Hydrochlorothiazide drug interactions
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Hydrochlorothiazide Drug Interactions: Overview and Key Findings
Hydrochlorothiazide (HCTZ) is a widely used diuretic, often prescribed in combination with other antihypertensive or chronic disease medications. Understanding its drug interactions is important for safe and effective therapy.
Interactions with Antihypertensive Agents
Angiotensin Receptor Blockers (ARBs): Telmisartan, Losartan, Valsartan, Olmesartan
Studies show that co-administration of HCTZ with ARBs such as telmisartan, losartan, and olmesartan does not result in clinically significant pharmacokinetic interactions. The absorption and systemic exposure of both drugs remain within bioequivalence ranges, and no major changes in efficacy or safety are observed when these drugs are used together in fixed-dose combinations or as separate tablets 123. However, when HCTZ is combined with valsartan, there is a significant decrease in the systemic exposure and absorption intensity of valsartan, though the decrease in HCTZ exposure is not significant. This suggests a possible interaction specific to valsartan that may not apply to all ARBs, and further research is recommended .
Calcium Channel Blockers: Amlodipine
When HCTZ is combined with amlodipine, either alone or as part of a triple therapy with telmisartan, there is no significant impact on the pharmacokinetics of any of the drugs. The combination is well tolerated and does not require dose adjustments .
Other Antihypertensive Combinations: Fimasartan
In animal studies, the combination of HCTZ with fimasartan and amlodipine did not show significant pharmacokinetic interactions, supporting the safety of such multi-drug regimens .
Interactions with Other Drug Classes
SGLT2 Inhibitors: Henagliflozin
Co-administration of HCTZ with the SGLT2 inhibitor henagliflozin slightly alters the maximum concentration (Cmax) of both drugs, but these changes are not clinically meaningful. No dose adjustment is needed, and the combination is generally safe, with only mild adverse events reported .
Anticancer Agents: Cyclophosphamide
Despite database warnings, real-world data in older women with breast cancer show that using HCTZ with cyclophosphamide does not increase the risk of neutropenia-related hospitalizations or early chemotherapy discontinuation. This suggests the interaction may not be as severe as previously thought .
Antiparasitic Agents: Ivermectin
In silico studies suggest that HCTZ may inhibit the CYP3A4 enzyme, potentially reducing the metabolism and clearance of ivermectin. This could increase ivermectin levels in the body, raising the risk of side effects if the drugs are used together .
Drug-Excipient and Formulation Interactions
Studies on fixed-dose combinations of HCTZ with olmesartan show only weak solid-state interactions, which do not affect the stability or performance of the final product. These interactions are not considered clinically relevant incompatibilities .
Protein Binding and Blood Glucose Effects
HCTZ binds to human serum albumin (HSA), and this interaction can be affected by high blood glucose levels. In hyperglycemic conditions, fewer binding sites are available for HCTZ, which may alter its distribution and effectiveness. Good glycemic control is recommended for optimal HCTZ therapy 810.
Conclusion
Hydrochlorothiazide generally has a low risk of clinically significant drug interactions with most commonly co-prescribed antihypertensive agents, SGLT2 inhibitors, and anticancer drugs. Notable exceptions include a potential interaction with valsartan and a theoretical risk with ivermectin due to CYP3A4 inhibition. Formulation and protein binding studies further support the safety of HCTZ in combination therapies, though blood glucose control may influence its pharmacokinetics. Overall, HCTZ remains a safe option in multi-drug regimens, with only a few specific interactions warranting closer attention.
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