Lithium and Acetaminophen And Codeine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Lithium
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
You've been prescribed lithium (for mood) along with acetaminophen with codeine (for pain). Both of these can raise serotonin, a chemical messenger in your body. When you take them together, there's a small, mostly theoretical chance of a condition called serotonin syndrome.
Watch for things like feeling agitated or confused, a fast heartbeat, sweating, shivering, muscle twitching or stiffness, tremor, or nausea and diarrhea. These would usually show up soon after starting the combination. The good news is your care team can manage this safely by keeping an eye on you. Keep taking both as prescribed, but call your doctor or pharmacist right away if you notice those symptoms.
Effect: Additive serotonergic activity from lithium plus codeine may increase the risk of serotonin syndrome. Codeine is a prodrug (CYP2D6-activated to morphine); this interaction is pharmacodynamic (additive serotonergic effect), not a metabolic one, so its analgesic activation is not the driver here.
- Direction: Additive serotonergic tone, increased risk.
- Evidence: Theoretical; severity rated major.
- Onset: Unspecified; highest vigilance at initiation/dose changes.
- Management: Monitor for mental status changes, autonomic instability, neuromuscular findings (clonus, hyperreflexia, rigidity), and GI symptoms. If serotonin syndrome develops, discontinue offending agents and provide supportive care.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
When lithium is taken together with other serotonergic agents or with medications that slow serotonin breakdown, serotonin syndrome can develop, a condition that may be fatal. The presentation can involve altered mental status (for example, agitation, hallucinations, delirium, and coma), autonomic instability (for example, tachycardia, fluctuating blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular findings (for example, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal complaints including nausea, vomiting, or diarrhea. Every patient receiving lithium should be watched for serotonin syndrome, particularly at the start of therapy. When combined use cannot be avoided, inform patients about the heightened risk of serotonin syndrome and observe for its manifestations. Should symptoms arise, promptly stop both lithium and any accompanying serotonergic drug and begin supportive care1.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
This combination can usually be used with appropriate caution, and your care team can manage it.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely, especially when either drug is first started or a dose changes.
- Learn the warning signs: agitation or confusion, fast heartbeat, sweating, fever, shivering, muscle twitching, tremor or stiffness, and nausea, vomiting, or diarrhea.
- Seek help right away if these symptoms appear, since treatment may need to be stopped and supportive care started.
Ask your pharmacist or doctor before adding any new medicines, especially other serotonin-raising drugs.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Lithium and Acetaminophen And Codeine together?
Taking lithium with acetaminophen/codeine carries a small, mainly theoretical risk of serotonin syndrome. Keep taking both as prescribed, but get medical help right away if you notice agitation, fever, fast heartbeat, sweating, or muscle twitching. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lithium and Acetaminophen And Codeine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Lithium and Acetaminophen And Codeine interaction managed?
This combination can usually be used with appropriate caution, and your care team can manage it. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely, especially when either drug is first started or a dose changes. Learn the warning signs: agitation or confusion, fast heartbeat, sweating, fever, shivering, muscle twitching, tremo… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Lithium or Acetaminophen And Codeine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: LITHOBID(R) oral extended-release tablets, lithium carbonate oral extended-release tablets. ANI Pharmaceuticals Inc (per DailyMed), Baudette, MN, 2018. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Lithium
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist