ESKALITH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ESKALITH (ESKALITH).
Lithium modulates neurotransmission by inhibiting inositol monophosphatase, leading to reduced phosphoinositide signaling; also inhibits glycogen synthase kinase-3 (GSK-3) and alters neuronal excitability via effects on sodium transport and neurotransmitter release.
| Metabolism | Lithium is not metabolized; it is excreted almost entirely (over 95%) unchanged by the kidneys. Renal clearance is proportional to creatinine clearance. It is not metabolized by the liver or CYP enzymes. |
| Excretion | Renal: >95% excreted unchanged in urine. Biliary/fecal: negligible (<1%). |
| Half-life | Terminal elimination half-life: 18-24 hours (range 12-27 hours) in adults; may be prolonged in elderly or renal impairment. Steady-state achieved in 5-7 days. |
| Protein binding | 0% (lithium is not bound to plasma proteins). |
| Volume of Distribution | 0.7-1.0 L/kg; indicates distribution throughout total body water, with higher concentrations in brain and thyroid. |
| Bioavailability | Oral: 95-100% (immediate-release); slightly reduced with extended-release formulations due to slower absorption. |
| Onset of Action | Oral: 1-3 hours for serum levels; therapeutic effects (mood stabilization) typically require 5-14 days. |
| Duration of Action | Therapeutic effect persists for the dosing interval (usually 12-24 hours for immediate-release formulations). Continuous dosing required for maintenance. |
Lithium carbonate extended-release: 300-600 mg orally twice daily, titrated to serum levels 0.6-1.2 mEq/L. Immediate-release: 300-600 mg three times daily.
| Dosage form | CAPSULE |
| Renal impairment | CrCl >60 mL/min: no adjustment; CrCl 30-60 mL/min: reduce dose by 25-50%; CrCl 15-29 mL/min: reduce dose by 50-75%; CrCl <15 mL/min: avoid use or use with extreme caution. |
| Liver impairment | No specific guidelines for Child-Pugh. Caution in severe hepatic impairment due to altered fluid and electrolyte balance. |
| Pediatric use | Not established for children <12 years. ≥12 years: initiate at 15-20 mg/kg/day in divided doses, titrate to serum levels 0.6-1.2 mEq/L. |
| Geriatric use | Initiate at lower dose (e.g., 150-300 mg daily due to reduced renal function). Target serum levels 0.4-0.8 mEq/L. Monitor lithium levels and renal function frequently. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ESKALITH (ESKALITH).
| Breastfeeding | Lithium is excreted into breast milk; M/P ratio approximately 0.3-0.6. Relative infant dose about 10-30% of maternal weight-adjusted dose. Breastfeeding generally contraindicated due to risk of infant toxicity, but cautious use with monitoring may be considered in selected cases; monitor infant serum lithium levels and thyroid function. |
| Teratogenic Risk | First trimester: Increased risk of Ebstein's anomaly (odds ratio 10-20) and other cardiac defects; risk approximately 2-6% for major malformations. Second/third trimester: Risks of preterm delivery, macrosomia, neonatal hypothyroidism, transient nephrogenic diabetes insipidus, and lithium toxicity. Late third trimester: Fetal/neonatal lithium toxicity with floppy infant syndrome, hypotonia, bradycardia, and cyanosis. |
■ FDA Black Box Warning
Lithium toxicity is closely related to serum concentrations. Serum lithium levels must be monitored carefully to avoid toxicity. Lithium should generally not be given to patients with significant renal disease or cardiovascular disease.
| Serious Effects |
Severe renal impairment (creatinine clearance <30 mL/min); advanced cardiovascular disease (e.g., severe cardiac arrhythmias); severe dehydration or sodium depletion; concurrent use with diuretics or NSAIDs (relative caution); lactation (excreted in breast milk).
| Precautions | Lithium toxicity (especially with dehydration, low sodium, or renal impairment); neurotoxicity (tremor, ataxia, cognitive impairment); renal effects (interstitial nephritis, nephrogenic diabetes insipidus); hypothyroidism; hypercalcemia; cardiac effects (ECG changes, arrhythmias); pregnancy risk (Ebstein's anomaly in first trimester); monitoring required (serum lithium, renal function, thyroid function, ECG). |
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| Fetal Monitoring | Maternal: Serum lithium levels every 2-4 weeks, renal function, thyroid function tests (TSH, free T4) every trimester, and cardiac monitoring if on high doses. Fetal: Detailed fetal echocardiography at 18-20 weeks, ultrasound for growth and anomalies. Neonatal: Assess for hypotonia, bradycardia, cyanosis, hypoglycemia; monitor serum lithium and thyroid function if exposed. |
| Fertility Effects | Lithium has no established direct effect on fertility. However, endocrine disturbances (e.g., hypothyroidism) secondary to lithium therapy may impair fertility. Untreated bipolar disorder may affect reproductive function. |