Chlorthalidone with Gossypol Interaction Details

Brand Names Associated with Chlorthalidone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 19, 2023

Interaction Effect

Increased risk of hypokalemia

Interaction Summary

Clinically significant potassium loss resulting in hypokalemic paralysis has occurred in patients receiving gossypol. Administration of gossypol along with a potassium supplement or a potassium-sparing diuretic such as triamterene may not protect against the potassium loss . When gossypol, an agent with demonstrated ability to induce hypokalemia, is combined with a diuretic, the patient may be at increased risk of developing significant hypokalemia. Gossypol use should be discontinued during diuretic treatment.

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Patients taking gossypol alone or with a diuretic may be at increased risk for hypokalemia and its associated symptoms of malaise, myalgia, muscle fatigue, and weakness. Concomitant use should be avoided if possible. If therapy is initiated with both agents, serum potassium levels should be monitored weekly for at least 4 weeks, then monthly for the duration of treatment, as levels may begin to fall within 8 weeks and decline further after several months. Administration of gossypol along with a potassium supplement or a potassium-sparing diuretic such as triamterene may not protect against the potassium loss.

Mechanism Of Interaction

Inhibition of the Na-K ATPase enzyme with associated renal potassium loss

Literature Reports

A) Gossypol reduced serum potassium levels in a double-blind, randomized, controlled study of 152 male volunteers to evaluate the efficacy of gossypol as a male contraceptive. Gossypol 20 milligrams (mg) was taken by 75 subjects per day initially, followed by a maintenance phase of 50 mg/week, and continued treatment for at least 14.5 months. One patient experienced a decrease in serum potassium level from 4.8 milliequivalents per liter (mEq/L) on admission to 3.7 mEq/L at the end of the loading phase (2.5 months), which then declined further to 2.6 mEq/L, after which treatment was stopped. An additional patient whose potassium was 3.5 mEq/L at admission declined to 2.4 mEq/L at 9 months, after which treatment was stopped. In the entire treatment group, potassium levels were 4.3 +/- 0.03 mEq/L at admission and 3.8 +/- 0.04 mEq/L after 14.5 months of gossypol use (p less than 0.05) .

B) Potassium loss was not deterred by coadministration of triamterene or supplementation with potassium in a randomized trial with 120 male volunteers. Volunteers received gossypol alone, gossypol plus potassium salt 1.5 grams daily, gossypol plus triamterene 50 mg daily, or no treatment. Gossypol treatment began with a 60 day loading phase of gossypol 20 mg daily, followed by gossypol 50 mg weekly for 10 months. At the end of the 60 day loading phase, potassium levels declined in gossypol treated groups, but not the control group (p less than 0.05). At the end of the maintenance phase, average serum potassium was 3.98 mEq/L in the gossypol group, 4.11 mEq/L in the gossypol/potassium supplementation group, 3.77 mEq/L in the gossypol/triamterene treated group, and 3.92 mEq/L in the control group. All gossypol treatment groups had potassium levels significantly lower at the end of the maintenance phase versus admission (p less than 0.05). One case of hypokalemic paralysis (serum potassium 2.0 mEq/L) occurred one month after the end of treatment with gossypol and triamterene. It was hypothesized that gossypol may cause renal impairment, such that potassium supplementation or blocking agent such as triamterene may not affect return of potassium levels to normal even after gossypol treatment is stopped .

C) Two patients taking gossypol for metastatic adrenal cancer developed hypokalemia two to three weeks after gossypol discontinuation. Serum potassium levels were 2.3 millimoles/liter (mmol/L) and 2.6 mmol/L (normal range 3.5 to 4.0 mmol/L) .

D) Over a 5-year period, 148 men took gossypol as a contraceptive. Seven men (5%) developed hypokalemic paralysis with associated serum potassium levels of 2 mEq/L to 2.73 mEq/L. It was noted that dietary potassium intake was low in these men and may have increased their risk of this adverse effect. Renal potassium excretion studies led to the conclusion that the majority of gossypol-related cases of hypokalemia involved renal potassium loss .

Chlorthalidone Overview

• 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.

• This medicine is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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.