Drug & supplement interaction

Adrafinil + Larotrectinib

Larotrectinib brand name: Vitrakvi.

Moderate Interaction
The bottom line Moderate

Larotrectinib falls into 2 drug categories that Adrafinil can interact with; the most serious is rated moderate. Theoretically, drugs that inhibit CYP3A4 might increase the levels and clinical effects of adrafinil.

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

Adrafinil and Larotrectinib

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

Why Are There 2 Interactions?

Adrafinil interacts with whole categories of medication. Larotrectinib falls into 2 of those categories, so it can interact with Adrafinil 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) INHIBITORS

1 of 2

Why this applies to Larotrectinib

Larotrectinib falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Adrafinil interacts with.

Theoretically, drugs that inhibit CYP3A4 might increase the levels and clinical effects of adrafinil.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil is metabolized by CYP3A4.
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 connection worth knowing. Once your liver turns adrafinil into modafinil, that modafinil is cleared partly by an enzyme called CYP3A4. Larotrectinib (Vitrakvi) is a mild blocker of that same CYP3A4 enzyme. So in theory, taking the two together could slow how fast modafinil leaves your body, letting it build up. That might mean stronger stimulant effects like trouble sleeping, a racing or pounding heart, jitteriness, anxiety, or headache.

To be fair, this is a theoretical concern based on how the drugs work, not something proven in studies, and larotrectinib is only a mild inhibitor. Still, since you're on cancer treatment, please loop in your oncologist or pharmacist before adding any adrafinil, especially given its liver risks.

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.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Larotrectinib 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 concern with combining these two. Your body turns adrafinil into modafinil, and modafinil can gently speed up a liver enzyme called CYP3A4. Larotrectinib (Vitrakvi) is cleared by that same enzyme. So in theory, taking adrafinil could nudge your body to break down larotrectinib a little faster, leaving lower levels in your blood. For a cancer medicine, that's the worry: a weaker drug may not control the tumor as well as it should.

I want to be honest that this is theoretical, based on how the drugs behave, not on real-world studies, and modafinil is only a weak booster of this enzyme. Still, larotrectinib is too important to risk. Please loop in your oncologist 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 Larotrectinib 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 Larotrectinib

This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Larotrectinib page lists 143 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 · 100 moderate · 40 minor.

From our pharmacist’s overview on the Larotrectinib page

“Nearly everything on this page interacts with larotrectinib (Vitrakvi) in one of two directions, raising or lowering how much of the drug ends up in your blood. Larotrectinib treats cancers driven by an NTRK gene fusion, and it is cleared by a liver enzyme called CYP3A4, so herbs that speed that enzyme up can drain the drug's effect wh…”

Reviewed by 2 · Jul 18, 2026

Open the Larotrectinib 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 Larotrectinib 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 Larotrectinib 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

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

29 days ago today
Medication Larotrectinib
Steady interest

#2,492 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 Larotrectinib

What Is Larotrectinib Used For?

Brand name: Vitrakvi

Vitrakvi is used to treat adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion — a specific genetic alteration that can drive tumor growth. It is used when the tumor is metastatic (has spread) or when surgery to remove it would likely cause serious harm, and when there are no satisfactory alternative treatments or the cancer has continued to grow after prior treatment.

Patients must be selected for Vitrakvi therapy based on an FDA-approved test that confirms the NTRK gene fusion in their tumor. This approval is under the FDA's accelerated approval pathway, based on how many patients responded to treatment and how long those responses lasted. Continued approval may depend on results from follow-up clinical trials.

See full Larotrectinib 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 Larotrectinib Together: Common Questions

Can you take Adrafinil with Larotrectinib?
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 Adrafinil and Larotrectinib?
Larotrectinib 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 Larotrectinib 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.