Chlorthalidone with Ketanserin Interaction Details
Brand Names Associated with Chlorthalidone
- Chlorthalidone
- Clorpres® (as a combination product containing Chlorthalidone, Clonidine)
- Edarbyclor® (as a combination product containing Azilsartan, Chlorthalidone)
- Hygroton®
- Lopressidone® (as a combination product containing Chlorthalidone, Metoprolol)
- Regroton® (as a combination product containing Chlorthalidone, Reserpine)
- Tenoretic® (as a combination product containing Atenolol, Chlorthalidone)
- Thalitone®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 19, 2023
Interaction Effect
Ventricular arrhythmias
Interaction Summary
Concurrent administration of ketanserin and potassium-wasting diuretics may result in ventricular arrhythmias. In one large randomized, placebo-controlled, double-blind study, ketanserin and potassium-wasting diuretics produced additive QT interval prolongation. Diuretic-induced hypokalemia and high doses of ketanserin may have exacerbated the arrhythmias in the affected patients . One study of the effects of hydrochlorothiazide on ketanserin pharmacokinetics found no significant difference in the kinetics of ketanserin alone compared with ketanserin plus hydrochlorothiazide, and failed to show any significant effect on the QT interval. However, this study utilized single doses of ketanserin and hydrochlorothiazide only .
Severity
Major
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
If patients must receive ketanserin and potassium-wasting diuretics, monitor for prolongation of the QT interval. Substituting a potassium-sparing diuretic would be advisable.
Mechanism Of Interaction
Diuretic-induced hypokalemia; theoretical additive QT prolongation
Literature Reports
A) In a large, double-blind trial involving 3899 patients in 14 countries, concurrent administration of ketanserin with potassium-losing diuretics was associated with a significant increase in the number of deaths from cardiovascular causes in patients with claudication . Ketanserin produced QT prolongation in this study (mean of 18 ms), as did potassium-losing diuretics, and their combination produced a significantly longer prolongation of the QT interval (mean 30 ms) than ketanserin alone. When comparing the number of sudden deaths in the patients taking potassium-losing diuretics, 16 patients receiving ketanserin died, versus only 5 patients on placebo. In the group receiving potassium-sparing diuretics, three patients in both the ketanserin and the placebo group experienced sudden death, and in the group receiving no diuretics, 17 patients on ketanserin and 15 patients on placebo had sudden death. Ketanserin was administered at a relatively high dose (40 mg orally three times daily) in this study. These combined effects on the QT interval, in addition to the reduction in potassium concentrations induced by the diuretics, may have precipitated or worsened ventricular arrhythmias in the affected patients.
B) In one study involving 221 patients, the QT prolongation induced by ketanserin did not appear to be associated with an increased risk of ventricular arrhythmias. Subjects were given ketanserin 20 mg twice daily for one week followed by ketanserin 40 mg twice daily for three weeks or placebo. The QTc interval was prolonged with ketanserin (mean 400 ms to 418 ms) but not with placebo. In the ketanserin group, 30% of patients had a QTc prolongation greater than 30 ms. However, malignant forms of ventricular arrhythmias are possible in particular patients with other contributing factors to their development, including the use of potassium-wasting diuretics .
C) A randomized, double-blind, cross-over, placebo-controlled study found no significant differences in maximum concentration, time to peak, or area under the concentration-time curve (AUC) in patients receiving a single 20 mg dose of ketanserin compared with those coadministered a single 20 mg dose of ketanserin plus a 25 mg hydrochlorothiazide dose. Twenty-two males with essential hypertension participated in the study. Neither ketanserin alone nor the combination significantly affected QTc interval, heart rate, or serum concentrations of sodium, potassium, magnesium, calcium, or chloride .
Chlorthalidone Overview
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Chlorthalidone, a 'water pill,' is used to treat high blood pressure and fluid retention caused by various conditions, including heart disease. It causes the kidneys to get rid of unneeded water and salt from the body into the urine.
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This medicine is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
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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:
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.