Drug & supplement interaction

Diosmin + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.

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

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 2 drug categories that Diosmin can interact with; the most serious is rated moderate. Theoretically, diosmin might inhibit the metabolism of CYP3A4 substrates.

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

Diosmin and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

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

Why Are There 2 Interactions?

Diosmin interacts with whole categories of medication. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 2 of those categories, so it can interact with Diosmin 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 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Diosmin interacts with.

Theoretically, diosmin might inhibit the metabolism of CYP3A4 substrates.
Laboratory research is conflicting with respect to the effects of diosmin on CYP3A4. Some research suggests that diosmin does not affect CYP3A4 activity. However, other research suggests that diosmin alters the metabolism of carbamazepine, a CYP3A4 substrate. Laboratory and animal research show that oral administration of diosmin for 7 days prior to oral administration of carbamazepine increases plasma concentrations of carbamazepine, decreases the clearance of carbamazepine, and decreases the formation of carbamazepine's active metabolite. Additionally, pharmacokinetic research in healthy male subjects shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of carbamazepine 200 mg increases blood levels of carbamazepine by approximately 58% and decreases carbamazepine clearance by 42%. It is speculated that diosmin reduces the metabolism of carbamazepine by inhibiting CYP3A4. Diosmetin, a metabolite of diosmin, may also inhibit CYP3A4.
Severity Moderate Likelihood Possible Evidence B

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 piece that matters in this combo product: hydrocodone leans on the CYP3A4 enzyme to be broken down. Diosmin might slow that enzyme a little, which could let hydrocodone build up more than usual. In plain terms, that could mean extra drowsiness, dizziness, nausea, constipation, or slowed breathing if it added up significantly.

I want to keep this in perspective. The evidence is mostly theoretical and lab-based, and studies on diosmin and CYP3A4 actually disagree with each other, so a big real-world problem is far from guaranteed. Still, since this product already contains an opioid plus a sedating antihistamine (chlorpheniramine), it's worth a quick chat with your pharmacist or doctor before adding diosmin, especially if you ever feel unusually sleepy.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bedada SK, Neerati P. Modulation of CYP3A enzyme activity by diosmin and its consequence on carbamazepine pharmacokinetics in rats. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(2):115-21. PubMed
  2. Burkina V, Zlabek V, Halsne R, Ropstad E, Zamaratskaia G. In vitro effects of the citrus flavonoids diosmin, naringenin and naringin on the hepatic drug-metabolizing CYP3A enzyme in human, pig, mouse and fish. Biochem Pharmacol. 2016;110-111:109-16 PubMed
  3. Bedada SK, Boga PK. Influence of diosmin on the metabolism and disposition of carbamazepine in healthy subjects. Xenobiotica. 2017;47(10):879-84. PubMed
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

2 of 2

Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, diosmin might inhibit the metabolism of CYP2E1 substrates.
Chlorzoxazone is metabolized by CYP2E1 enzymes. A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of chlorzoxazone (Paraflex 250) 250 mg increases blood levels of chlorzoxazone by 34% and decreases chlorzoxazone clearance by 40%. It is speculated that diosmin reduces the metabolism of chlorzoxazone by inhibiting CYP2E1.
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 piece of this combo product that matters most with diosmin: the acetaminophen (Tylenol) part. A small share of acetaminophen is handled by a liver enzyme called CYP2E1, the same enzyme diosmin may gently slow down. In theory, that could shift a little more acetaminophen away from the pathway that makes a harmful byproduct, which isn't really a danger to worry about at normal doses.

Honestly, this is a theoretical concern based on lab pharmacology, not real-world reports of people getting hurt. I wouldn't lose sleep over it. The bigger everyday cautions with this product are the drowsiness from hydrocodone and chlorpheniramine and not doubling up on acetaminophen from other cold meds. If you take diosmin regularly, just mention it to your pharmacist so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Rajnarayana K, Venkatesham A, Nagulu M, Srinivas M, Krishna DR. Influence of diosmin pretreatment on the pharmacokinetics of chlorzoxazone in healthy male volunteers. Drug Metabol Drug Interact. 2008;23(3-4):311-21. 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

Diosmin Also Interacts With Other Medications

Diosmin has 883 moderate known drug interactions in our database — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine one above is among them. If you take anything else, check it against the full list below.

Moderate 883 No known interaction 1,947 (incl. Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine)
Taking anything else?

Check Another of Your Medications Against Diosmin

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine

This page covers Diosmin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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: 17 major · 276 moderate · 46 minor.

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

“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction page

One more smart check

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

We hold 121 real supplement products containing Diosmin, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Diosmin. Your product may carry other ingredients that interact with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine too, on top of Diosmin — 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 Diosmin and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 Diosmin
Top half

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

29 days ago today
Medication Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Top 25%

#445 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 Diosmin

What is Diosmin?

  • Chronic venous insufficiency
  • Hemorrhoids
  • Leg swelling and heaviness
  • Varicose veins
  • Spider veins

Diosmin is a citrus-derived flavonoid most often used for vein-related problems such as chronic venous insufficiency and hemorrhoids, and it is usually combined with a related flavonoid called hesperidin. Some studies suggest it may help relieve leg swelling and hemorrhoid symptoms, but quality varies. Talk to your pharmacist or doctor before starting it, especially if you are pregnant or breastfeeding.

Read the full Diosmin monograph & all interactions
Keep checking

Other Drugs & Diosmin

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

0Major
883Moderate
0Minor
1,946No known interaction
883 Moderate 1,946 No interaction
Moderate

883 interactions

Showing 60 of 883 moderate interactions — see all 883 on the Diosmin page.

No interaction 1,946 drugs checked — show the list

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

Showing the 60 most looked-up of 1,946 medications checked with no known interaction — see the full Diosmin list.

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

Can you take Diosmin with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 Diosmin and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine belongs to more than one drug category, and Diosmin 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 Diosmin and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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

Still Have a Question About Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine and Diosmin?

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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.