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Pronunciation:

(LITH ee um)

U.S. Brand Names:

Eskalith®; Eskalith CR®; Lithobid®

Synonyms:

Lithium Carbonate; Lithium Citrate

Generic Available:

Yes

Canadian Brand Names:

Apo-Lithium®; Carbolith™; Duralith®; Lithane™; PMS-Lithium Carbonate; PMS-Lithium Citrate

Use:

Management of bipolar disorders; treatment of mania in individuals with bipolar disorder (maintenance treatment prevents or diminishes intensity of subsequent episodes)

Use - Unlabeled/Investigational:

Potential augmenting agent for antidepressants; aggression, post-traumatic stress disorder, conduct disorder in children

Pregnancy Risk Factor:

Pregnancy Implications:

Cardiac malformations in the infant, including Ebstein's anomaly, are associated with use of lithium during the first trimester of pregnancy. Nontoxic effects to the newborn include shallow respiration, hypotonia, lethargy, cyanosis, diabetes insipidus, thyroid depression, and nontoxic goiter when lithium is used near term. Efforts should be made to avoid lithium use during the first trimester; if an alternative therapy is not appropriate, the lowest possible dose of lithium should be used throughout the pregnancy. Fetal echocardiography and ultrasound to screen for anomalies should be conducted between 16-20 weeks of gestation. Lithium levels should be monitored in the mother and may need to be adjusted following delivery.

Lactation:

Enters breast milk/contraindicated

Contraindications:

Hypersensitivity to lithium or any component of the formulation; avoid use in patients with severe cardiovascular or renal disease, or with severe debilitation, dehydration, or sodium depletion; pregnancy

Warnings/Precautions:

Lithium toxicity is closely related to serum levels and can occur at therapeutic doses; serum lithium determinations are required to monitor therapy. Use with caution in patients with thyroid disease, mild-moderate renal impairment, or mild-moderate cardiovascular disease. Use caution in patients receiving medications which alter sodium excretion (eg, diuretics, ACE inhibitors, NSAIDs), or in patients with significant fluid loss (protracted sweating, diarrhea, or prolonged fever); temporary reduction or cessation of therapy may be warranted. Some elderly patients may be extremely sensitive to the effects of lithium, see Dosage and Reference Range. Chronic therapy results in diminished renal concentrating ability (nephrogenic DI); this is usually reversible when lithium is discontinued. Changes in renal function should be monitored, and re-evaluation of treatment may be necessary. Use caution in patients at risk of suicide (suicidal thoughts or behavior).

Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy; morphologic changes have also been reported in manic-depressive patients never exposed to lithium. The relationship between morphologic changes and renal function, and the association with lithium therapy, have not been established.

Use with caution in patients receiving neuroleptic medications - a syndrome resembling NMS has been associated with concurrent therapy. Lithium may impair the patient's alertness, affecting the ability to operate machinery or driving a vehicle. Neuromuscular-blocking agents should be administered with caution; the response may be prolonged.

Higher serum concentrations may be required and tolerated during an acute manic phase; however, the tolerance decreases when symptoms subside. Normal fluid and salt intake must be maintained during therapy.

Safety and efficacy have not been established in children <12 years of age.

Adverse Reactions:

Frequency not defined.

Cardiovascular: Cardiac arrhythmia, hypotension, sinus node dysfunction, flattened or inverted T waves (reversible), edema, bradycardia, syncope

Central nervous system: Dizziness, vertigo, slurred speech, blackout spells, seizure, sedation, restlessness, confusion, psychomotor retardation, stupor, coma, dystonia, fatigue, lethargy, headache, pseudotumor cerebri, slowed intellectual functioning, tics

Dermatologic: Dry or thinning of hair, folliculitis, alopecia, exacerbation of psoriasis, rash

Endocrine & metabolic: Euthyroid goiter and/or hypothyroidism, hyperthyroidism, hyperglycemia, diabetes insipidus

Gastrointestinal: Polydipsia, anorexia, nausea, vomiting, diarrhea, xerostomia, metallic taste, weight gain, salivary gland swelling, excessive salivation

Genitourinary: Incontinence, polyuria, glycosuria, oliguria, albuminuria

Hematologic: Leukocytosis

Neuromuscular & skeletal: Tremor, muscle hyperirritability, ataxia, choreoathetoid movements, hyperactive deep tendon reflexes, myasthenia gravis (rare)

Ocular: Nystagmus, blurred vision, transient scotoma

Miscellaneous: Coldness and painful discoloration of fingers and toes

Overdosage/Toxicology:

Symptoms include sedation, confusion, tremors, joint pain, visual changes, seizures, and coma. There is no specific antidote for lithium poisoning. For acute ingestion, following initiation of essential overdose management, discontinue lithium and remove any unabsorbed lithium via gastric lavage (activated charcoal is ineffective as it does not bind lithium). Correct fluid and electrolyte imbalances, provide supportive care. In severe cases, patient should be dialyzed. Hemodialysis is preferred (and more effective) than peritoneal dialysis. The goal is to decrease serum lithium level to <1 mEq/L on a serum sample drawn 6-8 hours after completion of dialysis. Agents that increase the excretion of lithium are of questionable value.

Drug Interactions:

ACE inhibitors: May increase the risk of lithium toxicity via sodium depletion; monitor

Angiotensin receptor antagonists (losartan): May reduce the renal clearance of lithium; monitor

Caffeine (xanthine derivatives): May lower lithium serum concentrations by increasing urinary lithium excretion; monitor.

Carbamazepine: Concurrent use of lithium with carbamazepine may increase the risk for neurotoxicity; monitor

Carbonic anhydrase inhibitors: May decrease lithium levels; includes acetazolamide; monitor

Calcium channel blockers (diltiazem and verapamil): May increase the risk for neurotoxicity (ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus); monitor; does not appear to involve dihydropyridine class

Chlorpromazine: May lower serum concentrations of both drugs; monitor

COX-2 inhibitors (celecoxib): May increase lithium plasma concentrations (similar to NSAIDs); monitor.

Haloperidol: May increase the risk for neurotoxicity and encephalopathy; a rare encephalopathic syndrome resulting in irreversible brain damage has been reported in a few patients (causal relationship not established); monitor

Iodine salts: May enhance the hypothyroid effects of lithium; monitor

Loop diuretics: May decrease the renal excretion of lithium, leading to toxicity; monitor

MAO inhibitors: Should generally be avoided due to use reports of fatal malignant hyperpyrexia when combined with lithium

Methyldopa: May increase the risk for neurotoxicity; monitor

Metronidazole: May increase lithium toxicity (rare); monitor

Neuromuscular-blocking agents: Lithium may potentiate the response to neuromuscular blockade, resulting in prolonged blockade and possible delayed recovery

NSAIDs: Renal lithium excretion may be decreased leading to increased serum lithium concentrations; sulindac and aspirin may be the exceptions; monitor

Phenothiazines: May increase the risk for neurotoxicity; monitor

Phenytoin: May enhance lithium toxicity; monitor

Selegiline: Risk of severe reactions when combined with MAO inhibitors may be decreased when administered with selective MAO type B inhibitor, particularly at selegiline doses <10 mg/day; however, theoretical risk is still present

SSRIs: May increase the risk for neurotoxicity; monitor; effect noted with fluoxetine, fluvoxamine

Sibutramine: Combined use of lithium with sibutramine may increase the risk of serotonin syndrome; this combination is best avoided

Sodium-containing products: Bicarbonate and/or high sodium intake may reduce serum lithium concentrations via enhanced excretion; monitor. Note: Reabsorption of lithium in the proximal convoluted tubule occurs against electrical and concentration gradients that do not distinguish between lithium and sodium. Therefore, lithium clearance may increase or decrease 30% to 50% with sodium load or depletion, respectively. Sodium depletion usually has the greater effect.

Sympathomimetics: Lithium may blunt the pressor response to sympathomimetics (epinephrine, phenylephrine, norepinephrine)

Tetracyclines: May increase lithium levels; monitor

Theophylline: May increase real clearance of lithium, resulting in a decrease in serum lithium concentrations; monitor

Thiazide diuretics: May increase serum lithium concentration via sodium depletion and decreased lithium clearance; a lithium dose reduction of 50% is commonly recommended

Tricyclic antidepressants: May increase the risk for neurotoxicity; monitor

Urea: May lower lithium serum concentrations by increasing urinary excretion; monitor.

Ethanol/Nutrition/Herb Interactions:

Food: Lithium serum concentrations may be increased if taken with food. Limit caffeine.

Mechanism of Action:

Alters cation transport across cell membrane in nerve and muscle cells and influences reuptake of serotonin and/or norepinephrine; second messenger systems involving the phosphatidylinositol cycle are inhibited; postsynaptic D2 receptor supersensitivity is inhibited

Pharmacodynamics/Kinetics:

Absorption: Rapid and complete

Distribution: Vd: Initial: 0.3-0.4 L/kg; Vdss: 0.7-1 L/kg; crosses placenta; enters breast milk at 35% to 50% the concentrations in serum; distribution is complete in 6-10 hours

CSF, liver concentrations: ¹/3 to ¹/2 of serum concentration

Erythrocyte concentration: ~¹/2 of serum concentration

Heart, lung, kidney, muscle concentrations: Equivalent to serum concentration

Saliva concentration: 2-3 times serum concentration

Thyroid, bone, brain tissue concentrations: Increase 50% over serum concentrations

Protein binding: Not protein bound

Metabolism: Not metabolized

Bioavailability: Not affected by food; Capsule, immediate release tablet: 95% to 100%; Extended release tablet: 60% to 90%; Syrup: 100%

Half-life elimination: 18-24 hours; can increase to more than 36 hours in elderly or with renal impairment

Time to peak, serum: Nonsustained release: ~0.5-2 hours; slow release: 4-12 hours; syrup: 15-60 minutes

Excretion: Urine (90% to 98% as unchanged drug); sweat (4% to 5%); feces (1%)

Clearance: 80% of filtered lithium is reabsorbed in the proximal convoluted tubules; therefore, clearance approximates 20% of GFR or 20-40 mL/minute

Dosage:

Oral: Monitor serum concentrations and clinical response (efficacy and toxicity) to determine proper dose

Children 6-12 years:

Bipolar disorder: 15-60 mg/kg/day in 3-4 divided doses; dose not to exceed usual adult dosage

Conduct disorder (unlabeled use): 15-30 mg/kg/day in 3-4 divided doses; dose not to exceed usual adult dosage

Adults: Bipolar disorder: 900-2400 mg/day in 3-4 divided doses or 900-1800 mg/day (sustained release) in 2 divided doses

Elderly: Bipolar disorder: Initial dose: 300 mg once or twice daily; increase weekly in increments of 300 mg/day, monitoring levels; rarely need >900-1200 mg/day

Dosing adjustment in renal impairment:

Clcr 10-50 mL/minute: Administer 50% to 75% of normal dose

Clcr<10 mL/minute: Administer 25% to 50% of normal dose

Hemodialysis: Dialyzable (50% to 100%); 4-7 times more efficient than peritoneal dialysis

Administration:

Administer with meals to decrease GI upset. Slow release tablets must be swallowed whole; do not crush or chew.

Monitoring Parameters:

Serum lithium every 4-5 days during initial therapy; draw lithium serum concentrations 8-12 hours postdose; renal, thyroid, and cardiovascular function; fluid status; serum electrolytes; CBC with differential, urinalysis; monitor for signs of toxicity; b-HCG pregnancy test for all females not known to be sterile

Reference Range:

Levels should be obtained twice weekly until both patient's clinical status and levels are stable then levels may be obtained every 1-3 months

Timing of serum samples: Draw trough just before next dose (8-12 hours after previous dose)

Therapeutic levels:

Acute mania: 0.6-1.2 mEq/L (SI: 0.6-1.2 mmol/L)

Protection against future episodes in most patients with bipolar disorder: 0.8-1 mEq/L (SI: 0.8-1.0 mmol/L); a higher rate of relapse is described in subjects who are maintained at <0.4 mEq/L (SI: 0.4 mmol/L)

Elderly patients can usually be maintained at lower end of therapeutic range (0.6-0.8 mEq/L)

Toxic concentration: >1.5 mEq/L (SI: >2 mmol/L)

Adverse effect levels:

GI complaints/tremor: 1.5-2 mEq/L

Confusion/somnolence: 2-2.5 mEq/L

Seizures/death: >2.5 mEq/L

Dietary Considerations:

May be taken with meals to avoid GI upset; have patient drink 2-3 L of water daily.

Patient Education:

Take exactly as directed; do not change dosage without consulting prescriber. Do not crush or chew extended or slow release tablets or capsules. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake (especially in summer). Avoid changes in sodium content (eg, low sodium diets); reduction of sodium can increase lithium toxicity. Limit caffeine intake (diuresis can increase lithium toxicity). Frequent blood test and monitoring will be necessary. You may experience decreased appetite or altered taste sensation (small, frequent meals may help maintain nutrition); or drowsiness or dizziness, especially during early therapy (use caution when driving or engaging in tasks requiring alertness until response to drug is known). Immediately report unresolved diarrhea, abrupt changes in weight, muscular tremors or lack of coordination, fever, or changes in urinary volume. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate contraceptive measures. Do not breast-feed.

Dental Health: Effects on Dental Treatment:

Avoid NSAIDs if analgesics are required since lithium toxicity has been reported with concomitant administration; acetaminophen products (ie, singly or with narcotics) are recommended.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

No information available to require special precautions

Mental Health: Child/Adolescent Considerations:

Information regarding the safety and effectiveness of lithium carbonate in children <12 years of age is not available; its use in this population group is not recommended.

Dosage Forms:

Capsule, as carbonate: 150 mg, 300 mg, 600 mg

Eskalith®: 300 mg [contains benzyl alcohol]

Syrup, as citrate: 300 mg/5 mL (5 mL, 10 mL, 480 mL) [contains alcohol]

Tablet, as carbonate: 300 mg

Tablet, controlled release, as carbonate (Eskalith CR®): 450 mg

Tablet, slow release, as carbonate (Lithobid®): 300 mg

International Brand Names:

Apo-Lithium® (CA); Biogam Li® (BE, CH); Camcolit® (BE, CY, GB, HK, IE, JO, KW, LB, LK, LU, NL, SG, ZA); Carbolim® (BR); Carbolit® (CO, MX); Carbolith™ (CA); Carbolithium® (IT); Carbolitium® (BR); Carbonat de Litiu® (RO); Carboron® (CL); Ceglution® (AR, EC); Contemnol® (CZ, RU); Duralith® (CA); Gammadyn Li® (BE); Granions de Lithium® (MC); Hypnorex® (DE); Karlit® (AR); Lentolith® (ZA); leukominerase® (DE); Li 450 Ziethen® (DE); Licab® (IN); Licarbium® (IL); Licarb® (TH); Li Liquid® (GB); Limas® (JP); Limed® (TH); Liskonum® (GB, KW); Lit 300® (TH); Litarex® (CH, DK, NL); Lithane™ (CA); Litheum® (MX); Lithicarb® (AU, NZ); Lithii Carbonatis® (SI); Lithioderm® (FR); Lithiofor® (CH, HK); Lithionit® (NO, SE); Lithium Apogepha® (DE, RO); Lithium-Aspartat® (DE); Lithiumcarbonaat FNA® (NL); Lithium Carbonate® (NZ); Lithium Carbonicum® (CZ, PL, RO); Lithium Microsol® (FR); Lithium Oligosol® (FR); Lithiun® (AR); Lithuril® (TR); Liticarb® (HU); Litij karbonat Jadran® (HR); Litij karbonat® (SI); Litijum karbonat® (YU); Litio carbonato® (IT); Litiocar® (BR); Litium-Karbonát® (HU); Litiumkarbonat Oba® (DK); Litiumkarbonat SAD® (DK); Lito® (FI); Maniprex® (BE, LU); Neurolepsin® (AT); Neurolithium® (BE, BR, CH, FR); Oligogranul Lithium® (FR); Oligosol Li® (BE, CH); Oligostim Li® (BE); Oligostim Lithium® (FR); Phanate® (TH); Plenur® (ES); PMS-Lithium Carbonate (CA); PMS-Lithium Citrate (CA); Priadel® (BE, CH, GB, HK, IE, LU, NL, NZ, PT, SG); Psicolit® (CL); Quilonorm® (CH); Quilonorm retard® (AT, CH); Quilonum® (DE, ZA); Quilonum retard® (DE, LU); Quilonum SR® (AU); Téralithe® (FR); Theralite® (CO)

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