Leflunomide

Leflunomide Brand Name– Arava

What is Leflunomide

Leflunomide is the first isoxazol derivative approved for the treatment of rheumatoid arthritis (RA).

Leflunomide was also the first agent for rheumatoid arthritis indicated for both symptomatic improvement and retardation of structural joint damage based on radiographic evidence of its disease modifying activity.

After 52 weeks of treatment in clinical trials, leflunomide showed similar improvements in tender and swollen joint counts, pain, and other symptoms when compared to methotrexate or sulfasalazine.

Leflunomide was significantly superior to placebo in time to progression of structural disease as evidenced by Sharp X-ray scores. Sharp scores were not consistently different between leflunomide and methotrexate.

Analysis of long-term studies will define whether or not leflunomide prevents RA-induced disability, but data are available to show that leflunomide subjectively improves functional daily activity and quality of life. Due to its unique mechanism of action, leflunomide efficacy may be additive to other antirheumatic agents, but certain drugs are not recommended for concurrent use (e.g., methotrexate).

Leflunomide has a fast onset of action (4 weeks) relative to other disease-modifying agents.

However, the long half-life of the drug (14—15 days) is problematic should adverse events like hepatotoxicity occur, and a drug elimination procedure is required for cases of pregnancy or significant overdose or toxicity to rapidly lower drug plasma levels (see Dosage).

Leflunomide is being evaluated for the treatment of systemic lupus erythematosus and for efficacy as an immunosupressant in organ transplantation.

Leflunomide received priority review and FDA approval in September 1998; at that time it was the first disease-modifying agent for RA approved in more than a decade.

In June 2003, leflunomide received an expanded indication for the improvement of physical function (e.g., ability to perform daily activities) in patients with rheumatoid arthritis.

Indications

  • juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA)
  • rheumatoid arthritis

For the treatment of active rheumatoid arthritis

Side Effects

  1. abdominal pain
  2. acne vulgaris
  3. agranulocytosis
  4. alopecia
  5. anaphylactoid reactions
  6. anemia
  7. angina
  8. angioedema
  9. anorexia
  10. anxiety
  11. arthralgia
  12. asthenia
  13. back pain
  14. blurred vision
  15. bone pain
  16. cataracts
  17. chest pain (unspecified)
  18. cholelithiasis
  19. cholestasis
  20. cirrhosis
  21. coagulopathy
  22. colitis
  23. conjunctivitis
  24. constipation
  25. contact dermatitis
  26. cough
  27. cystitis
  28. cystitis
  29. depression
  30. diabetes mellitus
  31. diarrhea
  32. dizziness
  33. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
  34. dysgeusia
  35. dyspepsia
  36. dyspnea
  37. dysuria
  38. ecchymosis
  39. elevated hepatic enzymes
  40. encephalopathy
  41. epistaxis
  42. erythema multiforme
  43. esophagitis
  44. fetal death
  45. fever
  46. flatulence
  47. gastritis
  48. gingivitis
  49. hair discoloration
  50. headache
  51. hematoma
  52. hematuria
  53. hepatic failure
  54. hepatic necrosis
  55. hepatitis
  56. hepatotoxicity
  57. hyperglycemia
  58. hyperhidrosis
  59. hyperlipidemia
  60. hypertension
  61. hyperthyroidism
  62. hypokalemia
  63. immunosuppression
  64. increased urinary frequency
  65. infection
  66. insomnia
  67. jaundice
  68. leukopenia
  69. maculopapular rash
  70. malaise
  71. melena
  72. menstrual irregularity
  73. migraine
  74. muscle cramps
  75. myalgia
  76. nausea
  77. neuritis
  78. neuropathic pain
  79. neutropenia
  80. oral ulceration
  81. palpitations
  82. pancreatitis
  83. pancytopenia
  84. paresthesias
  85. pelvic pain
  86. peripheral edema
  87. peripheral neuropathy
  88. pharyngitis
  89. pneumonitis
  90. proteinuria
  91. pruritus
  92. psoriasis
  93. pulmonary fibrosis
  94. rash
  95. rhinitis
  96. sinus tachycardia
  97. sinusitis
  98. skin discoloration
  99. skin ulcer
  100. Stevens-Johnson syndrome
  101. stomatitis
  102. synovitis
  103. tendon rupture
  104. teratogenesis
  105. thrombocytopenia
  106. toxic epidermal necrolysis
  107. urticaria
  108. vasculitis
  109. vertigo
  110. vomiting
  111. weight loss
  112. xerostomia

Monitoring Parameters

  • CBC with differential
  • LFTs
  • pregnancy testing
  • serum electrolytes

Contraindications

  • agranulocytosis
  • alcoholism
  • bone marrow suppression
  • breast-feeding
  • chemotherapy
  • children
  • contraception requirements
  • diabetes mellitus
  • eosinophilic pneumonia
  • geriatric
  • hepatic disease
  • hepatitis
  • hepatotoxicity
  • hypertension
  • immunosuppression
  • infection
  • jaundice
  • male-mediated teratogenicity
  • peripheral neuropathy
  • pneumonitis
  • pregnancy
  • pregnancy testing
  • pulmonary disease
  • pulmonary fibrosis
  • renal failure
  • renal impairment
  • reproductive risk
  • sarcoidosis
  • serious rash
  • tuberculosis
  • vaccination

Interactions

  • Abacavir; Lamivudine, 3TC; Zidovudine, ZDV
  • Alogliptin; Pioglitazone
  • Alosetron
  • Alpelisib
  • Amlodipine; Atorvastatin
  • Aspirin, ASA; Pravastatin
  • Atorvastatin
  • Atorvastatin; Ezetimibe
  • Azathioprine
  • Bacillus Calmette-Guerin Vaccine, BCG
  • Baricitinib
  • Bosentan
  • Cefaclor
  • Charcoal
  • Cholestyramine
  • Cimetidine
  • Ciprofloxacin
  • Dichlorphenamide
  • Dienogest; Estradiol valerate
  • Doxercalciferol
  • Dronabinol
  • Drospirenone
  • Drospirenone; Estradiol
  • Drospirenone; Ethinyl Estradiol
  • Drospirenone; Ethinyl Estradiol; Levomefolate
  • Duloxetine
  • Elagolix
  • Elagolix; Estradiol; Norethindrone acetate
  • Eluxadoline
  • Estradiol; Levonorgestrel
  • Estradiol; Norethindrone
  • Estradiol; Norgestimate
  • Ethanol
  • Ethinyl Estradiol
  • Ethinyl Estradiol; Desogestrel
  • Ethinyl Estradiol; Ethynodiol Diacetate
  • Ethinyl Estradiol; Etonogestrel
  • Ethinyl Estradiol; Levonorgestrel
  • Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate
  • Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
  • Ethinyl Estradiol; Norelgestromin
  • Ethinyl Estradiol; Norethindrone
  • Ethinyl Estradiol; Norethindrone Acetate
  • Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate
  • Ethinyl Estradiol; Norethindrone; Ferrous fumarate
  • Ethinyl Estradiol; Norgestimate
  • Ethinyl Estradiol; Norgestrel
  • Ezetimibe; Simvastatin
  • Fluvastatin
  • food
  • Fosphenytoin
  • Furosemide
  • Glimepiride; Pioglitazone
  • Glimepiride; Rosiglitazone
  • HMG-CoA reductase inhibitors
  • Influenza Virus Vaccine
  • Intranasal Influenza Vaccine
  • Isoniazid, INH
  • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
  • Isoniazid, INH; Rifampin
  • Itraconazole
  • Ketoconazole
  • Lamivudine, 3TC; Zidovudine, ZDV
  • Lesinurad
  • Lesinurad; Allopurinol
  • Leuprolide; Norethindrone
  • Levonorgestrel
  • Live Vaccines
  • Loperamide
  • Loperamide; Simethicone
  • Lovastatin
  • Lovastatin; Niacin
  • Maraviroc
  • Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live
  • Measles/Mumps/Rubella Vaccines, MMR
  • Mestranol; Norethindrone
  • Metformin; Pioglitazone
  • Metformin; Repaglinide
  • Metformin; Rosiglitazone
  • Methotrexate
  • Mitoxantrone
  • Nanoparticle Albumin-Bound Paclitaxel
  • Nateglinide
  • Niacin; Simvastatin
  • Nonsteroidal antiinflammatory drugs
  • Norethindrone
  • Norgestrel
  • Oral Contraceptives
  • Ozanimod
  • Paclitaxel
  • Penicillin G
  • Penicillin G Benzathine
  • Penicillin G Benzathine; Penicillin G Procaine
  • Penicillin G Procaine
  • Phenytoin
  • Pioglitazone
  • Pitavastatin
  • Pravastatin
  • Ramelteon
  • Repaglinide
  • Revefenacin
  • Rifampin
  • Riluzole
  • Rimegepant
  • Rituximab
  • Rituximab; Hyaluronidase
  • Rosiglitazone
  • Rosuvastatin
  • Rotavirus Vaccine
  • Rubella Virus Vaccine Live
  • Segesterone Acetate; Ethinyl Estradiol
  • Selexipag
  • Simvastatin
  • Simvastatin; Sitagliptin
  • Smallpox and Monkeypox Vaccine, Live, Nonreplicating
  • Smallpox Vaccine, Vaccinia Vaccine
  • Sulfasalazine
  • Tacrine
  • Talazoparib
  • Terbinafine
  • Teriflunomide
  • Theophylline, Aminophylline
  • Tizanidine
  • Tolbutamide
  • Topotecan
  • Tucatinib
  • Typhoid Vaccine
  • Ubrogepant
  • Varicella-Zoster Virus Vaccine, Live
  • Warfarin
  • Yellow Fever Vaccine, Live
  • Zidovudine, ZDV
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