Difference between revisions of "Methotrexate (MTX)"

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==General information==
 
==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.<ref name="insert">[http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Roxane/Methotrexate/Methotrexate%20Tablets%20USP%202.5mg.pdf Methotrexate (MTX) tablet package insert]</ref><ref>[[Media:Methotrexatetablet.pdf|Methotrexate (MTX) tablet package insert (locally hosted backup)]]</ref><ref>[https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011719s117lbl.pdf Methotrexate (MTX) injection package insert]</ref><ref>[[Media:Methotrexateinjection.pdf|Methotrexate (MTX) injection package insert (locally hosted backup)]]</ref><ref name="Otrexup">[http://www.otrexup.com/files/4014/8909/8025/Otrexup_PII-13-001_Rev_8.pdf Methotrexate (Otrexup) subcutaneous injection package insert]</ref><ref>[[Media:MethotrexateSQ.pdf|Methotrexate (Otrexup) subcutaneous injection package insert (locally hosted backup)]]</ref><ref>[http://www.otrexup.com Otrexup manufacturer's website]</ref>
+
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.<ref name="insert">[http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Roxane/Methotrexate/Methotrexate%20Tablets%20USP%202.5mg.pdf Methotrexate (MTX) tablet package insert]</ref><ref>[[:File:Methotrexatetablet.pdf|Methotrexate (MTX) tablet package insert (locally hosted backup)]]</ref><ref>[https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011719s117lbl.pdf Methotrexate (MTX) injection package insert]</ref><ref>[[:File:Methotrexateinjection.pdf|Methotrexate (MTX) injection package insert (locally hosted backup)]]</ref><ref name="Otrexup">[http://www.otrexup.com/files/4014/8909/8025/Otrexup_PII-13-001_Rev_8.pdf Methotrexate (Otrexup) subcutaneous injection package insert]</ref><ref>[[:File:MethotrexateSQ.pdf|Methotrexate (Otrexup) subcutaneous injection package insert (locally hosted backup)]]</ref><ref>[http://www.otrexup.com Otrexup manufacturer's website]</ref>
 
<br>Route: IV, PO, IM, IT, SC, intraarterial
 
<br>Route: IV, PO, IM, IT, SC, intraarterial
 
<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], [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==
 +
===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://doi.org/10.1056/NEJM197709222971203 link to original article] [https://pubmed.ncbi.nlm.nih.gov/302412/ 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
 
*[[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
  
−
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>
+
==Diseases for which it is established ''(work in progress)''==
 +
*[[Osteosarcoma]]
 +
*[[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 promyelocytic leukemia]]
 
*[[Acute promyelocytic leukemia]]
−
*[[Adult T-cell leukemia-lymphoma]]
 
 
*[[B-cell acute lymphoblastic leukemia]]
 
*[[B-cell acute lymphoblastic leukemia]]
−
*[[Bladder cancer]]
 
 
*[[Breast cancer]]
 
*[[Breast cancer]]
−
*[[Burkitt lymphoma]]
 
 
*[[CNS leukemia]]
 
*[[CNS leukemia]]
−
*[[CNS lymphoma]]
+
*[[Desmoid tumors]]
−
*[[Diffuse large B-cell lymphoma]]
+
*[[Gestational trophoblastic neoplasia]]
−
*[[Extranodal NK/T-cell lymphoma, nasal type]]
 
 
*[[Head and neck cancer]]
 
*[[Head and neck cancer]]
 
*[[Hemophagocytic lymphohistiocytosis]]
 
*[[Hemophagocytic lymphohistiocytosis]]
−
*[[Histiocytoses]]
+
*[[Langerhans cell histiocytosis]]
−
*[[HIV-associated lymphoma]]
 
 
*[[Large granular lymphocytic leukemia]]
 
*[[Large granular lymphocytic leukemia]]
−
*[[Mantle cell lymphoma]]
+
*[[Medulloblastoma]]
−
*[[NK/T-cell lymphoma]]
+
*Non-Hodgkin lymphoma
−
*[[Osteosarcoma]]
+
**[[Adult T-cell leukemia-lymphoma]]
 +
**[[Burkitt lymphoma]]
 +
**[[CNS lymphoma]]
 +
**[[Cutaneous T-cell lymphoma]]
 +
**[[Diffuse large B-cell lymphoma]]
 +
**[[Extranodal NK- and T-cell lymphoma, nasal type]]
 +
**[[HIV-associated lymphoma]]
 +
**[[Mantle cell lymphoma]]
 +
**[[NK- and T-cell lymphoma]]
 
*[[Penile cancer]]
 
*[[Penile cancer]]
−
*[[Peripheral T-cell lymphoma]]
+
*[[Testicular cancer]]
−
*[[Prostate cancer]]
 
−
*[[Small cell lung cancer]]
 
 
*[[T-cell acute lymphoblastic leukemia]]
 
*[[T-cell acute lymphoblastic leukemia]]
−
*[[Transplant conditioning regimens]]
+
*[[Urothelial carcinoma]]
 +
**[[Bladder cancer]]
 
</div>
 
</div>
 +
 +
==Diseases for which it was used==
 +
*[[Colon cancer - historical|Colon cancer]]
 +
*[[Follicular lymphoma - historical|Follicular lymphoma]]
 +
*[[Gastric cancer - historical|Gastric cancer]]
 +
*[[Classical Hodgkin lymphoma - historical|Hodgkin lymphoma]]
 +
*[[Non-small cell lung cancer - historical|Non-small cell lung cancer]]
 +
*[[Ovarian cancer - historical|Ovarian cancer]]
 +
*[[Prostate cancer - historical|Prostate cancer]]
 +
*[[Small cell lung cancer - historical|Small cell lung cancer]]
  
 
==Patient drug information==
 
==Patient drug information==
Line 41: 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
 +
* Uncertain date: Methotrexate is indicated in the treatment of [[Gestational trophoblastic neoplasia|gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole]]. ''(No supporting studies are cited)''
 +
*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)''
 +
*Uncertain date: Methotrexate is also indicated in the treatment of [[CNS leukemia|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]], [[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)''
 +
*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)''
 +
*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==
 
==Also known as==
−
{| border="1" style="text-align:center;"
+
*'''Generic names:''' amethopterin, MTX
 +
*'''Brand names:'''
 +
{| class="wikitable" style="text-align:center;"
 
!colspan="8" align="center" style="background-color:#0066FF"| '''Synonyms'''
 
!colspan="8" align="center" style="background-color:#0066FF"| '''Synonyms'''
 
|-
 
|-
 
|Abitrexate
 
|Abitrexate
 
|Alltrex
 
|Alltrex
−
|Amethopterin
 
 
|Antifolan
 
|Antifolan
−
|APO-Methotrexate
 
 
|Artrait
 
|Artrait
 
|Biometrox
 
|Biometrox
 
|Biotrexate
 
|Biotrexate
−
|-
 
 
|Caditrex
 
|Caditrex
 
|Cytotrexate
 
|Cytotrexate
 +
|-
 
|Ebetrexat
 
|Ebetrexat
 
|Emthexat
 
|Emthexat
 
|Emthexate
 
|Emthexate
−
|Emthexate PF
 
−
|Emthexate S
 
 
|Ervemin
 
|Ervemin
−
|-
 
 
|Farmitrexat
 
|Farmitrexat
 
|Fauldmetro
 
|Fauldmetro
 
|Folex PFS
 
|Folex PFS
 
|Folitrax
 
|Folitrax
 +
|-
 
|Hextrate
 
|Hextrate
 
|Ifamet
 
|Ifamet
−
|Imutrex,Ledertrexate
+
|Imutrex
−
|Ledertrexate Sodium
+
|Jylamvo
−
|-
+
|Ledertrexate
 
|Ledertrexato
 
|Ledertrexato
 
|Lumexon
 
|Lumexon
 
|Matrex
 
|Matrex
 +
|-
 
|Maxtrex
 
|Maxtrex
 
|Medsatrexate
 
|Medsatrexate
Line 82: Line 112:
 
|Metex
 
|Metex
 
|Methobax
 
|Methobax
−
|-
 
 
|Methoblastin
 
|Methoblastin
 
|Methorex
 
|Methorex
 
|Methotrexaat
 
|Methotrexaat
−
|Methotrexaat Sandoz
 
−
|Methotrexat Biosyn
 
−
|Methotrexat Ebewe
 
−
|Methotrexate Bigmar
 
−
|Methotrexate Bristol
 
−
|-
 
−
|Methotrexate DBL
 
−
|Methotrexate Disodium
 
−
|Methotrexate DUP
 
−
|Methotrexate Ebewe
 
−
|Methotrexate Farmos
 
−
|Methotrexate Knoll
 
−
|Methotrexate Lederle
 
−
|Methotrexate LPF
 
−
|-
 
−
|Methotrexate Mayne
 
−
|Methotrexate Merck
 
−
|Methotrexate Paranova
 
−
|Methotrexate R
 
−
|Methotrexate Remedica
 
−
|Methotrexate Singad
 
−
|Methotrexate Sodium
 
−
|Methotrexate Sodium Lederle
 
 
|-
 
|-
−
|Methotrexate Teva
+
|Methotrexat  
−
|Methotrexate Wyeth
 
−
|Methotrexat Lederle
 
−
|Methotrexat Medac
 
 
|Methotrexato
 
|Methotrexato
−
|Methotrexat Ridupharm
 
−
|Methotrexat Teva
 
 
|Methotrexatum
 
|Methotrexatum
−
|-
 
 
|Meticil
 
|Meticil
 
|Metolate
 
|Metolate
 
|Metotressato
 
|Metotressato
 
|Metotrexate
 
|Metotrexate
−
|Metotrexato Asofarma
+
|Metotrexato
−
|Metotrexato Chiesi
 
−
|Metotrexato Dosa
 
−
|Metotrexato Filaxis
 
 
|-
 
|-
−
|Metotrexato Lederle
 
−
|Metotrexato Martian
 
−
|Metotrexato Microsules
 
 
|Metotrexol
 
|Metotrexol
 
|Metrex
 
|Metrex
Line 136: Line 130:
 
|Metrexato
 
|Metrexato
 
|Metrotex
 
|Metrotex
−
|-
 
 
|Mexate
 
|Mexate
 
|Miantrex CS
 
|Miantrex CS
−
|MTX
 
−
|MTX Hexal
 
 
|Neometho
 
|Neometho
 +
|-
 
|Neotrexate
 
|Neotrexate
 +
|Nordimet
 
|Novatrex
 
|Novatrex
 
|Oncotrex
 
|Oncotrex
−
|-
 
−
|Oncotrex-PF
 
 
|O Trexat
 
|O Trexat
−
|P&U Methotrexate
 
 
|Pharmatrexate
 
|Pharmatrexate
−
|Ratio-Methotrexate
 
 
|Remtrex
 
|Remtrex
 
|Reumatrex
 
|Reumatrex
 +
|-
 
|Rextop
 
|Rextop
−
|-
 
 
|Rheumatrex
 
|Rheumatrex
 
|Tecnomet
 
|Tecnomet
 
|Texate
 
|Texate
−
|Texate T
 
 
|Texorate
 
|Texorate
 
|Tratoben
 
|Tratoben
−
|Trav Methotrexate
 
 
|Tremetex
 
|Tremetex
 +
|Trexall
 
|-
 
|-
−
|Trexall
 
 
|Trexan
 
|Trexan
 
|Trexeron
 
|Trexeron
 
|Trixilem
 
|Trixilem
−
|Trixilem RU
 
 
|Unitrexate
 
|Unitrexate
−
|Vero Methotrexate
 
 
|Zexate
 
|Zexate
 
|-
 
|-
Line 178: Line 163:
 
<references/>
 
<references/>
  
−
[[Category:Drug index]]
+
[[Category:Drugs]]
−
[[Category:Chemotherapy]]
 
 
[[Category:Intramuscular medications]]
 
[[Category:Intramuscular medications]]
 
[[Category:Intrathecal medications]]
 
[[Category:Intrathecal medications]]
−
[[Category:Intravenous chemotherapy]]
+
[[Category:Intravenous medications]]
−
[[Category:Oral chemotherapy]]
+
[[Category:Oral medications]]
−
[[Category:Inflammitant chemotherapy]]
+
[[Category:Subcutaneous medications]]
 +
[[Category:Inflammitant]]
  
 
[[Category:Antimetabolites]]
 
[[Category:Antimetabolites]]
 
[[Category:Antifolates]]
 
[[Category:Antifolates]]
−
[[Category:Immunosuppresants]]
+
[[Category:Immunosuppressants]]
  
 +
[[Category:Acute lymphoblastic leukemia, infant medications]]
 +
[[Category:Acute myeloid leukemia medications]]
 
[[Category:Acute promyelocytic leukemia medications]]
 
[[Category:Acute promyelocytic leukemia medications]]
 
[[Category:Adult T-cell leukemia-lymphoma medications]]
 
[[Category:Adult T-cell leukemia-lymphoma medications]]
Line 196: Line 183:
 
[[Category:Breast cancer medications]]
 
[[Category:Breast cancer medications]]
 
[[Category:Burkitt lymphoma medications]]
 
[[Category:Burkitt lymphoma medications]]
−
[[Category:Central nervous system (CNS) lymphoma medications]]
+
[[Category:CNS lymphoma medications]]
 
[[Category:CNS leukemia medications]]
 
[[Category:CNS leukemia medications]]
 +
[[Category:Cutaneous T-cell lymphoma medications]]
 +
[[Category:Desmoid tumor medications]]
 
[[Category:Diffuse large B-cell lymphoma medications]]
 
[[Category:Diffuse large B-cell lymphoma medications]]
−
[[Category:Extranodal NK/T-cell lymphoma, nasal type medications]]
+
[[Category:Extranodal NK- and T-cell lymphoma, nasal type medications]]
 +
[[Category:Gestational trophoblastic neoplasia medications]]
 
[[Category:Head and neck cancer medications]]
 
[[Category:Head and neck cancer medications]]
 
[[Category:Hemophagocytic lymphohistiocytosis medications]]
 
[[Category:Hemophagocytic lymphohistiocytosis medications]]
−
[[Category:Histiocytoses medications]]
 
 
[[Category:HIV-associated lymphoma medications]]
 
[[Category:HIV-associated lymphoma medications]]
 +
[[Category:Langerhans cell histiocytosis medications]]
 
[[Category:Large granular lymphocytic leukemia medications]]
 
[[Category:Large granular lymphocytic leukemia medications]]
 
[[Category:Mantle cell lymphoma medications]]
 
[[Category:Mantle cell lymphoma medications]]
−
[[Category:NK/T-cell lymphoma medications]]
+
[[Category:Medulloblastoma medications]]
 +
[[Category:NK- and T-cell lymphoma medications]]
 
[[Category:Osteosarcoma medications]]
 
[[Category:Osteosarcoma medications]]
 
[[Category:Penile cancer medications]]  
 
[[Category:Penile cancer medications]]  
 
[[Category:Peripheral T-cell lymphoma medications]]
 
[[Category:Peripheral T-cell lymphoma medications]]
−
[[Category:Prostate cancer medications]]
+
[[Category:Testicular cancer medications]]
−
[[Category:Small cell lung cancer medications]]
+
[[Category:T-cell acute lymphoblastic leukemia medications]]
−
[[Category:Transplant medications]]
+
[[Category:Urothelial carcinoma medications]]
 +
 
 +
[[Category:Colon cancer medications (historic)]]
 +
[[Category:Follicular lymphoma medications (historic)]]
 +
[[Category:Gastric cancer medications (historic)]]
 +
[[Category:Classical Hodgkin lymphoma medications (historic)]]
 +
[[Category:Non-small cell lung cancer medications (historic)]]
 +
[[Category:Ovarian cancer medications (historic)]]
 +
[[Category:Prostate cancer medications (historic)]]
 +
[[Category:Small cell lung cancer medications (historic)]]
  
−
[[Category:Drugs 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

  1. ↑ 1.0 1.1 Methotrexate (MTX) tablet package insert
  2. ↑ Methotrexate (MTX) tablet package insert (locally hosted backup)
  3. ↑ Methotrexate (MTX) injection package insert
  4. ↑ Methotrexate (MTX) injection package insert (locally hosted backup)
  5. ↑ 5.0 5.1 Methotrexate (Otrexup) subcutaneous injection package insert
  6. ↑ Methotrexate (Otrexup) subcutaneous injection package insert (locally hosted backup)
  7. ↑ Otrexup manufacturer's website
  8. ↑ Methotrexate (MTX) patient drug information (Chemocare)
  9. ↑ Methotrexate (MTX) patient drug information (UpToDate)
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