Drug & supplement interaction

Adrafinil + Hydrochlorothiazide, Lisinopril

Hydrochlorothiazide, Lisinopril brand names: Zestoretic, Prinzide.

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

Adrafinil has a moderate interaction with Hydrochlorothiazide, Lisinopril. Theoretically, adrafinil might reduce the effects of antihypertensive drugs.

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

Adrafinil and Hydrochlorothiazide, Lisinopril

Here is the interaction we found between these two, with the evidence behind it.

Moderate

ANTIHYPERTENSIVE DRUGS

Why this applies to Hydrochlorothiazide, Lisinopril

Hydrochlorothiazide, Lisinopril falls under ANTIHYPERTENSIVE DRUGS — the group Adrafinil interacts with.

Theoretically, adrafinil might reduce the effects of antihypertensive drugs.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to increase diastolic and systolic blood pressure. Retrospective analyses show that patients taking modafinil had a small but increased rate of requiring new antihypertensive drugs or increased use of antihypertensive drugs when compared with placebo.
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 simple version: your Zestoretic combo (lisinopril plus hydrochlorothiazide) is working hard to lower your blood pressure. Adrafinil turns into modafinil in your body, and modafinil has been shown to nudge blood pressure up a bit in some people. So in theory, it could push against your medication and make it work a little less well.

If that happened, you might notice your numbers creeping higher, or symptoms like headaches. To be clear, this is a theoretical concern based on how these drugs behave, not strong proof, and any effect is likely small. Still, since adrafinil is unregulated and rough on the liver, please check with your doctor or pharmacist before mixing it in, and keep an eye on your blood pressure readings.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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 Hydrochlorothiazide, Lisinopril one above is one of them. If you take anything else, check it against the full list below.

Major 1 Moderate 1,055 No known interaction 1,774 (incl. Hydrochlorothiazide, Lisinopril)
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 Hydrochlorothiazide, Lisinopril

This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrochlorothiazide, Lisinopril page lists 236 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), American Mistletoe (major), Asarabacca (major) and Dolomite (major).

By severity: 10 major · 199 moderate · 27 minor.

From our pharmacist’s overview on the Hydrochlorothiazide, Lisinopril page

“I would not add a supplement casually alongside hydrochlorothiazide and lisinopril (Zestoretic, Prinzide). This combination lowers blood pressure with a water pill plus an ACE inhibitor, and most interacting ingredients either drag pressure down too far or push back against the drug, while smaller groups strain the kidneys, drain potas…”

Reviewed by 2 · Jul 18, 2026

Open the Hydrochlorothiazide, Lisinopril 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 Hydrochlorothiazide, Lisinopril 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 Hydrochlorothiazide, Lisinopril 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

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

29 days ago today
Medication Hydrochlorothiazide, Lisinopril
Top 25%

#474 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 Lisinopril and Hydrochlorothiazide

What Is Lisinopril and Hydrochlorothiazide Used For?

Brand names: Zestoretic, Prinzide

Lisinopril and hydrochlorothiazide tablets — sold as the brand Zestoretic and as the generic combination — are used to treat high blood pressure (hypertension). Lowering blood pressure reduces the risk of serious cardiovascular events such as stroke and heart attack.

This is a fixed-dose combination product and is not intended as a first-line (initial) treatment for high blood pressure. It is typically prescribed for patients whose blood pressure is not adequately controlled on a single medication alone.

See full Lisinopril and Hydrochlorothiazide 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
1 Major 1,055 Moderate 1,773 No 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

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

Showing the 60 most looked-up of 1,773 medications checked with no known interaction — see the full Adrafinil list.

See the full Adrafinil interactions page
See every supplement checked against Hydrochlorothiazide, Lisinopril, 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
Adrafinil monograph › Uses, safety, and every drug interaction in one place Hydrochlorothiazide, Lisinopril supplement interactions › Every supplement checked against Hydrochlorothiazide, Lisinopril, ranked by severity Lisinopril and Hydrochlorothiazide drug information › The full plain-English guide to this medication 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 Adrafinil and Hydrochlorothiazide, Lisinopril Together: Common Questions

Can you take Adrafinil with Hydrochlorothiazide, Lisinopril?
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.
How serious is the Adrafinil and Hydrochlorothiazide, Lisinopril 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 Hydrochlorothiazide, Lisinopril 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.