Drug & supplement interaction

Lithium + Chlorpheniramine, Hydrocodone, Pseudoephedrine

Chlorpheniramine, Hydrocodone, Pseudoephedrine brand name: Tussend.

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

Lithium has a major interaction with Chlorpheniramine, Hydrocodone, Pseudoephedrine. Theoretically, taking lithium supplements with serotonergic drugs might both mask and increase the risk of serotonin syndrome.

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

Lithium and Chlorpheniramine, Hydrocodone, Pseudoephedrine

Here is the interaction we found between these two, with the evidence behind it.

Major

SEROTONERGIC DRUGS

Why this applies to Chlorpheniramine, Hydrocodone, Pseudoephedrine

Chlorpheniramine, Hydrocodone, Pseudoephedrine falls under SEROTONERGIC DRUGS — the group Lithium interacts with.

Theoretically, taking lithium supplements with serotonergic drugs might both mask and increase the risk of serotonin syndrome.
In a case report, a 67-year-old female with depression and bipolar disorder using lithium in combination with selective serotonin reuptake inhibitors (SSRIs) and other medications developed serotonin syndrome with symptoms of deep tendon hyperreflexia, muscle rigidity, tremor, and hyperthermia. However, agitation, one classical symptom of serotonin syndrome, was lacking. This was thought to be due to masking by lithium toxicity. Lithium can increase serotonin levels, thus, combining serotonergic drugs with lithium might increase the risk of serotonergic side effects including serotonin syndrome and cerebral vasoconstrictive disorders. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.
Severity Major 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 product (Tussend) mixes an antihistamine, the opioid cough suppressant hydrocodone, and the decongestant pseudoephedrine. The piece that matters here is that hydrocodone has mild serotonin activity, and lithium can nudge serotonin levels up too. Stack them together and there is a theoretical chance of serotonin syndrome, which can show up as agitation, shakiness, a fast heartbeat, sweating, muscle stiffness, or fever.

Honestly, this is a cautious, pharmacology-based concern rather than something proven at supplement doses. The reported cases involved prescription-strength lithium with stronger serotonin drugs, so the low amounts in lithium orotate may not pose much risk. Still, since both can raise serotonin, please run this past your pharmacist or doctor before combining them.

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. Landa E, Wagner S, Makkar A, Liu A, Jung D. An atypical presentation of serotonin syndrome. Cureus. 2021;13(2):e13377. PubMed

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 258 major, 256 moderate known drug interactions in our database — the Chlorpheniramine, Hydrocodone, Pseudoephedrine one above is one of them. If you take anything else, check it against the full list below.

Major 258 Moderate 256 No known interaction 2,316 (incl. Chlorpheniramine, Hydrocodone, Pseudoephedrine)
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 Chlorpheniramine, Hydrocodone, Pseudoephedrine

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 Chlorpheniramine, Hydrocodone, Pseudoephedrine, 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 Chlorpheniramine, Hydrocodone, Pseudoephedrine

This page covers Lithium only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Chlorpheniramine, Hydrocodone, Pseudoephedrine page lists 285 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 16 major · 228 moderate · 41 minor.

From our pharmacist’s overview on the Chlorpheniramine, Hydrocodone, Pseudoephedrine page

“Tussend combines three drugs in one cough medicine, the opioid hydrocodone, the antihistamine chlorpheniramine, and the decongestant pseudoephedrine, so supplements can collide with it from several directions. I treat its list of 285 interacting ingredients as one that deserves real respect, and the 16 rated major are what to understan…”

Reviewed by 2 · Jul 18, 2026

Open the Chlorpheniramine, Hydrocodone, Pseudoephedrine 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 Chlorpheniramine, Hydrocodone, Pseudoephedrine 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 Chlorpheniramine, Hydrocodone, Pseudoephedrine 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%

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

29 days ago today
Medication Chlorpheniramine, Hydrocodone, Pseudoephedrine
Top 25%

#547 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.

258Major
256Moderate
0Minor
2,315No known interaction
258 Major 256 Moderate 2,315 No interaction
Major

258 interactions

Showing 60 of 258 major interactions — see all 258 on the Lithium page.

Moderate

256 interactions

Showing 60 of 256 moderate interactions — see all 256 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 Chlorpheniramine, Hydrocodone, Pseudoephedrine, 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 Chlorpheniramine, Hydrocodone, Pseudoephedrine supplement interactions › Every supplement checked against Chlorpheniramine, Hydrocodone, Pseudoephedrine, 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 Chlorpheniramine, Hydrocodone, Pseudoephedrine Together: Common Questions

Can you take Lithium with Chlorpheniramine, Hydrocodone, Pseudoephedrine?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Lithium and Chlorpheniramine, Hydrocodone, Pseudoephedrine interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Chlorpheniramine, Hydrocodone, Pseudoephedrine 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.