Adverse Drug Reaction Classification System

Pharmaceutical Information
Drug Name Methotrexate
Drug ID BADD_D01418
Description Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis.[A180322] This inhibition leads to suppression of inflammation as well as prevention of cell division.[A180322] Because of these effects, methotrexate is often used to treat inflammation caused by arthritis or to control cell division in neoplastic diseases such as breast cancer and non-Hodgkin's lymphoma.[A180322,L7144,L7147,L7150,L7180] Due to the toxic effects of methotrexate, it is indicated for treatment of some forms of arthritis and severe psoriasis only if first line treatment has failed or patients are intolerant of those treatments.[L7180] Methotrexate was granted FDA approval on 7 December 1953.[L7198]
Indications and Usage Methotrexate is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. In acute lymphocytic leukemia, methotrexate is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents. Methotrexate is also indicated in the treatment of meningeal leukemia. Methotrexate is used alone or in combination with other anticancer agents in the treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T cell lymphoma), and lung cancer, particularly squamous cell and small cell types. Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin’s lymphomas. Methotrexate is indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis. Methotrexate is indicated in the management of selected adults with severe, active rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis.
Marketing Status Prescription; Discontinued
ATC Code L01BA01; L04AX03
DrugBank ID DB00563
KEGG ID D00142
MeSH ID D008727
PubChem ID 126941
TTD Drug ID D0SV8E
NDC Product Code 59137-530; 0703-3671; 59137-550; 0703-3678; 52652-2001; 0143-9516; 0143-9830; 61703-408; 69238-1423; 51285-367; 49452-4601; 66220-812; 66220-810; 0143-9519; 70518-1398; 0143-9517; 61703-350; 16729-277; 66220-822; 54436-012; 59137-535; 59137-540; 59137-510; 70771-1058; 54436-022; 70518-3263; 66220-817; 59137-520; 0703-3675; 54436-020; 51407-121; 51079-670; 71335-1772; 58623-0040; 0143-9367; 46014-1005; 50090-5457; 71335-0782; 42291-505; 59137-525; 0143-9518; 46014-1023; 0904-7141; 51285-369; 51927-1565; 54436-025; 0378-0014; 68382-775; 66220-815; 71335-1118; 59651-182; 66220-820; 59137-505; 59137-515; 63660-0006; 12780-0491; 51285-366; 66220-825; 54436-017; 46014-1133; 66220-807; 51285-368; 16729-486; 54436-010; 0555-0572; 54436-015; 50268-527
Synonyms Methotrexate | Amethopterin | Methotrexate, (D)-Isomer | Methotrexate, (DL)-Isomer | Mexate | Methotrexate Sodium | Sodium, Methotrexate | Methotrexate, Sodium Salt | Methotrexate, Disodium Salt | Methotrexate Hydrate | Hydrate, Methotrexate | Methotrexate, Dicesium Salt | Dicesium Salt Methotrexate
Chemical Information
Molecular Formula C20H22N8O5
CAS Registry Number 59-05-2
SMILES CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
Chemical Structure
ADR Related Proteins Induced by Drug
ADR Term Protein Name UniProt AC TTD Target ID PMID
ApoptosisThymidine kinase, cytosolicP04183T300813252959; 1626950
ApoptosisCellular tumor antigen p53P04637T157399681674; 16445776; 9358758
Chromosomal abnormalities and abnormal gene carriersUracil-DNA glycosylaseP13051Not Available12167490; 11425516; 10871356
DeathAspartate aminotransferase, cytoplasmicP17174T3336710461859; 9013204; 8742516
DeathAlanine aminotransferase 2Q28DB5Not Available10461859; 9013204; 8742516
EnterocolitisGlutathione peroxidase 3P23764Not Available3138440
HepatotoxicityTumor necrosis factorP16599Not Available25912852
HepatotoxicityNitric oxide synthase, inducibleQ06518Not Available25912852
HepatotoxicityGlutathione peroxidase 1P04041Not Available25912852
HepatotoxicitySuperoxide dismutase [Cu-Zn]P07632Not Available25912852
HepatotoxicityDiazepam-binding inhibitor-like 5P56702Not Available25912852
HepatotoxicityCatalaseP04762Not Available25912852
Intestinal angioedemaGlutathione peroxidase 3P23764Not Available3138440
Liver injuryLysosome-associated membrane glycoprotein 1P11279T311458915142; 15787813; 15787812; 8731673; 8864370; 7577576
Nephropathy toxicSuperoxide dismutase [Cu-Zn]P07632Not Available25912852
Nephropathy toxicDiazepam-binding inhibitor-like 5P56702Not Available25912852
Nephropathy toxicCatalaseP04762Not Available25912852
Nephropathy toxicTumor necrosis factorP16599Not Available25912852
Nephropathy toxicNitric oxide synthase, inducibleQ06518Not Available25912852
Nephropathy toxicGlutathione peroxidase 1P04041Not Available25912852
Traumatic lung injuryPulmonary surfactant-associated protein DP35247T3586212135181; 12322797; 9330247
ADRs Induced by Drug
ADR Term ADReCS ID ADR Frequency (FAERS) ADR Severity Grade (FAERS) ADR Severity Grade (CTCAE)
Inflammatory pain08.01.08.0280.000840%Not Available
Ligament rupture15.07.02.008; 12.01.07.0140.000560%Not Available
Pneumonia cryptococcal22.07.08.012; 11.03.04.0050.000560%Not Available
Quality of life decreased13.18.01.013--Not Available
Radiation interaction08.06.03.0060.000560%Not Available
Butterfly rash23.03.13.019; 15.06.02.010; 10.04.03.0100.000560%Not Available
Anti-cyclic citrullinated peptide antibody positive13.06.01.0140.002240%Not Available
Inflammatory marker increased13.09.02.0030.002240%Not Available
Hepatitis C virus test positive13.08.03.0240.000560%Not Available
Mycobacterium tuberculosis complex test positive13.08.05.0040.002800%Not Available
Epstein-Barr virus associated lymphoma16.28.01.003; 11.05.10.007; 01.15.01.0030.000365%Not Available
Chronic graft versus host disease in intestine12.02.09.023; 10.02.01.055; 07.11.01.0220.000146%Not Available
Chronic graft versus host disease in skin10.02.01.057; 23.07.04.022; 12.02.09.0250.000584%Not Available
Chronic graft versus host disease in liver12.02.09.024; 10.02.01.056; 09.01.07.0320.000365%Not Available
Enzyme level increased13.04.02.0150.000560%Not Available
Meniscus injury15.07.03.006; 12.04.03.0080.001120%Not Available
Small fibre neuropathy17.09.03.021; 14.07.04.007; 05.07.04.0070.000560%Not Available
Graft versus host disease in eye12.02.09.027; 10.02.01.058; 06.04.05.0280.000219%Not Available
Graft versus host disease in gastrointestinal tract12.02.09.028; 10.02.01.059; 07.11.01.0270.000292%Not Available
Internal haemorrhage24.07.01.072--Not Available
Burn oral cavity12.05.04.006; 07.11.01.0210.000840%Not Available
Lower respiratory tract congestion22.02.04.0100.000560%Not Available
Gastrointestinal wall thickening07.01.06.0320.000560%Not Available
Fine motor skill dysfunction17.01.02.0200.001680%Not Available
Steatohepatitis14.08.04.020; 09.01.07.0240.000560%Not Available
Soft tissue swelling15.03.02.0200.000560%Not Available
End stage renal disease20.01.03.019--Not Available
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