Drug & supplement interaction

Neem + Hydrocodone/Chlorpheniramine

Hydrocodone/Chlorpheniramine brand name: Tussionex.

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

Neem has a moderate interaction with Hydrocodone/Chlorpheniramine. Theoretically, neem leaf extract might increase the levels and clinical effects of CYP3A4 substrates.

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

Neem and Hydrocodone/Chlorpheniramine

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Hydrocodone/Chlorpheniramine

Hydrocodone/Chlorpheniramine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Neem interacts with.

Theoretically, neem leaf extract might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that neem leaf methanol extract inhibits CYP3A4 enzymes. So far, this reaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction 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.

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

Here's the basic idea with Tussionex (a combo of hydrocodone, an opioid cough medicine, and chlorpheniramine, an antihistamine). In lab dishes, neem leaf extract appears to slow down CYP3A4, one of the liver enzymes that helps clear hydrocodone. If that enzyme works more slowly, hydrocodone could potentially build up a bit and hit harder. That might mean more drowsiness, dizziness, constipation, or in a bigger concern, slowed breathing. The chlorpheniramine piece already adds its own sleepiness on top.

I want to be honest, though: this is only test-tube data, and it has not been seen in real people. So it's a theoretical caution, not a proven problem. Still, since Tussionex is a strong medicine, please run the combo by your pharmacist or doctor before adding neem.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Amaeze O, Eng H, Horlbogen L, Varma MVS, Slitt A. Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria. Eur J Drug Metab Pharmacokinet. 2021;46(3):437-450. 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

Neem Also Interacts With Other Medications

Neem has 1,012 moderate known drug interactions in our database — the Hydrocodone/Chlorpheniramine one above is one of them. If you take anything else, check it against the full list below.

Moderate 1,012 No known interaction 1,818 (incl. Hydrocodone/Chlorpheniramine)
Taking anything else?

Check Another of Your Medications Against Neem

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

Everything else you take

See Every Supplement That Interacts With Hydrocodone/Chlorpheniramine

This page covers Neem only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrocodone/Chlorpheniramine page lists 258 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), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 12 major · 204 moderate · 42 minor.

From our pharmacist’s overview on the Hydrocodone/Chlorpheniramine page

“Tussionex (hydrocodone with chlorpheniramine) pairs an opioid with a sedating antihistamine, so anything that deepens drowsiness or slows breathing is a genuine hazard, and 78 of the 258 supplements on file do exactly that. Alcohol in any form tops that group, and kava carries a major rating for the same reason.”

Reviewed by 2 · Jul 18, 2026

Open the Hydrocodone/Chlorpheniramine interaction page

One more smart check

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

We hold 288 real supplement products containing Neem, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Neem. Your product may carry other ingredients that interact with Hydrocodone/Chlorpheniramine too, on top of Neem — 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 Neem and Hydrocodone/Chlorpheniramine 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 Neem
Top 25%

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

29 days ago today
Medication Hydrocodone/Chlorpheniramine
Steady interest

#1,767 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 Neem

What is Neem?

Neem
  • Skin conditions
  • Dental and gum health
  • Antimicrobial and antiparasitic
  • Digestive upset
  • Blood sugar support
  • Insect repellent/pesticide

Neem is a tree from India used for centuries in traditional medicine, especially for skin, dental, and antimicrobial purposes. Some small studies are promising for oral health and skin, but high-quality human evidence is limited for most uses. Neem oil and seed extracts can be toxic if swallowed, especially in children, so use with caution and talk to your pharmacist or doctor first.

Read the full Neem monograph & all interactions
Keep checking

Other Drugs & Neem

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

0Major
1,012Moderate
0Minor
1,817No known interaction
1,012 Moderate 1,817 No interaction
Moderate

1,012 interactions

Showing 60 of 1,012 moderate interactions — see all 1,012 on the Neem page.

No interaction 1,817 drugs checked — show the list

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

Showing the 60 most looked-up of 1,817 medications checked with no known interaction — see the full Neem list.

See the full Neem interactions page
See every supplement checked against Hydrocodone/Chlorpheniramine, 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
Neem monograph › Uses, safety, and every drug interaction in one place Hydrocodone/Chlorpheniramine supplement interactions › Every supplement checked against Hydrocodone/Chlorpheniramine, 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 Neem and Hydrocodone/Chlorpheniramine Together: Common Questions

Can you take Neem with Hydrocodone/Chlorpheniramine?
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.
How serious is the Neem and Hydrocodone/Chlorpheniramine 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 Hydrocodone/Chlorpheniramine and Neem?

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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.