Meta Information
ID:lithium-carbonate
Name:Lithium Carbonate
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/thiazide-diuretics
Target name:
Thiazide Diuretics
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Thiazide diuretics increase sodium excretion, causing the kidneys to compensate by reabsorbing more sodium and lithium, which can lead to dangerously high lithium levels and toxicity.
Actionable advice:
Thiazide diuretics (e.g., hydrochlorothiazide) should not be used while taking lithium.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/class/nsaids
Target name:
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NSAIDs (e.g., ibuprofen, naproxen) can reduce blood flow to the kidneys and decrease lithium clearance by up to 40%, significantly increasing the risk of toxicity.
Actionable advice:
All NSAIDs should be avoided while taking lithium; alternatives like acetaminophen may be used if necessary after consulting a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
NSAID decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/class/ace-inhibitors
Target name:
ACE Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
ACE inhibitors (e.g., lisinopril) can impair the kidneys' ability to excrete lithium, leading to accumulation and a high risk of toxicity.
Actionable advice:
Concurrent use of ACE inhibitors and lithium should be avoided unless under strict medical supervision with frequent monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Renin-Angiotensin System Antagonists
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/class/arbs
Target name:
Angiotensin II Receptor Blockers (ARBs)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
ARBs (e.g., losartan, telmisartan) reduce renal clearance of lithium, which can cause lithium levels to rise to toxic concentrations.
Actionable advice:
Concurrent use of ARBs and lithium should be avoided unless under strict medical supervision with frequent monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Renin-Angiotensin System Antagonists
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/condition/renal-impairment
Target name:
Renal Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Since lithium is almost entirely cleared by the kidneys, any degree of renal impairment can dramatically decrease its excretion and lead to severe toxicity.
Actionable advice:
Lithium should not be used by those with significant kidney disease; dose adjustments are critical even in mild impairment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Lithium should not be used in severe renal insufficiency (creatinine clearance less than 30 mL/min evaluated by Cockcroft-Gault)
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/condition/dehydration
Target name:
Dehydration
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Dehydration triggers the body to conserve water and sodium, which also causes increased reabsorption of lithium in the kidneys, raising levels and risk of toxicity.
Actionable advice:
Consistent, adequate hydration should be maintained, and activities causing excessive fluid loss (e.g., saunas, intense exercise in heat) should be avoided.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Volume depletion or dehydration
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/dietary/water
Target name:
Adequate Hydration
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sufficient fluid intake is essential for the kidneys to properly filter and excrete lithium, preventing its accumulation to toxic levels.
Actionable advice:
Plenty of fluids (typically 2-3 liters) should be consumed consistently throughout the day.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
adequate fluid intake (2,500 to 3,000 mL)
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
informational_none
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lithium crosses the placenta and is associated with an increased risk of congenital malformations, particularly a heart defect known as Ebstein's anomaly.
Actionable advice:
Lithium should be strictly avoided during pregnancy, especially in the first trimester.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Lithium may cause harm when administered to a pregnant woman
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lithium is excreted into breast milk and can reach significant concentrations, potentially causing toxicity in the nursing infant.
Actionable advice:
Lithium should not be used while breastfeeding.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Breastfeeding is not recommended with maternal lithium use
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/class/serotonergic-agents
Target name:
Serotonergic Medications (SSRIs, SNRIs, TCAs, Triptans)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining lithium with other drugs that increase serotonin can raise the risk of serotonin syndrome, a potentially life-threatening condition.
Actionable advice:
Extreme caution is warranted, and it is worth watching for symptoms like confusion, agitation, and tremor when this is combined with serotonergic drugs.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Increased risk of serotonin syndrome when co-administered with lithium
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
monitor
Target id:
/class/antipsychotics
Target name:
Antipsychotic Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concurrent use, especially with first-generation antipsychotics like haloperidol, may increase the risk of neurotoxicity and extrapyramidal side effects (movement disorders).
Actionable advice:
Neurological side effects should be monitored closely if this combination is medically necessary.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Atypical and Typical Antipsychotic Drugs
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
monitor
Target id:
/class/calcium-channel-blockers
Target name:
Calcium Channel Blockers
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Medications like verapamil and diltiazem can increase the risk of lithium-induced neurotoxicity, even when lithium blood levels are within the normal range.
Actionable advice:
This combination is best used with caution, and it is worth being vigilant for signs of neurotoxicity like confusion or ataxia.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Calcium Channel Blocking Agents (CCB)
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
monitor
Target id:
/intervention/caffeine
Target name:
Caffeine
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Caffeine acts as a diuretic and increases the renal excretion of lithium, which can lower its concentration and effectiveness. Abruptly stopping caffeine can cause lithium levels to rise.
Actionable advice:
A very consistent daily caffeine intake is best maintained to ensure stable lithium levels.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Caffeine withdrawal increases lithium blood levels
Label source:
Natural Medicines Professional Database. Lithium monograph (accessed 2026-05-22). METHYLXANTHINES section: Xanthines such as aminophylline, caffeine, and theophylline might increase the clearance of lithium. Severity MODERATE, Occurrence PROBABLE, Level of Evidence D.
Action type:
informational_none
Target id:
/dietary/low-sodium-diet
Target name:
Low Sodium Diet
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A low-sodium diet signals the kidneys to conserve sodium, which also increases the reabsorption of lithium, raising the risk of toxicity.
Actionable advice:
A consistent and adequate daily sodium intake is best maintained, and sudden dietary changes are best avoided.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
low-sodium diet
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/dietary/sodium-rich-foods
Target name:
High Sodium Diet
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A high-sodium diet signals the kidneys to excrete more sodium, which also increases the excretion of lithium, potentially reducing its effectiveness.
Actionable advice:
A consistent and adequate daily sodium intake is best maintained, and large, sudden increases in salt consumption are best avoided.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Exact phrase from label:
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27) (mechanism class inference; label endorses "normal diet, including salt" consistency)
Action type:
avoid
Target id:
/biomarker/thyroid-panel
Target name:
Thyroid Panel
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lithium can interfere with the synthesis and release of thyroid hormones, commonly leading to hypothyroidism or goiter over time.
Actionable advice:
Obtain a baseline thyroid panel (TSH, Free T4) before starting and monitor every 6-12 months thereafter.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Monitor thyroid function before the initiation of treatment, at three months and every six to twelve months
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
monitor
Target id:
/intervention/theophylline
Target name:
Theophylline
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Theophylline is a methylxanthine (similar to caffeine) that increases the renal clearance of lithium, thereby lowering its blood levels and efficacy.
Actionable advice:
Concurrent use is best avoided, or lithium levels should be monitored closely if this combination is necessary.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The effect of steady state therapeutic theophylline serum levels on lithium renal clearance was investigated. Group mean lithium renal clearances and serum lithium levels varied in predicted fashion.
Label source:
Natural Medicines Professional Database. Lithium monograph (accessed 2026-05-22). METHYLXANTHINES section: Xanthines such as aminophylline, caffeine, and theophylline might increase the clearance of lithium. Severity MODERATE, Occurrence PROBABLE, Level of Evidence D.
Action type:
avoid
Target id:
/class/carbonic-anhydrase-inhibitors
Target name:
Carbonic Anhydrase Inhibitors
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Drugs like acetazolamide can increase the excretion of lithium by the kidneys, potentially lowering its concentration and effectiveness.
Actionable advice:
It is worth watching out for reduced lithium efficacy if these medications are taken concurrently.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Acetazolamide, Urea, Xanthine Preparations, Alkalinizing Agents
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
monitor
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
informational
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Taking lithium with food can slow its absorption and reduce the incidence of gastrointestinal side effects such as nausea, vomiting, or diarrhea.
Actionable advice:
A lithium dose is generally best taken with a meal or a snack to minimize stomach upset.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
concomitant administration with food
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
informational_none
Target id:
/intervention/iodine
Target name:
Iodine
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lithium can inhibit iodine uptake by the thyroid gland, which may increase the risk of developing hypothyroidism or goiter, especially if iodine intake is high.
Actionable advice:
High-dose iodine supplements are generally best avoided unless directed by a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Iodide Preparations
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
avoid
Target id:
/biomarker/serum-calcium
Target name:
Serum Calcium
Severity:
minor
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Long-term lithium use can affect the parathyroid glands, sometimes leading to elevated blood calcium levels (hypercalcemia).
Actionable advice:
Periodically monitor serum calcium and parathyroid hormone (PTH) levels during long-term use.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Monitor serum calcium concentrations regularly
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
monitor
Target id:
/biomarker/egfr
Target name:
Estimated Glomerular Filtration Rate (eGFR)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Monitoring eGFR is critical as it directly reflects the kidney's ability to clear lithium; a decline indicates an increased risk of toxicity.
Actionable advice:
Kidney function (eGFR, Creatinine) should be monitored at baseline and at least annually, or more frequently if there are risk factors.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Kidney function should be assessed prior to and during lithium treatment
Label source:
FDA label: Lithium Carbonate (effective 2026-04-27)
Action type:
monitor
Derived From
lithium
Provenance Note
Interactions duplicated from 'lithium'. Same lithium interaction partners, but THERAPEUTIC dose -> higher clinical severity.
Review Needed
True