Melatonin - Methotrexate Interaction
Herbal: Melatonin
Also Known As: N-Acetyl-5-Methoxytryptamine
Drug: Methotrexate
Brand names:
Rheumatrex, Otrexup, Rasuvo, Reditrex
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 25, 2025
Interaction Details
Methotrexate 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..
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.
Methotrexate Overview
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Methotrexate is used to treat severe psoriasis (a skin disease in which red, scaly patches form on some areas of the body) that cannot be controlled by other treatments. Methotrexate is also used along with rest, physical therapy, and sometimes other medications to treat severe active rheumatoid arthritis (RA; a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) that cannot be controlled by certain other medications. Methotrexate is also used to treat certain types of cancer including cancers that begin in the tissues that form around a fertilized egg in the uterus, breast cancer, lung cancer, certain cancers of the head and neck, certain types of lymphoma, and leukemia (cancer that begins in the white blood cells). Methotrexate is in a class of medications called antimetabolites. Methotrexate treats cancer by slowing the growth of cancer cells. Methotrexate treats psoriasis by slowing the growth of skin cells to stop scales from forming. Methotrexate may treat rheumatoid arthritis by decreasing the activity of the immune system.
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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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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