Drug & supplement interaction

Bulbine Natalensis + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine brand name: Colrex.

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

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls into 2 drug categories that Bulbine Natalensis can interact with; the most serious is rated moderate. Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP1A2 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Bulbine Natalensis and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Bulbine Natalensis interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls into 2 of those categories, so it can interact with Bulbine Natalensis in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Bulbine Natalensis interacts with.

Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that Bulbine natalensis stem extract slightly induces CYP1A2 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP1A2 substrates; however, this has not been studied 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 honest picture: this combo product (Colrex) has four ingredients, and the only one that really overlaps with the liver enzyme in question (CYP1A2) is acetaminophen, which uses several pathways to break down. In lab dishes, Bulbine natalensis appeared to slightly speed up that enzyme. In theory, speeding things up could clear acetaminophen a touch faster, which might mean a little less fever or pain relief. The codeine, chlorpheniramine, and phenylephrine pieces aren't really driven by this enzyme, so I wouldn't expect big changes there.

The big caveat: this is only test-tube data, never shown in real people, so it's pretty theoretical. I'd be more concerned about Bulbine's possible liver strain stacking with acetaminophen. Please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Husain I, Manda V, Alhusban M, et al. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine 2021;81:153416. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that Bulbine natalensis stem extract induces CYP3A4 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP3A4 substrates, but this has not been studied 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

This combo product is a mix, and one ingredient worth flagging is the codeine. Codeine is a prodrug: your body has to convert it into morphine to get pain relief and cough control. The conversion mostly runs through CYP2D6, but the broader handling of these ingredients also involves CYP3A4. In lab studies, Bulbine natalensis appeared to speed up (induce) CYP3A4, which in theory could push more codeine down a side pathway and leave less of the active pain-relieving form. That could mean weaker cough or pain relief than you expect.

Keep in mind this is theoretical, based only on test-tube and animal data, with nothing proven in people. Still, since Bulbine itself carries liver and kidney concerns, please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Husain I, Dale OR, Manda V, et al. Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp. Planta Med 2022;88(12):975-984. 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

Bulbine Natalensis Also Interacts With Other Medications

Bulbine Natalensis has 918 moderate known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine one above is among them. If you take anything else, check it against the full list below.

Moderate 918 No known interaction 1,912 (incl. Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Bulbine Natalensis

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine

This page covers Bulbine Natalensis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page lists 338 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), Asarabacca (major), Beer (major) and Ephedra (major).

By severity: 18 major · 275 moderate · 45 minor.

From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page

“Someone taking Colrex is usually fighting a miserable cold, and cold season is also when people reach for herbal sleep aids and energy boosters, which is exactly where this list bites hardest. Colrex combines acetaminophen, chlorpheniramine, codeine, and phenylephrine, and 18 of its 338 supplement interactions rate major, enough to war…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction page

One more smart check

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

We hold 51 real supplement products containing Bulbine Natalensis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bulbine Natalensis. Your product may carry other ingredients that interact with Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine too, on top of Bulbine Natalensis — 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 Bulbine Natalensis and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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 Bulbine Natalensis
Steady interest

#1,115 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
Top 10%

#252 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 Bulbine Natalensis

What is Bulbine Natalensis?

  • Boosting testosterone
  • Improving libido
  • Muscle building and athletic performance
  • General male vitality

Bulbine natalensis is a South African plant marketed mainly as a testosterone-boosting and libido supplement, but the human evidence is essentially absent and most claims come from animal studies. Animal research has also raised concerns about possible liver and kidney harm at higher doses, so caution is warranted. Talk to your pharmacist or doctor before trying it.

Read the full Bulbine Natalensis monograph & all interactions
Keep checking

Other Drugs & Bulbine Natalensis

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

0Major
918Moderate
0Minor
1,911No known interaction
918 Moderate 1,911 No interaction
Moderate

918 interactions

Showing 60 of 918 moderate interactions — see all 918 on the Bulbine Natalensis page.

No interaction 1,911 drugs checked — show the list

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

Showing the 60 most looked-up of 1,911 medications checked with no known interaction — see the full Bulbine Natalensis list.

See the full Bulbine Natalensis interactions page
See every supplement checked against Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine, 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
Bulbine Natalensis monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine supplement interactions › Every supplement checked against Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine, 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 Bulbine Natalensis and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine Together: Common Questions

Can you take Bulbine Natalensis with Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
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 2 interactions listed for Bulbine Natalensis and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine belongs to more than one drug category, and Bulbine Natalensis 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 Bulbine Natalensis and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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

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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.