Drug & supplement interaction

Melanotan + Methotrexate

Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Melanotan and Methotrexate in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Melanotan and Methotrexate

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Methotrexate and Melanotan in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

Worth understanding: our licensed dataset holds no drug-interaction record for Melanotan at all — not against Methotrexate, and not against any other medication we track. This verdict therefore rests on the absence of any recorded data, not on research that looked at this combination and found nothing. We cannot rule an interaction out.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Melanotan safety at a glance

Melanotan overall Avoid Melanotan is an unapproved, unregulated injectable peptide with real safety risks and no quality control.
Pregnancy Avoid There is no safety data; avoid use during pregnancy.
Breastfeeding Avoid There is no safety data; avoid use while breastfeeding.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Methotrexate and Melanotan? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
What to actually watch for

No Interaction Found — But Data Suggests Melanotan and Methotrexate May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. 2 of them are worth acting on rather than waiting out — marked below.

  • Seizures Worth acting on Additional detail

    Melanotan

    “Subcutaneously, melanotan can cause gastrointestinal cramping, nausea, decreased appetite, facial flushing, fatigue, somnolence, dizziness, yawning, stretching, and spontaneous penile erections. It can also cause increased pigmentation of the face, upper body, and buttocks.”

    Melanotan · Natural Medicines adverse-effect record, reported in anxiety.

    6 sources cited
    1. 5685. Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci 1996;58:1777-84. PubMed
    2. 5687. Wessells H, Fuciarelli K, Hansen J, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction; double-blind, placebo controlled crossover study. J Urol 1998;160:389-93. DOI
    3. 5688. Wessells H, Gralnek DR, Dorr RT, et al. Erectogenic properties of melanotan II in men with organic erectile dysfunction. 1999. Abstract Info-American Urological Association, Inc. DOI
    4. 99190. Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000;56(4):641-6. PubMed
    5. 106742. Mallory CW, Lopategui DM, Cordon BH. Melanotan tanning injection: a rare cause of priapism. Sex Med. 2021 Feb;9(1):100298. PubMed
    6. 99176. Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology. 2014;228(1):34-6. PubMed

    “Melanotan can cause fatigue and somnolence, as well as yawning and stretching.

    There is a case report of posterior reversible encephalopathy syndrome (PRES) occurring in a 20-year-old female who had a single seizure following use of subcutaneous melanotan daily for 1 week. The seizure resulted in reduced sensation on one side and reduced concentration and word-finding ability.”

    Melanotan · Natural Medicines adverse-effect record, reported in epilepsy.

    6 sources cited
    1. 5685. Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci 1996;58:1777-84. PubMed
    2. 5687. Wessells H, Fuciarelli K, Hansen J, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction; double-blind, placebo controlled crossover study. J Urol 1998;160:389-93. DOI
    3. 5688. Wessells H, Gralnek DR, Dorr RT, et al. Erectogenic properties of melanotan II in men with organic erectile dysfunction. 1999. Abstract Info-American Urological Association, Inc. DOI
    4. 99190. Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000;56(4):641-6. PubMed
    5. 99179. Kaski D, Stafford N, Mehta A, Jenkins IH, Malhotra P. Melanotan and the posterior reversible encephalopathy syndrome. Ann Intern Med. 2013;158(9):707-8. PubMed
    6. 99183. Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012;50(10):1169-73. PubMed

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Kidney problems Worth acting on Additional detail

    Melanotan

    Recorded for Melanotan in the same Natural Medicines adverse-effect record shown under Seizures above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Erection problems Additional detail

    Melanotan

    “Subcutaneously, melanotan-II can cause spontaneous penile erections and priapism. In two case reports, males aged 41 and 55 using subcutaneous melanotan-II for tanning developed ischemic priapism lasting 22 hours and 30 hours, respectively. In one case the dose was unknown, and in the other it was 2 mg.”

    Melanotan · Natural Medicines adverse-effect record, reported in erectile dysfunction (ed).

    5 sources cited
    1. 5685. Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci 1996;58:1777-84. PubMed
    2. 5687. Wessells H, Fuciarelli K, Hansen J, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction; double-blind, placebo controlled crossover study. J Urol 1998;160:389-93. DOI
    3. 5688. Wessells H, Gralnek DR, Dorr RT, et al. Erectogenic properties of melanotan II in men with organic erectile dysfunction. 1999. Abstract Info-American Urological Association, Inc. DOI
    4. 106742. Mallory CW, Lopategui DM, Cordon BH. Melanotan tanning injection: a rare cause of priapism. Sex Med. 2021 Feb;9(1):100298. PubMed
    5. 106744. Dreyer BA, Amer T, Fraser M. Melanotan-induced priapism: a hard-earned tan. BMJ Case Rep 2019;12(2):e227644. PubMed

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Sweating / Drowsiness / Tiredness reported in 6.7% of FDA reports for Methotrexate Additional detail

    Melanotan

    Recorded for Melanotan in the same Natural Medicines adverse-effect record shown under Seizures above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Reduced appetite / Nausea reported in 5.9% of FDA reports for Methotrexate Additional detail

    Melanotan

    “Subcutaneously, melanotan can cause gastrointestinal cramping, nausea, and decreased appetite. Severe nausea has occurred after up to 20% of injections, with vomiting rarely.”

    Melanotan · Natural Medicines adverse-effect record, reported in nausea and vomiting.

    5 sources cited
    1. 5685. Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci 1996;58:1777-84. PubMed
    2. 5687. Wessells H, Fuciarelli K, Hansen J, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction; double-blind, placebo controlled crossover study. J Urol 1998;160:389-93. DOI
    3. 5688. Wessells H, Gralnek DR, Dorr RT, et al. Erectogenic properties of melanotan II in men with organic erectile dysfunction. 1999. Abstract Info-American Urological Association, Inc. DOI
    4. 99176. Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology. 2014;228(1):34-6. PubMed
    5. 99190. Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000;56(4):641-6. PubMed

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Dizziness Additional detail

    Melanotan

    Recorded for Melanotan in the same Natural Medicines adverse-effect record shown under Seizures above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Vomiting Additional detail

    Melanotan

    Recorded for Melanotan in the same Natural Medicines adverse-effect record shown under Reduced appetite / Nausea above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

Reported for Melanotan but not commonly for Methotrexate: flushing, severe muscle breakdown, raised blood pressure and a fast or pounding heartbeat.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for Melanotan come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 489,806 voluntary FDA FAERS reports for Methotrexate that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

From our Q&A

Questions About Melanotan or Methotrexate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Melanotan or Methotrexate, 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 Methotrexate

This page covers Melanotan only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methotrexate page lists 82 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Grapefruit (major) and Siberian Cocklebur (major).

By severity: 7 major · 60 moderate · 15 minor.

From our pharmacist’s overview on the Methotrexate page

“The liver is where methotrexate and supplements clash most. Methotrexate (Rheumatrex, Otrexup, Rasuvo), used for rheumatoid arthritis, psoriasis, and certain cancers, can strain the liver on its own, and 38 of the 82 interacting ingredients on this list add liver risk of their own, alcohol included, which makes this a list to approach…”

Reviewed by 2 · Jul 18, 2026

Open the Methotrexate interaction page

How much people look this up

Where Melanotan and Methotrexate 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 Melanotan
Top half

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

29 days ago today
Medication Methotrexate
Top 5%

#49 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.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Melanotan reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Melanotan and Methotrexate records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Melanotan

What is Melanotan?

  • Skin tanning
  • Reducing sun exposure for tanning
  • Erectile dysfunction (Melanotan II)
  • Appetite or body composition (unproven)

Melanotan is a lab-made synthetic peptide (not an herb) marketed online to darken the skin and, in one form, to aid erections. It is not approved or regulated as a supplement, its purity and dosing are unreliable, and it has been linked to serious safety concerns, so we do not recommend using it.

Synthetic peptide (laboratory-made) · Injectable solution, nasal spray (sold illicitly online)

An interaction check asks whether these two react with each other — it does not ask whether Melanotan is a good idea for someone in your situation. Here is what our Melanotan record says about it on its own.

Melanotan: dosing

There is no established, safe, or standardized dose for Melanotan, and no health authority recommends its use as a supplement. The products sold online do not have reliable dosing instructions, and the actual amount of peptide in a vial can vary widely.Because of the safety concerns and lack of regulation, we do not provide dosing guidance for Melanotan.

From our Melanotan monograph — the full record covers uses, side effects and every documented interaction.

Read the full Melanotan monograph & all interactions
Medication

About Methotrexate

What Is Methotrexate Used For?

Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex

Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord).

Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Most-Reported Side Effects for Methotrexate

From FAERS, the FDA’s public side-effect reporting system (489,806 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Rheumatoid arthritis 42,798 reports
Arthralgia 40,830 reports
Fatigue 33,049 reports
Nausea 28,999 reports
Joint swelling 25,026 reports
See full Methotrexate drug information
Keep checking

Other Drugs & Melanotan

Browse every other medication we’ve checked against Melanotan — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
0Moderate
0Minor
2,829No known interaction
2,829 No interaction
No interaction 2,829 drugs checked — show the list

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

Showing the 60 most looked-up of 2,829 medications checked with no known interaction — see the full Melanotan list.

See the full Melanotan interactions page
See every supplement checked against Methotrexate, ranked by severity
Evidence & sources

Melanotan References

The 17 references that drive our Melanotan monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci 1996;58:1777-84. PubMed
  2. Wessells H, Fuciarelli K, Hansen J, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction; double-blind, placebo controlled crossover study. J Urol 1998;160:389-93. DOI
  3. Wessells H, Gralnek DR, Dorr RT, et al. Erectogenic properties of melanotan II in men with organic erectile dysfunction. 1999. Abstract Info-American Urological Association, Inc. DOI
  4. Hjuler KF, Lorentzen HF. Melanoma associated with the use of melanotan-II. Dermatology. 2014;228(1):34-6. PubMed
  5. Schulze F, Erdmann H, Hardkop LH, et al. Eruptive naevi and darkening of pre-existing naevi 24 h after a single mono-dose injection of melanotan II. Eur J Dermatol. 2014;24(1):107-9. PubMed
  6. Reid C, Fitzgerald T, Fabre A, Kirby B. Atypical melanocytic naevi following melanotan injection. Ir Med J. 2013;106(5):148-9.
  7. Kaski D, Stafford N, Mehta A, Jenkins IH, Malhotra P. Melanotan and the posterior reversible encephalopathy syndrome. Ann Intern Med. 2013;158(9):707-8. PubMed
  8. Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012;50(10):1169-73. PubMed
  9. Ong S, Bowling J. Melanotan-associated melanoma in situ. Australas J Dermatol. 2012;53(4):301-2.
  10. Paurobally D, El Hayderi L, Richert B, Andre J, Nikkels AF. Melanotan-associated transverse melanonychia. J Eur Acad Dermatol Venereol. 2013;27(1):128-9. PubMed
  11. Ferrándiz-Pulido C, Fernández-Figueras MT, Quer A, Ferrándiz C. An eruptive pigmented lesion after melanotan injection. Clin Exp Dermatol. 2011;36(7):801-2. PubMed
  12. Paurobally D, Jason F, Dezfoulian B, Nikkels AF. Melanotan-associated melanoma. Br J Dermatol. 2011;164(6):1403-5. PubMed
  13. Cousen P, Colver G, Helbling I. Eruptive melanocytic naevi following melanotan injection. Br J Dermatol. 2009;161(3):707-8. PubMed
  14. Langan EA, Ramlogan D, Jamieson LA, Rhodes LE. Change in moles linked to use of unlicensed "sun tan jab". BMJ. 2009;338:b277. PubMed
  15. Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000;56(4):641-6. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Melanotan and Methotrexate Together: Common Questions

Is it safe to take Melanotan with Methotrexate?
We do not list a known interaction between Melanotan and Methotrexate. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Melanotan and Methotrexate have any of the same side effects?
Yes — our sources link each of them separately to 10 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Does Methotrexate interact with any supplements?
Yes. Methotrexate has documented interactions with 82 supplements in our database — Melanotan is not one of them. The Methotrexate interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Melanotan monograph Uses, safety profile, and every drug interaction in one place Methotrexate drug information The full plain-English guide to this medication Methotrexate supplement interactions Every supplement checked against Methotrexate, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 17 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Methotrexate and Melanotan?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.