Drug & supplement interaction

Melatonin + Diltiazem

Diltiazem brand names: Cardizem, Cardizem SR, Diltiaz SR, Cardizem CD, Tiazac, and others.

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

Diltiazem falls into 2 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
Interactions2
EvidenceA
What do Severity, Likelihood & Evidence mean?
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Interaction report

Melatonin and Diltiazem

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

Why Are There 2 Interactions?

Melatonin interacts with whole categories of medication. Diltiazem falls into 2 of those categories, so it can interact with Melatonin in 2 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 2

Why this applies to Diltiazem

Diltiazem 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

Here's the wrinkle with pairing melatonin and diltiazem: you'd think a sleep hormone that can gently lower blood pressure would help your medicine along, but the clinical research actually points the other way. In people already taking a blood pressure medication, melatonin has been linked to a small bump in blood pressure and heart rate, which could work against what diltiazem is doing to relax your blood vessels and ease chest pain.

The good news is the effect seen in studies was modest, and most of this signal comes from a related calcium-channel blocker, so for diltiazem it's somewhat theoretical. Diltiazem isn't a prodrug, so this isn't about how your body activates it. Still, if you use melatonin regularly, it's worth a quick chat with your pharmacist or doctor and keeping an eye on your home blood pressure readings.

Contact Dr. Brian directly if you have additional questions on this interaction
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
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Diltiazem 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 for melatonin and your diltiazem. Diltiazem is cleared from your body partly by a liver enzyme called CYP3A4. Some lab studies suggest melatonin might slow that same enzyme down a bit. In theory, that could let a little more diltiazem build up than usual, which might nudge its effects up slightly (think more pronounced blood pressure lowering, a slower heart rate, dizziness, or feeling tired).

The important part: this is a minor, theoretical concern based only on test-tube and animal data, not on real patients. For most people it's unlikely to cause trouble. Still, if you notice extra lightheadedness or a slow pulse after starting melatonin, check in with your pharmacist or doctor before making any changes.

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

Moderate 1,115 Minor 345 No known interaction 1,370 (incl. Diltiazem)
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 Diltiazem

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 Diltiazem, 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 Diltiazem

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diltiazem page lists 260 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), Coleus (major) and Grapefruit (major).

By severity: 7 major · 214 moderate · 39 minor.

From our pharmacist’s overview on the Diltiazem page

“Someone on diltiazem (Cardizem, Tiazac) is usually managing blood pressure, angina, or a fast heart rhythm, so this list deserves genuine care. Seven of the 260 ingredients on file carry a major rating, and two of those are things people actually buy: grapefruit, which blocks the enzyme that clears diltiazem and can push its blood leve…”

Reviewed by 2 · Jul 18, 2026

Open the Diltiazem 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 Diltiazem 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 Diltiazem 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%

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

29 days ago today
Medication Diltiazem
Top 10%

#284 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
Medication

About Diltiazem

What Is Diltiazem Used For?

Brand names: Cardizem, Cardizem SR, Diltiaz SR, Cardizem CD, Tiazac, Diltiaz XT, Diltiaz CD, Dilacor, Diltiaz, Cardizem LA, Dilacor XR, Cartia XT, Tiamate, Adizem-SR, Adizem-XL, Angitil SR, Angitil XL, Calcicard CR, Dilcardia SR, Dilzem SR, Dilzem XL, Slozem, Tildiem LA, Tildiem Retard, Viazem XL, Zemtard 120XL, Zemtard 180XL, Zemtard 240XL, Zemtard 300XL

Oral extended-release forms of diltiazem — including Matzim LA, Cardizem LA, Cartia, Cartia XT, Tiadylt ER, and various generic capsules and tablets — are used to treat high blood pressure (hypertension) and chronic stable angina (chest pain brought on by activity). Some capsule formulations, including Cartia, Cartia XT, and certain generics, are also approved for angina due to coronary artery spasm (sudden chest pain caused by a sudden tightening of a coronary artery).

Injectable forms of diltiazem are used in hospital settings to temporarily slow a dangerously fast heart rate in atrial fibrillation or atrial flutter (rapid, irregular heart rhythms), and to restore a normal heart rhythm in paroxysmal supraventricular tachycardia (PSVT) — sudden episodes of a very fast but regular heartbeat originating above the heart's lower chambers.

See full Diltiazem drug information
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
1,115 Moderate 345 Minor 1,369 No 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

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

Showing the 60 most looked-up of 1,369 medications checked with no known interaction — see the full Melatonin list.

See the full Melatonin interactions page
See every supplement checked against Diltiazem, 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
Melatonin monograph › Uses, safety, and every drug interaction in one place Diltiazem supplement interactions › Every supplement checked against Diltiazem, ranked by severity Diltiazem 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 Melatonin and Diltiazem Together: Common Questions

Can you take Melatonin with Diltiazem?
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 Melatonin and Diltiazem?
Diltiazem 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 Diltiazem 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 Diltiazem and Melatonin?

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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.