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Pharmacologic Category
Lithium
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
D
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
Boxed warnings:
• Monitoring: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Renal effects: 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. 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.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with mild-moderate cardiovascular disease.
• Dehydration: Use with caution in patients with significant fluid loss (protracted sweating, diarrhea, or prolonged fever); temporary reduction or cessation of therapy may be warranted.
• Depression/suicidal ideation: Use with caution in patients at risk of suicide (suicidal thoughts or behavior).
• Renal impairment: Use with caution in patients with mild-moderate renal impairment.
• Thyroid disease: Use with caution in patients with thyroid disease.
Concurrent drug therapy issues:
• Medications altering sodium excretion: Use caution in patients receiving medications which alter sodium excretion (eg, diuretics, ACE inhibitors, NSAIDs).
• Neuroleptic medications: Use with caution in patients receiving neuroleptic medications - a syndrome resembling NMS has been associated with concurrent therapy.
• Neuromuscular-blocking agents: Administered neuromuscular-blocking agents with caution; the response may be prolonged.
Special populations:
• Elderly: Use with caution in the elderly; may be extremely sensitive to the effects of lithium, see Dosage and Reference Range.
• Pediatrics: Safety and efficacy have not been established in children <12 years of age.
Other warnings/precautions:
• Acute manic phase: Higher serum concentrations may be required and tolerated during an acute manic phase; however, the tolerance decreases when symptoms subside.
• Monitoring: [U.S. Boxed Warning]: Lithium toxicity is closely related to serum concentrations and can occur at therapeutic doses; serum lithium determinations are required to monitor therapy. Normal fluid and salt intake must be maintained during therapy.
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
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 (unlabeled use): 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: Oral
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; beta-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.
Geriatric Considerations
Some elderly patients may be extremely sensitive to the effects of lithium. Initial doses need to be adjusted for renal function in the elderly; thereafter, adjust doses based upon serum concentrations and response.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation), salivary gland swelling, and metallic taste. 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.
Mental Health: Comment
Lithium remains the gold standard for bipolar disorder. It is most useful for the management of euphoric mania and least effective for the mixed and rapid-cycling types of bipolar disorder. Among patients treated for bipolar disorder, risk of suicide attempt and suicide death is lower during treatment with lithium than during treatment with divalproex (Goodwin, 2003). Fine hand tremor associated with lithium therapy may be treated with propranolol. Incidence of hypothyroidism secondary to lithium therapy is 7% to 8% with a 9:1 female to male ratio. Diabetes insipidus may be treated with a thiazide diuretic (hydrochlorothiazide 25-50 mg/day) or amiloride (5-10 mg twice daily). The thiazide diuretics are thought to work by decreasing intracellular volume via sodium depletion, thereby enhancing reabsorption of sodium and water proximally leading to a decrease in fluid volume to the distal convoluted tubule and collecting duct which increases sodium reabsorption and decreases water excretion. Leukocytosis (without a left shift) begins in the first week of lithium therapy, peaks at 2 weeks.
Goodwin GM and Young AH, “The British Association for Psychopharmacology Guidelines for Treatment of Bipolar Disorder: A Summary,” J Psychopharmacol, 2003, 17(4 Suppl):3-6.
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Monitor cardiovascular status; assess for fluid retention. Monitor laboratory results at beginning of therapy, when adjusting dose, and periodically thereafter. Monitor effectiveness of therapy and adverse reactions at beginning of therapy and periodically with long-term use. Note: Lithium has a very small window of safety (TI). Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and importance of reporting adverse symptoms promptly.
cia aplamai licio:
Pharmacologic Category
Lithium
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
D
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
Boxed warnings:
• Monitoring: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Renal effects: 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. 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.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with mild-moderate cardiovascular disease.
• Dehydration: Use with caution in patients with significant fluid loss (protracted sweating, diarrhea, or prolonged fever); temporary reduction or cessation of therapy may be warranted.
• Depression/suicidal ideation: Use with caution in patients at risk of suicide (suicidal thoughts or behavior).
• Renal impairment: Use with caution in patients with mild-moderate renal impairment.
• Thyroid disease: Use with caution in patients with thyroid disease.
Concurrent drug therapy issues:
• Medications altering sodium excretion: Use caution in patients receiving medications which alter sodium excretion (eg, diuretics, ACE inhibitors, NSAIDs).
• Neuroleptic medications: Use with caution in patients receiving neuroleptic medications - a syndrome resembling NMS has been associated with concurrent therapy.
• Neuromuscular-blocking agents: Administered neuromuscular-blocking agents with caution; the response may be prolonged.
Special populations:
• Elderly: Use with caution in the elderly; may be extremely sensitive to the effects of lithium, see Dosage and Reference Range.
• Pediatrics: Safety and efficacy have not been established in children <12 years of age.
Other warnings/precautions:
• Acute manic phase: Higher serum concentrations may be required and tolerated during an acute manic phase; however, the tolerance decreases when symptoms subside.
• Monitoring: [U.S. Boxed Warning]: Lithium toxicity is closely related to serum concentrations and can occur at therapeutic doses; serum lithium determinations are required to monitor therapy. Normal fluid and salt intake must be maintained during therapy.
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
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 (unlabeled use): 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: Oral
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; beta-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.
Geriatric Considerations
Some elderly patients may be extremely sensitive to the effects of lithium. Initial doses need to be adjusted for renal function in the elderly; thereafter, adjust doses based upon serum concentrations and response.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation), salivary gland swelling, and metallic taste. 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.
Mental Health: Comment
Lithium remains the gold standard for bipolar disorder. It is most useful for the management of euphoric mania and least effective for the mixed and rapid-cycling types of bipolar disorder. Among patients treated for bipolar disorder, risk of suicide attempt and suicide death is lower during treatment with lithium than during treatment with divalproex (Goodwin, 2003). Fine hand tremor associated with lithium therapy may be treated with propranolol. Incidence of hypothyroidism secondary to lithium therapy is 7% to 8% with a 9:1 female to male ratio. Diabetes insipidus may be treated with a thiazide diuretic (hydrochlorothiazide 25-50 mg/day) or amiloride (5-10 mg twice daily). The thiazide diuretics are thought to work by decreasing intracellular volume via sodium depletion, thereby enhancing reabsorption of sodium and water proximally leading to a decrease in fluid volume to the distal convoluted tubule and collecting duct which increases sodium reabsorption and decreases water excretion. Leukocytosis (without a left shift) begins in the first week of lithium therapy, peaks at 2 weeks.
Goodwin GM and Young AH, “The British Association for Psychopharmacology Guidelines for Treatment of Bipolar Disorder: A Summary,” J Psychopharmacol, 2003, 17(4 Suppl):3-6.
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Monitor cardiovascular status; assess for fluid retention. Monitor laboratory results at beginning of therapy, when adjusting dose, and periodically thereafter. Monitor effectiveness of therapy and adverse reactions at beginning of therapy and periodically with long-term use. Note: Lithium has a very small window of safety (TI). Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and importance of reporting adverse symptoms promptly.
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