2 DOSAGE & ADMINISTRATION Recommended starting dosage for adults and pediatric patients over 30 kg ( 2.2 ): Tablets: 300 mg, three times daily Recommended starting dosage for pediatric patients 20 to 30 kg ( 2.2 ): Tablets: 300 mg twice daily Obtain serum lithium concentration assay after 3 days, drawn 12 hours after the last oral dose and regularly until patient is stabilized ( 2.2 ). Acute Manic or Mixed Episodes (patients 7 years and older): Titrate to serum lithium concentrations 0.8 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 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 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 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. 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 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 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 Tablets 300 mg three times daily 300 mg every 3 days 0.8 to 1.2 mEq/L 600 mg two to three times daily 0.8 to 1.0 mEq/L 300 to 600 mg two to three times daily Pediatric Patients 20 to 30 kg Tablets 300 mg twice daily 300 mg weekly 600 to 1500 mg in divided doses daily 600 to 1200 mg 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 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 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)] .