Hydrochlorothiazide interactions
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Hydrochlorothiazide Interactions: A Comprehensive Overview
Introduction to Hydrochlorothiazide
Hydrochlorothiazide (HCTZ) is a widely used thiazide diuretic for treating hypertension and edema. It is often prescribed in combination with other antihypertensive agents to enhance therapeutic efficacy. Understanding the interactions of HCTZ with other drugs is crucial for optimizing treatment regimens and minimizing adverse effects.
Interactions with Antihypertensive Agents
Telmisartan, Amlodipine, and Hydrochlorothiazide
A study evaluated the pharmacokinetic interactions among telmisartan, amlodipine, and HCTZ in healthy male subjects. The results indicated that the combination therapy did not significantly impact the pharmacokinetic parameters of each drug, suggesting that these drugs can be co-administered without altering their individual pharmacokinetic profiles 1.
Valsartan and Hydrochlorothiazide
Research on the co-administration of valsartan (VAL) and HCTZ revealed that while the combination was well tolerated, there was a significant interaction. The co-administration decreased the systemic exposure and intensity of VAL absorption, although the effect on HCTZ was nonsignificant 3. Another study confirmed that VAL increased the plasma concentration of HCTZ, indicating a pharmacokinetic interaction that enhances HCTZ bioavailability 8.
Losartan and Hydrochlorothiazide
A pharmacokinetic study involving losartan and HCTZ found no significant interaction between the two drugs. The combination did not affect the pharmacokinetics of either losartan or its active metabolite, nor did losartan impact the pharmacokinetics of HCTZ 10.
Benazepril and Hydrochlorothiazide
In contrast, benazepril (BENA) was found to decrease the bioavailability of HCTZ significantly. This interaction suggests that co-administration with BENA may require dosage adjustments of HCTZ to maintain its therapeutic efficacy 8.
Interactions with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Indomethacin and Sulindac
The influence of NSAIDs, such as indomethacin and sulindac, on HCTZ was investigated. Indomethacin did not affect HCTZ kinetics but altered body weight and plasma potassium levels. Sulindac, however, decreased the renal clearance of HCTZ and increased its plasma levels in subjects with lower creatinine clearance, indicating a potential for altered HCTZ pharmacokinetics with sulindac co-administration 2.
Interactions with Natural Products
Garlic
A study on the interaction between HCTZ and garlic homogenate (GH) in rats showed that GH increased the bioavailability and half-life of HCTZ while reducing its clearance and elimination rate. This interaction suggests that moderate doses of garlic could enhance the therapeutic effect of HCTZ while minimizing adverse effects 5.
Red Ginseng Extract
The effects of red ginseng extract (RGE) on the pharmacokinetics of HCTZ, when combined with fimasartan and amlodipine, were also studied. The results indicated no significant difference in the pharmacokinetic parameters of HCTZ, except for a delayed Tmax of amlodipine, suggesting that RGE does not significantly alter HCTZ pharmacokinetics 6.
Interactions with Chemotherapy Agents
Cyclophosphamide
An investigation into the potential interaction between HCTZ and cyclophosphamide in older women with breast cancer found no significant association with adverse chemotherapy-related events. This suggests that the concomitant use of HCTZ does not increase the risk of neutropenia-related hospitalizations or treatment discontinuation in this patient population 9.
Conclusion
Hydrochlorothiazide interacts with various drugs and natural products, affecting its pharmacokinetics and therapeutic efficacy. While some combinations, such as with telmisartan and losartan, show no significant interactions, others like valsartan and benazepril require careful consideration and possible dosage adjustments. Additionally, natural products like garlic can enhance HCTZ's bioavailability, offering potential benefits in hypertension management. Understanding these interactions is essential for optimizing HCTZ therapy and ensuring patient safety.
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Most relevant research papers on this topic
Pharmacokinetic Interaction Among Telmisartan, Amlodipine, and Hydrochlorothiazide After a Single Oral Administration in Healthy Male Subjects.
Combination therapy of telmisartan, amlodipine, and hydrochlorothiazide has no significant impact on the pharmacokinetic parameters of each drug when administered separately or co-administered.
RCTEffects of indomethacin and sulindac on hydrochlorothiazide kinetics
Indomethacin and hydrochlorothiazide interact through dynamic mechanisms, while sulindac may alter renal clearance of hydrochlorothiazide.
RCTPharmacokinetic interactions of valsartan and hydrochlorothiazide: an open-label, randomized, 4-period crossover study in healthy Egyptian male volunteers.
Valsartan and hydrochlorothiazide co-administration in a fixed-dose combination tablet is well-tolerated and safe, but their interaction significantly decreases valsartan's systemic exposure and intensity of absorption.
RCTInclusion complexes of hydrochlorothiazide and β-cyclodextrin: Physicochemical characteristics, in vitro and in vivo studies.
Using -cyclodextrin in inclusion complexes improves hydrochlorothiazide's solubility, stability, and biopharmaceutical properties, potentially enabling pediatric formulations.
In Vitro StudyThe potential for interaction of hydrochlorothiazide with garlic in rats.
Garlic in moderate doses may improve hypertension treatment by reducing potassium excretion, potentially reducing the dose of hydrochlorothiazide with minimal adverse effects.
Non-RCT
Animal StudySimultaneous Analysis of a Combination of Anti-Hypertensive Drugs, Fimasartan, Amlodipine, and Hydrochlorothiazide, in Rats Using LC-MS/MS and Subsequent Application to Pharmacokinetic Drug Interaction with Red Ginseng Extract
Using a validated analytical method and a combination of antihypertensive drugs, we efficiently conducted drug interaction and toxicokinetic studies in rats.
Non-RCTAnimal StudyHydrochlorothiazide binding to human serum albumin induces some compactness in the molecular structure of the protein: A multi‐spectroscopic and computational study
Hydrochlorothiazide binding to human serum albumin decreases surface hydrophobicity and affects both secondary and tertiary structures of the protein.
In Vitro StudyPharmacokinetic profiles of hydrochlorothiazide alone and in combination with benazepril or valsartan in healthy Chinese volunteers: evaluation of the potential interaction.
The combination of hydrochlorothiazide with benazepril decreases its bioavailability in Chinese healthy volunteers, while valsartan significantly increases its concentration in plasma, both being safe and well-tolerated.
RCTAssociation between Concomitant Use of Hydrochlorothiazide and Adverse Chemotherapy-Related Events among Older Women with Breast Cancer Treated with Cyclophosphamide
Concomitant hydrochlorothiazide use does not show a significant association with adverse chemotherapy-related events in older women with breast cancer treated with cyclophosphamide.
Observational StudyAbsence of a Pharmacokinetic Interaction between Losartan and Hydrochlorothiazide
A combination of hydrochlorothiazide and losartan for treating hypertension does not show a significant pharmacokinetic interaction, and both drugs are well-tolerated by patients.
RCT