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