Prescription medication · Disease-Modifying Antirheumatic Drug (DMARD)
methotrexate
Also sold as Trexall, Otrexup. Methotrexate can treat acute lymphoblastic leukemia, a type of cancer, in adults and children.
Data updated 2026-05-15
- 410,053
- FDA reportsHeavily reported
- 38
- InteractionsSeveral interactions
- 99% less
- Generic vs brandHuge savings
- In shortage
- FDA status
What the data shows
methotrexate (Trexall) is a prescription Disease-Modifying Antirheumatic Drug (DMARD), one of the most-reported medications in the FDA FAERS database (410,053 FDA reports), whose generic costs a fraction of the brand (about 99% less).
Reporting volume reflects how widely a drug is used and studied, not how dangerous it is, a FAERS report documents a temporal association, never proof of cause.
methotrexate (Trexall) is a prescription Disease-Modifying Antirheumatic Drug (DMARD). Methotrexate can treat acute lymphoblastic leukemia, a type of cancer, in adults and children.
Methotrexate is a drug that can treat certain cancers, rheumatoid arthritis, psoriasis, and other conditions. It works by slowing the growth of cells in the body.
Verify with FDA → · CMS NADAC pricing →
Drug Shortage Alert
methotrexate is currently listed as in shortage by the FDA. Affected manufacturer: Fresenius Kabi USA, LLC. Status: Available.
View all drug shortages →Drug Pricing (NADAC)
Brand Price
$470.62/unit
Generic Price
$0.16/unit
Generic Savings
99%
Generic Available
Yes (20 manufacturers)
Pricing data from NADAC (CMS), effective December 18, 2024. Compare all drug costs →
What it does
Methotrexate can treat acute lymphoblastic leukemia, a type of cancer, in adults and children.
Common side effects
Mouth sores, Nausea, Abdominal pain
Key warnings
Methotrexate can cause serious harm to an unborn baby, including death.
The sections below are summarized in plain English from methotrexate's FDA-approved prescribing information. They describe what the official label says, and are not personal medical advice.
How It Works
Methotrexate blocks an enzyme called dihydrofolate reductase. This enzyme is needed for cells to grow and multiply. By blocking this enzyme, methotrexate slows down the growth of cells, especially cancer cells and cells that cause inflammation in arthritis and psoriasis.
How to Take It
Take methotrexate exactly as your doctor tells you. It is important to take the correct dose to avoid serious problems. For leukemia, you may take it once a week. For other conditions, you may take it one to four times per week. Your doctor may adjust your dose based on how you respond to the medicine.
This is a plain-language summary of methotrexate's FDA labeling, not individualized dosing advice. Ask a pharmacist or prescriber before changing how you take this medication.
Pregnancy & Breastfeeding
Methotrexate can cause birth defects or fetal death if taken during pregnancy for non-cancer conditions. If you are pregnant or plan to become pregnant, talk to your doctor. Do not breastfeed while taking methotrexate, as it can pass into breast milk and harm your baby.
This is a plain-language summary of methotrexate's FDA labeling, not individualized advice. Ask a pharmacist or prescriber about pregnancy or breastfeeding on this medication.
Missed Dose
If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and take your next dose at the regular time.
This is a plain-language summary of methotrexate's FDA labeling, not individualized advice. Ask a pharmacist or prescriber what to do about your specific missed dose.
Storage
Store methotrexate tablets at room temperature, away from heat and moisture.
Side Effects (from patient reports)
Based on 410,053 FDA adverse event reports.
Most-reported reactions
Adverse reactions in FAERS for methotrexate, by number of reports
- Rheumatoid arthritis
Rheumatoid arthritis
38,053 reports
- Joint pain
Joint pain
36,283 reports
- Pain
Pain
35,412 reports
- Tiredness
Tiredness
29,061 reports
- Feeling sick to your stomach
Feeling sick to your stomach
24,011 reports
- Swollen joints
Swollen joints
22,295 reports
- Headache
Headache
20,812 reports
- Skin rash
Skin rash
19,774 reports
- The condition is getting worse
The condition is getting worse
19,607 reports
- Diarrhea
Diarrhea
18,207 reports
What this shows Bars show how often each reaction was reported, not how likely it is to happen, a report records a temporal association, never proof that the drug caused it.
Reports over time
Adverse-event reports filed for methotrexate each year to the FDA Adverse Event Reporting System (FAERS).
Year-to-year volume tracks usage, prescribing, and scrutiny, not a change in per-patient risk. Source: FDA FAERS.
Where methotrexate sits
methotrexate has more FDA adverse-event reports than 99% of the drugs FAERS tracks. A high position reflects how widely a drug is used and watched, not how dangerous it is.
Percentile across all drugs PlainMeds tracks by FAERS report volume. The dot is methotrexate; the line is the median (50th percentile).
FDA Adverse Event Report Analysis
Detailed analysis of 410,053 reports from the FDA Adverse Event Reporting System (FAERS). Reports span 1999–2025.
Total Reports
410,053
Reports Mentioning Death
32,502
7.9% of reports — not proof of cause
Hospitalization Reports
115,535
Top Indication
Rheumatoid Arthritis
Gender Distribution
Age Distribution
Most Reported Adverse Reactions (FAERS)
| # | Reaction | Reports |
|---|---|---|
| 2 | RHEUMATOID ARTHRITIS | 38,053 |
| 3 | ARTHRALGIA | 36,283 |
| 4 | PAIN | 35,413 |
| 6 | FATIGUE | 29,061 |
| 7 | NAUSEA | 24,009 |
| 8 | JOINT SWELLING | 22,294 |
| 9 | HEADACHE | 20,815 |
| 10 | RASH | 19,771 |
| 11 | CONDITION AGGRAVATED | 19,607 |
| 13 | DIARRHOEA | 18,210 |
| 14 | PAIN IN EXTREMITY | 17,887 |
| 15 | PYREXIA | 16,928 |
| 16 | PNEUMONIA | 16,118 |
| 17 | MALAISE | 15,153 |
| 18 | VOMITING | 15,002 |
Reactions in Death Reports
Reactions in Hospitalization Reports
Source: FDA FAERS (Adverse Event Reporting System) FDA FAERS (Adverse Event Reporting System) Reports are voluntary and do not establish causation
Serious Warnings
Methotrexate can cause serious harm to an unborn baby, including death. If you are pregnant, you should not take this medicine for non-cancer conditions. If you are taking it for cancer, talk to your doctor about the risks. This medicine can also cause severe allergic reactions and other serious side effects that can be life-threatening. Contact your doctor immediately if you experience any signs of infection, lung problems, or kidney problems.
Known Drug Interactions
Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Celecoxib has no effect on methotrexate pharmacokinetics. Intervention: During concomitant use of celecoxib and methotrexate, monitor patients for methotrexate toxicity.
Mechanism: Celecoxib can make methotrexate more harmful to your blood and kidneys. This happens even though the amount of methotrexate in your blood stays the same.
What to do: Your doctor should monitor you closely for signs of methotrexate toxicity while you are taking both drugs.
Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
Mechanism: Diflunisal can prevent your kidneys from clearing methotrexate out of your system, which can lead to toxic levels of the drug in your blood. This makes the side effects of methotrexate much more dangerous.
What to do: Be very careful when using these drugs together and make sure your doctor monitors your health and blood work closely.
Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of indomethacin capsules and methotrexate, monitor patients for methotrexate toxicity.
Mechanism: Indomethacin can cause methotrexate to build up to dangerous levels in your body, which may harm your kidneys or blood cells.
What to do: Your doctor should monitor you closely for signs of drug toxicity while you are using both medications.
Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of mefenamic acid and methotrexate, monitor patients for methotrexate toxicity.
Mechanism: This pain medicine can prevent your body from clearing out methotrexate, which can lead to toxic levels in your system.
What to do: Your doctor should monitor you for signs of toxicity, such as kidney issues or changes in your blood cell counts.
Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of meloxicam and methotrexate, monitor patients for methotrexate toxicity.
Mechanism: Meloxicam can cause methotrexate to build up in your body to unsafe levels. This can lead to serious issues like low blood cell counts and kidney damage.
What to do: Your doctor should monitor you closely for signs of drug toxicity while you are taking both medications. You may need frequent blood tests to check your kidneys and blood.
This is a plain-language summary of interactions documented in FDA labeling, not individualized advice. Ask a pharmacist or prescriber before combining medications.
Common Questions
Can methotrexate cure my condition?
How long does it take for methotrexate to work?
Can I drink alcohol while taking methotrexate?
What tests will I need while taking methotrexate?
Can methotrexate affect my ability to have children?
What should I do if I get an infection while taking methotrexate?
Can I take other medicines with methotrexate?
What if I have trouble swallowing the tablet?
Is there a risk of cancer with this medicine?
What should I do if I experience side effects?
What are the common side effects of methotrexate?
Does methotrexate interact with other medications?
What drug class is methotrexate?
Is there a generic version of methotrexate?
Is methotrexate safe during pregnancy?
Is methotrexate currently in shortage?
Related Medications in Disease-Modifying Antirheumatic Drug (DMARD)
Other drugs grouped near methotrexate - same-class peers and common alternatives.
abatacept
Orencia
Orencia is a medicine that helps to reduce inflammation.
Compare with methotrexate →
acetaminophen
Tylenol
Acetaminophen (Tylenol) is a medicine that can relieve pain and reduce fever.
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acetaminophen/hydrocodone
Vicodin, Norco
This medicine contains acetaminophen and hydrocodone.
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acetaminophen/oxycodone
Percocet
Percocet is a strong pain medicine.
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adalimumab
Humira
Idacio is a medicine that blocks a protein called TNF.
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Medication Guides
Understanding Drug Interactions
How CYP450 enzymes, inhibitors, and inducers affect your medications
Generic vs Brand Name Drugs
FDA requirements, cost savings, and when the difference matters
Narrow Therapeutic Index Drugs
Why some drugs demand precise dosing and monitoring
Common Drug Interactions
Dangerous medication combinations and how to protect yourself
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What the FDA Data Shows for methotrexate
The FDA label for methotrexate (sold under brand names such as Trexall, Otrexup) classifies it as a prescription-only medication in the Disease-Modifying Antirheumatic Drug (DMARD) class. Methotrexate can treat acute lymphoblastic leukemia, a type of cancer, in adults and children. Official labeling lists 4 commonly reported side effects, including Mouth sores, Nausea, Abdominal pain.
Post-market surveillance from the FDA Adverse Event Reporting System (FAERS) captures real-world experience. For this drug, FAERS contains 410,053 voluntary reports. The database also lists 38 documented drug interactions derived from FDA labeling, with the top-flagged interaction rated moderate severity. NADAC pricing from CMS shows a generic unit cost of $0.16 versus $470.62 for the brand - a 99% generic savings.
Report counts do not establish causation, a FAERS entry documents a temporal association, not proof that the drug produced the outcome. Widely prescribed medications naturally accumulate more reports than niche therapies, so raw totals must be interpreted alongside total exposure. Shortage status, recall history, and patent information further shape supply and switching decisions. This page summarizes public FDA data for educational purposes only and is not a substitute for professional medical advice, always consult a licensed healthcare provider before starting, stopping, or changing any medication.
Data Sources
Drug labeling: FDA Drug Labels (SPL/DailyMed). Adverse events: FDA Adverse Event Reporting System (FAERS). Pricing: CMS National Average Drug Acquisition Cost (NADAC). Shortage status: FDA Drug Shortages Database.
FAERS reports are voluntary and do not establish causation. Drug interactions are derived from FDA labeling and clinical references. Always consult a healthcare professional before making medication decisions.
Last updated: June 4, 2024
Read our methodology - how this data is sourced, computed, and verified.
Data currency: FDA FAERS adverse-event reports through 2025, CMS NADAC acquisition-cost pricing effective December 2024, compiled and last refreshed May 2026. See our methodology for per-source dates and refresh cadence. Spot a figure that looks wrong? Report a correction.
All federal data sources used on this page
- FDA Orange Book - approved drug products with therapeutic equivalence. accessdata.fda.gov/cder/ob
- FDA DailyMed - NIH-hosted drug labeling for FDA-approved meds. dailymed.nlm.nih.gov
- FDA Adverse Event Reporting System (FAERS) - post-marketing safety surveillance. fda.gov/drugs/faers
- NLM RxNorm - standardized clinical drug nomenclature. nlm.nih.gov/research/umls/rxnorm
- CMS Medicare Part B Drug Average Sales Price Files - federal drug pricing data. cms.gov/medicare/part-b-drugs/asp
- FDA Drug Shortages Database - current and resolved drug shortage tracking. accessdata.fda.gov/drugshortages