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

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H20N8O5.2Na
Molecular Weight 498.4029
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHOTREXATE SODIUM

SMILES

[Na+].[Na+].CN(CC1=NC2=C(N)N=C(N)N=C2N=C1)C3=CC=C(C=C3)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O

InChI

InChIKey=DASQOOZCTWOQPA-GXKRWWSZSA-L
InChI=1S/C20H22N8O5.2Na/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);;/q;2*+1/p-2/t13-;;/m0../s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including 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
5.19 pM [Ki]
0.18 mM [IC50]
15.0 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

1952
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

2001
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

2001
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

2001
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
n = 1
Health Status: unknown
Age Group: 10-19 years
Sex: M
Population Size: 1
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
n = 1
Health Status: unknown
Age Group: 10-19 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unknown
Age Group: 40-49 years
Sex: M
Population Size: 1
Sources:
3 g/m2 multiple, intravenous
Highest studied dose
Dose: 3 g/m2
Route: intravenous
Route: multiple
Dose: 3 g/m2
Co-administed with::
calcium folinate(oral, 50 mg at H24 and pursued this treatment every 6 h during 3 days (until day 4) for a total of 12 administrations)
Sources:
unhealthy, 41 years (range: 17–60 years)
n = 103
Health Status: unhealthy
Condition: aggressive lymphoma
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Population Size: 103
Sources:
Disc. AE: Toxicity renal...
AEs leading to
discontinuation/dose reduction:
Toxicity renal (grade 1-2, 2 patients)
Sources:
3 g/m2 multiple, intravenous
Highest studied dose
Dose: 3 g/m2
Route: intravenous
Route: multiple
Dose: 3 g/m2
Co-administed with::
(oral, 50 mg at H24 and pursued this treatment every 6 h during 3 days (until day 4) for a total of 12 administrations)
Sources:
unhealthy, 41 years (range: 17–60 years)
n = 103
Health Status: unhealthy
Condition: aggressive lymphoma
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Population Size: 103
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:
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 50-59 years
Sex: F
Population Size: 1
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
Co-administed with::
adalimumab(40 mg per every other week; 3 years)
guratimod(50 mg/day for approximately 3 years.)
Sources:
unhealthy, 54 years
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 54 years
Sex: F
Population Size: 1
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
n = 2
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 60-79 years
Sex: F
Population Size: 2
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 70-79 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Population Size: 1
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
Health Status: unhealthy
Condition: Mycosis fungoides
Age Group: adult
Sources:
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
Other AEs: Skin and subcutaneous conditions NEC...
Other AEs:
Skin and subcutaneous conditions NEC (severe|grade 5)
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
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Sources:
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:
30 mg 1 times / week multiple, subcutaneous
Dose: 30 mg, 1 times / week
Route: subcutaneous
Route: multiple
Dose: 30 mg, 1 times / week
Co-administed with::
Nonsteroidal anti-inflammatory drugs
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
n = 1
Health Status: unknown
Age Group: 10-19 years
Sex: M
Population Size: 1
Sources:
Vomiting 1 patient
75 mg single, oral
Overdose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources:
unknown, 10-19 years
n = 1
Health Status: unknown
Age Group: 10-19 years
Sex: M
Population Size: 1
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
n = 1
Health Status: unknown
Age Group: 10-19 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unknown
Age Group: 10-19 years
Sex: F
Population Size: 1
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
Co-administed with::
calcium folinate(oral, 50 mg at H24 and pursued this treatment every 6 h during 3 days (until day 4) for a total of 12 administrations)
Sources:
unhealthy, 41 years (range: 17–60 years)
n = 103
Health Status: unhealthy
Condition: aggressive lymphoma
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Population Size: 103
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
Co-administed with::
(oral, 50 mg at H24 and pursued this treatment every 6 h during 3 days (until day 4) for a total of 12 administrations)
Sources:
unhealthy, 41 years (range: 17–60 years)
n = 103
Health Status: unhealthy
Condition: aggressive lymphoma
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Population Size: 103
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
Co-administed with::
(oral, 50 mg at H24 and pursued this treatment every 6 h during 3 days (until day 4) for a total of 12 administrations)
Sources:
unhealthy, 41 years (range: 17–60 years)
n = 103
Health Status: unhealthy
Condition: aggressive lymphoma
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Population Size: 103
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
Co-administed with::
(oral, 50 mg at H24 and pursued this treatment every 6 h during 3 days (until day 4) for a total of 12 administrations)
Sources:
unhealthy, 41 years (range: 17–60 years)
n = 103
Health Status: unhealthy
Condition: aggressive lymphoma
Age Group: 41 years (range: 17–60 years)
Sex: M+F
Population Size: 103
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 50-59 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 50-59 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 50-59 years
Sex: F
Population Size: 1
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
Co-administed with::
adalimumab(40 mg per every other week; 3 years)
guratimod(50 mg/day for approximately 3 years.)
Sources:
unhealthy, 54 years
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 54 years
Sex: F
Population Size: 1
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
n = 2
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 60-79 years
Sex: F
Population Size: 2
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 70-79 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 70-79 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 70-79 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 70-79 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: 70-79 years
Sex: F
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Population Size: 1
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
n = 1
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Population Size: 1
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
Health Status: unhealthy
Condition: Mycosis fungoides
Age Group: adult
Sources:
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
Health Status: unhealthy
Condition: Mycosis fungoides
Age Group: adult
Sources:
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
Health Status: unhealthy
Condition: Mycosis fungoides
Age Group: adult
Sources:
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
Health Status: unhealthy
Condition: Mycosis fungoides
Age Group: adult
Sources:
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
Health Status: unhealthy
Condition: Mycosis fungoides
Age Group: adult
Sources:
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:
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
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
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Sources:
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
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Sources:
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
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Sources:
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
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Sources:
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
Health Status: unhealthy
Condition: rheumatoid arthritis
Age Group: adult
Sources:
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
Co-administed with::
Nonsteroidal anti-inflammatory drugs
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
Co-administed with::
Nonsteroidal anti-inflammatory drugs
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
Co-administed with::
Nonsteroidal anti-inflammatory drugs
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
Cerebral calcifications associated with intrathecal methotrexate therapy in acute lymphocytic leukemia.
1976 Apr
Letter: Vasculitis as a complication of high-dose methotrexate in the treatment of acute leukemia.
1976 Jun
Toxicity profile of methotrexate in rheumatoid arthritis. A preliminary survey.
1999
Influence of cyclosporin A on radiological progression in early rheumatoid arthritis patients: a 42-month prospective study.
2000
Methotrexate, uracil and tegafur, and leucovorin chemotherapy for patients with breast cancer in progression after high-dose chemotherapy with peripheral blood progenitor cell transplant: a phase II study.
2000 Dec
Atrial fibrillation occurring in a patient taking etanercept plus methotrexate for rheumatoid arthritis.
2000 Dec
Identification by RNA-based arbitrarily primed PCR of the involvement of cytochrome c oxidase in the development of resistance to methotrexate.
2000 Feb 28
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
Cortical laminar necrosis caused by immunosuppressive therapy and chemotherapy.
2000 Mar
Serious liver disease in a patient receiving methotrexate and leflunomide.
2000 Nov
White matter changes on MRI during treatment in children with acute lymphoblastic leukemia: correlation with neuropsychological findings.
2000 Nov
Acute neurotoxicity in children with B-lineage acute lymphoblastic leukemia (B-ALL) treated with intermediate risk protocols.
2000 Nov
Toxicity of methotrexate treatment in psoriasis and psoriatic arthritis--short- and long-term toxicity in 104 patients.
2001
[Conservative therapy in endocrine orbitopathy: "State of the art"].
2001
Stereoselectivity of the folate transporter in rabbit small intestine: studies with amethopterin enantiomers.
2001
Hospital resources used for ectopic pregnancy treatment by laparoscopy and methotrexate.
2001 Apr-Jun
Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury.
2001 Dec
Transient posterior encephalopathy induced by chemotherapy in children.
2001 Feb
[Listeria arthritis in chronic polyarthritis during low dose prednisolone and methotrexate therapy. Case report and review of the literature].
2001 Feb
A comparison of methods of loco-regional chemotherapy combined with systemic chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity.
2001 Feb
Neoadjuvant chemotherapy for high grade osteosarcoma of the extremities: long-term results for patients treated according to the Rizzoli IOR/OS-3b protocol.
2001 Feb
Development of fulminant hepatitis B (precore variant mutant type) after the discontinuation of low-dose methotrexate therapy in a rheumatoid arthritis patient.
2001 Feb
[Fatal outcome of a multisystemic sarcoidosis in a 54-year-old patient].
2001 Jul
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
Successful rescue with leucovorin and thymidine in a patient with high-dose methotrexate induced acute renal failure.
2001 Jun
Homocysteine modulation as a reason for continuous folic acid supplementation in methotrexate-treated rheumatoid arthritis patients.
2001 Jun
Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials.
2001 Mar
Inappropriate medical management of spinal epidural abscess.
2001 Mar
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.
2001 May
Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli's 4th protocol.
2001 Nov
Tamoxifen-based treatment induces clinically meaningful responses in multiple myeloma patients with relapsing disease after autotransplantation.
2001 Nov-Dec
[Meningeal carcinomatosis as the first manifestation of gastric adenocarcinoma].
2001 Oct 11
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
Methotrexate-induced nephrogenic diabetes insipidus: first case report.
2002 Feb
Methotrexate-induced systemic vasculitis.
2002 Feb
Leukemic leptomeningeal involvement in stage 0 and stage 1 chronic lymphocytic leukemia.
2002 Jan
Methotrexate-related nonnecrotizing multifocal axonopathy detected by beta-amyloid precursor protein immunohistochemistry.
2002 Jan
Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice.
2002 Jul
CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes.
2002 Jul
Oral methotrexate for treatment of ectopic pregnancy.
2002 Jun
Radiation myelitis in a 5-year-old girl.
2002 Mar
[A case of subacute transient cerebral dysfunction in a osteosarcoma patient following high-dose methotrexate].
2002 Mar
Nephrotoxicity due to intermediate-dose methotrexate without rescue in an obese adolescent with acute lymphoblastic leukemia.
2002 Mar
Quantitative MRI assessment of leukoencephalopathy.
2002 May
Patents

Sample Use Guides

Usual Adult Dose for Acute Lymphoblastic Leukemia Induction: 3.3 mg/m2/day orally or IM (in combination with prednisone 60 mg/m2) daily Usual Adult Dose for Psoriasis Single Dose: 7.5 mg/week orally, IM, or IV until adequate response is achieved Divided Dose: 2.5 mg orally, IM, or IV every 12 hours for 3 doses once a week Maximum weekly dose: 20 mg
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 SODIUM
MART.   ORANGE BOOK   VANDF   WHO-DD  
Common Name English
ABITREXATE
Brand Name English
METHOTREXATE SODIUM SALT
Common Name English
METHOTREXATE (AS DISODIUM)
Common Name English
METHOTREXATE SODIUM [VANDF]
Common Name English
MEXATE
Brand Name English
Methotrexate sodium [WHO-DD]
Common Name English
TREXALL
Brand Name English
ADX-2191 SODIUM
Code English
METHOTREXATE DISODIUM
Common Name English
SODIUM L-(+)-METHOTREXATE
Common Name English
FOLEX
Brand Name English
DISODIUM METHOTREXATE
Common Name English
METHOTREXATE SODIUM [ORANGE BOOK]
Common Name English
METHOTREXATE DISODIUM SALT [MI]
Common Name English
METHOTREXATE DISODIUM SALT
MI  
Common Name English
METHOTREXATE SODIUM [MART.]
Common Name English
METHOTREXATE, SODIUM SALT
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2153
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
FDA ORPHAN DRUG 9985
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
NCI_THESAURUS C511
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
Code System Code Type Description
CAS
7413-34-5
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
EVMPD
SUB03225MIG
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
FDA UNII
3IG1E710ZN
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
NCI_THESAURUS
C1735
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
WIKIPEDIA
Methotrexate sodium
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
CHEBI
50679
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
CAS
15475-56-6
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
NON-SPECIFIC STOICHIOMETRY
CHEBI
44185
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
RXCUI
287734
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY RxNorm
PUBCHEM
11329481
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
DRUG BANK
DBSALT000115
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
EVMPD
SUB16442MIG
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
ECHA (EC/EINECS)
231-022-0
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
ChEMBL
CHEMBL34259
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
MERCK INDEX
m7327
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID3037123
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
ECHA (EC/EINECS)
239-495-5
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
ALTERNATIVE
SMS_ID
100000078565
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY
DAILYMED
3IG1E710ZN
Created by admin on Fri Dec 15 14:57:43 GMT 2023 , Edited by admin on Fri Dec 15 14:57:43 GMT 2023
PRIMARY