Drug & supplement interaction

Lithium + Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine brand names: Norgesic Forte, Invagesic, Invagesic Forte, Orphengesic, Norgesic, and others.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Aspirin, Caffeine, Orphenadrine falls into 3 drug categories that Lithium can interact with; the most serious is rated moderate. Theoretically, taking lithium supplements with skeletal muscle relaxants might prolong neuromuscular blockade.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Lithium and Aspirin, Caffeine, Orphenadrine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Lithium interacts with whole categories of medication. Aspirin, Caffeine, Orphenadrine falls into 3 of those categories, so it can interact with Lithium in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

SKELETAL MUSCLE RELAXANTS

1 of 3

Why this applies to Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine falls under SKELETAL MUSCLE RELAXANTS — the group Lithium interacts with.

Theoretically, taking lithium supplements with skeletal muscle relaxants might prolong neuromuscular blockade.
Lithium might prolong neuromuscular blockade. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.
Severity Moderate Likelihood Probable Evidence D

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combo pill mixes aspirin, caffeine, and orphenadrine. Orphenadrine is the muscle relaxant part, and that's what this interaction is about. On paper, lithium can lengthen something called neuromuscular blockade, basically the relaxing effect on your muscles and nerve signals. Pairing it with a muscle relaxer like orphenadrine could, in theory, add to that effect and leave you feeling more drowsy, weak, or unsteady than usual.

I want to be honest though: this is a theoretical concern based on how these drugs work, not something proven in real patients. It's also unclear whether the tiny amounts in lithium supplements (like lithium orotate) are even enough to matter. Still, before combining them, please run it by your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017812s028,018421s027lbl.pdf. Accessed Nov. 21, 2018
Moderate

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

2 of 3

Aspirin, Caffeine, Orphenadrine also falls under NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs).

Theoretically, taking lithium supplements with NSAIDs might increase lithium levels and adverse effects.
NSAIDs can decrease the renal clearance of lithium and increase lithium levels. It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.
Severity Moderate Likelihood Probable Evidence D

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the connection worth knowing about. The aspirin part of this combo product is an NSAID, and NSAIDs can make your kidneys hold onto lithium instead of flushing it out. When that happens, lithium can slowly build up in your body. Higher lithium levels can bring on side effects like nausea, hand tremors, increased thirst, frequent urination, or feeling unsteady and foggy.

Now, the honest part: this is a theoretical concern based on how these drugs behave, not something proven in studies with low-dose lithium supplements like lithium orotate. The smaller amounts in supplements may not matter much. Still, lithium has a narrow safety window, so don't guess. Check with your pharmacist or doctor before combining them, especially if you take this pain product regularly.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
Moderate

METHYLXANTHINES

3 of 3

Aspirin, Caffeine, Orphenadrine also falls under METHYLXANTHINES.

Theoretically, taking lithium supplements with methylxanthines might decrease lithium levels.
Xanthines such as aminophylline, caffeine, and theophylline (Theo-Dur, Theo-24, others) might increase the clearance of lithium. It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.
Severity Moderate Likelihood Probable Evidence D

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the angle that matters with this particular combo product: the caffeine in your Norgesic-type pill is the piece that interacts with lithium. Caffeine is a methylxanthine, and the theory is that it can nudge your kidneys to clear lithium out a little faster, which could lower your lithium level. The aspirin and orphenadrine parts aren't really the players here.

In practice, this is a theoretical, pharmacology-based concern, not something proven in studies. The caffeine dose in one of these tablets is modest, similar to a cup of coffee, so a big swing in lithium is unlikely. Still, if you take prescription lithium for mood, a steady caffeine habit is worth mentioning to your pharmacist or doctor, since even small shifts in lithium can matter.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Lithium Also Interacts With Other Medications

Lithium has 259 major, 255 moderate known drug interactions in our database — the Aspirin, Caffeine, Orphenadrine one above is among them. If you take anything else, check it against the full list below.

Major 259 Moderate 255 No known interaction 2,316 (incl. Aspirin, Caffeine, Orphenadrine)
Taking anything else?

Check Another of Your Medications Against Lithium

Covers the 2,830 medications we’ve checked against Lithium. Pick one to open its full report.

From our Q&A

Questions About Lithium or Aspirin, Caffeine, Orphenadrine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Lithium or Aspirin, Caffeine, Orphenadrine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Aspirin, Caffeine, Orphenadrine

This page covers Lithium only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Orphenadrine page lists 350 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Ephedra (major).

By severity: 14 major · 289 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Caffeine, Orphenadrine page

“Aspirin, caffeine, and orphenadrine (the Norgesic and Orphengesic brands) come with a supplement list that deserves real vigilance, with 14 of its 350 entries rated major. Over 200 of those ingredients can add to aspirin's effect on platelets and raise bleeding risk, another 44 stack stimulant effects on top of the caffeine, and grapef…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Orphenadrine interaction page

One more smart check

Taking Lithium as Part of a Dietary Supplement Product? Check It for Interactions

We hold 330 real supplement products containing Lithium, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Lithium. Your product may carry other ingredients that interact with Aspirin, Caffeine, Orphenadrine too, on top of Lithium — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Lithium and Aspirin, Caffeine, Orphenadrine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Lithium
Top 25%

#254 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Aspirin, Caffeine, Orphenadrine
Steady interest

#1,929 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Lithium

What is Lithium?

Lithium
  • Mood support
  • Bipolar disorder (prescription)
  • Healthy mental function
  • Irritability or stress
  • Sleep support

Lithium is a naturally occurring metal that, in prescription form (lithium carbonate or citrate), is an FDA-approved, well-proven treatment for bipolar disorder. Low-dose supplement forms like lithium orotate are sold for mood support, but there is very little reliable evidence that they work, and even small amounts of lithium can be risky for some people. Always talk to a pharmacist or doctor before taking any lithium product.

Read the full Lithium monograph & all interactions
Keep checking

Other Drugs & Lithium

Browse every other medication we’ve checked against Lithium — both the ones with a known interaction and the ones without. Select any drug for the full detail.

259Major
255Moderate
0Minor
2,315No known interaction
259 Major 255 Moderate 2,315 No interaction
Major

259 interactions

Showing 60 of 259 major interactions — see all 259 on the Lithium page.

Moderate

255 interactions

Showing 60 of 255 moderate interactions — see all 255 on the Lithium page.

No interaction 2,315 drugs checked — show the list

We also checked Lithium against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,315 medications checked with no known interaction — see the full Lithium list.

See the full Lithium interactions page
See every supplement checked against Aspirin, Caffeine, Orphenadrine, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Lithium monograph › Uses, safety, and every drug interaction in one place Aspirin, Caffeine, Orphenadrine supplement interactions › Every supplement checked against Aspirin, Caffeine, Orphenadrine, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Lithium and Aspirin, Caffeine, Orphenadrine Together: Common Questions

Can you take Lithium with Aspirin, Caffeine, Orphenadrine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Lithium and Aspirin, Caffeine, Orphenadrine?
Aspirin, Caffeine, Orphenadrine belongs to more than one drug category, and Lithium interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Lithium and Aspirin, Caffeine, Orphenadrine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Aspirin, Caffeine, Orphenadrine and Lithium?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.