Side Effects of Chlorthalidone
Chlorthalidone commonly causes electrolyte abnormalities, particularly hypokalemia, which occurs at significantly higher rates compared to other thiazide diuretics. 1, 2, 3
Major Side Effects
Electrolyte Abnormalities
- Hypokalemia: Most significant concern
- Hyponatremia: 1.68 times higher risk compared to hydrochlorothiazide 3
- Hyperuricemia: Dose-dependent increase in uric acid levels 4
Metabolic Effects
- Hyperglycemia and glycosuria: Small increases in fasting glucose (1.5-4.0 mg/dL) 1, 2
- Hyperlipidemia: May affect cholesterol levels
Cardiovascular Effects
- Orthostatic hypotension: May be aggravated by alcohol, barbiturates, or narcotics 2
Gastrointestinal Effects
- Anorexia, gastric irritation, nausea, vomiting
- Cramping, diarrhea, constipation
- Jaundice (intrahepatic cholestatic)
- Pancreatitis 2
Central Nervous System Effects
- Dizziness, vertigo, paresthesias
- Headache, xanthopsia (yellow vision)
- Restlessness 2
Hematologic Effects
- Leukopenia, agranulocytosis
- Thrombocytopenia, aplastic anemia 2
Dermatologic/Hypersensitivity Reactions
- Purpura, photosensitivity, rash, urticaria
- Necrotizing angiitis (vasculitis, cutaneous vasculitis)
- Lyell's syndrome (toxic epidermal necrolysis) 2
Other Effects
- Sexual dysfunction: Higher incidence of erection problems 1
- Muscle spasm, weakness 2
- Reversible increases in serum creatinine 6
Risk Factors and Dose Considerations
The risk of side effects increases with higher doses:
- 25 mg daily is often as effective as 50 mg for blood pressure control 7
- Lower doses (12.5 mg) can be effective while minimizing adverse effects 8
- Patients with advanced chronic kidney disease require careful monitoring 5, 6
Monitoring Recommendations
Electrolytes: Check within 2-4 weeks after initiation or dose changes 5
- Monitor potassium levels closely, especially in patients also on loop diuretics
Renal function: Monitor eGFR, particularly in patients with pre-existing kidney disease 5
Metabolic parameters: Check uric acid and glucose periodically
Blood pressure: Home monitoring to avoid hypotension (SBP < 110 mm Hg) 5
Risk Mitigation Strategies
Dose optimization: Use lowest effective dose (typically 12.5-25 mg) 7, 8
Combination therapy: Consider combining with potassium-sparing agents when appropriate 1
Medication adjustments: Instruct patients to hold or reduce doses during periods of decreased oral intake, vomiting, or diarrhea 5
Special populations: Use with caution in elderly patients due to increased risk of hyponatremia 5
Pitfalls and Caveats
- Chlorthalidone has a longer half-life (40-60 hours) than hydrochlorothiazide (6-12 hours), leading to more sustained effects on electrolytes 1
- Despite higher rates of electrolyte abnormalities, chlorthalidone may be more effective for blood pressure control in certain populations, including those with advanced CKD 6
- Medication should be reduced or withdrawn if adverse reactions become moderate to severe 2
When side effects occur, consider dose reduction before discontinuation, as lower doses often maintain efficacy while reducing adverse effects 4, 7, 8.