Drug & supplement interaction

Adrafinil + Etravirine

Etravirine brand name: Intelence.

Moderate Interaction
The bottom line Moderate

Etravirine falls into 3 drug categories that Adrafinil can interact with; the most serious is rated moderate. Theoretically, adrafinil might increase the levels and clinical effects of CYP2C19 substrates.

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

Adrafinil and Etravirine

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

Why Are There 3 Interactions?

Adrafinil interacts with whole categories of medication. Etravirine falls into 3 of those categories, so it can interact with Adrafinil 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 2C19 (CYP2C19) SUBSTRATES

1 of 3

Why this applies to Etravirine

Etravirine falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES — the group Adrafinil interacts with.

Theoretically, adrafinil might increase the levels and clinical effects of CYP2C19 substrates.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to inhibit CYP2C19 activity in vitro.
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 gist of this one. When your body turns adrafinil into modafinil, that modafinil can gently block a liver enzyme called CYP2C19. Your HIV medicine etravirine (Intelence) is partly handled by that same enzyme, so in theory slowing it down could let a bit more etravirine build up in your blood. That might mean a slightly stronger drug effect, with the possibility of more side effects like rash, nausea, or trouble sleeping.

I want to be honest though: this is a theoretical concern based on lab studies, not real patient reports, so the actual risk is uncertain. Etravirine is an important part of an HIV regimen you don't want to disturb, so please don't start or stop anything on your own. Run it by your doctor or pharmacist first.

References
  1. Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
  2. Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs. 2008;68(13):1803-39. PubMed
  3. Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

Etravirine also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, adrafinil might increase the levels and clinical effects of CYP2C9 substrates.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to reduce CYP2C9 expression in vitro.
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 short version: your body turns adrafinil into modafinil, and lab research hints that modafinil may quiet down an enzyme called CYP2C9. Since your liver uses that same enzyme to help clear etravirine, slowing it could let etravirine build up a bit higher than usual. Etravirine isn't a prodrug, so more of it in your blood means stronger effects and possibly more side effects, like rash, nausea, or headache.

I want to be honest about how soft this evidence is. It's theoretical, based on test-tube data, not real patient reports, so we don't truly know if it matters in people. Still, HIV therapy is too important to gamble with, so please check with your doctor or pharmacist before combining the two.

References
  1. Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
  2. Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs. 2008;68(13):1803-39. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Etravirine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, adrafanil might reduce levels and clinical effects of CYP3A4 substrates.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to weakly induce CYP3A4 activity.
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 gist for you. Once your liver turns adrafinil into modafinil, that modafinil can mildly speed up an enzyme called CYP3A4. Etravirine is partly broken down by that same enzyme, so in theory revving it up could clear etravirine out a little faster and lower its levels in your blood.

Why that matters: etravirine is one of your HIV medicines, and keeping its level steady is what keeps the virus suppressed. If levels dip too low, you could lose some of that control or, over time, risk resistance. To be fair, this is only a theoretical concern based on how the drugs work, not proven in studies. Still, with HIV treatment I'd play it safe. Please check with your doctor or pharmacist before adding adrafinil.

References
  1. Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
  2. Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.

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

Adrafinil Also Interacts With Other Medications

Adrafinil has 1 major, 1,055 moderate known drug interactions in our database — the Etravirine 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 Adrafinil

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

Everything else you take

See Every Supplement That Interacts With Etravirine

This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Etravirine page lists 169 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and African Wild Potato (moderate).

By severity: 3 major · 127 moderate · 39 minor.

From our pharmacist’s overview on the Etravirine page

“For someone taking etravirine (Intelence), an HIV medicine often used when the virus has already resisted other drugs, keeping a steady blood level is the whole point, and this list of 169 supplements and herbs deserves genuine care. The three major-rated entries come first: St.”

Reviewed by 2 · Jul 18, 2026

Open the Etravirine interaction page

One more smart check

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

We hold 7 real supplement products containing Adrafinil, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Adrafinil. Your product may carry other ingredients that interact with Etravirine too, on top of Adrafinil — 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 Adrafinil and Etravirine 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 Adrafinil
Top half

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

29 days ago today
Medication Etravirine
Steady interest

#2,652 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 Adrafinil

What is Adrafinil?

Adrafinil
  • Wakefulness and alertness
  • Fatigue
  • Focus and concentration
  • Cognitive enhancement (nootropic)
  • Daytime sleepiness

Adrafinil is a synthetic compound that the body converts into modafinil, a prescription wakefulness-promoting drug. It is sometimes sold as a nootropic supplement, but it is unregulated, carries real risks (especially to the liver), and is banned in some sports and countries. Talk with a doctor or pharmacist before using it.

Read the full Adrafinil monograph & all interactions
Medication

About Etravirine

What Is Etravirine Used For?

Brand name: Intelence

Etravirine (brand name Intelence) is used to treat HIV-1 infection in people who have already received other antiretroviral (HIV) treatments — meaning it is meant for patients whose HIV has had a chance to develop resistance to earlier therapies. It is always used as part of a combination regimen with other HIV medications, never on its own.

Both the brand Intelence and generic etravirine tablets are approved for adults and for children ages 2 to under 18 who weigh at least 10 kg (about 22 pounds) and who have already been treated with other HIV drugs.

See full Etravirine drug information
Keep checking

Other Drugs & Adrafinil

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

1Major
1,055Moderate
0Minor
1,773No known interaction
Major

1 interaction

Moderate

1,055 interactions

Showing 60 of 1,055 moderate interactions — see all 1,055 on the Adrafinil page.

No interaction 1,773 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 Adrafinil and Etravirine Together: Common Questions

Can you take Adrafinil with Etravirine?
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 Adrafinil and Etravirine?
Etravirine belongs to more than one drug category, and Adrafinil 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 Adrafinil and Etravirine 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 Etravirine and Adrafinil?

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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.