Melatonin - Ephedrine, Hydroxyzine, Theophylline Interaction
Herbal: Melatonin
Also Known As: N-Acetyl-5-Methoxytryptamine
Drug: Ephedrine, Hydroxyzine, Theophylline
Brand names:
Marax, Ami Rax
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 04, 2025
Interaction Details
Ephedrine, Hydroxyzine, Theophylline 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
Likelihood of Occurrence
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
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
Ephedrine, Hydroxyzine, Theophylline is classified as belonging to the following category: 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.
Interaction Rating
Likelihood of Occurrence
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.
Pharmacist Analysis
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes.
Some studies suggest that melatonin might increase levels of drugs metabolized by CYP1A2. This is because melatonin may inhibit the activity of CYP1A2, leading to reduced metabolism of CYP1A2 substrates and increased serum levels of these drugs.
On the other hand, some drugs metabolized by CYP1A2 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin.
Overall, studies suggest that any inhibition of CYP1A2 by melatonin, when used at typical dosages, is likely to be very minor, and clinically significant drug interactions are thought to be unlikely.
- Dr. Brian Staiger, PharmDReferences
- 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.
- Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31.
Melatonin Overview
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.
Melatonin - More Interactions
Melatonin interacts with 1425 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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Dr. Brian Staiger, PharmD
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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