Thiazide diuretics

Drug interaction
  • Thiazides: Bendroflumethiazide, Chlorothiazide, Hydrochlorothiazide, Hydroflumethiazide, Polythiazide
  • Thiazide-like: Chlorthalidone, Indapamide, Metolazone, Xipamide

 

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Thiazide diuretics

Interacting drugPharmacodynamic interactionPharmacokinetic interactionClinical implications
α-blockersIncreased risk of 1st-dose hypotension with α-blockersMonitor BP
ACE inhibitors/ARBsPotentiation of the antihypertensive effectsThe risk of hypotension can be minimized by discontinuing or reducing the dose of the diuretic, gradual titration of RAAS inhibitors and careful monitoring of BP
Alcohol
General anesthetics
Baclofen
Barbiturates
MAO inhibitors
Opioids
Tizanidine
TADs
Increase the risk of orthostatic hypotensionMonitor BP
AllopurinolCoadministration of thiazides with allopurinol increases the risk of severe allergic reactions in patients with CKDClose monitoring of patients, particularly those with chronic kidney disease
Antiarrhythmics: - Class IA and IIIThiazides produce hypopotassemia and increase the risk of torsades de pointes Monitor the ECG.
Antigout agentsThiazides can increase uric acid levelsIt may be necessary to increase the dose of antigout agents
Antihypertensive agentsAdditive effect or potentiation of the antihypertensive effects Monitor BP
Bile-acid binding resins:
- Cholestyramine
- Colestipol
Decrease the diuretic and antihypertensive effectsCholestyramine and colestipol reduce the absorption of the diureticReadjust the dose of the diuretic. Administer 2 to 3 hours apart
DigitalisThiazides increase potassium and magnesium loss and may increase the risk of toxicityMonitor digitalis response
Drugs producing hypokalemia:
- Antimicrobial: amphotericin B, Aminoglycosides, Penicillins*
- β-adrenergic agonists
- Cisplatin
- Corticosteroids
- Fludrocortisone
- Insulin (high dose)
- Laxatives
- Ritodrine
- Theophylline
The increase the risk of hypokalemia Monitor serum potassium levels and signs of hypokalemia (ECG, fatigue, muscular pain). Administer potassium salts if necessary
GlucocorticoidsGlucocorticoids inhibit the diuretic and antihypertensive effects. They produce hypopotassemia and hyperglycemia and increase potassium lossMonitor serum potassium and plasma glucose levels as well as the diuretic and antihypertensive effects
Insulin and oral hypoglycaemic agentsThiazides inhibit the release of insulin from the pancreas and may reduce the effectiveness of hypoglycaemic drugsMonitor plasma glucose levels. Dose adjustment of the antidiabetic drug may be required
LithiumThiazides increases the risk of lithium toxicity. In patients with lithium-induced nephrogenic diabetes insipidus, thiazides paradoxically decrease urine volume and increase urine osmolarityThiazides reduce the renal clearance of lithiumLithium levels should be monitored closely
Loop diureticsThey deliver a greater fraction of filtered Na+ to the site of action of thiazides in the distal tubule. Their combination produces a synergistic diuretic effect. This combination can be used in patients resistant to diuretic monotherapy
Nephrotoxic drugs:
- Aminoglycosides
- Cisplatin
Their nephrotoxic effects may be potentiated by thiazides.Monitor the renal function.
Non-depolarizing neuromuscular blockersThiazides produce hypokalemia and potentiate their effects Monitor the response and change the dose accordingly
NSAIDsInhibit the diuretic effects of thiazides. NSAIDs cause Na+ retention and can predispose to functional renal insufficiency and heart failureMonitor the diuretic response
Oral contraceptives Inhibit the diuretic effects of thiazides. Monitor the diuretic response and increase the diuretic dose if needed
Quinidine Thiazides can increase renal tubular reabsorptionMonitor the ECG. AVoid the combination
QTc prolonging drugsThiazides produce hypopotassemia and hypomagnesemia and increase the risk of torsades de pointesMonitor the QT on the ECG. Avoid QT prolonging drugs
Potassium-sparing diuretics:
- Amiloride
- Eplerenone
- Spironolactone
- Triamterene
Exert additive diuretic effects and reduce the risk of hypokalemia and of of cardiac arrhythmiasMonitor BP and electrolyte balance. Potassium-sparing diuretics are preferred to K+ supplements as they correct both hypokalemia and hypomagnesemia
Vitamin D preparations and Ca2+ saltsThiazides decrease renal Ca2+ excretion and increase the risk of hypercalcemiaThiazides decrease the urinary excretion of calciumMonitor calcium plasma levels

 

Disclaimer: The information contained in these tables is intended for use by medical professionals and is for informational purposes only. The tables do not cover all possible drug interactions. As a medical professional you retain full responsibility and should use your own clinical judgement and expertise. Although we attempt to provide accurate and up-to-date information, no guarantee is made to that effect.