Hydrochlorothiazide with Naproxen Interaction Details

Brand Names Associated with Hydrochlorothiazide

Brand Names Associated with Naproxen

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 15, 2023

Interaction Effect

Reduced diuretic effectiveness and possible nephrotoxicity

Interaction Summary

Risk of renal toxicity is increased with combined use of NSAIDs and diuretics due to NSAID-associated dose-dependent reduction in prostaglandin formation and in renal blood flow. Coadministration of NSAIDs and thiazide diuretics has reduced the natriuretic effect of the diuretic in some patients, also related to the effect of NSAID inhibition of renal prostaglandin synthesis. . During concomitant use of NSAIDs and diuretics, monitor for signs of worsening renal function and assure diuretic efficacy, including appropriate effects on blood pressure .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Risk of renal toxicity is increased with combined use of NSAIDs and diuretics and use of NSAIDs with thiazide diuretics has reduced the natriuretic effect of the diuretic in some patients. During concomitant use of NSAIDs and diuretics, monitor for signs of worsening renal function and assure diuretic efficacy, including appropriate effects on blood pressure.

Mechanism Of Interaction

Decreased renal prostaglandin production

Literature Reports

A) NSAIDs may increase blood pressure and antagonize the effects of antihypertensive agents. They can cause salt and water retention and increase the extracellular volume. NSAIDs also cause a decrease in prostaglandin synthesis in blood vessel walls, which removes a direct vasodilatory influence and also increases the vascular response to vasoconstrictor stimuli. The antagonism of the hypotensive effect of diuretics is probably due to NSAID-induced inhibition of prostaglandin synthesis. NSAIDs also have independent and opposing actions on the various physiological mechanisms that regulate blood pressure .

B) The effect of tenidap 120 mg on the hypotensive efficacy of hydroCHLOROthiazide or bendrofluazide was assessed in 23 patients with controlled mild to moderate, uncomplicated, essential hypertension. Blood pressure increased marginally, and the increase in mean standing diastolic pressure observed with tenidap was significantly greater than the change in the placebo group .

C) The effect of a single dose challenge of naproxen (500 mg) and sulindac (200 mg) on renal function was studied in 5 volunteers, and the effect of a single dose challenge of hydrochlorothiazide (100 mg) on renal function when the diuretic was given alone or when superimposed on chronic therapy of either naproxen or sulindac. None of the NSAID or diuretic exposures significantly influenced the glomerular filtration rate, as measured by creatinine clearance. Over the first 4 hours of the study, both naproxen and sulindac reduced fractional excretion of sodium by approximately 50%. Concurrent hydroCHLOROthiazide and sulindac therapy resulted in a blunting of the natriuresis by approximately 30% compared with when the diuretic was given alone. The action of the diuretic was unchanged by naproxen .

D) Administration of indomethacin 25 mg 3 times daily in young healthy adults did not alter the pharmacokinetics of hydroCHLOROthiazide, but caused an increase in body weight and plasma potassium levels and a decrease in plasma renin activity . This evidence indirectly supports the hypothesis that the attenuation of diuretic action by indomethacin results from an alteration in hydroCHLOROthiazide pharmacodynamics.

E) A base cohort study involving 10,519 patients older than 55 years who were receiving NSAIDs and diuretics was conducted to investigate the relationship between congestive heart failure (CHF) and the use of these 2 classes of drugs. The patient population was 72.2% female, with an average age of 70.8 years. During periods of concomitant NSAID and diuretic use, the risk of hospitalization for CHF was twice that of periods of diuretic use only. Patients who used diuretics on a regular basis also had an increased risk of hospitalization due to CHF compared with irregular users of diuretics. A combination of a thiazide and a potassium-sparing diuretic was the most frequently used diuretic type, and the incidence density of hospitalizations during times of use with this combination and an NSAID resulted in a 3-fold increase over that for diuretic use only .

Hydrochlorothiazide Overview

• Hydrochlorothiazide is used alone or in combination with other medications to treat high blood pressure. Hydrochlorothiazide is used to treat edema (fluid retention; excess fluid held in body tissues) caused by various medical problems, including heart, kidney, and liver disease and to treat edema caused by using certain medications including estrogen and corticosteroids. Hydrochlorothiazide is in a class of medications called diuretics ('water pills'). It works by causing the kidneys to get rid of unneeded water and salt from the body into the urine.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

Naproxen Overview

• Prescription naproxen is used to relieve pain, tenderness, swelling, and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints), rheumatoid arthritis (arthritis caused by swelling of the lining of the joints), juvenile arthritis (a form of joint disease in children), and ankylosing spondylitis (arthritis that mainly affects the spine). Prescription naproxen tablets, extended-release tablets, and suspension are also used to relieve shoulder pain caused by bursitis (inflammation of a fluid-filled sac in the shoulder joint), tendinitis (inflammation of the tissue that connects muscle to bone), gouty arthritis (attacks of joint pain caused by a build-up of certain substances in the joints), and pain from other causes, including menstrual pain (pain that happens before or during a menstrual period). Nonprescription naproxen is used to reduce fever and to relieve mild pain from headaches, muscle aches, arthritis, menstrual periods, the common cold, toothaches, and backaches. Naproxen is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.