Drug & supplement interaction

Melatonin + Trandolapril, Verapamil

Trandolapril, Verapamil brand name: Tarka.

Moderate Interaction
The bottom line Moderate

Trandolapril, Verapamil falls into 3 drug categories that Melatonin can interact with; the most serious is rated moderate. Theoretically, taking melatonin with antihypertensive drugs might increase the risk of hypotension or hypertension.

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

Melatonin and Trandolapril, Verapamil

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

Why Are There 3 Interactions?

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

Moderate

ANTIHYPERTENSIVE DRUGS

1 of 3

Why this applies to Trandolapril, Verapamil

Trandolapril, Verapamil falls under ANTIHYPERTENSIVE DRUGS — the group Melatonin interacts with.

Theoretically, taking melatonin with antihypertensive drugs might increase the risk of hypotension or hypertension.
Some clinical research suggests that taking melatonin decreases blood pressure in healthy adults. Also, melatonin seems to lower systolic and diastolic blood pressure in individuals with high blood pressure at nighttime or untreated essential hypertension. However, melatonin seems to worsen blood pressure in patients who are taking antihypertensive medications. Immediate-release melatonin 5 mg at night in combination with nifedipine GITS (Procardia XL) increases systolic blood pressure an average of 6.5 mmHg, diastolic blood pressure by an average of 4.9 mmHg, and heart rate by 3.9 bpm. Also, results from animal research suggest that melatonin reduces the effectiveness of certain antihypertensive drugs, including methoxamine and clonidine.
Severity Moderate Likelihood Possible Evidence A

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

Tarka combines two blood pressure medicines: trandolapril (an ACE inhibitor) and verapamil (a calcium channel blocker). Together they help relax your blood vessels and steady your heart rate. Here's the wrinkle with melatonin: even though melatonin can lower blood pressure on its own, some research has shown the opposite when people are already on blood pressure medication. In one study, melatonin actually nudged blood pressure and heart rate back up in treated patients, which could make your Tarka work a little less well than expected.

This is a moderate, possible interaction, so it's not a reason to panic. If you take melatonin for sleep and notice your readings creeping up, or you feel off, mention it to your pharmacist or doctor before changing anything.

References
  1. Arangino S, Cagnacci A, Angiolucci M, et al. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol 1999;83:1417-9. PubMed
  2. Lusardi P, et al. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol 2000;49:423-7. PubMed
  3. Cagnacci, A., Arangino, S., Angiolucci, M., Melis, G. B., Facchinetti, F., Malmusi, S., and Volpe, A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clin Endocrinol (Oxf PubMed
  4. Kitajima, T., Kanbayashi, T., Saitoh, Y., Ogawa, Y., Sugiyama, T., Kaneko, Y., Sasaki, Y., Aizawa, R., and Shimisu, T. The effects of oral melatonin on the autonomic function in healthy subjects. Psychiatry Clin Neurosci. 2001;55(3):299-300. PubMed
  5. Scheer, F. A., Van Montfrans, G. A., van Someren, E. J., Mairuhu, G., and Buijs, R. M. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004;43(2):192-197. PubMed
  6. Cagnacci, A., Cannoletta, M., Renzi, A., Baldassari, F., Arangino, S., and Volpe, A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005;18(12 Pt 1):1614-1618. PubMed
  7. Weekley, L. B. Melatonin-induced relaxation of rat aorta: interaction with adrenergic agonists. J Pineal Res 1991;11(1):28-34. PubMed
  8. Grossman, E., Laudon, M., Yalcin, R., Zengil, H., Peleg, E., Sharabi, Y., Kamari, Y., Shen-Orr, Z., and Zisapel, N. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med 2006;119(10):898-902. PubMed
  9. Grossman, E., Laudon, M., and Zisapel, N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials. Vasc.Health Risk Manag. 2011;7:577-584. PubMed
  10. Cagnacci, A., Arangino, S., Angiolucci, M., Maschio, E., and Melis, G. B. Influences of melatonin administration on the circulation of women. Am J Physiol 1998;274(2 Pt 2):R335-R338. PubMed
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Trandolapril, Verapamil also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2. Also, other CYP1A2 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with drugs metabolized by the CYP1A2 enzyme might reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP1A2 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.
Severity Moderate Likelihood Probable Evidence D

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 gist with Tarka (which combines trandolapril, an ACE inhibitor, and verapamil, a calcium channel blocker). On paper, melatonin might slow down how your liver clears certain medications that go through an enzyme called CYP1A2. If your blood pressure medication clears a little slower, levels could nudge up, which in theory could mean more of its usual effects like lightheadedness, dizziness, very low blood pressure, slow heart rate, or some ankle swelling from verapamil.

I want to be honest though: this is a theoretical concern based on how these drugs are processed, not something we see causing real problems in patients. For most people, short-term melatonin is fine here. Still, mention it to your pharmacist or doctor, and watch for unusual dizziness, especially when standing up.

References
  1. Yeleswaram, K., Vachharajani, N., and Santone, K. Involvement of cytochrome P-450 isozymes in melatonin metabolism and clinical implications. J Pineal Res 1999;26(3):190-191. PubMed
  2. Faber, M. S., Jetter, A., and Fuhr, U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97(3):125-134. PubMed
  3. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Trandolapril, Verapamil also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, melatonin might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that certain lots of melatonin inhibit CYP3A4. Theoretically, combined administration of melatonin with certain drugs metabolized by CYP3A4 may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these 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 gist with Tarka (which combines trandolapril and verapamil). The verapamil portion is cleared in part by a liver enzyme called CYP3A4. Some lab studies suggest certain batches of melatonin can slow that enzyme down a bit. In theory, that could let verapamil build up slightly, which might nudge you toward effects like lower blood pressure, a slower heart rate, dizziness, or feeling lightheaded when you stand up.

I want to be straight with you though: this is rated as a minor interaction, and the evidence is only test-tube and animal data, not real patients. So for most people taking short-term melatonin for sleep, this is unlikely to cause a real problem. Still, since blood pressure and heart-rate meds matter, it's worth a quick mention to your pharmacist or doctor, especially if you notice new dizziness.

References
  1. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31. 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

Melatonin Also Interacts With Other Medications

Melatonin has 1,115 moderate, 345 minor known drug interactions in our database — the Trandolapril, Verapamil 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 Melatonin

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

From our Q&A

Questions About Melatonin or Trandolapril, Verapamil

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Melatonin or Trandolapril, Verapamil, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Trandolapril, Verapamil

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Trandolapril, Verapamil page lists 304 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 Beer (major).

By severity: 11 major · 250 moderate · 43 minor.

From our pharmacist’s overview on the Trandolapril, Verapamil page

“This is one of the supplement lists I would want a patient to read closely, not skim. Tarka combines trandolapril and verapamil to lower blood pressure, and most of these interactions pull on that same lever, either dropping pressure further than intended or working against the medicine altogether.”

Reviewed by 2 · Jul 18, 2026

Open the Trandolapril, Verapamil interaction page

One more smart check

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

We hold 2,885 real supplement products containing Melatonin, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Melatonin. Your product may carry other ingredients that interact with Trandolapril, Verapamil too, on top of Melatonin — 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 Melatonin and Trandolapril, Verapamil 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 Melatonin
Top 5%

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

29 days ago today
Medication Trandolapril, Verapamil
Top 25%

#531 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 Melatonin

What is Melatonin?

Melatonin
  • Trouble falling asleep (insomnia)
  • Jet lag
  • Delayed sleep phase syndrome
  • Non-24-hour sleep-wake disorder
  • Shift-work sleep problems
  • Sleep problems in some children with conditions like autism or ADHD

Melatonin is a hormone your body makes naturally to help control your sleep-wake cycle, and the supplement form is widely used to help with sleep timing problems and jet lag. The evidence is strongest for certain circadian (body-clock) disorders and is more mixed for everyday insomnia. It is generally well tolerated for short-term use, but talk with your pharmacist or doctor before starting, especially for children or during pregnancy.

Read the full Melatonin monograph & all interactions
Keep checking

Other Drugs & Melatonin

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

0Major
1,115Moderate
345Minor
1,369No known interaction
Moderate

1,115 interactions

Showing 60 of 1,115 moderate interactions — see all 1,115 on the Melatonin page.

Minor

345 interactions

Showing 60 of 345 minor interactions — see all 345 on the Melatonin page.

No interaction 1,369 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

Keep exploring
Pharmacist Counseling Corner

Taking Melatonin and Trandolapril, Verapamil Together: Common Questions

Can you take Melatonin with Trandolapril, Verapamil?
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 Melatonin and Trandolapril, Verapamil?
Trandolapril, Verapamil belongs to more than one drug category, and Melatonin 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 Melatonin and Trandolapril, Verapamil 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.