Methotrexate

Methotrexate Brand Names

Otrexup | Rasuvo | Rheumatrex | Trexall | Xatmep

What is Methotrexate

Methotrexate is a folate antimetabolite.

It is an analog of aminopterin, which is also derived from folic acid. The molecular structure of methotrexate differs from folic acid in that it has a hydroxyl group in place of the 4-amino group on the pteridine ring and there is no methyl group at the N10 position.

Methotrexate is a weak bicarboxylic acid with a pKa of 4.8 to 5.5. Methotrexate was first used in the treatment of childhood acute lymphocytic leukemia in 1948.

Methotrexate has since been used in the treatment of various malignancies including gestational choriocarcinoma, chorioadenoma destruens, hydatidiform mole, osteosarcoma, non-Hodgkin’s lymphoma, cutaneous T-cell lymphoma (mycosis fungoides), head and neck cancer, lung cancer, and breast cancer.

Intrathecal methotrexate is used for prophylaxis and treatment of meningeal leukemia.

Methotrexate also has immunosuppressive effects and is used in the treatment of rheumatoid arthritis, including polyarticular juvenile idiopathic arthritis, and in the prevention of graft-versus-host disease.

Methotrexate is used in other nonmalignant conditions including psoriasis.

The FDA approved methotrexate in 1953.

Indications

  1. acute lymphocytic leukemia (ALL)
  2. bladder cancer
  3. breast cancer
  4. Burkitt’s lymphoma
  5. carcinomatous meningitis
  6. choriocarcinoma
  7. Crohn’s disease
  8. cutaneous T-cell lymphoma (CTCL)
  9. dermatomyositis
  10. desmoid tumor
  11. ectopic pregnancy
  12. head and neck cancer
  13. hydatidiform mole
  14. leukemic meningitis
  15. lung cancer
  16. mycosis fungoides
  17. non-Hodgkin’s lymphoma (NHL)
  18. osteogenic sarcoma
  19. penile cancer
  20. polyarticular juvenile idiopathic arthritis
  21. polymyositis
  22. psoriasis
  23. psoriatic arthritis
  24. rheumatoid arthritis
  25. sarcoidosis
  26. small cell lung cancer (SCLC)
  27. systemic lupus erythematosus (SLE)
  28. trophoblastic disease

Side Effects

  1. acne vulgaris
  2. alopecia
  3. amenorrhea
  4. anaphylactoid reactions
  5. anemia
  6. anorexia
  7. aphasia
  8. aplastic anemia
  9. arachnoiditis
  10. arthralgia
  11. ataxia
  12. azotemia
  13. back pain
  14. blurred vision
  15. bone fractures
  16. bone marrow suppression
  17. bradycardia
  18. chest pain (unspecified)
  19. cirrhosis
  20. coma
  21. confusion
  22. conjunctivitis
  23. cough
  24. crystalluria
  25. cystitis
  26. diabetes mellitus
  27. diarrhea
  28. dizziness
  29. drowsiness
  30. dysarthria
  31. dysuria
  32. ecchymosis
  33. elevated hepatic enzymes
  34. encephalopathy
  35. epistaxis
  36. erythema multiforme
  37. exfoliative dermatitis
  38. fatigue
  39. fetal death
  40. fever
  41. folate deficiency
  42. furunculosis
  43. GI bleeding
  44. GI perforation
  45. gingivitis
  46. gonadal suppression
  47. gynecomastia
  48. headache
  49. hematemesis
  50. hematuria
  51. hepatic failure
  52. hepatotoxicity
  53. hyperglycemia
  54. hyperhidrosis
  55. hypoalbuminemia
  56. hypotension
  57. impaired cognition
  58. impotence (erectile dysfunction)
  59. infection
  60. infertility
  61. irritability
  62. leukoencephalopathy
  63. leukopenia
  64. libido decrease
  65. lymphadenopathy
  66. lymphoma
  67. malaise
  68. melena
  69. myalgia
  70. nausea
  71. nephrotoxicity
  72. neutropenia
  73. new primary malignancy
  74. ocular irritation
  75. oligospermia
  76. optic atrophy
  77. osteonecrosis
  78. osteoporosis
  79. pancreatitis
  80. pancytopenia
  81. paresis
  82. peptic ulcer
  83. pericardial effusion
  84. pericarditis
  85. pharyngitis
  86. phlebitis
  87. photosensitivity
  88. pneumonitis
  89. premature ventricular contractions (PVCs)
  90. proteinuria
  91. pruritus
  92. pulmonary embolism
  93. pulmonary fibrosis
  94. pulmonary toxicity
  95. radiation recall reaction
  96. rash
  97. renal failure (unspecified)
  98. renal tubular obstruction
  99. retinal thrombosis
  100. scotomata
  101. seizures
  102. skin necrosis
  103. skin ulcer
  104. spermatogenesis inhibition
  105. spontaneous fetal abortion
  106. Stevens-Johnson syndrome
  107. stomatitis
  108. telangiectasia
  109. teratogenesis
  110. thrombocytopenia
  111. thrombosis
  112. tinnitus
  113. tissue necrosis
  114. toxic epidermal necrolysis
  115. tumor lysis syndrome (TLS)
  116. urticaria
  117. vaginal discharge
  118. vasculitis
  119. ventricular tachycardia
  120. visual impairment
  121. vitamin B12 deficiency
  122. vitamin B6 deficiency
  123. vomiting
  124. xerophthalmia

Monitoring Parameters

  • CBC with differential
  • chest x-ray
  • LFTs
  • pregnancy testing
  • pulmonary function tests (PFTs)
  • serum albumin
  • serum creatinine/BUN
  • serum electrolytes
  • serum uric acid

Contraindications

  • acquired immunodeficiency syndrome (AIDS)
  • alcoholism
  • anemia
  • ascites
  • benzyl alcohol hypersensitivity
  • bone marrow suppression
  • breast-feeding
  • contraception requirements
  • dehydration
  • diabetes mellitus
  • diarrhea
  • ensure correct formulation selection
  • exfoliative dermatitis
  • geriatric
  • GI bleeding
  • GI disease
  • GI perforation
  • hepatic disease
  • hepatitis
  • hepatotoxicity
  • herpes infection
  • hyperkalemia
  • hyperlipidemia
  • hyperphosphatemia
  • hyperuricemia
  • hypoalbuminemia
  • hypocalcemia
  • immunosuppression
  • infection
  • infertility
  • intrathecal administration
  • intrauterine fetal death
  • menstrual irregularity
  • neonates
  • nephrotoxicity
  • neutropenia
  • new primary malignancy
  • obesity
  • peptic ulcer disease
  • pleural effusion
  • pregnancy
  • pregnancy testing
  • pulmonary disease
  • pulmonary fibrosis
  • pulmonary toxicity
  • radiation therapy
  • renal disease
  • renal failure
  • renal impairment
  • reproductive risk
  • requires an experienced clinician
  • serious rash
  • stomatitis
  • sunburn
  • sunlight (UV) exposure
  • thrombocytopenia
  • tumor lysis syndrome (TLS)
  • ulcerative colitis
  • vaccination
  • varicella
  • viral infection
  • vomiting

Interactions

  • Abciximab
  • Acalabrutinib
  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Acitretin
  • Acyclovir
  • Adalimumab
  • Aldesleukin, IL-2
  • Alefacept
  • Allopurinol
  • Alpha interferons
  • Alteplase
  • Aminosalicylate sodium, Aminosalicylic acid
  • Amlodipine; Celecoxib
  • Amoxicillin; Clarithromycin; Lansoprazole
  • Amoxicillin; Clarithromycin; Omeprazole
  • Anagrelide
  • Anticoagulants
  • Antithrombin III
  • Antithymocyte Globulin
  • Apixaban
  • Argatroban
  • Asparaginase Erwinia chrysanthemi
  • Aspirin, ASA
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Aspirin, ASA; Caffeine; Dihydrocodeine
  • Aspirin, ASA; Caffeine; Orphenadrine
  • Aspirin, ASA; Carisoprodol
  • Aspirin, ASA; Carisoprodol; Codeine
  • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
  • Aspirin, ASA; Dipyridamole
  • Aspirin, ASA; Omeprazole
  • Aspirin, ASA; Oxycodone
  • Aspirin, ASA; Pravastatin
  • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Bacillus Calmette-Guerin Vaccine, BCG
  • Basiliximab
  • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Betrixaban
  • Bexarotene
  • Bismuth Subsalicylate
  • Bismuth Subsalicylate; Metronidazole; Tetracycline
  • Bivalirudin
  • Carbamazepine
  • Celecoxib
  • Certolizumab pegol
  • Chloramphenicol
  • Cholestyramine
  • Choline Salicylate; Magnesium Salicylate
  • Cilostazol
  • Ciprofloxacin
  • Cisplatin
  • Clofarabine
  • Clopidogrel
  • Clozapine
  • Colchicine; Probenecid
  • Cyclosporine
  • Cytarabine, ARA-C
  • Dabigatran
  • Daclatasvir
  • Dalteparin
  • Danaparoid
  • Dantrolene
  • Dapsone
  • Darolutamide
  • Desirudin
  • Dexlansoprazole
  • Dichlorphenamide
  • Diclofenac
  • Diclofenac; Misoprostol
  • Diflunisal
  • Digoxin
  • Diphenhydramine; Ibuprofen
  • Diphenhydramine; Naproxen
  • Dipyridamole
  • Drospirenone; Ethinyl Estradiol; Levomefolate
  • Echinacea
  • Edoxaban
  • Efalizumab
  • Elbasvir; Grazoprevir
  • Eltrombopag
  • Enoxaparin
  • Eptifibatide
  • Esomeprazole
  • Esomeprazole; Naproxen
  • Esterified Estrogens; Methyltestosterone
  • Ethanol
  • Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
  • Ethotoin
  • Etodolac
  • Famotidine; Ibuprofen
  • Febuxostat
  • Fenoprofen
  • Filgrastim, G-CSF
  • Floxuridine
  • Fluorouracil, 5-FU
  • Flurbiprofen
  • Folic Acid, Vitamin B9
  • Fondaparinux
  • food
  • Foscarnet
  • Fosphenytoin
  • Fostamatinib
  • Furosemide
  • Gadobenate Dimeglumine
  • Glecaprevir; Pibrentasvir
  • Golimumab
  • Heparin
  • Hydantoins
  • Hydrocodone; Ibuprofen
  • Hydroxychloroquine
  • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
  • Ibrutinib
  • Ibuprofen
  • Ibuprofen; Oxycodone
  • Ibuprofen; Pseudoephedrine
  • Indomethacin
  • Infliximab
  • Influenza Virus Vaccine
  • Intranasal Influenza Vaccine
  • Isotretinoin
  • Itraconazole
  • Ketoprofen
  • Ketorolac
  • L-Asparaginase Escherichia coli
  • Lamotrigine
  • Lansoprazole
  • Lansoprazole; Naproxen
  • Leflunomide
  • Lepirudin
  • Lesinurad; Allopurinol
  • Levomefolate
  • Live Vaccines
  • Lomitapide
  • Magnesium Salicylate
  • Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live
  • Measles/Mumps/Rubella Vaccines, MMR
  • Meclofenamate Sodium
  • Mefenamic Acid
  • Meloxicam
  • Methoxsalen
  • Methyltestosterone
  • Mipomersen
  • Muromonab-CD3
  • Nabumetone
  • Naproxen
  • Naproxen; Pseudoephedrine
  • Naproxen; Sumatriptan
  • Natalizumab
  • Neomycin
  • Nitisinone
  • Nonsteroidal antiinflammatory drugs
  • Omeprazole
  • Omeprazole; Amoxicillin; Rifabutin
  • Omeprazole; Sodium Bicarbonate
  • Osimertinib
  • Oxaliplatin
  • Oxaprozin
  • Palifermin
  • Pantoprazole
  • Paromomycin
  • Pegaspargase
  • Pegfilgrastim
  • Penicillamine
  • Penicillins
  • Pentosan
  • Pexidartinib
  • Phenytoin
  • Photosensitizing agents (topical)
  • Piroxicam
  • Platelet Inhibitors
  • Ponatinib
  • Porfimer
  • Prasugrel
  • Probenecid
  • Proton pump inhibitors
  • Purine analogs
  • Pyrimethamine
  • Pyrimethamine; Sulfadoxine
  • Rabeprazole
  • Regorafenib
  • Reteplase, r-PA
  • Rilonacept
  • Riluzole
  • Rituximab
  • Rituximab; Hyaluronidase
  • Rivaroxaban
  • Rofecoxib
  • Rolapitant
  • Rotavirus Vaccine
  • Rubella Virus Vaccine Live
  • Safinamide
  • Salicylates
  • Salsalate
  • Sapropterin
  • Simeprevir
  • Smallpox and Monkeypox Vaccine, Live, Nonreplicating
  • Smallpox Vaccine, Vaccinia Vaccine
  • Sofosbuvir; Velpatasvir; Voxilaprevir
  • Streptokinase
  • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
  • Sulfonamides
  • Sulfonylureas
  • Sulindac
  • Tacrine
  • Tafamidis
  • Tbo-Filgrastim
  • Tedizolid
  • Temozolomide
  • Tenecteplase
  • Teniposide
  • Teriflunomide
  • Tetracyclines
  • Theophylline, Aminophylline
  • Thiazide diuretics
  • Thrombolytic Agents
  • Ticagrelor
  • Ticlopidine
  • Tinzaparin
  • Tirofiban
  • Tolmetin
  • Tolvaptan
  • Tretinoin, ATRA
  • Trimethoprim
  • Tuberculin Purified Protein Derivative, PPD
  • Typhoid Vaccine
  • Urokinase
  • Valacyclovir
  • Valdecoxib
  • Vancomycin
  • Varicella-Zoster Virus Vaccine, Live
  • Verteporfin
  • Vincristine
  • Vincristine Liposomal
  • Vorapaxar
  • Warfarin
  • Yellow Fever Vaccine, Live
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