Drug & supplement interaction

Yohimbe + Chlorpheniramine, Phenylephrine, Phenyltoloxamine

Chlorpheniramine, Phenylephrine, Phenyltoloxamine brand names: Com Time, Q Hist LA, Comhist LA, Linhist LA, Comhist.

Moderate Interaction
The bottom line Moderate

Chlorpheniramine, Phenylephrine, Phenyltoloxamine falls into 3 drug categories that Yohimbe can interact with; the most serious is rated moderate. CYP2D6 inhibitors may increase the levels and adverse effects of yohimbine, a constituent of yohimbe.

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

Yohimbe and Chlorpheniramine, Phenylephrine, Phenyltoloxamine

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

Why Are There 3 Interactions?

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

Moderate

CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS

1 of 3

Why this applies to Chlorpheniramine, Phenylephrine, Phenyltoloxamine

Chlorpheniramine, Phenylephrine, Phenyltoloxamine falls under CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS — the group Yohimbe interacts with.

CYP2D6 inhibitors may increase the levels and adverse effects of yohimbine, a constituent of yohimbe.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP2D6 isoenzymes. Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine and reduces the clearance of yohimbine compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers..
Severity Moderate Likelihood Probable Evidence B

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 thing to know about pairing yohimbe with this combination cold product. One of the antihistamines in it, chlorpheniramine, can act as a mild blocker of an enzyme called CYP2D6, which happens to be the same enzyme your body uses to clear yohimbine (the active part of yohimbe). When that pathway is slowed, yohimbine can build up higher than expected.

Why that matters: yohimbe on its own can spike your blood pressure and heart rate, cause jitteriness, anxiety, and trouble sleeping. The phenylephrine in this product is also a stimulant-type decongestant, so you could be stacking two things that raise blood pressure and pulse. I wouldn't combine these without checking with your pharmacist or doctor first.

References
  1. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139-53.
  2. Mueller-Schoell A, Michelet R, Weinelt F, Kloft C, Mikus G. CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications. Arch Toxicol. 2021. PubMed
  3. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
  4. Vay M, Meyer MJ, Blank A, et al. Oral yohimbine as a new probe drug to predict CYP2D6 activity: results of a fixed-sequence phase I trial. Clin Pharmacokinet. 2020;59(7):927-939. PubMed
Moderate

STIMULANT DRUGS

2 of 3

Chlorpheniramine, Phenylephrine, Phenyltoloxamine also falls under STIMULANT DRUGS.

Theoretically, taking yohimbe with stimulant drugs can have additive effects.
Yohimbine, a constituent of yohimbe, has sympathomimetic effects and increases blood pressure in a dose-dependent manner. Theoretically, taking yohimbe with stimulant drugs can have additive stimulant and hypertensive effects.
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 thing with this combo product: the phenylephrine in it is a decongestant that works by tightening blood vessels, which can nudge your blood pressure up and your heart rate along with it. Yohimbe (from its active compound yohimbine) does something similar by revving up your body's own adrenaline-type signals. Stacking them together could, in theory, add up to higher blood pressure, a faster or pounding heartbeat, jitteriness, headache, or trouble sleeping.

To be fair, this concern is based on how these ingredients work rather than solid studies, so it's more of a caution than a proven problem. Still, since over-the-counter yohimbe is unpredictable in strength, I'd run this past your pharmacist or doctor before combining them, especially if you already deal with blood pressure issues.

References
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  3. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

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

Theoretically, yohimbe might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that yohimbe extract induces CYP3A4 enzymes.
Severity Minor 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 bigger picture with this combo. This product mixes an antihistamine (chlorpheniramine), a decongestant (phenylephrine), and another antihistamine (phenyltoloxamine). On paper, yohimbe may slightly speed up a liver enzyme called CYP3A4, which could in theory lower the levels of medicines it processes. So if anything, that part would make the cold-medicine effects a touch weaker, not stronger. Honestly though, this is based only on lab studies, so it's a very weak, theoretical concern.

My real worry is different. Yohimbe can raise blood pressure and speed up your heart, and phenylephrine (a decongestant) does the same thing. Stacking them could leave you jittery, with a pounding heart or elevated blood pressure. Please run this by your pharmacist or doctor first.

References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. 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

Yohimbe Also Interacts With Other Medications

Yohimbe has 9 major, 679 moderate, 436 minor known drug interactions in our database — the Chlorpheniramine, Phenylephrine, Phenyltoloxamine one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Yohimbe

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

Everything else you take

See Every Supplement That Interacts With Chlorpheniramine, Phenylephrine, Phenyltoloxamine

This page covers Yohimbe only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Chlorpheniramine, Phenylephrine, Phenyltoloxamine page lists 229 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Henbane (major) and Lithium (major).

By severity: 10 major · 175 moderate · 44 minor.

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

“If you take Comhist (chlorpheniramine, phenylephrine, and phenyltoloxamine, a cold and allergy combination), treat its supplement list with real care. Ten of the 229 ingredients on file carry a major rating, and the biggest patterns are worth knowing.”

Reviewed by 2 · Jul 18, 2026

Open the Chlorpheniramine, Phenylephrine, Phenyltoloxamine interaction page

One more smart check

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

We hold 1,054 real supplement products containing Yohimbe, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Yohimbe. Your product may carry other ingredients that interact with Chlorpheniramine, Phenylephrine, Phenyltoloxamine too, on top of Yohimbe — 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 Yohimbe and Chlorpheniramine, Phenylephrine, Phenyltoloxamine 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 Yohimbe
Top 25%

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

29 days ago today
Medication Chlorpheniramine, Phenylephrine, Phenyltoloxamine
Steady interest

#1,448 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 Yohimbe

What is Yohimbe?

Yohimbe
  • Erectile dysfunction
  • Low sex drive
  • Sexual performance
  • Weight loss
  • Athletic performance

Yohimbe is a West African tree bark that contains yohimbine, a compound mainly promoted for erectile dysfunction and as an aphrodisiac. A prescription form of yohimbine has some evidence for erectile dysfunction, but over-the-counter yohimbe supplements vary widely in content and can cause serious side effects like high blood pressure and fast heart rate. Because of these safety concerns, talk to your pharmacist or doctor before using it.

Read the full Yohimbe monograph & all interactions
Keep checking

Other Drugs & Yohimbe

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

9Major
679Moderate
436Minor
1,705No known interaction
Major

9 interactions

Moderate

679 interactions

Showing 60 of 679 moderate interactions — see all 679 on the Yohimbe page.

Minor

436 interactions

Showing 60 of 436 minor interactions — see all 436 on the Yohimbe page.

No interaction 1,705 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Yohimbe and Chlorpheniramine, Phenylephrine, Phenyltoloxamine Together: Common Questions

Can you take Yohimbe with Chlorpheniramine, Phenylephrine, Phenyltoloxamine?
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 Yohimbe and Chlorpheniramine, Phenylephrine, Phenyltoloxamine?
Chlorpheniramine, Phenylephrine, Phenyltoloxamine belongs to more than one drug category, and Yohimbe 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 Yohimbe and Chlorpheniramine, Phenylephrine, Phenyltoloxamine 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.