lithium carbonate
Carbolith ◆, Duralith ◆, Eskalith, Eskalith CR, Lithane, Lithizine ◆, Lithobid, Lithonate, Lithotabs

lithium citrate
Cibalith-S

Available forms
Available by prescription only
lithium carbonate
Capsules: 150 mg, 300 mg, 600 mg
Tablets: 300 mg
Tablets (extended-release, film-coated): 300 mg
Tablets (film-coated): 300 mg
Tablets (sustained-release): 300 mg, 450 mg
lithium citrate
Syrup (sugarless): 300 mg/5 ml (with 0.3% alcohol)

Indications and dosages
 Prevention or control of mania; prevention of depression in patients with bipolar illness. Adults: For acute episodes: 1.8 g or 30 ml of lithium citrate P.O. daily in two or three divided doses or 20 to 30 mg/kg daily in two or three divided doses to maintain lithium levels at 1 to 1.5 mEq/L. For maintenance dosage: 900 mg to 1.2 g or 15 to 20 ml of oral solution P.O. daily in two to four divided doses to maintain serum lithium concentration of 0.6 to 1.2 mEq/L. Usual maintenance dosage doesn’t exceed 2.4 g daily.
Elderly patients: 600 to 900 mg daily for acute episodes.
 Major depression ◇, schizoaffective disorder ◇, schizophrenic disorder ◇, alcohol dependence ◇. Adults: 300 mg lithium carbonate P.O. t.i.d. or q.i.d.
 Apparent mixed bipolar disorder in children ◇. Children: Initially, 15 to 60 mg/kg or 0.5 to 1.5 g/m² lithium carbonate P.O. daily in three divided doses. Don’t exceed usual adult dosage. Adjust dosage based on patient response and serum lithium levels; usual dosage range is 150 to 300 mg daily in divided doses to maintain lithium levels of 0.5 to 1.2 mEq/L.
 Chemotherapy-induced neutropenia in children and patients with AIDS receiving zidovudine ◇. Adults and children: 300 to 1,000 mg P.O. daily.

Pharmacodynamics
Antimanic action: Lithium is thought to exert its antipsychotic and antimanic effects by competing with other cations for exchange at the sodium-potassium ion pump, thus altering cation exchange at the tissue level. It also inhibits adenyl cyclase, reducing intracellular levels of cAMP and, to a lesser extent, cyclic guanosine monophosphate (cGMP).

Pharmacokinetics
Absorption: Rate and extent of absorption vary with dosage form; absorption is complete within 6 hours of oral administration from conventional tablets and capsules.
Distribution: Distributed widely throughout the body, including breast milk; levels in thyroid gland, bone, and brain tissue exceed serum levels. Steady state serum level achieved in 12 hours. Therapeutic effect begins in 5 to 10 days and is maximal within 3 weeks. Therapeutic and toxic serum levels and therapeutic effects show good correlation. Therapeutic range is 0.6 to 1.2 mEq/L; adverse reactions increase as level reaches 1.5 to 2 mEq/L; such levels may be needed in acute mania. Toxicity usually occurs at levels above 2 mEq/L.
Metabolism: Not metabolized.
Excretion: Excreted 95% unchanged in urine; about 50% to 80% of a given dose is excreted within 24 hours. Level of renal function determines elimination rate.

Contraindications and precautions
Contraindicated if therapy can’t be closely monitored and during pregnancy. Use cautiously in elderly patients; in patients with thyroid disease, seizure disorders, renal or CV disease, severe dehydration or debilitation, or sodium depletion; and in those receiving neuroleptics, neuromuscular blockers, and diuretics.

Interactions
Drug-drug. Antacids and other drugs containing aminophylline, caffeine, calcium, sodium, or theophylline: May increase lithium excretion by renal competition for elimination, thus decreasing therapeutic effect of lithium. Monitor patient for effect.
Carbamazepine, mazindol, methyldopa, phenytoin, tetracyclines: May increase lithium toxicity. Monitor lithium levels.
Chlorpromazine: Decreases effects of chlorpromazine. Avoid administering together.
Fluoxetine: Increases lithium serum levels. Monitor lithium levels.
Haloperidol: May result in severe encephalopathy characterized by confusion, tremors, extrapyramidal effects, and weakness. Use this combination cautiously.
Indomethacin, phenylbutazone, piroxicam, other NSAIDs: Decreases renal excretion of lithium. May require a 30% reduction in lithium dosage.
Neuromuscular blockers, such as atracurium, pancuronium, and succinylcholine: May potentiate effects of these drugs. Monitor patient closely.
Sympathomimetics, especially norepinephrine: May interfere with pressor effects of these drugs. Monitor patient closely.
Thiazide diuretics: May decrease renal excretion and enhance lithium toxicity. Diuretic dosage may need to be reduced by 30%.
Drug-herb. Ispaghula, plantain: May decrease lithium absorption, reducing effect. Discourage use together.
Parsley: May promote or produce serotonin syndrome. Discourage use together.
Psyllium seed: Inhibits GI absorption. Discourage use together.
Drug-food. Caffeine: Decreases lithium levels and may decrease effect. Tell patient who ingests large amounts of caffeine to seek medical approval before eliminating caffeine. It may be necessary to adjust lithium dosage.
Dietary sodium: May alter renal elimination of lithium. Increased sodium intake may increase elimination of drug; decreased intake may decrease elimination. Monitor serum lithium levels.

Adverse reactions
CNS: tremors, drowsiness, headache, confusion, restlessness, dizziness, psychomotor retardation, lethargy, coma, blackouts, epileptiform seizures, EEG changes, worsened organic mental syndrome, impaired speech, ataxia, muscle weakness, incoordination.
CV: reversible ECG changes, arrhythmias, hypotension, bradycardia.
EENT: tinnitus, blurred vision.
GI: dry mouth, metallic taste, nausea, vomiting, anorexia, diarrhea, thirst, abdominal pain, flatulence, indigestion.
GU: polyuria, glycosuria, renal toxicity with long-term use, albuminuria.
Hematologic: leukocytosis with WBC count of 14,000 to 18,000/mm³ (reversible); elevated neutrophil count.
Metabolic: goiter, transient hyperglycemia, hypothyroidism, hyponatremia.
Skin: pruritus, rash, diminished or absent sensation, drying and thinning of hair, psoriasis, acne, alopecia.
Other: ankle and wrist edema.

Effects on lab test results
• May increase glucose level. May decrease sodium, T₃, T₄, and protein-bound iodine levels.
• May increase ¹³¹I uptake and WBC and neutrophil counts. May decrease creatinine clearance.

Overdose and treatment
Vomiting and diarrhea occur within 1 hour of acute ingestion (induce vomiting in noncomatose patients if it’s not spontaneous). Death has occurred in patients ingesting 10 to 60 g of lithium; patients have ingested 6 g with minimal toxic effects. Serum lithium levels above 3.4 mEq/L are potentially fatal.
 Overdose from long-term lithium ingestion may follow altered pharmacokinetics, drug interactions, or volume or sodium depletion; sedation, confusion, hand tremors, joint pain, ataxia, muscle stiffness, increased deep tendon reflexes, visual changes, and nystagmus may occur. Symptoms may progress to coma, movement abnormalities, tremors, seizures, and CV collapse.
 Treatment is symptomatic and supportive; closely monitor vital signs. If emesis isn’t feasible, treat with gastric lavage. Monitor fluid and electrolyte balance; correct sodium depletion with normal saline solution. Institute hemodialysis if serum level is above 3 mEq/L, and in severely symptomatic patients unresponsive to fluid and electrolyte correction, or if urine output decreases significantly. Serum rebound of tissue lithium stores (from high volume distribution) commonly occurs after dialysis and may necessitate prolonged or repeated hemodialysis. Peritoneal dialysis may help but is less effective.

Special considerations
• Lithium is used investigationally to increase WBC count in patients undergoing cancer chemotherapy. It also has been used investigationally to treat cluster headaches, aggression, organic brain syndrome, and tardive dyskinesia. Drug has been used to treat SIADH.
• EEG changes include diffuse slowing, widening of frequency spectrum, potentiation, and disorganization of background rhythm.
• Shake syrup formulation before administration.
• Discontinue drug before electroconvulsive therapy (ECT).
• Administer drug with food or milk to reduce GI upset.
• Expect lag of 1 to 3 weeks before beneficial effects of drug are noticed. Other psychotropic drugs (such as chlorpromazine) may be needed during interim period.
• Adjust fluid and salt ingestion to compensate if excessive loss occurs through protracted sweating or diarrhea. Patient should have fluid intake of 2,500 to 3,000 ml daily and a balanced diet with adequate salt intake.
• Lithane tablets contain tartrazine, a dye that may precipitate an allergic reaction in certain individuals, particularly asthmatics sensitive to aspirin.
• Drug causes false-positive test results on thyroid function tests.
• Acute neurotoxicity with delirium has occurred in patients receiving lithium and ECT. Reduce lithium dosage or withdraw before ECT.
• Monitor baseline ECG, thyroid and renal studies, and electrolyte levels. Monitor lithium blood levels 8 to 12 hours after first dose, usually before morning dose, two or three times weekly the first month, then weekly to monthly on maintenance therapy.
• Determination of serum drug levels is crucial to safe use of drug. Don’t use drug in patients who can’t have regular serum drug level checks. Make sure patient or responsible family member can comply with instructions.
• When lithium blood levels are below 1.5 mEq/L, adverse reactions usually remain mild.
• Monitor fluid intake and output, especially when surgery is scheduled.
• Observe patient for signs of edema or sudden weight gain.
• Outpatient follow-up of thyroid and renal functions should occur every 6 to 12 months. Thyroid should be palpated to check for enlargement.
• Check urine for specific gravity below 1.015, which may indicate diabetes insipidus.
• Drug may alter glucose tolerance in diabetic patients. Monitor blood glucose levels closely.
• Monitor drug dosing carefully when patient’s initial manic symptoms begin to subside because the ability to tolerate high serum lithium levels decreases as symptoms resolve. Adjust dosage based on lithium level, patient tolerance, and clinical response.
Pregnant patients
• Lithium has been used during pregnancy in life-threatening situations and severe disease when other therapies couldn’t be used or were ineffective. Fetal toxicity includes increased risk of CV abnormalities, Down syndrome, clubfoot, meningomyelocele, transient hypothyroidism with goiter, transient nephrogenic diabetes insipidus, muscular hypotonia, and apnea.
Breast-feeding patients
• Lithium level in breast milk is 33% to 50% that of maternal serum level. Women should avoid breast-feeding during treatment with lithium.
Pediatric patients
• Drug isn’t recommended for use in children younger than age 12.
Geriatric patients
• Elderly patients are more susceptible to overdose and toxic effects, especially dyskinesias. These patients usually respond to a lower dosage.

Patient education
• Explain that lithium has a narrow therapeutic margin of safety and that a serum drug level that’s even slightly high can be dangerous.
• Warn patient and family to watch for signs of toxicity (diarrhea, vomiting, dehydration, drowsiness, muscle weakness, tremor, fever, and ataxia) and to expect transient nausea, polyuria, thirst, and discomfort during first few days. If toxic symptoms occur, tell patient to withhold one dose and report symptoms promptly.
• Warn patient to avoid activities that require alertness and good psychomotor coordination until CNS response to drug is determined.
• Advise patient to maintain adequate water intake and adequate-but not excessive-salt in diet.
• Explain importance of regular follow-up visits to measure lithium serum levels.
• Tell patient to avoid large amounts of caffeine, which will interfere with effectiveness of drug.
• Advise patient to seek medical approval before beginning a weight-loss program.
• Tell patient not to switch brands of lithium or take other prescription or OTC drugs or herbal remedies without medical approval. Different brands may not provide equivalent effect.
• Tell patient to take drug with food or milk.
• Warn patient against stopping this drug abruptly.
• Tell patient to explain to close friend or family members the signs of lithium overdose in case emergency aid is needed.
• Instruct patient to carry identification and instruction card with toxicity and emergency information.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use