Are there prescription medicines I should avoid if I am taking chlorthalidone?

The prescribing information for dofetilide cites a drug interaction with hydrochlorothiazide (HCTZ).¹ Co-administration of dofetilide (500 mcg twice daily) with HCTZ (50 mg once daily) for five days, followed by two days of HCTZ at half dose, resulted in an increased dofetilide plasma concentration by 27% and an increased maximum serum concentration of dofetilide of 21%.¹ QTc prolongation caused by dofetilide increased 197% overtime, with a 95% increase in maximum interval prolongation with HCTZ co-administration.¹ Although the listed contraindication specifically notes hydrochlorothiazide, thiazides are often considered equivalent to thiazide-like diuretics,² therefore the likelihood of chlorthalidone producing a similar interaction should be considered. Furthermore, dofetilide prescribing information cautions the use of potassium-depleting diuretics as hypokalemia or hypomagnesemia may occur, increasing the potential for Torsade de Pointes.¹ Studies have found that chlorthalidone causes a greater reduction in potassium than HCTZ.^3-5

The promazine hydrochloride drug label also notes increased risk of hypokalemia when promazine hydrochloride is taken with diuretics which can increase the risk of ventricular arrhythmias, including Torsade de Pointes.⁶

Levosulpride (which is not used in the United States) and mecamylamine are also categorized as drugs to avoid combining with chlorthalidone.⁷ Thiazide and thiazide-like diuretics may enhance adverse/toxic effects of levosulpride and mecamylamine. ⁷ Urinary excretion of mecamylamine is pH dependent, where alkalinization of urine reduces and acidification increases excretion.⁸ The pH sensitive elimination of mecamylamine along with the possibility of electrolyte disturbances caused by diuretics⁷ may be involved in the mecamylamine and thiazide-like diuretics interaction.

There are numerous potential interactions between diuretics and other pharmaceuticals.

Bile acid sequestrants such as cholestyramine and colestipol may decrease the efficacy of thiazide and thiazide-like diuretics.^9-11 Studies have shown that combination therapy of bile acid sequestrants with thiazide and thiazide-like diuretics reduce serum concentration of the diuretic. In one study, co-administration with cholestyramine reduced plasma concentration of HCTZ by >50%.⁹ A follow-up study found that dosing cholestyramine four hours after HCTZ to be the most ideal dosing schedule, although plasma concentration of HCTZ still decreased by at least 30% to 35%.¹⁰

Diuretics may increase the risk of acute phosphate nephropathy in patients taking sodium phosphates such as OsmoPrep and Visicol. ^12-14

Amifostine, a cytoprotective agent used during chemotherapy and radiation¹⁵, and obinutuzumab, a chemotherapy drug¹⁶, may cause hypotension when used with diuretics.^15,16

In a pharmacokinetic study, drug interactions between topiramate and three antihypertensive agents (diltiazem, HCTZ, and propranolol) were evaluated. Renal clearance of topiramate decreased 22-30% (P<0.05) and systemic exposure increased 27-29% when taken with 25 mg of hydrochlorothiazide.¹⁷ The prescribing information for topiramate lists an interaction with thiazides and thiazide-like diuretics, citing an increased risked of hypokalemia when the two drugs are taken concurrently.¹⁸ Incidence of hypokalemia with combination therapy of HCTZ and topiramate was 61% compared to monotherapy, which was 27% with topiramate and 25% with HCTZ.¹⁸

A few studies provide evidence of an interaction between diuretics and lithium.^19-22 Concurrent use of lithium and thiazide diuretics can lead to an increased concentration of lithium.²³ Thiazide diuretics increase reabsorption of sodium in the proximal tubule. This subsequently causes reabsorption of lithium which leads to decreased elimination of lithium and the potential for lithium toxicity.²³

^References

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16. Gazyva Full Prescribing Information. 2016. Accessed 02/16/2017.
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