There are multiple interactions reported between these two agents.

Interaction Details

Phenobarbital, Phenytoin is classified as belonging to the following category: Cns Depressants

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.

Interaction Rating

Moderate

Likelihood of Occurrence

Possible

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

Pharmacist Analysis

Melatonin can interact with drugs that cause sedation or CNS depression, such as benzodiazepines, opioids, and alcohol, leading to additive effects (i.e., additive sedation and drowsiness effects).

This interaction can increase drowsiness and impair cognitive and motor functions, which may be unsafe for activities that require alertness and concentration, such as driving or operating heavy machinery.

However, if you are using melatonin solely for sleep at night, the interaction is generally not of significant concern.

Nevertheless, it is advisable to consult with a healthcare provider before taking melatonin with other medications, especially those that affect the central nervous system.

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References

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

Interaction Details

Phenobarbital, Phenytoin is classified as belonging to the following category: Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.
Some clinical evidence suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological disabilities.

Interaction Rating

Moderate

Likelihood of Occurrence

Possible

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

References

  • Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254.
  • Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85..

Interaction Details

Phenobarbital, Phenytoin is classified as belonging to the following category: Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP2C19. Also, other CYP2C19 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 certain drugs metabolized by the CYP2C19 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP2C19 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.

Interaction Rating

Moderate

Likelihood of Occurrence

Probable

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.

References

  • 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.
  • 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.

Interaction Details

Phenobarbital, Phenytoin is classified as belonging to the following category: 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.

Interaction Rating

Moderate

Likelihood of Occurrence

Possible

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

References

  • Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254.
  • Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85..

Melatonin Overview

Melatonin Melatonin is a hormone that is produced naturally in the pineal gland. It is involved in several different bodily processes, such as the regulation of the body's sleep-wake cycle. Melatonin is available as a dietary supplement and is often used to help people with sleep disorders, such as insomnia, fall asleep more easily. There is some evidence to suggest that melatonin supplements may be helpful in reducing the time it takes to fall asleep and improving sleep quality, although the results of studies on this topic have been mixed. Studies show better support for some specific conditions, such as Delayed sleep phase syndrome (DSPS) and Non-24-hour sleep-wake disorder. Melatonin is generally considered to be safe when used in the short term, although it can cause side effects in some people, such as dizziness, headache, and nausea. While melatonin is a natural hormone, it is often synthesized for its use in dietary supplements.
See More Information Regarding Melatonin

Melatonin - More Interactions

Melatonin interacts with 1404 drugs

Interaction Rating Key

These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.

Major The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur.
Moderate Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur.
Minor Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction.
Unknown No interactions have been reported or no interaction data is currently available.

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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

Drug descriptions are provided by MedlinePlus.

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In addition to being a clinical pharmacist specializing in pharmacotherapy, Dr. Brian Staiger is a registered herbalist through the American Herbalist Guild. He has combined his passion for pharmacy practice with the study of medical ethnobotany to improve patient care. Feel free to reach out about any of your herbal or medication questions!

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