Lithium with Diflunisal Interaction Details
Brand Names Associated with Lithium
- Eskalith®
- Eskalith® CR
- Lithium
- Lithobid®
Brand Names Associated with Diflunisal
- Diflunisal
- Dolobid®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 21, 2023
Interaction Effect
Increased lithium exposure and an increased risk of lithium toxicity
Interaction Summary
NSAIDs may affect renal function and increase serum lithium concentrations. If concomitant use is necessary, reduce the initial lithium dosage and titrate slowly to clinical response. Monitor serum lithium levels frequently and observe for signs and symptoms of lithium toxicity. The mean minimum lithium concentration increased by 15%, and the renal clearance decreased by approximately 20% .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
NSAIDs may affect renal function and increase serum lithium concentrations. If concomitant use is necessary, reduce the initial lithium dosage and titrate slowly to clinical response. Monitor serum lithium levels frequently and observe for signs and symptoms of lithium toxicity.
Mechanism Of Interaction
Inhibition of renal prostaglandin synthesis; reduced renal lithium clearance
Literature Reports
A) A 64-year-old woman with bipolar disorder who was maintained on lithium carbonate 300 mg 4 times daily (steady-state serum lithium level of 0.99 mEq/L) became lithium toxic following the concomitant administration of ibuprofen 400 mg 3 times daily. Upon transfer to a long-term facility, the patient had a serum lithium level of 0.33 mEq/L, and was switched to lithium citrate syrup 600 mg 2 times daily. No lithium level was measured after the medication change; however, the patient appeared to be responding favorably to therapy. Six weeks after the medication change, ibuprofen was initiated and within 24 hours the patient experienced nausea, anorexia, tremor, and hyperreflexia. The serum lithium reached a maximum of 2.84 mEq/L .
B) The influence of the NSAID diclofenac on lithium kinetics was studied in five normal women on a 150 mmol sodium diet. Diclofenac decreased lithium renal clearance by 23% and increased lithium plasma levels by 26%. Renal prostaglandin synthesis was suppressed by 53% of control values .
C) Five healthy males participated in a study to determine the effects of ketorolac on lithium serum and RBC levels. All subjects ingested lithium 900 mg daily on days 1 through 13, and ketorolac 10 mg 4 times daily on days 8 through 12. Each subject served as their own control. A 24% increase in the serum lithium AUC was seen on day 13 (concomitant lithium and ketorolac therapy) as compared to day 7 (lithium monotherapy). This AUC increase correlated to a 21% decrease in lithium clearance. The mean increase in RBC lithium AUC was 27% at day 13. In addition, the Cmax of serum lithium and lithium RBC increased by 29% and 37%, respectively, with concurrent ketorolac therapy. An increased incidence and severity of lithium adverse effects were also reported during coadministration with ketorolac .
D) Nine healthy male volunteers completed a prospective, crossover, 3-phase study examining the effects of over-the-counter doses of acetaminophen and naproxen sodium on plasma levels of lithium. All participants received lithium carbonate 300 mg every 12 hours for 7 days during phase 1. During phase 2, either naproxen sodium 220 mg every 8 hours or acetaminophen 650 mg every 6 hours was coadministered with lithium for 5 days. A 2-day washout period elapsed between phase 2 and 3. The final phase consisted of lithium being given with the alternate drug that was not received during phase 2 for 5 days. Mean plasma concentrations of lithium were 0.4 mEq/L during phase one, 0.41 mEq/L while receiving lithium and acetaminophen, and 0.43 mEq/L during lithium and naproxen therapy. All subjects had good renal function and subtherapeutic steady-state levels of lithium, so they were at minimal risk of lithium toxicity .
E) NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased by 15%, and the renal clearance decreased by approximately 20% .
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.
Diflunisal Overview
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Diflunisal is used to relieve pain, tenderness, swelling and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints) and rheumatoid arthritis (arthritis caused by swelling of the lining of the joints). Diflunisal is also used to relieve mild to moderate pain from other causes. Diflunisal is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.
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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.