Lithium with Chlorthalidone Interaction Details

Brand Names Associated with Lithium

Brand Names Associated with Chlorthalidone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 21, 2023

Interaction Effect

Increased lithium concentrations and lithium toxicity (weakness, tremor, excessive thirst, confusion)

Interaction Summary

Concurrent use of lithium and thiazide diuretics results in elevated serum levels of lithium due to reabsorption of sodium and lithium ions at the proximal renal tubule . Decreased lithium renal clearance and increases the risk of lithium toxicity . Consider initiating lithium at lower doses and titrating slowly while frequently monitoring serum lithium levels and for signs of lithium toxicity .

Severity

Major

Onset

Delayed

Evidence

Theoretical

How To Manage Interaction

Concomitant use of lithium and chlorthalidone decreases lithium renal clearance and increases the risk of lithium toxicity. Consider initiating lithium at lower doses and titrating slowly while frequently monitoring serum lithium levels and for signs of lithium toxicity .

Mechanism Of Interaction

Decreased lithium clearance

Literature Reports

A) Concomitant administration of lithium with either furosemide or hydrochlorothiazide in six healthy volunteers resulted in an increase in lithium levels when coadministered with hydrochlorothiazide but not furosemide. The subjects received lithium 300 mg three times daily for nine days, furosemide 40 mg daily plus lithium for 14 days, lithium alone for seven days, and lithium plus hydrochlorothiazide 50 mg daily for 14 days. Serum lithium was measured intermittently throughout the 44-day study. Of the six subjects, one withdrew after developing adverse effects during the lithium-only portion of the study. During coadministration of lithium with hydrochlorothiazide, serum lithium levels rose significantly compared to the lithium-only phase and the lithium plus furosemide phase. The authors suggested that patients given thiazide diuretics may need a downward adjustment of their lithium dosage to maintain acceptable serum lithium levels .

B) A 60-year old woman developed lithium toxicity after the addition of a thiazide diuretic to control hypertension. The patient had taken lithium 600 mg twice daily and maintained serum lithium levels of 0.8 mEq/L to 1.2 mEq/L. Two weeks after hydrochlorothiazide 50 mg daily was added to the patient's regimen, she developed insomnia, confusion, tremor, muscle fasciculations, dysarthria, and ataxia. The patient's serum lithium level was measured at 3.9 mEq/L. After hemodialysis, the patient's lithium level was 1.4 mEq/L but mental status continued to deteriorate. The patient's condition gradually improved over the next five days with osmotic diuresis and supportive treatment .

C) A case of severe lithium toxicity (diarrhea, dyspnea, drowsiness, confusion, peripheral vasodilatation, and hyperreflexia) in a 51-year old non-insulin dependent female patient with diabetes was reportedly caused by a thiazide diuretic and an angiotensin converting enzyme inhibitor . Lithium carbonate 1.6 grams daily had been given for seven years for manic depression, as well as glibenclamide 5 mg daily (18 months). Perindopril 8 mg daily and bendrofluazide 5 mg daily had been added for hypertension three months prior to presentation. Diarrhea, dyspnea, confusion, and hypotension developed over a two-week period. Her lithium level was 4.28 mmol/L on admission to the hospital, and her blood pressure was 80/60 mmHg. Dopamine and dobutamine were started but were not effective. Her blood pressure was eventually maintained with norepinephrine, epinephrine, and dobutamine at doses normally associated with marked alpha-adrenoceptor-mediated vasoconstriction. The patient became more alert when the lithium level dropped to 1.6 mmol/L following three hemodialysis sessions, and cardiovascular support was then withdrawn.

Lithium Overview

• Lithium is used to treat and prevent episodes of mania (frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Lithium is in a class of medications called antimanic agents. It works by decreasing abnormal activity in the brain.

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.

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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.