Difference between revisions of "Methotrexate (MTX)"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m
m (Text replacement - "[http://online.lexi.com/ Lexicomp]" to "[https://online.lexi.com/lco/action/login UpToDate Lexidrug]")
(13 intermediate revisions by 2 users not shown)
Line 4: Line 4:
 
<br>Extravasation: [[inflammitant]]
 
<br>Extravasation: [[inflammitant]]
  
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>  
+
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [https://online.lexi.com/lco/action/login UpToDate Lexidrug], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>  
  
 
==Toxicity==
 
==Toxicity==
 
===Monitoring of plasma levels===
 
===Monitoring of plasma levels===
# Stoller RG, Hande KR, Jacobs SA, Rosenberg SA, Chabner BA. Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity. N Engl J Med. 1977 Sep 22;297(12):630-4. [https://www.nejm.org/doi/full/10.1056/NEJM197709222971203 link to original article] [https://pubmed.ncbi.nlm.nih.gov/302412 PubMed]
+
# Stoller RG, Hande KR, Jacobs SA, Rosenberg SA, Chabner BA. Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity. N Engl J Med. 1977 Sep 22;297(12):630-4. [https://doi.org/10.1056/NEJM197709222971203 link to original article] [https://pubmed.ncbi.nlm.nih.gov/302412/ PubMed]
 
===Reversal agents===
 
===Reversal agents===
 
*[[Glucarpidase (Voraxaze)]] can be used to treat toxic plasma methotrexate concentrations (greater than 1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function
 
*[[Glucarpidase (Voraxaze)]] can be used to treat toxic plasma methotrexate concentrations (greater than 1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function
  
==Diseases for which it is established==
+
==Diseases for which it is established ''(work in progress)''==
 +
*[[Osteosarcoma]]
 
*[[Peripheral T-cell lymphoma]]
 
*[[Peripheral T-cell lymphoma]]
  
 
==Diseases for which it is used==
 
==Diseases for which it is used==
 
<div style="column-count:3;-moz-column-count:3;-webkit-column-count:3">
 
<div style="column-count:3;-moz-column-count:3;-webkit-column-count:3">
 +
*[[Acute lymphoblastic leukemia, infant]]
 
*[[Acute myeloid leukemia]]
 
*[[Acute myeloid leukemia]]
 
*[[Acute promyelocytic leukemia]]
 
*[[Acute promyelocytic leukemia]]
 
*[[B-cell acute lymphoblastic leukemia]]
 
*[[B-cell acute lymphoblastic leukemia]]
*[[Bladder cancer]]
 
 
*[[Breast cancer]]
 
*[[Breast cancer]]
 
*[[CNS leukemia]]
 
*[[CNS leukemia]]
Line 40: Line 41:
 
**[[Mantle cell lymphoma]]
 
**[[Mantle cell lymphoma]]
 
**[[NK- and T-cell lymphoma]]
 
**[[NK- and T-cell lymphoma]]
*[[Osteosarcoma]]
 
 
*[[Penile cancer]]
 
*[[Penile cancer]]
 
*[[Testicular cancer]]
 
*[[Testicular cancer]]
 
*[[T-cell acute lymphoblastic leukemia]]
 
*[[T-cell acute lymphoblastic leukemia]]
 +
*[[Urothelial carcinoma]]
 +
**[[Bladder cancer]]
 
</div>
 
</div>
  
Line 50: Line 52:
 
*[[Follicular lymphoma - historical|Follicular lymphoma]]
 
*[[Follicular lymphoma - historical|Follicular lymphoma]]
 
*[[Gastric cancer - historical|Gastric cancer]]
 
*[[Gastric cancer - historical|Gastric cancer]]
*[[Hodgkin lymphoma - historical|Hodgkin lymphoma]]
+
*[[Classical Hodgkin lymphoma - historical|Hodgkin lymphoma]]
 
*[[Non-small cell lung cancer - historical|Non-small cell lung cancer]]
 
*[[Non-small cell lung cancer - historical|Non-small cell lung cancer]]
 
*[[Ovarian cancer - historical|Ovarian cancer]]
 
*[[Ovarian cancer - historical|Ovarian cancer]]
Line 62: Line 64:
  
 
==History of changes in FDA indication==
 
==History of changes in FDA indication==
* 12/7/1953: Initial FDA approval
+
* 1953-12-07: Initial FDA approval
* Most recent package insert:
+
* Uncertain date: Methotrexate is indicated in the treatment of [[Gestational trophoblastic neoplasia|gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole]]. ''(No supporting studies are cited)''
**Methotrexate is indicated in the treatment of [[Gestational trophoblastic neoplasia|gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole]].
+
*Uncertain date: In [[:Category:Acute lymphoblastic leukemias|acute lymphocytic leukemia]], methotrexate is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents. ''(No supporting studies are cited)''
**In [[:Category:Acute lymphoblastic leukemias|acute lymphocytic leukemia]], methotrexate is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents.  
+
*Uncertain date: Methotrexate is also indicated in the treatment of [[CNS leukemia|meningeal leukemia]]. ''(No supporting studies are cited)''
**Methotrexate is also indicated in the treatment of [[CNS leukemia|meningeal leukemia]].
+
*Uncertain date: Methotrexate is used alone or in combination with other anticancer agents in the treatment of [[breast cancer]], [[Head and neck cancer|epidermoid cancers of the head and neck]], advanced [[Cutaneous T-cell lymphoma|mycosis fungoides (cutaneous T cell lymphoma)]], and lung cancer, particularly [[Non-small cell lung cancer, squamous|squamous cell]] and [[Small cell lung cancer|small cell]] types. ''(No supporting studies are cited)''
**Methotrexate is used alone or in combination with other anticancer agents in the treatment of [[breast cancer]], [[Head and neck cancer|epidermoid cancers of the head and neck]], advanced [[Cutaneous T-cell lymphoma|mycosis fungoides (cutaneous T cell lymphoma)]], and lung cancer, particularly [[Non-small cell lung cancer, squamous|squamous cell]] and [[Small cell lung cancer|small cell]] types.  
+
*Uncertain date: Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage [[:Category:Non-Hodgkin lymphomas|non-Hodgkin’s lymphomas]]. ''(No supporting studies are cited)''
**Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage [[:Category:Non-Hodgkin lymphomas|non-Hodgkin’s lymphomas]].
+
*Uncertain date: Methotrexate 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. ''(No supporting studies are cited)''
**Methotrexate 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.
+
==History of changes in EMA indication==
 +
*1962-01-01: EURD
  
 
==Also known as==
 
==Also known as==
Line 98: Line 101:
 
|Ifamet
 
|Ifamet
 
|Imutrex
 
|Imutrex
 +
|Jylamvo
 
|Ledertrexate
 
|Ledertrexate
 
|Ledertrexato
 
|Ledertrexato
 
|Lumexon
 
|Lumexon
 
|Matrex
 
|Matrex
 +
|-
 
|Maxtrex
 
|Maxtrex
|-
 
 
|Medsatrexate
 
|Medsatrexate
 
|Merex
 
|Merex
Line 111: Line 115:
 
|Methorex
 
|Methorex
 
|Methotrexaat
 
|Methotrexaat
 +
|-
 
|Methotrexat  
 
|Methotrexat  
|-
 
 
|Methotrexato
 
|Methotrexato
 
|Methotrexatum
 
|Methotrexatum
Line 120: Line 124:
 
|Metotrexate
 
|Metotrexate
 
|Metotrexato
 
|Metotrexato
 +
|-
 
|Metotrexol
 
|Metotrexol
|-
 
 
|Metrex
 
|Metrex
 
|Metrexan
 
|Metrexan
Line 129: Line 133:
 
|Miantrex CS
 
|Miantrex CS
 
|Neometho
 
|Neometho
 +
|-
 
|Neotrexate
 
|Neotrexate
|-
+
|Nordimet
 
|Novatrex
 
|Novatrex
 
|Oncotrex
 
|Oncotrex
Line 137: Line 142:
 
|Remtrex
 
|Remtrex
 
|Reumatrex
 
|Reumatrex
 +
|-
 
|Rextop
 
|Rextop
 
|Rheumatrex
 
|Rheumatrex
|-
 
 
|Tecnomet
 
|Tecnomet
 
|Texate
 
|Texate
Line 146: Line 151:
 
|Tremetex
 
|Tremetex
 
|Trexall
 
|Trexall
 +
|-
 
|Trexan
 
|Trexan
 
|Trexeron
 
|Trexeron
|-
 
 
|Trixilem
 
|Trixilem
 
|Unitrexate
 
|Unitrexate
Line 170: Line 175:
 
[[Category:Immunosuppressants]]
 
[[Category:Immunosuppressants]]
  
 +
[[Category:Acute lymphoblastic leukemia, infant medications]]
 
[[Category:Acute myeloid leukemia medications]]
 
[[Category:Acute myeloid leukemia medications]]
 
[[Category:Acute promyelocytic leukemia medications]]
 
[[Category:Acute promyelocytic leukemia medications]]
Line 197: Line 203:
 
[[Category:Testicular cancer medications]]
 
[[Category:Testicular cancer medications]]
 
[[Category:T-cell acute lymphoblastic leukemia medications]]
 
[[Category:T-cell acute lymphoblastic leukemia medications]]
 +
[[Category:Urothelial carcinoma medications]]
  
 
[[Category:Colon cancer medications (historic)]]
 
[[Category:Colon cancer medications (historic)]]
 
[[Category:Follicular lymphoma medications (historic)]]
 
[[Category:Follicular lymphoma medications (historic)]]
 
[[Category:Gastric cancer medications (historic)]]
 
[[Category:Gastric cancer medications (historic)]]
[[Category:Hodgkin lymphoma medications (historic)]]
+
[[Category:Classical Hodgkin lymphoma medications (historic)]]
 
[[Category:Non-small cell lung cancer medications (historic)]]
 
[[Category:Non-small cell lung cancer medications (historic)]]
 
[[Category:Ovarian cancer medications (historic)]]
 
[[Category:Ovarian cancer medications (historic)]]
Line 208: Line 215:
  
 
[[Category:FDA approved in 1953]]
 
[[Category:FDA approved in 1953]]
 +
[[Category:EMA approved in 1962]]
 
[[Category:WHO Essential Cancer Medicine]]
 
[[Category:WHO Essential Cancer Medicine]]

Revision as of 01:04, 27 June 2024

General information

Class/mechanism: Folate analog, antimetabolite, interferes with DNA synthesis. Methotrexate inhibits dihydrofolic acid reductase, which catalyzes reactions that produce tetrahydrofolates, which are used in purine nucleotide and thymidylate synthesis.[1][2][3][4][5][6][7]
Route: IV, PO, IM, IT, SC, intraarterial
Extravasation: inflammitant

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, UpToDate Lexidrug, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]

Toxicity

Monitoring of plasma levels

  1. Stoller RG, Hande KR, Jacobs SA, Rosenberg SA, Chabner BA. Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity. N Engl J Med. 1977 Sep 22;297(12):630-4. link to original article PubMed

Reversal agents

  • Glucarpidase (Voraxaze) can be used to treat toxic plasma methotrexate concentrations (greater than 1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function

Diseases for which it is established (work in progress)

Diseases for which it is used

Diseases for which it was used

Patient drug information

History of changes in FDA indication

  • 1953-12-07: Initial FDA approval
  • Uncertain date: Methotrexate is indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. (No supporting studies are cited)
  • Uncertain date: 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. (No supporting studies are cited)
  • Uncertain date: Methotrexate is also indicated in the treatment of meningeal leukemia. (No supporting studies are cited)
  • Uncertain date: 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. (No supporting studies are cited)
  • Uncertain date: Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin’s lymphomas. (No supporting studies are cited)
  • Uncertain date: Methotrexate 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. (No supporting studies are cited)

History of changes in EMA indication

  • 1962-01-01: EURD

Also known as

  • Generic names: amethopterin, MTX
  • Brand names:
Synonyms
Abitrexate Alltrex Antifolan Artrait Biometrox Biotrexate Caditrex Cytotrexate
Ebetrexat Emthexat Emthexate Ervemin Farmitrexat Fauldmetro Folex PFS Folitrax
Hextrate Ifamet Imutrex Jylamvo Ledertrexate Ledertrexato Lumexon Matrex
Maxtrex Medsatrexate Merex Metex Methobax Methoblastin Methorex Methotrexaat
Methotrexat Methotrexato Methotrexatum Meticil Metolate Metotressato Metotrexate Metotrexato
Metotrexol Metrex Metrexan Metrexato Metrotex Mexate Miantrex CS Neometho
Neotrexate Nordimet Novatrex Oncotrex O Trexat Pharmatrexate Remtrex Reumatrex
Rextop Rheumatrex Tecnomet Texate Texorate Tratoben Tremetex Trexall
Trexan Trexeron Trixilem Unitrexate Zexate

References