Lithium is a mood stabiliser used in bipolar disorder, mainly to prevent episodes of mania and depression. It is very effective, but has a narrow therapeutic window — it requires regular blood tests and close medical supervision.
Also known as: Priadel, Camcolit, carbonato de lítio
Combining Lithium with Ibuprofen increases serum Lithium concentrations, with a risk of toxicity.
NSAIDs, by inhibiting the synthesis of renal prostaglandins, reduce renal blood flow and lithium excretion, potentially raising serum lithium and precipitating toxicity (nausea, coarse tremor, confusion, ataxia, seizures) within days. The effect is particularly relevant in the elderly and in patients with reduced renal function. The lithium label and the Portuguese Prontuário Terapêutico recommend monitoring serum lithium and signs of toxicity when starting, adjusting or stopping the NSAID, and preferring paracetamol as the analgesic.
Ibuprofen + lithium: the NSAID reduces renal lithium clearance, with a risk of raised serum lithium and toxicity (tremor, confusion, seizures). Monitor lithium levels.
Non-steroidal anti-inflammatory drugs such as Ibuprofen reduce the renal excretion of Lithium, raising its levels.
Lithium levels after starting or adjusting the NSAID.
Confusion, coarse tremor, ataxia, vomiting, diarrhoea or seizures suggest Lithium toxicity and require urgent evaluation.
Avoid NSAIDs in patients taking Lithium; if unavoidable, use the lowest dose and monitor Lithium levels.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Lithium with Metronidazole increases serum Lithium concentrations, with a risk of toxicity.
In patients stabilised on relatively high lithium doses, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity; the metronidazole label recommends obtaining serum lithium and creatinine levels a few days after starting metronidazole, to detect any increase that may precede clinical symptoms of lithium intoxication. The lithium label includes metronidazole among the drugs that can raise lithium levels, with a recommendation for frequent monitoring and dose adjustment.
Lithium + metronidazole: can raise lithium levels and cause toxicity. Check lithium and creatinine a few days after starting metronidazole.
Metronidazole may increase serum Lithium concentrations; the mechanism involves reduced renal excretion.
Confusion, tremor or vomiting after starting Metronidazole require level testing and reassessment.
Confusion, tremor or vomiting after starting Metronidazole require level testing and reassessment.
Monitor Lithium levels and watch for signs of toxicity during Metronidazole use.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Metronidazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5784eeb-6b99-4e8a-847b-b0d1090ed48a — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Haloperidol with Lithium increases the risk of neurotoxicity and severe extrapyramidal symptoms.
An encephalopathic syndrome (weakness, lethargy, fever, tremulousness, confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes) followed by irreversible brain damage has occurred in a few patients treated with lithium plus haloperidol, although a causal relationship has not been established; the haloperidol label recommends monitoring patients on this combination closely for early evidence of neurological toxicity and discontinuing treatment promptly if such signs appear. Use the lowest effective doses of both, monitor neurological signs and lithium levels, and reassess the combination if symptoms arise.
Haloperidol + lithium: encephalopathic syndrome/neurotoxicity described. Monitor closely for early neurological signs.
Co-administration of antipsychotics and Lithium can produce encephalopathy, confusion and extrapyramidal syndrome, especially at high doses.
Confusion, rigidity, tremor or signs of neuroleptic malignant syndrome require discontinuation and urgent evaluation.
Confusion, rigidity, tremor or fever require discontinuation and urgent evaluation.
Use cautious doses of both and monitor for the onset of neurological signs.
DailyMed/FDA (NIH/NLM) — approved Haloperidol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2eed126-cb82-42b1-9b48-9cbeb6873b50 ; approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Lithium with Captopril increases serum Lithium concentrations, with a risk of toxicity.
Angiotensin-converting enzyme (ACE) inhibitors such as captopril can raise serum lithium levels and cause signs of lithium toxicity in patients on concomitant lithium; the captopril label recommends co-administering with caution and monitoring serum lithium levels frequently, noting that if a diuretic is also used, the risk of lithium toxicity increases. Monitoring is especially important when starting the ACE inhibitor and at any dose change, and should include signs of lithium toxicity (tremor, confusion, ataxia, dysarthria, diarrhoea).
Captopril + lithium: the ACE inhibitor can raise lithium levels and cause toxicity. Use with caution and monitor lithium levels frequently.
Captopril, an angiotensin-converting enzyme inhibitor, reduces the renal excretion of Lithium, raising its levels.
Monitor Lithium levels after starting Captopril.
Signs of Lithium toxicity require discontinuation and evaluation.
Monitor Lithium levels and renal function during co-administration.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Captopril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a43a5373-ded9-4912-8c98-edaec8352836 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Lithium with Diclofenac increases serum Lithium concentrations, with a risk of toxicity.
NSAIDs, including diclofenac, reduce renal lithium clearance by inhibiting renal prostaglandin synthesis: the diclofenac label documents increases in the mean minimum plasma lithium concentration of about 15% and a reduction in renal clearance of approximately 20%. The rise in lithium levels can precipitate lithium toxicity (tremor, confusion, ataxia, dysarthria), especially in the elderly, with dehydration or renal impairment. Monitor lithium levels when starting, adjusting or stopping the NSAID, use the lowest effective dose and watch for signs of toxicity.
Diclofenac + lithium: the NSAID reduces renal lithium clearance and raises lithium levels. Monitor levels and signs of toxicity.
NSAIDs such as Diclofenac decrease the renal excretion of Lithium, raising its serum levels.
Watch for signs of Lithium toxicity after starting Diclofenac.
Signs of Lithium toxicity (confusion, tremor, vomiting, seizures) require urgent evaluation.
Avoid the combination; if needed, use the lowest Diclofenac dose and monitor Lithium levels.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Diclofenac label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b0931350-28a9-4f00-9254-1d72e31f04c3 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Lithium with Enalapril increases serum Lithium concentrations, with a risk of toxicity.
Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs that cause sodium elimination, including ACE inhibitors; the enalapril label describes cases of lithium toxicity in patients on enalapril and lithium, reversible after discontinuation of both, and recommends monitoring serum lithium levels frequently if enalapril is given with lithium. The mechanism involves reduced renal lithium elimination associated with sodium depletion. Monitor lithium levels at the start and during the combination and watch for signs of toxicity (tremor, confusion, ataxia, diarrhoea).
Enalapril + lithium: lithium toxicity reported with ACE inhibitors. Monitor lithium levels frequently during the combination.
Angiotensin-converting enzyme inhibitors such as Enalapril reduce the renal clearance of Lithium, raising its levels.
Watch for signs of Lithium toxicity after starting Enalapril.
Signs of Lithium toxicity after starting Enalapril require level testing and evaluation.
Monitor Lithium levels and renal function if the combination is needed.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b31372f7-cda3-4ead-a481-4cde62e843fd — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Lithium with Fluoxetine increases the risk of serotonin syndrome and may raise Lithium levels.
Lithium can precipitate serotonin syndrome, potentially life-threatening, and the risk increases with concomitant use of other serotonergic drugs, including SSRIs such as fluoxetine; the lithium and fluoxetine labels recommend informing the patient of the increased risk and monitoring symptoms (agitation, hallucinations, delirium, tachycardia, hyperthermia, tremor, rigidity, myoclonus, hyperreflexia, seizures, gastrointestinal symptoms), especially at initiation and dose increases. If symptoms arise, stop lithium and the serotonergic agents and start supportive treatment.
Fluoxetine + lithium: risk of serotonin syndrome. Inform the patient and monitor symptoms, especially at initiation and dose increases.
Lithium and Fluoxetine increase serotonergic activity; SSRIs may also reduce Lithium excretion, raising its levels.
Watch for agitation, tremor, hyperthermia, hyperreflexia, myoclonus or diarrhoea (serotonin syndrome).
Fever, agitation, hyperreflexia or myoclonus (serotonin syndrome) require discontinuation and urgent evaluation.
Use the combination cautiously, at low doses, and monitor Lithium levels.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Fluoxetine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09fb3100-1e06-4cdc-8016-7e4f5d097490 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Lithium with Hydrochlorothiazide increases serum Lithium concentrations, with a risk of toxicity.
Thiazides such as hydrochlorothiazide reduce renal lithium clearance: diuretic-induced sodium loss decreases lithium elimination and markedly increases the risk of toxicity. The hydrochlorothiazide label states that lithium generally should not be given with diuretics and refers to the lithium package insert; the lithium label confirms that diuretic-induced sodium loss can reduce lithium clearance and raise lithium levels. If the combination is unavoidable, reduce the lithium dose, monitor lithium levels frequently and watch for signs of toxicity (tremor, confusion, ataxia, dysarthria); ensure adequate sodium intake.
Hydrochlorothiazide + lithium: thiazides reduce renal lithium clearance and greatly increase the risk of toxicity. Avoid; if unavoidable, monitor lithium levels.
Thiazide diuretics reduce the renal excretion of Lithium (increased tubular reabsorption), raising its serum levels.
Frequent Lithium levels and electrolyte/creatinine checks.
Signs of Lithium toxicity (confusion, tremor, vomiting, seizures) require discontinuation and urgent evaluation.
Avoid the combination whenever possible; if needed, closely monitor Lithium levels and renal function.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
NSAID + lithium: risk of raised serum lithium and lithium toxicity.
NSAIDs, including naproxen, reduce renal lithium clearance by inhibiting renal prostaglandin synthesis: the naproxen label documents increases in the mean minimum plasma lithium concentration of about 15% and a reduction in renal clearance of approximately 20%. The rise in lithium levels can precipitate lithium toxicity (tremor, confusion, ataxia, dysarthria), especially in the elderly, with dehydration or renal impairment. Monitor lithium levels when starting, adjusting or stopping the NSAID, use the lowest effective dose and watch for signs of toxicity.
Lithium + naproxen: the NSAID reduces renal lithium clearance and raises lithium levels. Monitor levels and signs of toxicity.
NSAIDs reduce renal lithium clearance (decreased excretion), raising lithium levels.
Serum lithium and renal function during combined therapy.
Nausea, confusion, tremor, signs of neurotoxicity; arrhythmias.
Stop or reduce the NSAID with serum lithium monitoring; watch for signs of lithium toxicity.
DailyMed (FDA) — approved Naproxen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=24d44eb6-921e-4150-a6b2-81f42ced32ab ; approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=582697c1-063f-366f-e063-6294a90a8d1b — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Caffeine has a diuretic effect and can alter serum lithium; abrupt changes in caffeine intake can precipitate toxicity or loss of efficacy.
Keep caffeine intake consistent; changes should be gradual and monitored.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72
Lithium excretion depends on sodium: low-salt diets or dehydration raise serum lithium; high-salt diets lower it.
Keep salt and fluid intake consistent; avoid radical diets and dehydration.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72
Lithium is eliminated almost exclusively renally; renal impairment reduces clearance and increases the risk of toxicity.
Monitor serum lithium frequently and adjust the dose; avoid NSAIDs and thiazide diuretics.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72
Sodium depletion (low-salt diet, diuretics, dehydration) increases tubular lithium reabsorption and serum lithium.
Correct and avoid sodium-depleting factors; monitor serum lithium and electrolytes.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72
Lithium is associated with cardiac malformations (Ebstein anomaly) and neonatal toxicity; maternal levels fluctuate in pregnancy.
Avoid in the first trimester; if unavoidable, monitor serum lithium closely and watch the newborn.
Present in breast milk at relevant concentrations; generally avoided in breastfeeding.
Use effective contraception during treatment.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Mood stabiliser; the mechanism of action as a mood stabiliser is unknown. The distribution space approximates total body water and plasma protein binding is negligible; apparent volume of distribution of 0.7 to 1 L/kg at equilibrium.
The exact mechanism is not clarified. Lithium is not metabolised in the body — the pharmacokinetics reflect only absorption, distribution in body water and renal excretion.
Complete absorption in the upper gastrointestinal tract after oral administration; peak serum concentrations 0.25 to 3 hours (immediate release) and 2 to 6 hours (sustained release).
It is not metabolised. It is excreted mainly in the urine, proportionally to the serum concentration: filtered at the glomerulus, 80% is reabsorbed by passive diffusion in the proximal tubule. Faecal excretion is insignificant.
Elimination half-life of approximately 18 to 36 hours. Apparent clearance and volume of distribution increase with body weight in children.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
