Lithium with Spironolactone Interaction Details
Brand Names Associated with Lithium
- Eskalith®
- Eskalith® CR
- Lithium
- Lithobid®
Brand Names Associated with Spironolactone
- Aldactone®
- Carospir®
- Spironolactone
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
Renal clearance of lithium is reduced by spironolactone and other diuretics potentially resulting in elevated serum levels of lithium and lithium toxicity due to reabsorption of sodium and lithium ions at the proximal renal tubule . Cotherapy is useful in cases of lithium polyuria or lithium-induced nephrogenic diabetes insipidus . However, lithium generally should not be given with diuretics . When concurrent use is required, initiate lithium at lower doses or reduce current doses, monitor lithium concentrations frequently, and observe for signs of lithium toxicity ,
Severity
Major
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
Lithium generally should not be given with diuretics. Concomitant use of lithium with a diuretic, including spironolactone, may increase serum lithium concentrations and lead to lithium toxicity. When concurrent use is required, initiate lithium at lower doses or reduce current doses, monitor lithium concentrations frequently, and observe for signs of lithium toxicity .
Mechanism Of Interaction
Decreased lithium clearance
Literature Reports
A) A 24% reduction in lithium clearance in 22 patients on long-term therapy with bendroflumethiazide and hydroflumethiazide has been demonstrated . Bendroflumethiazide may impair renal elimination of lithium, and should be used with caution in patients receiving lithium .
B) The effects of concomitant administration of lithium with either furosemide or hydrochlorothiazide has been studied in six health volunteers. 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 .
C) A case report exists describing a 60-year old woman who 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 to 1.2 mEq/L. Two weeks after hydrochlorothiazide 50 mg daily was added to the patient's regimen, the patient 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 .
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.
Spironolactone Overview
-
Spironolactone is used to treat certain patients with hyperaldosteronism (the body produces too much aldosterone, a naturally occurring hormone); low potassium levels; heart failure; and in patients with edema (fluid retention) caused by various conditions, including liver, or kidney disease. It is also used alone or with other medications to treat high blood pressure. Spironolactone is in a class of medications called aldosterone receptor antagonists. It causes the kidneys to eliminate unneeded water and sodium from the body into the urine but reduces the loss of potassium from the body.
-
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.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.