{
 "query": "leflunomide",
 "ingredient": "leflunomide",
 "slug": "leflunomide",
 "rxcui": "27169",
 "brands": [
  "Arava"
 ],
 "names": [
  "leflunomide"
 ],
 "classes": [
  {
   "id": "L04AK",
   "name": "Dihydroorotate dehydrogenase (DHODH) inhibitors"
  }
 ],
 "alternatives": [
  "teriflunomide"
 ],
 "label": {
  "route_mode": "ORAL",
  "route_counts": {
   "ORAL": 24
  },
  "boxed_warning": "WARNING: EMBRYO-FETAL TOXICITY and HEPATOTOXICITY WARNING: EMBRYO-FETAL TOXICITY and HEPATOTOXICITY See full prescribing information for complete boxed warning. Embryo-Fetal Toxicity Teratogenicity and embryo-lethality occurred in animals administered leflunomide. ( 5.1 , 8.1 ) Exclude pregnancy prior to initiating ARAVA therapy. ( 5.1 , 8.3 ) Advise use of effective contraception in females of reproductive potential during treatment and during a drug elimination procedure. ( 5.1 , 5.3 , 8.3 ) Stop ARAVA and use an accelerated drug elimination procedure if the patient becomes pregnant. ( 5.1 , 5.3 , 8.1 ) Hepatotoxicity Severe liver injury and fatal liver failure have been reported. ( 5.2 ) Avoid ARAVA use in patients with pre-existing liver disease, or those with serum alanine aminotransferase (ALT) >2 \u00d7 ULN. ( 5.2 , 8.6 ) Use caution when ARAVA is given with other potentially hepatotoxic drugs. ( 5.2 ) Monitor ALT levels. Interrupt ARAVA treatment if ALT elevation >3-fold ULN. If likely leflunomide-induced, start accelerated drug elimination procedure and monitor liver tests weekly until normalized. ( 5.2 , 5.3 ) Embryo-Fetal Toxicity ARAVA is contraindicated for use in pregnant ...",
  "indications_and_usage": "is indicated for the treatment of adults with active rheumatoid arthritis (RA). ARAVA is a pyrimidine synthesis inhibitor indicated for the treatment of adults with active rheumatoid arthritis. ( 1 )",
  "contraindications": "is contraindicated in: Pregnant women. ARAVA may cause fetal harm. If a woman becomes pregnant while taking this drug, stop ARAVA, apprise the patient of the potential hazard to the fetus, and begin a drug elimination procedure [see Warnings and Precautions (5.1 , 5.3) and Use in Specific Populations (8.1) ] . Patients with severe hepatic impairment [see Warnings and Precautions (5.2) ] . Patients with known hypersensitivity to leflunomide or any of the other components of ARAVA. Known reactions include anaphylaxis [see Adverse Reactions (6.1) ] . Patients being treated with teriflunomide [see Drug Interactions (7) ] . Pregnancy. ( 4 , 5.1 , 8.1 ) Severe hepatic impairment. ( 4 , 5.2 ) Hypersensitivity to ARAVA or any of its inactive components. ( 4 ) Current teriflunomide treatment. ( 4 )",
  "warnings_and_cautions": "After stopping ARAVA, it is recommended that an accelerated drug elimination procedure be used to reduce the plasma concentrations of the active metabolite, teriflunomide. ( 5.3 ) Severe infections (including sepsis), pancytopenia, agranulocytosis, and thrombocytopenia: Stop ARAVA and use accelerated elimination procedure. Do not start ARAVA in patients with active infection. Monitor CBCs during treatment with ARAVA. ( 5.4 ) Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS): Stop ARAVA and use accelerated elimination procedure. ( 5.5 ) Skin ulcers: If skin ulcer is suspected, discontinue leflunomide treatment and consider an accelerated drug elimination procedure. ( 5.6 ) Peripheral neuropathy: If patient develops symptoms consistent with peripheral neuropathy, evaluate patient and consider discontinuing ARAVA. ( 5.8 ) Interstitial lung disease: May be fatal. New onset or worsening symptoms may necessitate discontinuation of ARAVA and initiation of accelerated elimination procedure. ( 5.9 ) Increased blood pressure: Monitor and treat. ( 5.11 ) 5.1 Embryo-Fetal Toxicity ARAVA may cause fetal harm when administered ...",
  "warnings": "",
  "adverse_reactions": "The following serious adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.2) ] Immunosuppression [see Warnings and Precautions (5.4) ] Bone marrow suppression [see Warnings and Precautions (5.4) ] Serious infections [see Warnings and Precautions (5.4) ] Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reactions with eosinophilia and systemic symptoms [see Warnings and Precautions (5.5) ] Skin ulcers [see Warnings and Precautions (5.6) ] Peripheral neuropathy [see Warnings and Precautions (5.8) ] Interstitial lung disease [see Warnings and Precautions (5.9) ] The most commonly reported adverse reactions (\u226510%) regardless of relation to ARAVA treatment were diarrhea, respiratory infection, nausea, headache, rash, abnormal liver enzymes, and dyspepsia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical st...",
  "drug_abuse_and_dependence": "",
  "controlled_substance": "",
  "recent_major_changes": "Warnings and Precautions, Skin Ulcers ( 5.6 ) 6/2024",
  "information_for_patients": "Embryo-Fetal Toxicity Advise females of reproductive potential: Of the potential for fetal harm if ARAVA is taken during pregnancy. To notify their healthcare provider immediately if a pregnancy occurs or is suspected. To use effective contraception during treatment with ARAVA and until the active metabolite (teriflunomide) plasma concentration is verified to be less than 0.02 mg/L [see Warnings and Precautions (5.1 , 5.3) , Use in Specific Populations (8.1 , 8.3) , and Clinical Pharmacology (12.3) ] . Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARAVA during pregnancy [see Use in Specific Populations (8.1) ] . Lactation Advise nursing women to discontinue breastfeeding during treatment with ARAVA [see Use in Specific Populations (8.2) ] . Serious Skin Reactions Advise patients of the possibility of rare, serious skin reactions. Instruct patients to promptly seek medical attention if they develop a skin rash, mucous membrane lesions, or skin ulcers. Investigations Advise patients of the potential hepatotoxic effects of ARAVA and of the need for monitoring liver enzymes. Instruct patients to report if they de...",
  "spl_medguide": "",
  "clinical_studies": "The efficacy of ARAVA in the treatment of rheumatoid arthritis (RA) was demonstrated in three controlled trials showing reduction in signs and symptoms, and inhibition of structural damage. In two placebo-controlled trials, efficacy was demonstrated for improvement in physical function. In these trials, efficacy was evaluated by: Reduction of signs and symptoms Relief of signs and symptoms was assessed using the American College of Rheumatology (ACR) 20 Responder Index, a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An \"ACR20 Responder\" is a patient who had \u226520% improvement in both tender and swollen joint counts and in 3 of the following 5 criteria: physician global assessment, patient global assessment, functional ability measure (Modified Health Assessment Questionnaire [MHAQ]), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein. An \"ACR20 Responder at Endpoint\" is a patient who completed the study and was an ACR20 Responder at the completion of the study. Inhibition of structural damage Inhibition of structural damage compared to control was assessed using the Sharp score, a composite score of x-ray erosions...",
  "brand_name": "Arava",
  "manufacturer": "sanofi-aventis U.S. LLC",
  "application_number": "NDA020905",
  "pharm_class_epc": [
   "Antirheumatic Agent [EPC]"
  ],
  "route": [
   "ORAL"
  ],
  "effective_time": "20250604",
  "set_id": "320f63f2-fac3-4aee-aff8-85724e00ef52",
  "has_boxed_warning": true,
  "controlled": false,
  "mentions_rems": false
 },
 "faers": {
  "total": 90432,
  "serious": 77529,
  "death": 8093,
  "hospitalization": 23739,
  "primary_suspect": 90340,
  "top_reactions": [
   [
    "Drug Ineffective",
    38270
   ],
   [
    "Rheumatoid Arthritis",
    25388
   ],
   [
    "Pain",
    20113
   ],
   [
    "Arthralgia",
    16673
   ],
   [
    "Drug Intolerance",
    16350
   ],
   [
    "Joint Swelling",
    15929
   ],
   [
    "Fatigue",
    15326
   ],
   [
    "Rash",
    13431
   ],
   [
    "Off Label Use",
    12333
   ],
   [
    "Contraindicated Product Administered",
    12135
   ],
   [
    "Abdominal Discomfort",
    12054
   ],
   [
    "Alopecia",
    11914
   ],
   [
    "Arthropathy",
    11105
   ],
   [
    "Condition Aggravated",
    10609
   ],
   [
    "Swelling",
    10539
   ]
  ],
  "by_year": {
   "2019": 11245,
   "2020": 15515,
   "2021": 9538,
   "2022": 8135,
   "2023": 5361,
   "2024": 6335,
   "2025": 5336,
   "2026": 1845
  },
  "by_year_primary": {
   "2019": 11244,
   "2020": 15509,
   "2021": 9528,
   "2022": 8112,
   "2023": 5352,
   "2024": 6314,
   "2025": 5327,
   "2026": 1837
  }
 },
 "faers_base": {
  "total": 20692304,
  "serious_share": 0.5742697381596559,
  "death_share": 0.09102355155810585
 },
 "recalls": [],
 "recall_total": 0,
 "drugsfda": {
  "applications": 13,
  "nda": 1,
  "anda": 12,
  "first_approval": "19980910",
  "rems": false,
  "rems_last": "",
  "labeling_supplements": 14,
  "labeling_recent": 1,
  "sponsors": [
   "ABHAI LLC",
   "AET PHARMA",
   "ALEMBIC PHARMS LTD",
   "APOTEX",
   "AUROBINDO PHARMA",
   "BARR",
   "FOSUN WANBANG",
   "HERITAGE"
  ],
  "unapproved": false,
  "first_approval_fmt": "09/10/1998"
 },
 "trials": {
  "total": 141,
  "completed": 69,
  "terminated": 15,
  "with_results": 32,
  "industry": 45,
  "phase3": 33,
  "results_share": 0.463768115942029,
  "terminated_share": 0.10638297872340426
 },
 "pubmed": {
  "rct": 84,
  "meta": 19,
  "recent_rct": 12,
  "cochrane": [
   {
    "pmid": "12535423",
    "title": "Leflunomide for treating rheumatoid arthritis",
    "year": "2003"
   }
  ]
 },
 "payments": {
  "year": "2024",
  "usd": 0.0,
  "records": 0,
  "by_name": [],
  "names_checked": [
   "leflunomide",
   "Arava"
  ],
  "source": "bulk-index"
 },
 "partd": {
  "year": "2024",
  "claims": 578502,
  "beneficiaries": 147574,
  "spend": 35665147.42,
  "by_brand": [
   {
    "brand": "Leflunomide",
    "claims": 578121,
    "per_claim": 60.110165554,
    "is_generic": true
   },
   {
    "brand": "Arava",
    "claims": 381,
    "per_claim": 2399.4708661,
    "is_generic": false
   }
  ],
  "per_claim": 61.65086278007682
 },
 "mdl": [],
 "dsc": [],
 "settlements": [],
 "prescrire": null,
 "eml": {
  "listed": false,
  "status": "",
  "name": "",
  "matched": null,
  "stewardship": []
 },
 "exposure": {
  "years": [
   "2024",
   "2025",
   "2026"
  ],
  "reports_recent": 13478,
  "fills": 578502,
  "per_million": 23298.104414505047,
  "ratio": 8.414058212003326,
  "median": 2768.949753790441
 },
 "scores": {
  "safety": {
   "score": 55,
   "letter": "D",
   "why": [
    "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)",
    "23,298 FDA reports naming it as the suspect drug per million Medicare fills, 8.4x the median drug on this site (-15)",
    "Death share in reports is near or below the FAERS average (1.0x)"
   ],
   "weight": 0.35
  },
  "evidence": {
   "score": 50,
   "letter": "D",
   "why": [
    "84 randomized trials and 19 systematic reviews/meta-analyses indexed in PubMed",
    "1 independent Cochrane review(s) exist",
    "Only 46% of completed registered trials posted results (-8)",
    "'Drug ineffective' is the single most-reported item about this drug in FAERS (-5)"
   ],
   "weight": 0.25
  },
  "regulatory": {
   "score": 95,
   "letter": "A",
   "why": [
    "No recalls on record since 2016",
    "Label lists recent major changes to warnings or indications (-5)"
   ],
   "weight": 0.15
  },
  "conflict": {
   "score": 100,
   "letter": "A",
   "why": [
    "Pharma paid doctors $0 tied to this drug last year: negligible",
    "Not named in any pending federal MDL"
   ],
   "weight": 0.15
  },
  "options": {
   "score": 90,
   "letter": "A",
   "why": [
    "Generic versions approved (12 applications)",
    "1 same-class alternative(s) (-10)"
   ],
   "weight": 0.1
  }
 },
 "total": 70,
 "grade": "C",
 "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, arthralgia. How would we recognize and handle those?",
  "Why this one over teriflunomide? 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.)"
 ]
}