LITHIUM CARBONATE
Clinical safety rating: avoid
NSAIDs and diuretics can decrease renal clearance and increase levels Can cause lithium toxicity which requires monitoring of serum levels.
Lithium modulates neuronal excitability and neurotransmitter release; inhibits inositol monophosphatase, affecting phosphoinositide signaling; alters G-protein coupled receptor signaling; inhibits glycogen synthase kinase-3 (GSK-3); modulates neuroplasticity and neuroprotection.
| Metabolism | Lithium is not metabolized; it is excreted primarily by the kidneys (95% as unchanged drug). It undergoes reabsorption in the proximal tubule; its clearance is reduced by sodium depletion, dehydration, and diuretics. |
| Excretion | Renal: >95% unchanged; <5% fecal (non-renal). |
| Half-life | Terminal half-life: 18-24 hours (single dose), 24-36 hours (steady state). Extended in elderly (up to 36-48 h) and renal impairment. Dosing interval adjusted based on renal function. |
| Protein binding | 0-10% bound; primarily to albumin. Negligible binding. |
| Volume of Distribution | 0.7-1.0 L/kg (0.7-1.4 L/kg). High Vd indicates extensive tissue distribution; crosses blood-brain barrier. |
| Bioavailability | Oral: 80-100% (immediate-release); 60-90% (extended-release). Food does not significantly affect absorption. |
| Onset of Action | Oral: 1-3 days for acute mania; 1-2 weeks for full antimanic effect. No parenteral route. |
| Duration of Action | Duration: 24 hours (steady state). Once-daily dosing maintains therapeutic levels. Fluctuations minimized with extended-release formulations. |
Oral: Initial 300 mg 3 times daily or 450 mg extended-release twice daily; adjust based on serum levels to achieve therapeutic concentration 0.6-1.2 mEq/L; typical maintenance 900-1200 mg/day divided doses.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated if CrCl <15 mL/min. CrCl 15-30 mL/min: reduce dose by 50% and monitor levels closely. CrCl 30-60 mL/min: reduce dose by 25-50%. Avoid in acute kidney injury. |
| Liver impairment | No specific Child-Pugh based adjustments; use with caution due to potential electrolyte disturbances; monitor lithium levels and renal function. |
| Pediatric use | Children ≥7 years: initial 15-20 mg/kg/day orally divided 3-4 times, maximum 900 mg/day. Adjust to serum levels; target 0.6-1.2 mEq/L. |
| Geriatric use | Start with lowest dose (e.g., 150-300 mg once daily); increase slowly; monitor levels and renal function; target lower therapeutic range 0.4-0.8 mEq/L. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
NSAIDs and diuretics can decrease renal clearance and increase levels Can cause lithium toxicity which requires monitoring of serum levels.
| FDA category | Positive |
| Breastfeeding | Excreted into breast milk; M/P ratio ~0.4-0.6. Infant serum levels can be therapeutically significant. Generally avoid breastfeeding; if used, monitor infant for hypothermia, hypotonia, poor feeding, and monitor serum lithium levels. |
| Teratogenic Risk | First trimester: Increased risk of Ebstein's anomaly (absolute risk 0.1-0.2% vs 0.01% baseline). Second/third trimester: Risks include preterm delivery, macrosomia, neonatal hypotonia, thyroid dysfunction, nephrogenic diabetes insipidus, and cardiac effects. Fetal echocardiography recommended. |
■ FDA Black Box Warning
Lithium toxicity is closely related to serum concentrations and can occur at doses close to therapeutic levels. Monitor serum lithium levels, renal and thyroid function regularly. Neurotoxicity may occur even at therapeutic levels; discontinue if signs of toxicity appear.
| Common Effects | Nausea |
| Serious Effects |
Severe renal impairment, severe cardiovascular disease, uncorrected hypothyroidism, Brugada syndrome, lithium hypersensitivity, pregnancy (first trimester and peripartum period), breastfeeding (relative), concurrent use with drugs that significantly elevate lithium levels (e.g., thiazide diuretics, NSAIDs) without careful monitoring.
| Precautions | Narrow therapeutic index; monitor serum lithium levels (therapeutic range 0.6-1.2 mEq/L). Chronic therapy may cause nephrogenic diabetes insipidus, chronic tubulointerstitial nephritis, and reduced renal concentrating ability. Thyroid function abnormalities (hypothyroidism, goiter). Neurotoxicity (tremor, ataxia, dysarthria, cognitive impairment). Cardiac effects (T-wave changes, arrhythmias). Teratogenicity (Ebstein anomaly) in first trimester. May impair driving and operating machinery. Use with caution in elderly, renal impairment, volume depletion, and those taking NSAIDs, ACE inhibitors, diuretics. |
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| Fetal Monitoring | Maternal: Serum lithium levels every 2-4 weeks; renal function, thyroid function, and weight gain. Fetal: Detailed anatomy ultrasound at 18-22 weeks, fetal echocardiography. Neonatal: Assess for hypotonia, poor feeding, lethargy; monitor glucose, thyroid function. |
| Fertility Effects | Limited data; lithium does not impair fertility in women or men in therapeutic doses. Potential for menstrual irregularities due to hyperprolactinemia or hypothyroidism, reversible upon dose adjustment or treatment. |