The toxic concentrations for lithium (≥1.5 mEq/L) are close to the therapeutic range (0.8 to 1.2mEq/L). Some patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are considered within the therapeutic range [see Boxed Warning, Dosage and Administration (2.6)]. Lithium may take up to 24 hours to distribute into brain tissue, so occurrence of acute toxicity symptoms may be delayed.   
Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of lithium toxicity, and can occur at lithium concentrations below 2.0 mEq/L. At higher concentrations, giddiness, ataxia, blurred vision, tinnitus and a large output of dilute urine may be seen. Serum lithium concentrations above 3.0 mEq/L may produce a complex clinical picture involving multiple organs and organ systems, coma, and eventually death. Serum lithium concentrations should not be permitted to exceed 2.0 mEq/L.   
Neurological signs of lithium toxicity range from mild neurological adverse reactions such as fine tremor, lightheadedness, and weakness; to moderate manifestations like apathy, drowsiness, hyperreflexia, muscle twitching, and slurred speech; and severe manifestations such as clonus, confusion, seizure, coma and death. Cardiac manifestations involve electrocardiographic changes, such as prolonged QT interval, ST and T-wave changes and myocarditis. Renal manifestations include urine concentrating defect, nephrogenic diabetes insipidus, and renal failure. Respiratory manifestations include dyspnea, aspiration pneumonia, and respiratory failure. Gastrointestinal manifestations include nausea, vomiting, and bloating. No specific antidote for lithium poisoning is known. Early symptoms of lithium toxicity can usually be treated by reduction or cessation of lithium, before restarting treatment at a lower dose 24 to 48 hours later [See Overdosage (10)].   
The risk of acute toxicity is increased with a recent onset of concurrent illness or with the concomitant administration of drugs which increase lithium serum concentrations by pharmacokinetic interactions [see Drug Interactions (7)]. Additional risk factors for acute lithium toxicity include acute ingestion, age-related decline in renal function, volume depletion and/or changes in electrolyte concentrations, especially sodium and potassium. Dose requirements during the acute manic phase are higher to maintain therapeutic serum concentrations and decrease when manic symptoms subside. The risk of lithium toxicity is very high in patients with significant renal or cardiovascular disease, severe debilitation or dehydration, or sodium depletion, and for patients receiving prescribed medications that may affect kidney function, such as angiotensin converting enzyme inhibitors (ACE inhibitors), diuretics (loops and thiazides) and NSAIDs. For these patients, consider starting with lower doses and titrating slowly while frequently monitoring serum lithium concentrations and signs of lithium toxicity.   
To reduce the risk of acute lithium toxicity during treatment initiation, facilities for prompt and accurate serum lithium determinations should be available before initiating treatment [see Boxed Warning, Dosage and Administration (2.6)]. Advise patients and caregivers to watch for signs of early toxicity and to discontinue lithium and immediately inform their health care provider if they occur.