Drug & supplement interaction

Melatonin + Gabapentin enacarbil

Gabapentin enacarbil brand name: Horizant.

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

Gabapentin enacarbil falls into 2 drug categories that Melatonin can interact with; the most serious is rated moderate. Theoretically, taking melatonin might increase the sedative effects of CNS depressants.

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

Melatonin and Gabapentin enacarbil

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. Gabapentin enacarbil 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

CNS DEPRESSANTS

1 of 2

Why this applies to Gabapentin enacarbil

Gabapentin enacarbil falls under CNS DEPRESSANTS — the group Melatonin interacts with.

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.
Melatonin has sedative effects. Theoretically, concomitant use of melatonin with alcohol, benzodiazepines, or other sedative drugs might cause additive sedation.
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: both melatonin and Horizant (gabapentin enacarbil) can make you feel drowsy and relaxed. Melatonin tells your brain it's nighttime, and Horizant calms down nerve signaling. Put them together and those calming effects can stack up. You might feel sleepier than usual, a bit dizzy, foggy, or unsteady on your feet, which raises the risk of stumbles, especially if you get up during the night.

This is more of a theoretical concern based on how each one works, not something proven in studies, so it's a moderate caution rather than a red alert. Many people use both without trouble, often by taking them at bedtime when sleepiness is the goal. Still, it's worth a quick chat with your pharmacist or doctor before pairing them, particularly if you're older or already feel groggy.

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
Moderate

ANTICONVULSANTS

2 of 2

Gabapentin enacarbil also falls under ANTICONVULSANTS.

Theoretically, melatonin may reduce the effects of anticonvulsants. Some clinical research suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological impairment.
Severity Moderate Likelihood Possible Evidence B

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 for Horizant (gabapentin enacarbil): the concern isn't about how your body breaks down the drug. Gabapentin enacarbil doesn't rely on those liver enzymes the way many medicines do, so melatonin isn't speeding it up or slowing it down. The flag here is different. Some clinical research has suggested melatonin might lower the seizure threshold in certain people, especially children with neurological problems, which could in theory make a seizure medicine less reliable.

For most adults using Horizant, especially for restless legs or nerve pain after shingles, this is more of a theoretical caution than a strong warning. If you take it to control seizures, that's where I'd be more careful. Either way, just give your pharmacist or doctor a heads-up before pairing them so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254. PubMed
  2. Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85.. 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 Gabapentin enacarbil 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. Gabapentin enacarbil)
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 Gabapentin enacarbil

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 Gabapentin enacarbil, 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 Gabapentin enacarbil

This page covers Melatonin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Gabapentin enacarbil page lists 105 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 7 major · 82 moderate · 16 minor.

From our pharmacist’s overview on the Gabapentin enacarbil page

“Alcohol tops the list of supplement and food risks for gabapentin enacarbil (Horizant), a nerve pain and restless legs medicine that already slows the central nervous system. Beer and wine both carry major ratings because their sedation stacks on the drug's own, and 78 of the 105 ingredients on file act the same way, deepening drowsine…”

Reviewed by 2 · Jul 18, 2026

Open the Gabapentin enacarbil 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 Gabapentin enacarbil 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 Gabapentin enacarbil 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 Gabapentin enacarbil
Steady interest

#1,756 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 Gabapentin

What Is Gabapentin Used For?

Brand name: Horizant

Gabapentin (brands include Neurontin, Relgaabi, Gabarone, Gralise, and Horizant) is primarily used to manage postherpetic neuralgia (PHN) — the nerve pain that lingers after a shingles outbreak — in adults. Neurontin, Relgaabi, Gabarone, and gabapentin capsules, tablets, and oral solution are also used as add-on therapy for partial onset seizures (a type of epilepsy) in adults and children aged 3 and older.

Horizant (gabapentin enacarbil extended-release tablet) has two specific approvals: treatment of moderate-to-severe primary restless legs syndrome (RLS) in adults, and management of postherpetic neuralgia in adults. Horizant is not recommended for people who need to sleep during the day and stay awake at night. Gralise is approved only for postherpetic neuralgia and cannot be substituted for other gabapentin products due to its different release profile.

See full Gabapentin 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 Gabapentin enacarbil, 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 Gabapentin enacarbil supplement interactions › Every supplement checked against Gabapentin enacarbil, ranked by severity Gabapentin 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 Gabapentin enacarbil Together: Common Questions

Can you take Melatonin with Gabapentin enacarbil?
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 Gabapentin enacarbil?
Gabapentin enacarbil 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 Gabapentin enacarbil 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.