Yes

Lithium

Management of bipolar disorders

D

Hypersensitivity to lithium or any component; severe cardiovascular or renal disease; severe debilitation, dehydration, or sodium depletion

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 cardiovascular or thyroid disease, or in patients receiving medications which alter sodium excretion (eg, diuretics, ACE inhibitors, NSAIDs). Some elderly patients may be extremely sensitive to the effects of lithium, see Usual Dosage and Reference Range. Chronic therapy results in diminished renal concentrating ability (nephrogenic DI). Changes in renal function should be monitored, and re-evaluation of treatment may be necessary.

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.

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

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

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

Genitourinary: Incontinence, polyuria, glycosuria, oliguria, albuminuria

Hematologic: Leukocytosis

Neuromuscular & skeletal: Tremor, muscle hyperirritability, ataxia, choreoathetoid movements, hyperactive deep tendon reflexes

Ocular: Nystagmus, blurred vision

Miscellaneous: Discoloration of fingers and toes

Symptoms of overdose include sedation, confusion, tremors, joint pain, visual changes, seizures, coma

There is no specific antidote for lithium poisoning. In the acute ingestion following initiation of essential overdose management, correction of fluid and electrolyte imbalances should be commenced. Hemodialysis and whole bowel irrigation is the treatment of choice for severe intoxications; charcoal is ineffective.

Concurrent use of lithium with carbamazepine, diltiazem, fluoxetine, fluvoxamine, haloperidol, methyldopa, phenothiazines, TCAs, and verapamil may increase the risk for neurotoxicity; monitor

NSAIDs decrease renal lithium excretion leading to increased serum lithium concentrations; sulindac and aspirin may be the exceptions; monitor

Combined use of lithium and chlorpromazine may lower serum concentrations of both drugs; monitor

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

Lithium and MAOIs should generally be avoided due to use reports of fatal malignant hyperpyrexia

Losartan may reduce the renal clearance of lithium; monitor

Phenytoin may enhance lithium toxicity; monitor

Potassium iodide may enhance the hypothyroid effects of lithium; monitor

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

Sodium bicarbonate and high sodium intake may reduce serum lithium concentrations via enhanced excretion; monitor

Thiazide diuretics increase serum lithium concentration via sodium depletion

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

Distribution: V_d: Initial: 0.3-0.4 L/kg; V_dss: 0.7-1 L/kg; crosses the placenta; appears in breast milk at 35% to 50% the concentrations in serum

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

Time to peak serum concentration (nonsustained release product): Within 0.5-2 hours following oral absorption

Elimination: 90% to 98% of dose excreted in urine as unchanged drug; other excretory routes include feces (1%) and sweat (4% to 5%)

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

Adults: 900-2400 mg/day in 3-4 divided doses or 900-1800 mg/day in two divided doses of sustained release

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

Dosing adjustment in renal impairment:

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

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

Hemodialysis: Dialyzable (50% to 100%)

May be administered with meals to avoid GI upset; avoid changes in sodium content of diet; limit caffeine; food increases absorption; have patient drink 2-3 L of water daily; avoid changes in sodium content of diet (reduction in sodium intake can increase lithium toxicity), sodium is exchanged with lithium which may lead to elevated lithium levels; syrup may precipitate in tube feedings

Serum lithium every 3-4 days during initial therapy; draw lithium serum concentrations 8-12 hours postdose; renal, hepatic, thyroid, and cardiovascular function; fluid status; serum electrolytes; CBC with differential, urinalysis; monitor for signs of toxicity

Levels should be obtained twice weekly until both patient's clinical status and levels are stable then levels may be obtained every 1-2 months

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: >2 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

calcium (S), glucose, magnesium, potassium (S); thyroxine (S)

No information available to require special precautions

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

Take exactly as directed; do not change dosage without consulting prescriber. Do not crush or chew tablets or capsules. Maintain adequate fluid intake (2-3 L/day of fluids unless instructed to restrict fluid intake) especially in summer. 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 barrier contraceptive measures. Do not breast-feed.

Avoid dehydration

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

Syrup, as citrate: 300 mg/5 mL (5 mL, 10 mL, 480 mL)

Tablet, as carbonate: 300 mg

Tablet:

Controlled release, as carbonate: 450 mg

Slow release, as carbonate: 300 mg

Belanger DR, Tierney MG, and Dickinson G, "Effect of Sodium Polystyrene Sulfonate on Lithium Bioavailability," Ann Emerg Med, 1992, 21(11):1312-5.

Farag S, Watson RD, and Honeybourne D, "Symptomatic Junctional Bradycardia Due to Lithium Intoxication in Patient With Previously Normal Electrocardiogram," Lancet, 1994, 343(8909):1371.

Finley PR, Warner MD, Peabody CA, "Clinical Relevance of Drug Interactions With Lithium," Clin Pharmacokinet, 1995, 29(3):172-91.

Flaherty B, Dean BS, and Krenzelok EP, "Neonatal Lithium Toxicity as a Result of Maternal Toxicity," Clin Toxicol, 1995, 33(5):555.

Foster JF, Gershell WJ, and Goldfarb AI, "Lithium Treatment in the Elderly. I. Clinical Usage," J Gerontol, 1977, 32(3):299-302.

Groleau G, "Lithium Toxicity," Emerg Med Clin North Am, 1994, 12(2):511-31.

Groleau G, Barish R, Tso E, et al, "Lithium Intoxication: Manifestations and Management," Am J Emerg Med, 1987, 5(6):527-32.

Hambrecht M, "Lithium and Pseudohallucinations: A Rare Side Effect," Biol Psychiatry, 1995, 37(2):120-1.

Hicks R, Dysken MW, Davis JM, et al, "The Pharmacokinetics of Psychotropic Medication in the Elderly: A Review," J Clin Psychiatry, 1981, 42(10):374-85.

"Hyperosmolar Coma Due to Lithium-Induced Diabetes Insipidus," Lancet, 1995, 346(8972):413-7.

Joseph M and Vieweg V, "Electrocardiographic Changes of Sinus Bradycardia and Sinus Node Dysfunction Among Patients With Therapeutic Levels of Lithium," Depression, 1994-95, 2(4):226-31.

Langlois R and Paquette D, "Increased Serum Lithium Levels Due to Ketorolac Therapy," Can Med Assoc J, 1994, 150(9):1455-6.

Lehmann K and Ritz E, "Angiotensin-Converting Enzyme Inhibitors May Cause Renal Dysfunction in Patients on Long-Term Lithium Treatment," Am J Kidney Dis, 1995, 25(1):82-7.

Levy HB, Harper CR, and Weinberg WA, "A Practical Approach to Children Failing in School," Pediatr Clin North Am, 1992, 39(4):895-928.

Linakis JG, Hull KM, Lee CM, et al, "Effect of Delayed Treatment With Sodium Polystyrene Sulfonate on Serum Lithium Concentrations in Mice," Acad Emerg Med, 1995, 2(8):681-5.

Moster R, Toren P, Mizrachi I, et al, "Caffeine Withdrawal Increases Lithium Blood Levels," Biol Psychiatry, 1995, 37(5):348-50.

Oshika T, "Ocular Adverse Effects of Neuropsychiatric Agents. Incidence and Management," Drug Saf, 1995, 12(3):256-63.

Perrier A, Martin PY, Favre H, et al, "Very Severe Self-Poisoning Lithium Carbonate Intoxication Causing a Myocardial Infarction," Chest, 1991, 100(3):863-5.

Price LH and Heninger GR, "Lithium in the Treatment of Mood Disorders," N Engl J Med, 1994, 331(9):591-8.

Rampes H and Bhandari S, "Hypersalivation and Lithium Toxicity," J Psychopharmacol, 1994, 8(4):261.

Smith SW, Ling LJ, and Halstenson CE, "Whole Bowel Irrigation as a Treatment for Acute Lithium Overdose," Ann Emerg Med, 1991, 20(5):536-9.

Swanson CL Jr, Price WA, and McEvoy JP, "Effects of Concomitant Risperidone and Lithium Treatment," Am J Psychiatry, 1995, 152(7):1096.

Szerlip HM, Heeger P, and Feldman GM, "Comparison Between Acetate and Bicarbonate Dialysis for the Treatment of Lithium Intoxication," Am J Nephrol, 1992, 12(1-2):116-20.

Tomaszewski C, Musso C, and Pearson JR, "Lithium Absorption Prevented by Sodium Polystyrene Sulfonate in Volunteers," Ann Emerg Med, 1992, 21(11):1308-11.

Ward ME, Musa MN, Bailey L, "Clinical Pharmacokinetics of Lithium," J Clin Pharmacol, 1994, 34(4):280-5.

Watling SM, Gehrke JC, Gehrke CW, et al, " In vitro Binding of Lithium Using the Cation Exchange Resin Sodium Polystyrene Sulfonate," Am J Emerg Med, 1995, 13(3):294-6.

Worthley LT, "Lithium Toxicity and Refractory Cardiac Arrhythmia Treated With Intravenous Magnesium," Anaesth Intensive Care, 1974, 4:357-60.