Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING Lithium oral solution, USP, is supplied as a clear, slightly yellow liquid with citrus aroma packed in 16 oz white HDPE modern round bottle with CRC or 7 mL blue unit-dose cup with peelable HDPE lidding. Bottle of 473 mL (16 oz) NDC 71656-072-16 5 mL (8 mEq) fill, case of 5 trays x 10s NDC 71656-072-50 Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Dispense in a tight, child-resistant container as defined in the USP/NF.; PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Lot#21XXXAX Exp:MMM/YYYY 71656-072-05 Lithium Oral Solution, USP 8 mEq per 5 mL Unit-dose delivers 5 mL Orange Flavor image description; PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 71656-072-16 Lithium Oral Solution, USP 8 mEq per 5 mL Orange Flavor PHARMACIST: Dispense the Medication Guide to each patient. Rx only 473 mL(16 oz) image description; PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 71656-072-50 Lithium Oral Solution, USP 8 mEq per 5 mL Unit-dose delivers 5 mL Orange Flavor PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 5 Trays contain 50 Unit-dose Cups image description
- 16 HOW SUPPLIED/STORAGE AND HANDLING Lithium oral solution, USP, is supplied as a clear, slightly yellow liquid with citrus aroma packed in 16 oz white HDPE modern round bottle with CRC or 7 mL blue unit-dose cup with peelable HDPE lidding. Bottle of 473 mL (16 oz) NDC 71656-072-16 5 mL (8 mEq) fill, case of 5 trays x 10s NDC 71656-072-50 Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Dispense in a tight, child-resistant container as defined in the USP/NF.
- PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Lot#21XXXAX Exp:MMM/YYYY 71656-072-05 Lithium Oral Solution, USP 8 mEq per 5 mL Unit-dose delivers 5 mL Orange Flavor image description
- PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 71656-072-16 Lithium Oral Solution, USP 8 mEq per 5 mL Orange Flavor PHARMACIST: Dispense the Medication Guide to each patient. Rx only 473 mL(16 oz) image description
- PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 71656-072-50 Lithium Oral Solution, USP 8 mEq per 5 mL Unit-dose delivers 5 mL Orange Flavor PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 5 Trays contain 50 Unit-dose Cups image description
Overview
Each 5 mL of solution for oral administration contains lithium ion (Li + ), 8 mEq (equivalent to amount of lithium in 300 mg of lithium carbonate, USP), and the following other inactive ingredients: citric acid, glycerin, orange flavor, propylene glycol, purified water, sodium benzoate, sorbitol solution, and sucralose. Lithium oral solution, USP is a palatable oral dosage form of lithium ion. It is prepared in solution from lithium carbonate, USP and citric acid in a ratio approximately di-lithium citrate. Lithium is an element of the alkali-metal group with atomic number 3, atomic weight 6.94, and an emission line at 671 nm on the flame photometer. The empirical formula for lithium citrate is C 6 H 5 Li 3 O 7 ; molecular weight 209.93. Lithium acts as an antimanic.
Indications & Usage
Lithium oral solution is a mood-stabilizing agent indicated as monotherapy for the treatment of bipolar I disorder: Treatment of acute manic and mixed episodes in patients 7 years and older [see Clinical Studies ( 14 )]. Maintenance treatment in patients 7 years and older [see Clinical Studies ( 14 )]. Lithium is a mood-stabilizing agent indicated as monotherapy for the treatment of bipolar I disorder: Treatment of acute manic and mixed episodes in patients 7 years and older ( 1 ). Maintenance treatment in patients 7 years and older ( 1 ).
Dosage & Administration
Recommended starting dosage for adults and pediatric patients over 30 kg ( 2.2 ): Oral Solution: 8 mEq lithium (5 mL) three times daily. Recommended starting dosage for pediatric patients 20 kg to 30 kg ( 2.2 ): Oral Solution: 8 mEq (5mL), twice daily. Obtain serum lithium concentration assay after 3 days, drawn 12 hours after the last oral dose and regularly until patient is stabilized. Acute Manic or Mixed Episodes (patients 7 years and older): Titrate to serum lithium concentrations 0.8 mEq/L to 1.2 mEq/L ( 2.2 ). Maintenance Treatment for Bipolar I Disorder (patients 7 years and older): Titrate to serum lithium concentrations 0.8 mEq/L to 1 mEq/L ( 2.2 ). Pre-treatment Screening: Evaluate renal function, vital signs, electrolytes, thyroid function, concurrent medications, and pregnancy status ( 2.1 ). Mild to Moderate Renal Impairment (CLer 30 mL/min to 89 mL/min): Start with dosages less than those for patients with normal renal function, titrate slowly with frequent monitoring ( 2.5 ). Severe Renal Impairment (CLer< 30mL/min): Avoid use of lithium ( 2.5 ). 2.1 Pre-treatment Screening Before initiating treatment with lithium, renal function, vital signs, serum electrolytes, and thyroid function should be evaluated. Concurrent medications should be assessed, and if the patient is a woman of childbearing potential, pregnancy status and potential should be considered. 2.2 Recommended Dosage See Table 1 for dosage recommendations for acute and maintenance treatment of bipolar I disorder in adult and pediatric patients (7 years to 17 years). Obtain serum lithium concentration assay after 3 days, drawn 12 hours after the last oral dose and regularly until patient is stabilized. Fine hand tremor, polyuria, and thirst may occur during initial therapy for the acute manic phase and may persist throughout treatment. Nausea and general discomfort may also appear during the first few days of lithium administration. These adverse reactions may subside with continued treatment, concomitant administration with food, or temporary reduction or cessation of dosage. Table 1. Lithium Oral Solution Dosing for Bipolar I Disorder Patient Group Formulation Starting Dose Dose Titration Acute Goal Maintenance Goal Serum Level Usual Dose Serum Level Usual Dose Adult and Pediatric Patients over 30 kg Liquid 8 mEq (5 mL) three times daily 8 mEq (5 mL) every 3 days 0.8 mEq/L to 1.2 mEq/L 16 mEq (10 mL) two to three times daily 0.8 mEq/L to 1 mEq/L 8 mEq to 16 mEq (5 mL to 10 mL) two to three times daily Pediatric Patients 20 kg to 30 kg Liquid 8 mEq (5 mL) twice daily 8 mEq (5 mL) weekly 16 mEq to 40 mEq (10 mL to 25 mL) in divided doses daily 16 mEq to 32 mEq (10 mL to 20 mL) in divided doses daily Each 5 mL of lithium oral solution contains 8 mEq of lithium ion (Li + ) which is equivalent to the amount of lithium in 300 mg of lithium carbonate. See Table 2 for lithium carbonate and lithium oral solution dose conversion. Table 2. Lithium Carbonate and Lithium Oral Solution Dose Conversion Lithium Carbonate Tablets or Capsules Lithium Oral Solution 150 mg 4 mEq (2.5 mL) 300 mg 8 mEq (5 mL) 600 mg 16 mEq (10 mL) 2.3 Serum Lithium Monitoring Blood samples for serum lithium determination should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 12 hours after the previous dose). Total reliance must not be placed on serum concentrations alone. Accurate patient evaluation requires both clinical and laboratory analysis. In addition to regular monitoring of serum lithium concentrations for patients on maintenance treatment, serum lithium concentrations should be monitored after any change in dosage, concurrent medication (e.g., diuretics, non-steroidal anti-inflammatory drugs, renin-angiotensin system antagonists, or metronidazole), marked increase or decrease in routinely performed strenuous physical activity (such as an exercise program) and in the event of a concomitant disease [See Boxed Warning , Warnings and Precautions ( 5.1 ), Drug Interactions ( 7.1 )]. Patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are within what is considered the therapeutic range. Geriatric patients often respond to reduced dosage, and may exhibit signs of toxicity at serum concentrations ordinarily tolerated by other patients [see Specific Populations ( 8.5 )]. 2.4 Dosage Adjustments during Pregnancy and the Postpartum Period If the decision is made to continue lithium treatment during pregnancy, monitor serum lithium concentrations and adjust the dosage as needed in a pregnant woman because renal lithium clearance increases during pregnancy. Avoid sodium restriction or diuretic administration. To decrease the risk of postpartum lithium intoxication, decrease or discontinue lithium therapy two to three days before the expected delivery date to reduce neonatal concentrations and reduce the risk of maternal lithium intoxication due to the change in vascular volume which occurs during delivery. At delivery, vascular volume rapidly decreases and the renal clearance of lithium may decrease to pre-pregnancy concentrations. Restart treatment at the preconception dose when the patient is medically stable after delivery with careful monitoring of serum lithium concentrations [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )]. 2.5 Dosage Adjustments for Patients with Renal Impairment Start patients with mild to moderately impaired renal function (creatinine clearance 30 mL/min to 89 mL/min evaluated by Cockcroft-Gault) with dosages less than those for patients with normal renal function [see Dosage and Administration ( 2.2 )] . Titrate slowly while frequently monitoring serum lithium concentrations and monitoring for signs of lithium toxicity. Lithium is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min evaluated by Cockcroft-Gault) [see Use in Specific Populations ( 8.6 )].
Warnings & Precautions
Lithium-Induced Polyuria: May develop during initiation of treatment. Increases risk of lithium toxicity. Educate patient to avoid dehydration. Monitor for lithium toxicity and metabolic acidosis. Discontinue lithium or treat with amiloride as a therapeutic agent ( 5.2 ). Hyponatremia: Symptoms are more severe with faster-onset hyponatremia. Dehydration from protracted sweating, diarrhea, or elevated temperatures from infection increases risk of hyponatremia and lithium toxicity. Educate patients on maintaining a normal diet with salt and staying hydrated. Monitor for and treat hyponatremia and lithium toxicity, which may necessitate a temporary reduction or cessation of lithium and infusion of serum sodium ( 5.3 ). Lithium-Induced Chronic Kidney Disease: Associated with structural changes in patients on chronic lithium therapy. Monitor kidney function during treatment with lithium ( 5.4 ). Encephalopathic Syndrome: Increased risk in patients treated with lithium and an antipsychotic. Monitor routinely for changes to cognitive function ( 5.5 ). Hypothyroidism and Hyperthyroidism: Monitor thyroid function regularly ( 5.7 ). Hypercalcemia and Hyperparathyroidism: Associated with long-term lithium use. Monitor serum calcium ( 5.8 ). 5.1 Lithium Toxicity The toxic concentrations for lithium (≥ 1.5 mEq/L) are close to the therapeutic range (0.8 mEq/L to 1.2 mEq/L). Some patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are considered within the therapeutic range [see Boxed Warning , Dosage and Administration ( 2.3 )]. Lithium may take up to 24 hours to distribute into brain tissue, so occurrence of acute toxicity symptoms may be delayed. Neurological signs of lithium toxicity range from mild neurological adverse reactions such as fine tremor, lightheadedness, lack of coordination, and weakness; to moderate manifestations like giddiness, apathy, drowsiness, hyperreflexia, muscle twitching, ataxia, blurred vision, tinnitus, and slurred speech; and severe manifestations such as clonus, confusion, seizure, coma, and death. In rare cases, neurological sequelae may persist despite discontinuing lithium treatment and may be associated with cerebellar atrophy. Cardiac manifestations involve electrocardiographic changes, such as prolonged QT interval, ST and T-wave changes and myocarditis. Renal manifestations include urine concentrating defect, nephrogenic diabetes insipidus, and renal failure. Respiratory manifestations include dyspnea, aspiration pneumonia, and respiratory failure. Gastrointestinal manifestations include nausea, vomiting, diarrhea, and bloating. No specific antidote for lithium poisoning is known [see Overdosage ( 10 )]. The risk of lithium toxicity is increased by: Recent onset of concurrent febrile illness Concomitant administration of drugs which increase lithium serum concentrations by pharmacokinetic interactions or drugs affecting kidney function [ see Drug Interactions ( 7 ) ] . Acute ingestion Impaired renal function Volume depletion or dehydration Significant cardiovascular disease Changes in electrolyte concentrations (especially sodium and potassium) Monitor for signs and symptoms of lithium toxicity. If symptoms occur, decrease dosage or discontinue lithium treatment. 5.2 Lithium-Induced Polyuria Chronic lithium treatment may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. The concentrating defect and natriuretic effect characteristic of this condition may develop within weeks of lithium initiation. Lithium can also cause renal tubular acidosis, resulting in hyperchloremic metabolic acidosis. Such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is usually reversible when lithium is discontinued, although for patients treated with long-term lithium, nephrogenic diabetes insipidus may be only partly reversible upon discontinuation of lithium. Amiloride may be considered as a therapeutic agent for lithium-induced nephrogenic diabetes insipidus. 5.3 Hyponatremia Lithium can cause hyponatremia by decreasing sodium reabsorption by the renal tubules, leading to sodium depletion. Therefore, it is essential for patients receiving lithium treatment to maintain a normal diet, including salt, and an adequate fluid intake (2,500 mL to 3,000 mL) at least during the initial stabilization period. Decreased tolerance to lithium has also been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and lithium intake reduced or suspended until the condition is resolved. In addition, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication. Symptoms are also more severe with faster-onset hyponatremia. Mild hyponatremia (i.e., serum Na > 120 mEq/L) can be asymptomatic. Below this threshold, clinical signs are usually present, consisting mainly of changes in mental status, such as altered personality, lethargy, and confusion. For more severe hyponatremia (serum Na < 115 mEq/L), stupor, neuromuscular hyperexcitability, hyperreflexia, seizures, coma, and death can result. During treatment of hyponatremia, serum sodium should not be elevated by more than 10 mEq/L to 12 mEq/L in 24 hours, or 18 mEq/L in 48 hours. In the case of severe hyponatremia where severe neurologic symptoms are present, a faster infusion rate to correct serum sodium concentration may be needed. Patients rapidly treated or with serum sodium < 120 mEq/L are more at risk of developing osmotic demyelination syndrome (previously called central pontine myelinolysis). Occurrence is more common among patients with alcoholism, undernutrition, or other chronic debilitating illness. Common signs include flaccid paralysis, dysarthria. In severe cases with extended lesions patients may develop a locked-in syndrome (generalized motor paralysis). Damage often is permanent. If neurologic symptoms start to develop during treatment of hyponatremia, serum sodium correction should be suspended to mitigate the development of permanent neurologic damage. 5.4 Lithium-Induced Chronic Kidney Disease The predominant form of chronic renal disease associated with long-term lithium treatment is a chronic tubulointerstitial nephropathy (CTIN). The biopsy findings in patients with lithium induced CTIN include tubular atrophy, interstitial fibrosis, sclerotic glomeruli, tubular dilation, and nephron atrophy with cyst formation. The relationship between renal function and morphologic changes and their association with lithium treatment has not been established. CTIN patients might present with nephrotic proteinuria (> 3 g/dL), worsening renal insufficiency and/or nephrogenic diabetes insipidus. Postmarketing cases consistent with nephrotic syndrome in patients with or without CTIN have also been reported. The biopsy findings in patients with nephrotic syndrome include minimal change disease and focal segmental glomerulosclerosis. The discontinuation of lithium in patients with nephrotic syndrome has resulted in remission of nephrotic syndrome. Kidney function should be assessed prior to and during lithium treatment. Routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function (e.g., serum creatinine, creatinine clearance, or proteinuria). During lithium treatment, progressive or sudden changes in renal function, even within the normal range, indicate the need for re-evaluation of treatment. 5.5 Encephalopathic Syndrome An encephalopathic syndrome, characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and fasting blood glucose, has occurred in patients treated with lithium and an antipsychotic. In some instances, the syndrome was followed by irreversible brain damage. Because of a possible causal relationship between these events and the concomitant administration of lithium and antipsychotics, patients receiving such combined treatment should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS). 5.6 Serotonin Syndrome Lithium can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, fentanyl, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Drug Interactions ( 7.1 )]. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Monitor all patients taking lithium for the emergence of serotonin syndrome. Discontinue treatment with lithium and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of lithium with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.7 Hypothyroidism or Hyperthyroidism Lithium is concentrated within the thyroid and can inhibit thyroid synthesis and release which can lead to hypothyroidism. Where hypothyroidism exists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters, if any. Where hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may be used. Paradoxically, some cases of hyperthyroidism have been reported including Grave’s disease, toxic multinodular goiter and silent thyroiditis. Monitor thyroid function before the initiation of treatment, at three months and every six to twelve months while treatment is ongoing. If serum thyroid tests warrant concern, monitoring should occur more frequently. 5.8 Hypercalcemia and Hyperparathyroidism Long-term lithium treatment is associated with persistent hyperparathyroidism and hypercalcemia. When clinical manifestations of hypercalcemia are present, lithium withdrawal and change to another mood stabilizer may be necessary. Hypercalcemia may not resolve upon discontinuation of lithium, and may require surgical intervention. Lithium-induced cases of hyperparathyroidism are more often multiglandular compared to standard cases. False hypercalcemia due to plasma volume depletion resulting from nephrogenic diabetes insipidus should be excluded in individuals with mildly increased serum calcium. Monitor serum calcium concentrations regularly. 5.9 Unmasking of Brugada Syndrome There have been postmarketing reports of a possible association between treatment with lithium and the unmasking of Brugada Syndrome. Brugada Syndrome is a disorder characterized by abnormal electrocardiographic (ECG) findings and a risk of sudden death. Lithium should be avoided in patients with Brugada Syndrome or those suspected of having Brugada Syndrome. Consultation with a cardiologist is recommended if: (1) treatment with lithium is under consideration for patients suspected of having Brugada Syndrome or patients who have risk factors for Brugada Syndrome, e.g., unexplained syncope, a family history of Brugada Syndrome, or a family history of sudden unexplained death before the age of 45 years, (2) patients who develop unexplained syncope or palpitations after starting lithium treatment. 5.10 Pseudotumor Cerebri Cases of pseudotumor cerebri (increased intracranial pressure and papilledema) have been reported with lithium use. If undetected, this condition may result in enlargement of the blind spot, constriction of visual fields and eventual blindness due to optic atrophy. Consider discontinuing lithium if this syndrome occurs.
Boxed Warning
LITHIUM TOXICITY Lithium toxicity is closely related to serum lithium concentrations, and can occur at doses close to therapeutic concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating treatment [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.1 ) ] . WARNING: LITHIUM TOXICITY See full prescribing information for complete boxed warning. Lithium toxicity is closely related to serum lithium concentrations, and can occur at doses close to therapeutic concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy ( 2.3 , 5.1 ).
Contraindications
Lithium is contraindicated in patients with known hypersensitivity to any inactive ingredient in the lithium citrate products [see Adverse Reactions ( 6 )]. Known hypersensitivity to any inactive ingredient in the drug product ( 4 ).
Adverse Reactions
The following adverse reactions are described in greater detail in other sections: Acute Lithium Toxicity [see Warnings and Precautions ( 5.1 )] Lithium-Induced Polyuria [see Warnings and Precautions ( 5.2 )] Hyponatremia [see Warnings and Precautions ( 5.3 )] Lithium-Induced Chronic Kidney Disease [see Warnings and Precautions ( 5.4 )] Encephalopathic Syndrome [see Warnings and Precautions ( 5.5 )] Serotonin Syndrome [see Warnings and Precautions ( 5.6 )] Hypothyroidism or Hyperthyroidism [see Warnings and Precautions ( 5.7 )] Hypercalcemia and Hyperparathyroidism [see Warnings and Precautions ( 5.8 )] Unmasking of Brugada Syndrome [see Warnings and Precautions ( 5.9 )] Pseudotumor Cerebri [see Warnings and Precautions ( 5.10 )] Common Adverse Reactions: Adult Patients: fine hand tremor, polyuria, mild thirst, nausea, general discomfort during initial treatment ( 6 ). Pediatric Patients (7 years to 17 years): nausea/vomiting, polyuria, thyroid abnormalities, tremor, thirst/polydipsia, dizziness, rash/dermatitis, ataxia/gait disturbance, decreased appetite, and blurry vision ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Saptalis Pharmaceuticals, LLC. at 1-833-727-8254 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Pediatric Patients (7 years to 17 years): Bipolar I Disorder: The following findings are based on an 8-week, placebo-controlled study for acute manic or mixed episodes of bipolar I disorder in pediatric patients 7 years to 17 years (N = 81). In this study, lithium was administered at daily doses ranging from 300 to 3,600 (mean dose 1,483 mg ± 584) with serum levels ranging from 0 to 2 (mean level 0.98 mEq/L ± 0.47). Common Adverse Reactions (incidence ≥ 5% and at least twice the rate of placebo ): nausea/vomiting, polyuria, thyroid abnormalities, tremor, thirst/polydipsia, dizziness, rash/dermatitis, ataxia/gait disturbance, decreased appetite, and blurry vision. Adverse Reactions Occurring at an Incidence of 2% or More in Lithium-Treated Pediatric Patients : Adverse reactions associated with the use of lithium (incidence of 2% or greater, rounded to the nearest percent, and lithium incidence greater than placebo) that occurred during acute therapy (up to 8-weeks in pediatric patients with bipolar disorder) are shown in Table 3. Table 3: Adverse Reactions Reported in 2% or More of Pediatric Patients on Lithium and That Occurred at Greater Incidence Than in the Placebo Group in the 8-Week Acute Bipolar Trial System Organ Class/ Preferred Term Placebo N = 28 % Lithium N = 53 % Gastrointestinal Disorders Nausea/vomiting 29 57 General Disorders Fatigue 4 26 Genitourinary Disorders Polyuria (Including Enuresis) 14 38 Investigations Increased TSH 0 25 Metabolism and nutrition disorders Thirst/polydipsia 11 28 Decreased appetite 4 9 Nervous system disorders Ataxia/gait disturbance 0 13 Blurry vision 0 9 Disorientation 0 6 Dizziness 7 23 Tremor 7 32 Skin and subcutaneous tissue disorders Rash/dermatitis 0 13 Adult Patients: The following adverse reactions have been identified following use of lithium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Central Nervous System: tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreoathetotic movements, hyperactive deep tendon reflexes, extrapyramidal symptoms including acute dystonia, cogwheel rigidity, blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, downbeat nystagmus, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, tongue movements, tics, tinnitus, hallucinations, poor memory, slowed intellectual functioning, startled response, worsening of organic brain syndromes, myasthenic syndromes (rarely). EEG Changes: diffuse slowing, widening of frequency spectrum, potentiation and disorganization of background rhythm. Cardiovascular: conduction disturbance (mostly sinus node dysfunction with possibly severe sinus bradycardia and sinoatrial block), ventricular tachyarrhythmia, peripheral vasculopathy (resembling Raynaud’s Syndrome). ECG Changes: reversible flattening, isoelectricity or rarely inversion of T-waves, prolongation of the QTc interval. Gastrointestinal : anorexia, nausea, vomiting, diarrhea, gastritis, salivary gland swelling, abdominal pain, excessive salivation, flatulence, indigestion. Genitourinary: glycosuria, decreased creatinine clearance, albuminuria, oliguria, and symptoms of nephrogenic diabetes insipidus including polyuria, thirst, and polydipsia. Dermatologic: drying and thinning of hair, alopecia, anesthesia of skin, chronic folliculitis, xerosis cutis, psoriasis onset or exacerbation, generalized pruritus with or without rash, cutaneous ulcers, angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS). Autonomic Nervous System: blurred vision, dry mouth, impotence/sexual dysfunction. Miscellaneous: fatigue, lethargy, transient scotoma, exopthalmos, dehydration, weight loss, leukocytosis, headache, transient hyperglycemia, hypermagnesemia, excessive weight gain, edematous swelling of ankles or wrists, dysgeusia/taste distortion (e.g., metallic or salty taste), thirst, swollen lips, tightness in chest, swollen and/or painful joints, fever, polyarthralgia, and dental caries.
Drug Interactions
Diuretics, NSAID, renin-angiotensin system antagonists, or metronidazole may increase lithium serum concentrations. Recommend frequent monitoring of serum lithium concentration and adjust dosage when necessary ( 2.3 , 7.1 ). Serotonergic Agents: Increased risk of serotonin syndrome when co-administered with lithium ( 5.6 , 7.1 ). Antipsychotics: There have been reports of neurologic adverse reactions in patients treated with lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome ( 5.5 , 7.1 ). 7.1 Drugs Having Clinically Important Interactions with Lithium Table 4: Clinically Important Drug Interactions with Lithium Diuretics Clinical Impact: Diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations . Intervention: More frequent monitoring of serum electrolyte and lithium concentrations. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 ), Warning and Precautions ( 5.3 )]. Non-Steroidal Anti-inflammatory Drugs (NSAID) Clinical Impact: NSAID decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations. Intervention: More frequent serum lithium concentration monitoring. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 )] . Renin-Angiotensin System Antagonists Clinical Impact: Concomitant use increases steady-state serum lithium concentrations. Intervention: More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 )] . Serotonergic Drugs Clinical Impact: Concomitant use can precipitate serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.6 )]. Nitroimidazole Antibiotics Clinical Impact: Concomitant use may increase serum lithium concentrations due to reduced renal clearance. Intervention: More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 )]. Acetazolamide, Urea, Xanthine Preparations, Alkalinizing Agents Clinical Impact: Concomitant use can lower serum lithium concentrations by increasing urinary lithium excretion. Intervention: More frequent serum lithium concentration monitoring. Increase lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.3 )] . Methyldopa, Phenytoin and Carbamazepine Clinical Impact: Concomitant use may increase risk of adverse reactions of these drugs. Intervention: Monitor patients closely for adverse reactions of methyldopa, phenytoin, and carbamazepine. Iodide Preparations Clinical Impact: Concomitant use may produce hypothyroidism. Intervention: Monitor patients for signs or symptoms of hypothyroidism [ see Warnings and Precautions ( 5.7 )] . Calcium Channel Blocking Agents (CCB) Clinical Impact: Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. Intervention: Monitor for neurologic adverse reactions. Atypical and Typical Antipsychotic Drugs Clinical Impact: Reports of neurotoxic reactions in patients treated with both lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome, as well as reports of an encephalopathic syndrome in few patients treated with concomitant therapy [see Warnings and Precautions ( 5.5 )]. Intervention: Monitor for neurologic adverse reactions. Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor Clinical Impact: Concomitant use of lithium with an SGLT2 inhibitor may decrease serum lithium concentrations. Intervention: Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes. Neuromuscular Blocking Agents Clinical Impact: Lithium may prolong the effects of neuromuscular blocking agents. Intervention: Monitor for prolonged paralysis.
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