Lithium

lithium (lith' ee um)

lithium carbonate Carbolith (CAN), Duralith (CAN), Eskalith, Eskalith CR, Lithizine (CAN), Lithobid, Lithonate, Lithotabs, PMS-Lithium Carbonate (CAN)

lithium citrate Cibalith-S (CAN) Pregnancy Category D Drug class

Antimanic drug Therapeutic actions

Mechanism is not known; alters sodium transport in nerve and muscle cells; inhibits release of norepinephrine and dopamine, but not serotonin, from stimulated neurons; slightly increases intraneuronal stores of catecholamines; decreases intraneuronal content of second messengers and may thereby selectively modulate the responsiveness of hyperactive neurons that might contribute to the manic state. Indications

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Treatment of manic episodes of manic-depressive illness; maintenance therapy to prevent or diminish frequency and intensity of subsequent manic episodes Unlabeled use: Improvement of neutrophil counts in patients with cancer chemotherapy–induced neutropenia and in children with chronic neutropenia and HIV patients on zidovudine therapy (doses of 300–1,000 mg/day, serum levels of 0.5 and 1 mEq/L); prophylaxis of cluster headache and cyclic migraine headache, treatment of SIADH, hypothyroidism (doses of 600–900 mg/day)

Contraindications and cautions

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Contraindicated with hypersensitivity to tartrazine; significant renal or CV disease; severe debilitation, dehydration; sodium depletion, patients on diuretics (lithium decreases sodium reabsorption, and hyponatremia increases lithium retention); pregnancy; lactation. Use cautiously with protracted sweating and diarrhea; suicidal or impulsive patients; infection with fever.

Available forms

Capsules—150, 300, 600 mg; tablets—300 mg; SR tablets—300 mg; CR tablets— 450 mg; syrup—300 mg/5 mL Dosages

Individualize dosage according to serum levels and clinical response.

ADULTS

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Acute mania: 600 mg PO tid or 900 mg slow-release form PO bid to produce effective serum levels between 1 and 1.5 mEq/L. Serum levels should be determined twice per wk in samples drawn immediately before a dose (at least 8– 12 hr after previous dose). Long-term use: 300 mg PO tid to qid to produce a serum level of 0.6 to 1.2 mEq/L. Serum levels should be determined at least every 2 mo in samples drawn immediately before a dose (at least 8–12 hr after previous dose). Conversion from conventional to slow-release dosage forms: Give the same total daily dose divided into 2 or 3 doses.

PEDIATRIC PATIENTS

Safety and efficacy for children < 12 yr not established. GERIATRIC PATIENTS AND PATIENTS WITH RENAL IMPAIRMENT

Reduced dosage may be necessary. Elderly patients often respond to reduced dosage and may exhibit signs of toxicity at serum levels tolerated by other patients. Plasma half-life is prolonged in renal impairment. Pharmacokinetics Route Oral

Onset 5–7 days

Peak 10–21 days

Metabolism: Hepatic; T1/2: 17–36 hr Distribution: Crosses placenta; enters breast milk Excretion: Urine Adverse effects

Reactions are related to serum lithium levels (toxic lithium levels are close to therapeutic levels: therapeutic levels in acute mania range between 1 and 1.5 mEq/L; therapeutic levels for maintenance are 0.6 to 1.2 mEq/L). < 1.5 mEq/L

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CNS: Lethargy, slurred speech, muscle weakness, fine hand tremor GI: Nausea, vomiting, diarrhea, thirst GU: Polyuria

1.5–2 mEq/L (mild to moderate toxic reactions)

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CNS: Coarse hand tremor, mental confusion, hyperirritability of muscles, drowsiness, incoordination CV: ECG changes GI: Persistent GI upset, gastritis, salivary gland swelling, abdominal pain, excessive salivation, flatulence, indigestion

2–2.5 mEq/L (moderate to severe toxic reactions)

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CNS: Ataxia, giddiness, fasciculations, tinnitus, blurred vision, clonic movements, seizures, stupor, coma CV: Serious ECG changes, severe hypotension with cardiac arrythmias GU: Large output of dilute urine Respiratory: Fatalities secondary to pulmonary complications

> 2.5 mEq/L (life-threatening toxicity)

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General: Complex involvement of multiple organ systems, including seizures, arrythmias, CV collapse, stupor, coma

Reactions unrelated to serum levels

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CNS: Headache, worsening of organic brain syndromes, fever, reversible shortterm memory impairment, dyspraxia CV: ECG changes; hyperkalemia associated with ECG changes; syncope; tachycardia-bradycardia syndrome; rarely, arrhythmias, CHF, diffuse myocarditis, death Dermatologic: Pruritus with or without rash; maculopapular, acneiform, and follicular eruptions; cutaneous ulcers; edema of ankles or wrists Endocrine: Diffuse nontoxic goiter; hypothyroidism; hypercalcemia associated with hyperparathyroidism; transient hyperglycemia; irreversible nephrogenic diabetes insipidus, which improves with diuretic therapy; impotence or sexual dysfunction GI: Dysgeusia (taste distortion), salty taste; swollen lips; dental caries Miscellaneous: Weight gain (5–10 kg); chest tightness; swollen or painful joints, eye irritation, worsening of cataracts, disturbance of visual accommodation, leukocytosis

Interactions

Drug-drug • Increased risk of toxicity with thiazide diuretics due to decreased renal clearance of lithium—reduced lithium dosage may be necessary • Increased plasma lithium levels with indomethacin and some other NSAIDs— phenylbutazone, piroxicam, ibuprofen, as well as fluoxetine and methyldopa • Increased CNS toxicity with carbamazepine • Encephalopathic syndrome (weakness, lethargy, fever, tremulousness, confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes) with irreversible brain damage when taken with haloperidol • Greater risk of hypothyroidism with iodide salts • Decreased effectiveness due to increased excretion of lithium with urinary alkalinizers, including antacids, tromethamine Drug-alternative therapy • Increased effects and toxicity with juniper, dandelion Nursing considerations Assessment

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History: Hypersensitivity to tartrazine; significant renal or CV disease; severe debilitation, dehydration; sodium depletion, patients on diuretics; protracted sweating, diarrhea; suicidal or impulsive patients; infection with fever; pregnancy; lactation Physical: Weight and T; skin color, lesions; orientation, affect, reflexes; ophthalmic exam; P, BP, R, adventitious sounds; bowel sounds, normal output; normal fluid intake, normal output, voiding pattern; thyroid, renal glomerular and tubular function tests, urinalysis, CBC and differential, baseline ECG

Interventions

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Give with caution and daily monitoring of serum lithium levels to patients with renal or CV disease, debilitation, or dehydration or life-threatening psychiatric disorders. Give drug with food or milk or after meals. Monitor clinical status closely, especially during initial stages of therapy; monitor for therapeutic serum levels of 0.6–1.2 mEq/L. Individuals vary in their reponse to this drug; some patients may exhibit toxic signs at serum lithium levels considered within the therapeutic range. Advise patient that this drug may cause serious fetal harm and cannot be used during pregnancy; urge use of barrier contraceptives. Decrease dosage after the acute manic episode is controlled; lithium tolerance is greater during the acute manic phase and decreases when manic symptoms subside. Ensure that patient maintains adequate intake of salt and adequate intake of fluid (2,500–3,000 mL/day).

Teaching points

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Take this drug exactly as prescribed, after meals or with food or milk. Eat a normal diet with normal salt intake; maintain adequate fluid intake (at least 2.5 quarts/day). Arrange for frequent checkups, including blood tests. Keep all appointments for checkups to receive maximum benefits and minimum risks of toxicity. Use contraception to avoid pregnancy. If you wish to become pregnant or believe that you have become pregnant, consult your care provider. Discontinue drug, and notify care provider if toxicity occurs—diarrhea, vomiting, ataxia, tremor, drowsiness, lack of coordination or muscular weakness. These side effects may occur: Drowsiness, dizziness (avoid driving or performing tasks that require alertness); GI upset (eat frequent small meals); mild thirst, greater than usual urine volume, fine hand tremor (may persist throughout therapy; notify heath care provider if severe). Report diarrhea or fever.

Adverse effects in Italic are most common; those in Bold are life-threatening.