Mechlorethamine (topical): Difference between revisions

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__NOTOC__
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==Overview==
<!--Pill Image-->
'''Chlormethine''' ([[International Nonproprietary Name|INN]], [[British Approved Name|BAN]]), '''mechlorethamine''' (widely used in the US, not the [[United States Adopted Name|USAN]], however) also known as '''mustine''' and '''HN2''' and in former [[USSR]] known as '''Embichin''' is a [[nitrogen mustard]] sold under the brand name '''Mustargen'''. It is the prototype of [[alkylating agent]]s, a group of [[cancer|anticancer]] chemotherapeutic drugs. It works by binding to DNA, crosslinking two strands and preventing cell duplication. It binds to the N7 nitrogen on the DNA base [[guanine]]. As the chemical is a [[blister agent]], its use is strongly restricted within the [[Chemical Weapons Convention]] where it is classified as a [[List of Schedule 1 substances (CWC)|Schedule 1 substance]].


Mechlorethamine belongs to the group of [[nitrogen mustard]] [[alkylating antineoplastic agent|alkylating agents]].<ref name="pmid10746948">{{cite journal |author=Rappeneau S, Baeza-Squiban A, Jeulin C, Marano F |title=Protection from cytotoxic effects induced by the nitrogen mustard mechlorethamine on human bronchial epithelial cells in vitro |journal=Toxicol. Sci. |volume=54 |issue=1 |pages=212–21 |date=March 2000 |pmid=10746948 |doi= 10.1093/toxsci/54.1.212|url=http://toxsci.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10746948}}</ref><ref>Takimoto CH, Calvo E. [http://www.cancernetwork.com/cancer-management-11/chapter03/article/10165/1402628 "Principles of Oncologic Pharmacotherapy"] in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) [http://www.cancernetwork.com/cancer-management-11/ Cancer Management: A Multidisciplinary Approach]. 11 ed. 2008.</ref>


==Uses==
It has been derivatized into the [[estrogen]] analogue [[estramustine]], used to treat [[prostate cancer]]. It can also be used in [[chemical warfare]] where it has the code-name '''HN2'''. This chemical is a form of nitrogen [[mustard gas]] and a powerful [[vesicant]]. Historically, some uses of mechlorethamine have included lymphoid malignancies such as Hodgkin’s disease, lymphosarcoma, chronic myelocytic leukemia, polycythemia vera, and bronchogenic carcinoma <ref>Bunn P, Hoffman S, Norris D, Golitz L, Aeling J. Systemic therapy of cutaneous T-cell lymphoma (mycosis fungoides and the Sezary syndrome). Ann Intern Med. 1994; 121(8):592–602. [PubMed:8085692]</ref> Mechlorethamine is often administered intravenously,<ref>Medline (2012). Mechlorethamine. Retrieved from http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682223.html</ref> but when compounded into a topical formulation it can also be used to treat skin diseases. There have been studies demonstrating that topical administration of mechlorethamine has efficacy in mycosis fungoides-type cutaneous T cell lymphoma <ref>Lindahl LM, Fenger-Gron M, Iversen L. Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis. J Eur Acad Dermatol Venereol. 2013 Feb;27(2):163-8.</ref><ref>Galper SL, Smith BD, Wilson LD. Diagnosis and management of mycosis fungoides. Oncology (Williston Park). 2010 May;24(6):491-501.</ref><ref>Lessin SR, Duvic M, Guitart J, Pandya AG, Strober BE, Olsen EA, Hull CM, Knobler EH, Rook AH, Kim EJ, Naylor MF, Adelson DM, Kimball AB, Wood GS, Sundram U, Wu H, Kim YH. Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol. 2013 Jan;149(1):25-32.</ref>


Another important use of chlormethine is in the synthesis of [[meperidine]] (aka pethidine, demerol).
<!--Label Display Image-->
==Side effects==
Mechlorethamine is a highly toxic medication, especially for women who are pregnant, breastfeeding, or of childbearing age.<ref>Recordati Rare Diseases Inc. (2013). Mustargen Package Insert. Retrieved from http://www.drugs.com/pro/mustargen.html</ref><ref>Actelion Pharmaceuticals Ltd. (2013) Valchlor Package Insert.  Retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf</ref>


The adverse effects of mechlorethamine depend on the formulation.<ref>[http://www.drugs.com/pro/mustargen.html Mustargen] and [http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Valchlor]</ref> Adverse effect include:
{{LabelImage
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“Hypersensitivity reactions, including anaphylaxis…. Nausea, vomiting and depression of formed elements in the circulating blood are dose-limiting side effects and usually occur with the use of full doses of MUSTARGEN. Jaundice, alopecia, vertigo, tinnitus and diminished hearing may occur infrequently. Rarely, hemolytic anemia associated with such diseases as the lymphomas and chronic lymphocytic leukemia may be precipitated by treatment with alkylating agents including MUSTARGEN. Also, various chromosomal abnormalities have been reported in association with nitrogen mustard therapy.”
{{LabelImage
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
}}


==Synthesis==
<!--Category-->
The compound is produced from readily available methyl[[diethanolamine]].<ref>{{Cite doi|10.1135/cccc19350093}}</ref><ref>{{Cite doi|10.1039/JR9470000513}}</ref><ref>{{Cite doi|10.1002/jctb.5000680908}}</ref>
[[File:Mechlorethamine01.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
==History==
Successful clinical use of chlormethine (mechlorethamine) resulted in development of the field of anticancer chemotherapy, led by [[Cornelius P. Rhoads]] at [[Memorial Sloan-Kettering]].  The drug is a nitrogen-based analogue of [[mustard gas]] (which is sulfur-based) and was derived from [[chemical warfare]] research.  Secret clinical trials of the agent for [[Hodgkin's disease]] and several other [[lymphoma]]s and [[leukemia]]s in humans began in December 1942.  Because of wartime secrecy restrictions, it was not until 1946 that the results of these trials were published openly.<ref>{{cite journal | author = Gilman A. | title = The initial clinical trial of nitrogen mustard | journal = Am J Surg. | year = 1963 | volume = 105 | pages = 574–578 | pmid = 13947966 |doi= 10.1016/00029610(63)90232-0 | issue = 5}}</ref>


[[Category:Chemotherapy]]
[[Category:Drug]]
[[Category:Chemotherapeutic agents]]
[[Category:Alkylating agents]]
[[Category:Nitrogen mustards]]

Revision as of 15:46, 12 May 2015

Mechlorethamine (topical)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

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Black Box Warning

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content

Overview

Mechlorethamine (topical) is a that is FDA approved for the {{{indicationType}}} of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Mechlorethamine (topical) FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Mechlorethamine (topical) in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Mechlorethamine (topical) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Mechlorethamine (topical) in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Mechlorethamine (topical) in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Mechlorethamine (topical) in pediatric patients.

Contraindications

  • Condition1

Warnings

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content
  • Description

Precautions

  • Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Mechlorethamine (topical) in the drug label.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Mechlorethamine (topical) in the drug label.

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mechlorethamine (topical) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Mechlorethamine (topical) during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Mechlorethamine (topical) with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Mechlorethamine (topical) with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Mechlorethamine (topical) with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Mechlorethamine (topical) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Mechlorethamine (topical) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Mechlorethamine (topical) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Mechlorethamine (topical) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Mechlorethamine (topical) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Mechlorethamine (topical) in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Mechlorethamine (topical) in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Mechlorethamine (topical) in the drug label.

Overdosage

There is limited information regarding Chronic Overdose of Mechlorethamine (topical) in the drug label.

Pharmacology

There is limited information regarding Mechlorethamine (topical) Pharmacology in the drug label.

Mechanism of Action

Structure

File:Mechlorethamine (topical)01.png
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Mechlorethamine (topical) in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Mechlorethamine (topical) in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Mechlorethamine (topical) in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Mechlorethamine (topical) in the drug label.

How Supplied

Storage

There is limited information regarding Mechlorethamine (topical) Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Mechlorethamine (topical) |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Mechlorethamine (topical) |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Mechlorethamine (topical) in the drug label.

Precautions with Alcohol

  • Alcohol-Mechlorethamine (topical) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Empty citation (help)
  2. ↑ "http://www.ismp.org". External link in |title= (help)




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