Lithium with Metolazone Interaction Details
Brand Names Associated with Lithium
- Eskalith®
- Eskalith® CR
- Lithium
- Lithobid®
Brand Names Associated with Metolazone
- Metolazone
- Mykrox®
- Zaroxolyn®
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 . Although cotherapy is useful in cases of lithium polyuria or lithium-induced nephrogenic diabetes insipidus , concomitant use of these drugs should be avoided.
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Monitor serum lithium levels within the first five to seven days of adding or discontinuing metolazone and periodically thereafter. Lower lithium doses may be required with concomitant metolazone therapy.
Mechanism Of Interaction
Decreased lithium clearance
Literature Reports
A) 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.
B) 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 mEq/L 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.
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
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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.
Metolazone Overview
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Metolazone, is used to reduce the swelling and fluid retention caused by heart failure or kidney disease. It also is used alone or with other medications to treat high blood pressure. Metolazone is in a class of medications called diuretics ('water pills'). It causes the kidneys to reduce the amount of water and salt in the body by increasing the amount of urine.
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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.