U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H22N8O5
Molecular Weight 454.4401
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHOTREXATE

SMILES

CN(Cc1cnc2c(c(N)[nH]c(=N)n2)n1)c3ccc(cc3)C(=O)N[C@@]([H])(CCC(=O)O)C(=O)O

InChI

InChIKey=FBOZXECLQNJBKD-ZDUSSCGKSA-N
InChI=1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment:: https://www.drugs.com/methotrexate.html

Methotrexate is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Methotrexate inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydrofolic acid. At two stages in the biosynthesis of purines and at one stage in the synthesis of pyrimidines, one-carbon transfer reactions occur which require specific coenzymes synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it quite strongly and inhibits the enzyme. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Methotrexate selectively affects the most rapidly dividing cells (neoplastic and psoriatic cells). 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.

CNS Activity

Curator's Comment:: modest blood-brain barrier (BBB) permeability

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
5.19000000000000039 pM [Ki]
0.179999999999999993 mM [IC50]
15 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
OTREXUP

Approved Use

Otrexup is a folate analog metabolic inhibitor indicated for the: • Management of patients with severe, active rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA), who are intolerant of or had an inadequate response to first-line therapy • Symptomatic control of severe, recalcitrant, disabling psoriasis in adults who are not adequately responsive to other forms of therapy

Launch Date

-536544000000
Primary
TREXALL

Approved Use

Neoplastic Diseases Methotrexate, USP is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. In acute lymphocytic leukemia, methotrexate, USP is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents. Methotrexate, USP is also indicated in the treatment of meningeal leukemia. Methotrexate, USP 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, USP is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin's lymphomas. Methotrexate, USP in high doses followed by leucovorin rescue in combination with other chemotherapeutic agents is effective in prolonging relapse-free survival in patients with non-metastatic osteosarcoma who have undergone surgical resection or amputation for the primary tumor. Psoriasis Methotrexate, USP is indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis "flare" is not due to an undiagnosed concomitant disease affecting immune responses. Rheumatoid Arthritis including Polyarticular-Course Juvenile Rheumatoid Arthritis Methotrexate, USP is indicated in the management of selected adults with severe, active rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs).

Launch Date

985046400000
Primary
TREXALL

Approved Use

Neoplastic Diseases Methotrexate, USP is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. In acute lymphocytic leukemia, methotrexate, USP is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents. Methotrexate, USP is also indicated in the treatment of meningeal leukemia. Methotrexate, USP 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, USP is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin's lymphomas. Methotrexate, USP in high doses followed by leucovorin rescue in combination with other chemotherapeutic agents is effective in prolonging relapse-free survival in patients with non-metastatic osteosarcoma who have undergone surgical resection or amputation for the primary tumor. Psoriasis Methotrexate, USP is indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis "flare" is not due to an undiagnosed concomitant disease affecting immune responses. Rheumatoid Arthritis including Polyarticular-Course Juvenile Rheumatoid Arthritis Methotrexate, USP is indicated in the management of selected adults with severe, active rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs).

Launch Date

985046400000
Primary
TREXALL

Approved Use

Neoplastic Diseases Methotrexate, USP is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. In acute lymphocytic leukemia, methotrexate, USP is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents. Methotrexate, USP is also indicated in the treatment of meningeal leukemia. Methotrexate, USP 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, USP is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin's lymphomas. Methotrexate, USP in high doses followed by leucovorin rescue in combination with other chemotherapeutic agents is effective in prolonging relapse-free survival in patients with non-metastatic osteosarcoma who have undergone surgical resection or amputation for the primary tumor. Psoriasis Methotrexate, USP is indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis "flare" is not due to an undiagnosed concomitant disease affecting immune responses. Rheumatoid Arthritis including Polyarticular-Course Juvenile Rheumatoid Arthritis Methotrexate, USP is indicated in the management of selected adults with severe, active rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs).

Launch Date

985046400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.205 μM
20 mg/m² single, oral
dose: 20 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
METHOTREXATE plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3533 nM × h
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHOTREXATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
55 h
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHOTREXATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3.25 h
20 mg/m² single, oral
dose: 20 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
METHOTREXATE plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
50%
METHOTREXATE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
75 mg single, oral
Overdose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
unknown, 10-19 years
Health Status: unknown
Age Group: 10-19 years
Sex: M
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (1 patient)
Vomiting (1 patient)
Sources:
87.5 mg single, oral
Overdose
Dose: 87.5 mg
Route: oral
Route: single
Dose: 87.5 mg
Sources:
unknown, 10-19 years
Health Status: unknown
Age Group: 10-19 years
Sex: F
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (1 patient)
Vomiting (1 patient)
Sources:
50 mg single, oral
Overdose
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
unknown, 40-49 years
Health Status: unknown
Age Group: 40-49 years
Sex: M
Sources:
3 g/m2 multiple, intravenous
Highest studied dose
Dose: 3 g/m2
Route: intravenous
Route: multiple
Dose: 3 g/m2
Sources:
unhealthy, 41 years (range: 17–60 years)
Health Status: unhealthy
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Sources:
Disc. AE: Cytolysis, Neutropenia...
AEs leading to
discontinuation/dose reduction:
Cytolysis (grade 2-3, 2 patients)
Neutropenia (grade 3, 1 patient)
Digestion impaired (grade 3, 1 patient)
Sources:
3 g/m2 multiple, intravenous
Highest studied dose
Dose: 3 g/m2
Route: intravenous
Route: multiple
Dose: 3 g/m2
Sources:
unhealthy, 41 years (range: 17–60 years)
Health Status: unhealthy
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Sources:
Disc. AE: Toxicity renal...
AEs leading to
discontinuation/dose reduction:
Toxicity renal (grade 1-2, 2 patients)
Sources:
50 mg 1 times / week multiple, oral
Overdose
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Sources:
unhealthy, 50-59 years
Health Status: unhealthy
Age Group: 50-59 years
Sex: F
Sources:
Other AEs: Skin lesion, Mucosal ulceration...
Other AEs:
Skin lesion (1 patient)
Mucosal ulceration (1 patient)
Abdominal pain (1 patient)
Sources:
10 mg 1 times / week multiple, oral
Recommended
Dose: 10 mg, 1 times / week
Route: oral
Route: multiple
Dose: 10 mg, 1 times / week
Sources:
unhealthy, 54 years
Health Status: unhealthy
Age Group: 54 years
Sex: F
Sources:
Disc. AE: Lymphoproliferative disorder...
AEs leading to
discontinuation/dose reduction:
Lymphoproliferative disorder (1 patient)
Sources:
70 mg 1 times / week multiple, oral
Overdose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Sources:
unhealthy, 60-79 years
Health Status: unhealthy
Age Group: 60-79 years
Sex: F
Sources:
Other AEs: Mucosal ulceration...
Other AEs:
Mucosal ulceration (2 patients)
Sources:
17.5 mg 1 times / week multiple, oral
Overdose
Dose: 17.5 mg, 1 times / week
Route: oral
Route: multiple
Dose: 17.5 mg, 1 times / week
Sources:
unhealthy, 70-79 years
Health Status: unhealthy
Age Group: 70-79 years
Sex: F
Sources:
Other AEs: Mucosal ulceration, Nausea...
Other AEs:
Mucosal ulceration (1 patient)
Nausea (1 patient)
Vomiting (1 patient)
Diarrhea (1 patient)
Abdominal pain (1 patient)
Sources:
10 mg 1 times / day multiple, oral
Overdose
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Other AEs: Adverse event...
Other AEs:
Adverse event (grade 5)
Sources:
15 mg 1 times / day multiple, oral
Overdose
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Other AEs: Adverse event...
Other AEs:
Adverse event (grade 5)
Sources:
2.5 mg 2 times / day multiple, oral
Overdose
Dose: 2.5 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 2 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Other AEs: Adverse event...
Other AEs:
Adverse event (grade 5)
Sources:
25 mg 1 times / week steady, oral
Recommended
Dose: 25 mg, 1 times / week
Route: oral
Route: steady
Dose: 25 mg, 1 times / week
Sources:
pregnant, adult
Other AEs: Fetal damage...
25 mg 1 times / week steady, oral
Recommended
Dose: 25 mg, 1 times / week
Route: oral
Route: steady
Dose: 25 mg, 1 times / week
Sources:
unhealthy, adult
Other AEs: Gastrointestinal disorder (NOS), Hepatic and hepatobiliary disorders...
Other AEs:
Gastrointestinal disorder (NOS)
Hepatic and hepatobiliary disorders (serious)
Respiratory tract disorders NEC (serious)
Skin and subcutaneous conditions NEC (serious)
Kidney disorder (serious)
Sources:
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
pregnant, adult
Health Status: pregnant
Age Group: adult
Sex: F
Sources:
Other AEs: Fetal damage...
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
unhealthy, adult
Disc. AE: Interstitial pneumonitis...
Other AEs: Hepatic and hepatobiliary disorders, Respiratory tract disorders NEC...
AEs leading to
discontinuation/dose reduction:
Interstitial pneumonitis (serious)
Other AEs:
Hepatic and hepatobiliary disorders (serious)
Respiratory tract disorders NEC (serious)
Skin and subcutaneous conditions NEC (serious)
Kidney disorder (serious)
Sources:
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
unhealthy, adult
Other AEs: Skin and subcutaneous conditions NEC...
Other AEs:
Skin and subcutaneous conditions NEC (severe|grade 5)
Sources:
30 mg 1 times / week multiple, subcutaneous
Dose: 30 mg, 1 times / week
Route: subcutaneous
Route: multiple
Dose: 30 mg, 1 times / week
Sources:
unhealthy, adult
Other AEs: Bone marrow depression, Aplastic anemia...
Other AEs:
Bone marrow depression (severe|grade 5)
Aplastic anemia (severe|grade 5)
Gastrointestinal toxicity (severe|grade 5)
Sources:
AEs

AEs

AESignificanceDosePopulation
Nausea 1 patient
75 mg single, oral
Overdose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
unknown, 10-19 years
Health Status: unknown
Age Group: 10-19 years
Sex: M
Sources:
Vomiting 1 patient
75 mg single, oral
Overdose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
unknown, 10-19 years
Health Status: unknown
Age Group: 10-19 years
Sex: M
Sources:
Nausea 1 patient
87.5 mg single, oral
Overdose
Dose: 87.5 mg
Route: oral
Route: single
Dose: 87.5 mg
Sources:
unknown, 10-19 years
Health Status: unknown
Age Group: 10-19 years
Sex: F
Sources:
Vomiting 1 patient
87.5 mg single, oral
Overdose
Dose: 87.5 mg
Route: oral
Route: single
Dose: 87.5 mg
Sources:
unknown, 10-19 years
Health Status: unknown
Age Group: 10-19 years
Sex: F
Sources:
Cytolysis grade 2-3, 2 patients
Disc. AE
3 g/m2 multiple, intravenous
Highest studied dose
Dose: 3 g/m2
Route: intravenous
Route: multiple
Dose: 3 g/m2
Sources:
unhealthy, 41 years (range: 17–60 years)
Health Status: unhealthy
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Sources:
Digestion impaired grade 3, 1 patient
Disc. AE
3 g/m2 multiple, intravenous
Highest studied dose
Dose: 3 g/m2
Route: intravenous
Route: multiple
Dose: 3 g/m2
Sources:
unhealthy, 41 years (range: 17–60 years)
Health Status: unhealthy
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Sources:
Neutropenia grade 3, 1 patient
Disc. AE
3 g/m2 multiple, intravenous
Highest studied dose
Dose: 3 g/m2
Route: intravenous
Route: multiple
Dose: 3 g/m2
Sources:
unhealthy, 41 years (range: 17–60 years)
Health Status: unhealthy
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Sources:
Toxicity renal grade 1-2, 2 patients
Disc. AE
3 g/m2 multiple, intravenous
Highest studied dose
Dose: 3 g/m2
Route: intravenous
Route: multiple
Dose: 3 g/m2
Sources:
unhealthy, 41 years (range: 17–60 years)
Health Status: unhealthy
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Sources:
Abdominal pain 1 patient
50 mg 1 times / week multiple, oral
Overdose
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Sources:
unhealthy, 50-59 years
Health Status: unhealthy
Age Group: 50-59 years
Sex: F
Sources:
Mucosal ulceration 1 patient
50 mg 1 times / week multiple, oral
Overdose
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Sources:
unhealthy, 50-59 years
Health Status: unhealthy
Age Group: 50-59 years
Sex: F
Sources:
Skin lesion 1 patient
50 mg 1 times / week multiple, oral
Overdose
Dose: 50 mg, 1 times / week
Route: oral
Route: multiple
Dose: 50 mg, 1 times / week
Sources:
unhealthy, 50-59 years
Health Status: unhealthy
Age Group: 50-59 years
Sex: F
Sources:
Lymphoproliferative disorder 1 patient
Disc. AE
10 mg 1 times / week multiple, oral
Recommended
Dose: 10 mg, 1 times / week
Route: oral
Route: multiple
Dose: 10 mg, 1 times / week
Sources:
unhealthy, 54 years
Health Status: unhealthy
Age Group: 54 years
Sex: F
Sources:
Mucosal ulceration 2 patients
70 mg 1 times / week multiple, oral
Overdose
Dose: 70 mg, 1 times / week
Route: oral
Route: multiple
Dose: 70 mg, 1 times / week
Sources:
unhealthy, 60-79 years
Health Status: unhealthy
Age Group: 60-79 years
Sex: F
Sources:
Abdominal pain 1 patient
17.5 mg 1 times / week multiple, oral
Overdose
Dose: 17.5 mg, 1 times / week
Route: oral
Route: multiple
Dose: 17.5 mg, 1 times / week
Sources:
unhealthy, 70-79 years
Health Status: unhealthy
Age Group: 70-79 years
Sex: F
Sources:
Diarrhea 1 patient
17.5 mg 1 times / week multiple, oral
Overdose
Dose: 17.5 mg, 1 times / week
Route: oral
Route: multiple
Dose: 17.5 mg, 1 times / week
Sources:
unhealthy, 70-79 years
Health Status: unhealthy
Age Group: 70-79 years
Sex: F
Sources:
Mucosal ulceration 1 patient
17.5 mg 1 times / week multiple, oral
Overdose
Dose: 17.5 mg, 1 times / week
Route: oral
Route: multiple
Dose: 17.5 mg, 1 times / week
Sources:
unhealthy, 70-79 years
Health Status: unhealthy
Age Group: 70-79 years
Sex: F
Sources:
Nausea 1 patient
17.5 mg 1 times / week multiple, oral
Overdose
Dose: 17.5 mg, 1 times / week
Route: oral
Route: multiple
Dose: 17.5 mg, 1 times / week
Sources:
unhealthy, 70-79 years
Health Status: unhealthy
Age Group: 70-79 years
Sex: F
Sources:
Vomiting 1 patient
17.5 mg 1 times / week multiple, oral
Overdose
Dose: 17.5 mg, 1 times / week
Route: oral
Route: multiple
Dose: 17.5 mg, 1 times / week
Sources:
unhealthy, 70-79 years
Health Status: unhealthy
Age Group: 70-79 years
Sex: F
Sources:
Adverse event grade 5
10 mg 1 times / day multiple, oral
Overdose
Dose: 10 mg, 1 times / day
Route: oral
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Adverse event grade 5
15 mg 1 times / day multiple, oral
Overdose
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Adverse event grade 5
2.5 mg 2 times / day multiple, oral
Overdose
Dose: 2.5 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2.5 mg, 2 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Fetal damage severe|grade 5
25 mg 1 times / week steady, oral
Recommended
Dose: 25 mg, 1 times / week
Route: oral
Route: steady
Dose: 25 mg, 1 times / week
Sources:
pregnant, adult
Gastrointestinal disorder (NOS)
25 mg 1 times / week steady, oral
Recommended
Dose: 25 mg, 1 times / week
Route: oral
Route: steady
Dose: 25 mg, 1 times / week
Sources:
unhealthy, adult
Hepatic and hepatobiliary disorders serious
25 mg 1 times / week steady, oral
Recommended
Dose: 25 mg, 1 times / week
Route: oral
Route: steady
Dose: 25 mg, 1 times / week
Sources:
unhealthy, adult
Kidney disorder serious
25 mg 1 times / week steady, oral
Recommended
Dose: 25 mg, 1 times / week
Route: oral
Route: steady
Dose: 25 mg, 1 times / week
Sources:
unhealthy, adult
Respiratory tract disorders NEC serious
25 mg 1 times / week steady, oral
Recommended
Dose: 25 mg, 1 times / week
Route: oral
Route: steady
Dose: 25 mg, 1 times / week
Sources:
unhealthy, adult
Skin and subcutaneous conditions NEC serious
25 mg 1 times / week steady, oral
Recommended
Dose: 25 mg, 1 times / week
Route: oral
Route: steady
Dose: 25 mg, 1 times / week
Sources:
unhealthy, adult
Fetal damage severe|grade 5
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
pregnant, adult
Health Status: pregnant
Age Group: adult
Sex: F
Sources:
Hepatic and hepatobiliary disorders serious
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
unhealthy, adult
Kidney disorder serious
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
unhealthy, adult
Respiratory tract disorders NEC serious
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
unhealthy, adult
Skin and subcutaneous conditions NEC serious
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
unhealthy, adult
Interstitial pneumonitis serious
Disc. AE
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
unhealthy, adult
Skin and subcutaneous conditions NEC severe|grade 5
7.5 mg 1 times / week steady, subcutaneous
Recommended
Dose: 7.5 mg, 1 times / week
Route: subcutaneous
Route: steady
Dose: 7.5 mg, 1 times / week
Sources:
unhealthy, adult
Aplastic anemia severe|grade 5
30 mg 1 times / week multiple, subcutaneous
Dose: 30 mg, 1 times / week
Route: subcutaneous
Route: multiple
Dose: 30 mg, 1 times / week
Sources:
unhealthy, adult
Bone marrow depression severe|grade 5
30 mg 1 times / week multiple, subcutaneous
Dose: 30 mg, 1 times / week
Route: subcutaneous
Route: multiple
Dose: 30 mg, 1 times / week
Sources:
unhealthy, adult
Gastrointestinal toxicity severe|grade 5
30 mg 1 times / week multiple, subcutaneous
Dose: 30 mg, 1 times / week
Route: subcutaneous
Route: multiple
Dose: 30 mg, 1 times / week
Sources:
unhealthy, adult
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer








Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
Drug as victim
PubMed

PubMed

TitleDatePubMed
[Methotrexate pneumonitis arising during the treatment of non-Hodgkin's lymphomas with the m-BACOD protocol].
1995 Jan
Management of separation pain after single-dose methotrexate therapy for ectopic pregnancy.
1999 Apr
Prospective evaluation of high-dose ifosfamide-related nephrotoxicity in young adult patients with recurrent osteosarcoma previously treated with cisplatin, methotrexate and standard-dose ifosfamide.
1999 Jan
Delayed methotrexate clearance in a patient with sickle cell anemia and osteosarcoma.
1999 Mar-Apr
Influence of cyclosporin A on radiological progression in early rheumatoid arthritis patients: a 42-month prospective study.
2000
Impotence in a patient with rheumatoid arthritis treated with methotrexate.
2000 Jul
Acute stroke-like encephalopathy associated with high-dose methotrexate impurities.
2000 Jul-Aug
Veno-occlusive disease of the liver associated with thiopurines in a child with acute lymphoblastic leukemia.
2000 Jul-Aug
Hepatocellular carcinoma: a rare late event in childhood acute lymphoblastic leukemia.
2000 May-Jun
Long-term cerebral metabolite changes on proton magnetic resonance spectroscopy in patients cured of acute lymphoblastic leukemia with previous intrathecal methotrexate and cranial irradiation prophylaxis.
2001 Jul 1
Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy.
2001 Jul-Aug
Homocysteine modulation as a reason for continuous folic acid supplementation in methotrexate-treated rheumatoid arthritis patients.
2001 Jun
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.
2001 May
Mutation of Trp1254 in the multispecific organic anion transporter, multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity and results in loss of methotrexate transport activity.
2001 Oct 12
Methylation-dependent silencing of the reduced folate carrier gene in inherently methotrexate-resistant human breast cancer cells.
2001 Oct 26
Isolation of rat dihydrofolate reductase gene and characterization of recombinant enzyme.
2001 Sep
Multiple anomalies in a fetus exposed to low-dose methotrexate in the first trimester.
2002 Apr
CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes.
2002 Jul
Patents

Sample Use Guides

Usual Adult Dose for Acute Lymphoblastic Leukemia
Route of Administration: Other
VEGF and Ang-1 levels were significantly lower, and Ang-2 levels were significantly higher in NPs (organ-cultured nasal polyps) treated with 100-umolar Methotrexate than in nontreated NPs
Name Type Language
METHOTREXATE
EP   HSDB   INN   MART.   MI   USAN   USP   VANDF   WHO-DD   WHO-IP  
INN   USAN  
Official Name English
METHOTREXATE [WHO-IP]
Common Name English
METHOTREXATE [USP-RS]
Common Name English
METHYLAMINOPTERIN
Common Name English
METHOTREXATE [EP MONOGRAPH]
Common Name English
METHOTREXATE [INN]
Common Name English
METHOTREXATUM [WHO-IP LATIN]
Common Name English
METHOTREXATE [IARC]
Common Name English
METHOTREXATE [USAN]
Common Name English
METHOTREXATE [ORANGE BOOK]
Common Name English
AMETHOPTERIN
Common Name English
XATMEP
Brand Name English
METHOTREXATE [MART.]
Common Name English
ADX-2191
Code English
METHOTREXATE [MI]
Common Name English
REDITREX
Brand Name English
R-9985
Code English
CL-14377
Code English
METHOTREXATE [USP MONOGRAPH]
Common Name English
METHOTREXATE [INCI]
Common Name English
METHOTREXATE [HSDB]
Common Name English
MTX
Common Name English
RASUVO
Brand Name English
METHOTREXATE [WHO-DD]
Common Name English
CL 14377
Code English
NSC-740
Code English
METHOTREXATE [JAN]
Common Name English
METHOTREXATE [USP]
Common Name English
(2S)-2-((4-(((2,4-DIAMINOPTERIDIN-6-YL)METHYL)(METHYL)AMINO)BENZOYL)AMINO)PENTANEDIOIC ACID
Systematic Name English
METHOTREXATE [VANDF]
Common Name English
Classification Tree Code System Code
IARC Methotrexate
FDA ORPHAN DRUG 469315
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
LIVERTOX 619
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
FDA ORPHAN DRUG 440314
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
FDA ORPHAN DRUG 679019
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
WHO-VATC QL01BA01
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
FDA ORPHAN DRUG 479515
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 8.2
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
NCI_THESAURUS C511
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
FDA ORPHAN DRUG 76693
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
WHO-ATC L01BA01
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
NDF-RT N0000175584
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
NCI_THESAURUS C2153
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
EU-Orphan Drug EU/3/07/495
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
FDA ORPHAN DRUG 286409
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
FDA ORPHAN DRUG 479615
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
WHO-VATC QL04AX03
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
NDF-RT N0000000111
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
WHO-ATC L04AX03
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
FDA ORPHAN DRUG 43389
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 2.4
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
FDA ORPHAN DRUG 630518
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL34259
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
FDA UNII
YL5FZ2Y5U1
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
RXCUI
6851
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY RxNorm
USP_CATALOG
1414003
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY USP-RS
MERCK INDEX
M7327
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY Merck Index
PUBCHEM
126941
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
DRUG BANK
DB00563
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
DRUG CENTRAL
1751
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-413-8
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
HSDB
3123
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
CAS
59-05-2
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
IUPHAR
4815
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
METHOTREXATE
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY Description: A yellow to orange, crystalline powder. Solubility: Practically insoluble in water, ethanol (~750 g/l) TS, dichloroethane R, and ether R; very soluble in diluted solutions of alkali hydroxides and carbonates. Category: Cytotoxic drug.Storage: Methotrexate should be kept in a tightly closed container, protected from light. Additional information: Methotrexate is gradually affected by light. CAUTION: Methotrexate must be handled with care, avoiding contact with the skin and inhalation of airborne particles. Definition: Methotrexate contains not less than 96.0% and not more than 102.0% of C20H22N8O5, calculated with reference to the anhydrous substance.
EPA CompTox
59-05-2
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
INN
926
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
WIKIPEDIA
METHOTREXATE
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
UCSF-FDA TRANSPORTAL
Methotrexate
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
LACTMED
Methotrexate
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
MESH
D008727
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
NCI_THESAURUS
C642
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY
EVMPD
SUB08856MIG
Created by admin on Fri Jun 25 20:53:34 UTC 2021 , Edited by admin on Fri Jun 25 20:53:34 UTC 2021
PRIMARY