{
 "query": "methotrexate",
 "ingredient": "methotrexate",
 "slug": "methotrexate",
 "rxcui": "6851",
 "brands": [
  "Trexall",
  "Xatmep",
  "Jylamvo",
  "Otrexup",
  "Rasuvo",
  "Reditrex"
 ],
 "names": [
  "methotrexate",
  "methotrexate sodium"
 ],
 "classes": [
  {
   "id": "L01BA",
   "name": "Folic acid analogues"
  }
 ],
 "alternatives": [
  "pemetrexed",
  "pralatrexate",
  "raltitrexed"
 ],
 "label": {
  "route_mode": "ORAL",
  "route_counts": {
   "ORAL": 32,
   "INTRAMUSCULAR": 13,
   "INTRAVENOUS": 13,
   "INTRATHECAL": 12,
   "SUBCUTANEOUS": 8,
   "INTRA-ARTERIAL": 7
  },
  "boxed_warning": "WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, SEVERE ADVERSE REACTIONS, AND RISK OF MEDICATION ERRORS Methotrexate tablets can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, methotrexate tablets are contraindicated in pregnancy. For neoplastic diseases, advise females and males of reproductive potential to use effective contraception [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.1 , 8.3 )] . Methotrexate tablets are contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis [Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] . Serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys. Withhold or discontinue methotrexate tablets as appropriate [Warnings and Precautions ( 5.3 , 5.4 , 5.5 , 5.6 , 5.7 , 5.8 )] . Methotrexate tablets when inadvertently administered once daily have resulted in death [ Warnings and Precautions ( 5.9 )] . WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REA...",
  "indications_and_usage": "Methotrexate tablets are a dihydrofolate reductase inhibitor indicated for the: Treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen ( 1.1 ) Treatment of adults with mycosis fungoides ( 1.1 ) Treatment of adults with relapsed or refractory non-Hodgkin lymphoma as part of a metronomic combination regimen ( 1.1 ) Treatment of adults with rheumatoid arthritis ( 1.2 ) Treatment of pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA) ( 1.3 ) Treatment of adults with severe psoriasis ( 1.4 ) 1.1 Neoplastic Diseases Methotrexate tablets are indicated for the: treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen treatment of adults with mycosis fungoides (cutaneous T-cell lymphoma) as a single agent or as part of a combination chemotherapy regimen treatment of adults with relapsed or refractory non-Hodgkin lymphomas as part of a metronomic combination chemotherapy regimen 1.2 Rheumatoid Arthritis Methotrexate tablets are indicated for the treatment of adults with rheumatoid arthritis. 1.3 Polyar...",
  "contraindications": "Methotrexate tablets are contraindicated in: Pregnant women receiving methotrexate tablets for treatment of non-neoplastic diseases [see Warnings and Precautions ( 5.1 ), and Use in Specific Populations ( 8.1 , 8.3 )] . Patients with a history of a severe hypersensitivity reactions, including anaphylaxis, to methotrexate [see Warnings and Precautions ( 5.2 )] . In pregnancy for non-neoplastic diseases ( 4 ) History of severe hypersensitivity to methotrexate ( 4 )",
  "warnings_and_cautions": "Serious Infections : Monitor patients for infection during and after treatment with methotrexate tablets. Withhold or discontinue methotrexate tablets for serious infections as appropriate. ( 5.11 ) Neurotoxicity : Monitor patients for neurotoxicity and withhold or discontinue methotrexate tablets as appropriate. ( 5.12 ) Secondary Malignancies : Can occur with methotrexate. ( 5.13 ) Tumor Lysis Syndrome : Institute appropriate prophylactic measures in patients at risk for tumor lysis syndrome prior to initiation of methotrexate tablets. ( 5.14 ) Immunizations and Risk Live Vaccines : Immunizations with live vaccines is not recommended. Follow current vaccination practice guidelines. ( 5.15 ) Infertility : Can cause impairment of fertility, oligospermia, and menstrual dysfunction. ( 5.16 , 8.3 ) 5.1 Embryo-Fetal Toxicity Based on published reports and its mechanism of action, methotrexate tablets can cause fetal harm, including fetal death, when administered to a pregnant woman. Methotrexate tablets are contraindicated for use in pregnant women receiving methotrexate tablets for the treatment of non-malignant diseases. Advise pregnant women with neoplastic diseases of the potential...",
  "warnings": "",
  "adverse_reactions": "The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] Myelosuppression [see Warnings and Precautions ( 5.3 )] Gastrointestinal Toxicity [see Warnings and Precautions ( 5.4 )] Hepatotoxicity [see Warnings and Precautions ( 5.5 )] Pulmonary Toxicity [see Warnings and Precautions ( 5.6 )] Dermatologic Reactions [see Warnings and Precautions ( 5.7 )] Renal Toxicity [see Warnings and Precautions ( 5.8 )] Serious Infections [see Warnings and Precautions ( 5.11 )] Neurotoxicity [see Warnings and Precautions ( 5.12 )] Secondary Malignancies [see Warnings and Precautions ( 5.13 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.14 )] Increased Risk of Adverse Reactions Due to Third-Space Accumulation [see Warnings and Precautions ( 5.17 )] Common adverse reactions include ulcerative stomatitis, leukopenia, nausea, abdominal distress. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials and other studies are conducted under widely varying conditions, adv...",
  "drug_abuse_and_dependence": "",
  "controlled_substance": "",
  "recent_major_changes": "Boxed Warning 05/2026",
  "information_for_patients": "Advise the patient to read the FDA-approved patient labeling (Patient Information). Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective contraception during treatment with methotrexate tablets and for 6 months after the final dose [see Use in Specific Populations ( 8.3 )] . Advise males of reproductive potential to use effective contraception during treatment with methotrexate tablets and for 3 months after the final dose [see Use in Specific Populations ( 8.3 )] . Hypersensitivity Reactions Advise patients and their caregivers of the potential risk of hypersensitivity and that methotrexate tablets is contraindicated in patients with a history of hypersensitivity reactions to methotrexate. Instruct patients to seek immediate medical attention for signs of a hypersensitivity reaction [see Warnings and Precautions ( 5.2 )] . Myelosuppression and Serious Infections Inform patients and their caregivers that meth...",
  "spl_medguide": "",
  "clinical_studies": "",
  "brand_name": "Methotrexate",
  "manufacturer": "A-S Medication Solutions",
  "application_number": "ANDA081099",
  "pharm_class_epc": [],
  "route": [
   "ORAL"
  ],
  "effective_time": "20260827",
  "set_id": "22e10810-16fb-4c84-bccf-972405b77ef8",
  "has_boxed_warning": true,
  "controlled": false,
  "mentions_rems": false
 },
 "faers": {
  "total": 411354,
  "serious": 317640,
  "death": 30378,
  "hospitalization": 112615,
  "primary_suspect": 410349,
  "top_reactions": [
   [
    "Drug Ineffective",
    91094
   ],
   [
    "Rheumatoid Arthritis",
    40163
   ],
   [
    "Off Label Use",
    40087
   ],
   [
    "Pain",
    37254
   ],
   [
    "Arthralgia",
    36740
   ],
   [
    "Fatigue",
    30455
   ],
   [
    "Nausea",
    26463
   ],
   [
    "Drug Intolerance",
    25413
   ],
   [
    "Joint Swelling",
    23805
   ],
   [
    "Condition Aggravated",
    23150
   ],
   [
    "Rash",
    21030
   ],
   [
    "Headache",
    20397
   ],
   [
    "Drug Hypersensitivity",
    19724
   ],
   [
    "Diarrhoea",
    19047
   ],
   [
    "Pain In Extremity",
    17661
   ]
  ],
  "by_year": {
   "2019": 46776,
   "2020": 50109,
   "2021": 33164,
   "2022": 35529,
   "2023": 32913,
   "2024": 28316,
   "2025": 24019,
   "2026": 9095
  },
  "by_year_primary": {
   "2019": 46751,
   "2020": 50081,
   "2021": 33106,
   "2022": 35355,
   "2023": 32696,
   "2024": 28097,
   "2025": 23874,
   "2026": 8989
  }
 },
 "faers_base": {
  "total": 20692304,
  "serious_share": 0.5742697381596559,
  "death_share": 0.09102355155810585
 },
 "recalls": [
  {
   "class": "Class III",
   "date": "20230922",
   "reason": "Failed Tablet/Capsule Specifications: Tablets were observed to have an unsmooth surface with two tablets demonstrating illegible tablet identification and scoring.",
   "firm": "West-Ward Columbus Inc",
   "status": "Ongoing"
  },
  {
   "class": "Class II",
   "date": "20210315",
   "reason": "CGMP Deviations: Intermittent exposure to temperature excursion during storage.",
   "firm": "Cardinal Health Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20120627",
   "reason": "The affected lots of Carboplatin Injection, Cytarabine  Injection, Methotrexate Injection, USP, and Paclitaxel Injection are being recalled due to visible particles embedded in the glass located at the neck of the vial. There may be the pot",
   "firm": "Hospira Inc.",
   "status": "Terminated"
  }
 ],
 "recall_total": 3,
 "drugsfda": {
  "applications": 66,
  "nda": 8,
  "anda": 42,
  "first_approval": "19531207",
  "rems": false,
  "rems_last": "",
  "labeling_supplements": 55,
  "labeling_recent": 12,
  "sponsors": [
   "ABIC",
   "ABRAXIS PHARM",
   "ACCORD HLTHCARE",
   "ALEMBIC",
   "AMNEAL PHARMS",
   "AZURITY",
   "BARR",
   "BRISTOL"
  ],
  "unapproved": false,
  "first_approval_fmt": "12/07/1953"
 },
 "trials": {
  "total": 2362,
  "completed": 1334,
  "terminated": 286,
  "with_results": 679,
  "industry": 882,
  "phase3": 574,
  "results_share": 0.5089955022488756,
  "terminated_share": 0.12108382726502964
 },
 "pubmed": {
  "rct": 1562,
  "meta": 333,
  "recent_rct": 213,
  "cochrane": [
   {
    "pmid": "42439855",
    "title": "Methotrexate for hand osteoarthritis",
    "year": "2026"
   },
   {
    "pmid": "38334147",
    "title": "Methotrexate for juvenile idiopathic arthritis",
    "year": "2024"
   },
   {
    "pmid": "30656673",
    "title": "Methotrexate for psoriatic arthritis",
    "year": "2019"
   },
   {
    "pmid": "28481462",
    "title": "Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis",
    "year": "2017"
   },
   {
    "pmid": "27571502",
    "title": "Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: A network meta-analysis",
    "year": "2016"
   },
   {
    "pmid": "27175934",
    "title": "Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis",
    "year": "2016"
   },
   {
    "pmid": "26263042",
    "title": "Methotrexate for maintenance of remission in ulcerative colitis",
    "year": "2015"
   },
   {
    "pmid": "25162749",
    "title": "Methotrexate for induction of remission in ulcerative colitis",
    "year": "2014"
   },
   {
    "pmid": "25157445",
    "title": "Methotrexate for maintenance of remission in Crohn's disease",
    "year": "2014"
   },
   {
    "pmid": "25099640",
    "title": "Methotrexate for induction of remission in refractory Crohn's disease",
    "year": "2014"
   },
   {
    "pmid": "25061777",
    "title": "Mycophenolate mofetil versus methotrexate for prevention of graft-versus-host disease in people receiving allogeneic hematopoietic stem cell transplantation",
    "year": "2014"
   },
   {
    "pmid": "24916606",
    "title": "Methotrexate for treating rheumatoid arthritis",
    "year": "2014"
   }
  ]
 },
 "payments": {
  "year": "2024",
  "usd": 1373.06,
  "records": 61,
  "by_name": [
   [
    "Jylamvo",
    741.1
   ],
   [
    "Xatmep",
    631.96
   ]
  ],
  "names_checked": [
   "methotrexate",
   "Trexall",
   "Xatmep",
   "Jylamvo",
   "Otrexup",
   "Rasuvo",
   "Reditrex"
  ],
  "source": "bulk-index"
 },
 "partd": {
  "year": "2024",
  "claims": 2421601,
  "beneficiaries": 553599,
  "spend": 59780461.150000006,
  "by_brand": [
   {
    "brand": "Methotrexate",
    "claims": 2414242,
    "per_claim": 23.698212975,
    "is_generic": false
   },
   {
    "brand": "Trexall",
    "claims": 7121,
    "per_claim": 325.90566213,
    "is_generic": false
   },
   {
    "brand": "Xatmep",
    "claims": 238,
    "per_claim": 1035.5707563,
    "is_generic": false
   }
  ],
  "per_claim": 24.686338149843845
 },
 "mdl": [],
 "dsc": [],
 "settlements": [],
 "prescrire": null,
 "eml": {
  "listed": true,
  "status": "AddedToEml",
  "name": "methotrexate",
  "matched": "methotrexate",
  "stewardship": []
 },
 "exposure": {
  "years": [
   "2024",
   "2025",
   "2026"
  ],
  "reports_recent": 60960,
  "fills": 2421601,
  "per_million": 25173.42865319266,
  "ratio": 9.09132735931106,
  "median": 2768.949753790441
 },
 "scores": {
  "safety": {
   "score": 50,
   "letter": "D",
   "why": [
    "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)",
    "25,173 FDA reports naming it as the suspect drug per million Medicare fills, 9.1x the median drug on this site (-15)",
    "Death share in reports is near or below the FAERS average (0.8x)",
    "Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)"
   ],
   "weight": 0.35
  },
  "evidence": {
   "score": 94,
   "letter": "A",
   "why": [
    "1562 randomized trials and 333 systematic reviews/meta-analyses indexed in PubMed",
    "On the WHO Model List of Essential Medicines (shown for context; no score effect)",
    "12 independent Cochrane review(s) exist",
    "'Drug ineffective' is the single most-reported item about this drug in FAERS (-5)"
   ],
   "weight": 0.25
  },
  "regulatory": {
   "score": 85,
   "letter": "B",
   "why": [
    "Recalls since 2016: 0 Class I, 1 Class II, 1 Class III across 42 generic makers (-2)",
    "12 label changes approved since 2021: the safety story is still moving (-8)",
    "Label lists recent major changes to warnings or indications (-5)"
   ],
   "weight": 0.15
  },
  "conflict": {
   "score": 100,
   "letter": "A",
   "why": [
    "Pharma paid doctors $1,373 tied to this drug last year: negligible",
    "Not named in any pending federal MDL"
   ],
   "weight": 0.15
  },
  "options": {
   "score": 100,
   "letter": "A",
   "why": [
    "Generic versions approved (42 applications)",
    "3 same-class alternatives exist"
   ],
   "weight": 0.1
  }
 },
 "total": 79,
 "grade": "B",
 "questions": [
  "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?",
  "The most-reported problems in FDA's adverse event data are rheumatoid arthritis, pain. How would we recognize and handle those?",
  "Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?",
  "Why this one over pemetrexed, pralatrexate, raltitrexed? What would make you pick one of those instead?",
  "What result are we expecting, by when, and what is the plan if it does not happen?",
  "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)"
 ]
}