlorothiazide are preferred over chlorothiazide due to superior outcome data 3, 4
• Edema from various causes: Including renal disease, though loop diuretics are often more effective in advanced chronic kidney disease 5

Typical Dosing

• Initial dose: 500-1000 mg once or twice daily 2
• Maintenance dose: Adjust to the minimum dose necessary to maintain euvolemia (the patient's "dry weight") 2
• Maximum dose: Up to 2000 mg daily in divided doses, though higher doses increase adverse effects without proportional benefit 2

Contraindications

• Anuria or severe renal dysfunction (creatinine >221 μmol/L [>2.5 mg/dL] or eGFR <30 mL/min/1.73 m²) 2
• Known allergic reaction to sulfonamide-derived drugs 2
• Significant hypokalaemia (K+ ≤3.5 mmol/L) that may be worsened by diuretic therapy 2
• Symptomatic or severe hypotension (systolic blood pressure <90 mmHg) 2
• Never indicated if the patient has never had symptoms or signs of congestion 2

Common Side Effects and Adverse Reactions

Electrolyte Disturbances

• Hypokalaemia: Most common metabolic complication, can contribute to ventricular ectopy and possible sudden death 2, 1
• Hyponatraemia: Occurs in up to 17% of elderly patients, may contribute to confusion, delirium, and irreversible brain damage 6
• Hyperuricaemia: Results from volume contraction and competition with uric acid for renal tubular secretion, may precipitate gout 1
• Hyperglycaemia: Thiazides have diabetogenic activity, though this does not reduce efficacy in preventing cardiovascular events 4

Volume-Related Effects

• Hypovolaemia and dehydration: Leading to postural hypotension and falls 2
• Pre-renal azotaemia: Particularly in patients with baseline renal impairment 2

Other Effects

• Nocturia and poor sleep: Due to increased urinary frequency 2
• Metabolic disturbances: Including hyperlipidemia 2

Critical Monitoring Requirements

Initial Phase (First 1-2 Weeks)

• Check renal function and electrolytes within 1-2 weeks after initiation or any dose increase 2
• Monitor blood pressure to assess therapeutic response and avoid excessive hypotension 2

Ongoing Monitoring

• Serum potassium: Most critical parameter, as hypokalaemia increases arrhythmia risk 2, 1
• Serum sodium: Especially in elderly patients at heightened risk of hyponatraemia 2
• Renal function (creatinine/eGFR): Watch for worsening azotaemia 2
• Uric acid levels: Monitor for hyperuricaemia, particularly in patients with gout history 1
• Fasting glucose: Periodic monitoring for new-onset hyperglycemia 1

High-Risk Populations Requiring Closer Monitoring

• Elderly patients (≥75 years): Higher risk of hyponatraemia, falls, and confusion 2, 6
• Patients with chronic kidney disease: Risk of worsening renal function and electrolyte disturbances 2
• Patients with poor mobility or urinary incontinence: Diuresis may worsen functional status 2

Important Drug Interactions

• NSAIDs: May attenuate diuretic effect and cause renal impairment; avoid unless essential 2, 1
• ACE inhibitors/ARBs: Risk of hypotension (usually manageable) and additive effects on renal function 2
• Combination with other diuretics (loop or thiazide): Increased risk of hypovolaemia, hypotension, hypokalaemia, and renal impairment 2
• Beta-blockers: May increase fatigue, lethargy, and glucose intolerance when combined 1
• Digoxin: Thiazide-induced hypokalaemia increases digoxin toxicity risk 2

Clinical Pitfalls and Cautions

Common Prescribing Errors

• Using as first-line for hypertension: Chlorothiazide is not the preferred thiazide; chlorthalidone or hydrochlorothiazide have superior outcome data 3, 4
• Excessive dosing in heart failure: Doses often reflect acute decompensation requirements rather than maintenance needs, leading to "morbus diureticus" 6
• Inappropriate use for peripheral edema: Not indicated for obesity-related edema, calcium antagonist-induced edema, or venous insufficiency 6
• Failure to discontinue when not needed: Diuretics should be reassessed at 3-6 month intervals with consideration for dose reduction or discontinuation 6

Special Populations

• Patients with gout: Thiazides may precipitate acute attacks unless patient is on uric acid-lowering therapy 2, 1
• Patients with diabetes or metabolic syndrome: Despite theoretical concerns about hyperglycemia, thiazides remain effective for cardiovascular protection 1, 4
• Patients with HFpEF: Avoid excessive diuresis, which can worsen symptoms 2

Patient Education Points

• Expect rapid symptom improvement: Usually within days of starting treatment for congestion 2
• Report excessive thirst: May indicate overdiuresis; avoid excessive consumption of hypotonic fluids which can cause hyponatraemia 2
• Report dizziness or lightheadedness: May indicate symptomatic hypotension requiring dose adjustment 2
• Avoid over-the-counter NSAIDs: Can cause diuretic resistance and renal impairment 2
• Monitor weight regularly: Patients can be trained to adjust their own dose based on symptoms, signs, and weight changes 2
• Reduce dose with fluid loss: From diarrhea, vomiting, or excessive sweating 2

When to Consider Alternative Agents

• For hypertension: Chlorthalidone 12.5-25 mg daily is preferred over chlorothiazide due to superior cardiovascular outcome data 3, 4
• For advanced CKD (eGFR <30 mL/min/1.73 m²): Loop diuretics are more effective than thiazides, though chlorthalidone may still have a role 5
• For acute volume overload: Loop diuretics (furosemide, bumetanide, torsemide) provide more rapid and potent diuresis 7, 1