ESKALITH CR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ESKALITH CR (ESKALITH CR).
Lithium modulates neurotransmitter activity, inhibits inositol monophosphatase, affects G-protein signaling, and alters gene expression for neuroprotective effects.
| Metabolism | Not metabolized; excreted renally (90% unchanged). |
| Excretion | Renal: >95% unchanged. Biliary/fecal: negligible (<1%). |
| Half-life | Terminal half-life: 18–24 hours (single dose); 24–36 hours (steady state). Extended due to slow tissue redistribution and age-related decreased GFR. |
| Protein binding | 0% (not bound to plasma proteins). |
| Volume of Distribution | 0.7–1.0 L/kg. Reflects wide distribution into total body water; decreases with age and renal impairment. |
| Bioavailability | Oral (CR tablet): 80–95% (relative to immediate-release). |
| Onset of Action | Oral: 3–5 days for initial effect; 7–14 days for full antimanic effect. |
| Duration of Action | Oral: serum levels maintained over 24 hours with once-daily dosing; but clinical effect persists for days as Li+ redistributes from CNS. |
Lithium carbonate extended-release (Eskalith CR) is administered orally. Typical adult starting dose: 300 mg 2-3 times daily. Maintenance dose: 900-1200 mg/day in 2-3 divided doses. Dose adjustments guided by serum lithium levels (target 0.6-1.2 mEq/L). Maximum dose: 2400 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <30 mL/min). For moderate impairment (CrCl 30-59 mL/min): reduce dose by 25-50% and monitor serum lithium levels closely. For mild impairment (CrCl 60-89 mL/min): use with caution and monitor levels. GFR-based dosing is not established; adjust based on levels. |
| Liver impairment | No specific dose adjustment for hepatic impairment. Lithium is not metabolized by the liver. However, close monitoring of lithium levels and clinical status is recommended in severe hepatic impairment due to potential fluid and electrolyte imbalances. |
| Pediatric use | Approved for children ≥12 years for bipolar disorder. Initial dose: 15-20 mg/kg/day divided into 2-3 doses, not to exceed 600 mg/day. Titrate based on serum levels (target 0.6-1.2 mEq/L). Typical maintenance: 300-600 mg/day. Not recommended under 12 years due to limited data. |
| Geriatric use |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ESKALITH CR (ESKALITH CR).
| Breastfeeding | Excreted into breast milk (M/P ratio 0.4-0.6). Infant serum levels 10-50% of maternal. Monitor infant for toxicity (lethargy, hypotonia, feeding difficulties). Benefits vs risks should be considered; alternatives preferred. |
| Teratogenic Risk | Pregnancy category D. First trimester: Increased risk of Ebstein's anomaly (10-20x baseline) and other congenital heart defects. Second/third trimesters: Risk of fetal goiter, hypothyroidism, nephrogenic diabetes insipidus, preterm birth. Neonatal toxicity (lethargy, hypotonia, poor suckling) may occur if used near term. |
■ FDA Black Box Warning
Lithium toxicity: narrow therapeutic index; monitor serum levels closely. Risk of renal impairment, hypothyroidism, and neurotoxicity.
| Serious Effects |
["Severe renal disease","Severe cardiovascular disease","Low sodium levels","Breastfeeding (excreted in milk)"]
| Precautions | ["Renal impairment","Hypothyroidism","Neurologic toxicity","Cardiac effects (ECG changes)","Dehydration/sodium depletion","Pregnancy (risk of Ebstein anomaly)","Neuroleptic malignant syndrome"] |
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| Elderly patients have reduced renal function and lower volume of distribution. Start with lower doses (e.g., 150-300 mg once or twice daily). Titrate slowly. Therapeutic serum levels may be lower (0.4-0.8 mEq/L). Monitor renal function, thyroid, and electrolytes regularly. |
| Fetal Monitoring |
| Monitor serum lithium levels (therapeutic range 0.6-1.0 mEq/L), renal function, thyroid function (TSH, free T4) monthly. Fetal monitoring: serial fetal echocardiography at 18-22 weeks for Ebstein's anomaly; ultrasound for growth and anatomy. Newborn: monitor for lithium toxicity, hypoglycemia, thyroid function, and polyuria. |
| Fertility Effects | Lithium may cause menstrual irregularities and potential ovarian dysfunction in women; no established effect on male fertility. Hyperprolactinemia reported but rare. |