LITHIUM CITRATE
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 citrate modulates intracellular signaling pathways, including inhibition of inositol monophosphatase and glycogen synthase kinase-3 (GSK-3), affecting neurotransmission and neuroprotection.
| Metabolism | Not metabolized; excreted renally (99% unchanged). Reabsorption occurs in proximal tubules; clearance affected by sodium intake and renal function. |
| Excretion | Renal: >95% excreted unchanged in urine. No significant biliary or fecal elimination. |
| Half-life | 18–24 hours in young adults; up to 36 hours in elderly. Steady state reached in 5–7 days. |
| Protein binding | Not bound to plasma proteins (0% bound). |
| Volume of Distribution | 0.7–0.9 L/kg; distributes freely into total body water, with higher concentrations in thyroid and bone. |
| Bioavailability | Oral: >95% for immediate-release formulations; no IV formulation used clinically. |
| Onset of Action | Oral: 1–2 weeks for antimanic effect; 5–7 days for augmentation in depression. |
| Duration of Action | Sustained therapeutic effect with continuous dosing; withdrawal may lead to relapse within weeks. |
300-600 mg orally 3 times daily, adjusted to achieve serum lithium levels of 0.6-1.2 mEq/L (maintenance) or 0.8-1.5 mEq/L (acute mania).
| Dosage form | SYRUP |
| Renal impairment | GFR 30-89 mL/min: reduce dose by 25-50%; GFR 15-29 mL/min: reduce dose by 50-75%; GFR <15 mL/min: use with caution, consider alternative therapy. |
| Liver impairment | No specific dosage adjustments recommended; monitor serum levels and renal function closely due to potential fluid and electrolyte disturbances. |
| Pediatric use | Children ≥6 years: initial 15-20 mg/kg/day in 3-4 divided doses, adjust based on serum levels (target 0.6-1.2 mEq/L). |
| Geriatric use | Initiate at lower doses (e.g., 150-300 mg once or twice daily), monitor serum levels closely (target 0.4-0.8 mEq/L), and adjust for age-related renal decline. |
| 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 | Contraindicated. Lithium excreted into breast milk with M/P ratio ~0.24-0.5; infant serum levels ~10-50% maternal. Risk of neonatal toxicity (hypotonia, feeding difficulties, lethargy). Avoid breastfeeding; if absolutely necessary, monitor infant serum lithium levels. |
| Teratogenic Risk |
■ FDA Black Box Warning
Lithium toxicity is narrow and potentially fatal; serum lithium levels must be monitored closely, especially during initiation and dose changes.
| Common Effects | Nausea |
| Serious Effects |
Severe renal impairment, severe cardiovascular disease, untreated hypothyroidism, Brugada syndrome, concomitant use with serotonergic drugs (risk of serotonin syndrome), pregnancy (especially first trimester) unless benefit outweighs risk.
| Precautions | Neurotoxicity (tremor, ataxia, confusion), nephrogenic diabetes insipidus, hypothyroidism, cardiac arrhythmias, risk of toxicity with dehydration or drug interactions (NSAIDs, diuretics, ACE inhibitors). |
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| First trimester: Increased risk of Ebstein's anomaly (1-7 per 1000 exposed vs 1 per 20,000 in general), cardiac malformations. Second/third trimester: Risk of fetal goiter, hypothyroidism, neonatal lithium toxicity (floppy baby syndrome: hypotonia, lethargy, poor suck). |
| Fetal Monitoring | Monitor maternal serum lithium levels every 4 weeks (target 0.6-1.0 mEq/L). Fetal echocardiogram at 16-18 weeks for Ebstein's anomaly. Third trimester: Ultrasound for fetal goiter. Neonatal: Thyroid function tests, serum lithium, ECG for rhythm disturbances. |
| Fertility Effects | No known adverse effects on fertility. Lithium may cause menstrual irregularities in some women, but reversible upon dose adjustment or discontinuation. |