Mechlorethamine (topical)

Mechlorethamine (topical)
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

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]

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Overview

Mechlorethamine (topical) is an nitrogen mustard that is FDA approved for the {{{indicationType}}} of . Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy.

Dosage

• For Topical Dermatological Use Only
• Apply a thin film of VALCHLOR gel once daily to affected areas of the skin.
• Stop treatment with VALCHLOR for any grade of skin ulceration, blistering, or moderately-severe or severe dermatitis (i.e., marked skin redness with edema) [see Warnings and Precautions (5.3)]. Upon improvement, treatment with VALCHLOR can be restarted at a reduced frequency of once every 3 days. If reintroduction of treatment is tolerated for at least one week, the frequency of application can be increased to every other day for at least one week and then to once daily application if tolerated.

Application Instructions

• VALCHLOR is a cytotoxic drug. Follow applicable special handling and disposal procedures.1

• Patients must wash hands thoroughly with soap and water after handling or applying VALCHLOR.
• Caregivers must wear disposable nitrile gloves when applying VALCHLOR to patients and wash hands thoroughly with soap and water after removal of gloves. If there is accidental skin exposure to VALCHLOR, caregivers must immediately wash exposed areas thoroughly with soap and water for at least 15 minutes and remove contaminated clothing.
• Patients or caregivers should follow these instructions when applying VALCHLOR:

• Apply immediately or within 30 minutes after removal from the refrigerator. Return VALCHLOR to the refrigerator immediately after each use.
• Apply to completely dry skin at least 4 hours before or 30 minutes after showering or washing. Allow treated areas to dry for 5 to 10 minutes after application before covering with clothing.
• Emollients (moisturizers) may be applied to the treated areas 2 hours before or 2 hours after application.
• Do not use occlusive dressings on areas of the skin where VALCHLOR was applied.
• Avoid fire, flame, and smoking until VALCHLOR has dried

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

• The use of VALCHLOR is contraindicated in patients with known severe hypersensitivity to mechlorethamine. Hypersensitivity reactions, including anaphylaxis, have occurred with topical formulations of mechlorethamine.

Warnings

• Mucosal or Eye Injury

• Exposure of the eyes to mechlorethamine causes pain, burns, inflammation, photophobia, and blurred vision. Blindness and severe irreversible anterior eye injury may occur. Advise patients that if eye exposure occurs, (1) immediately irrigate for at least 15 minutes with copious amounts of water, normal saline, or a balanced salt ophthalmic irrigating solution and (2) obtain immediate medical care (including ophthalmologic consultation).

• Exposure of mucous membranes such as the oral mucosa or nasal mucosa causes pain, redness, and ulceration, which may be severe. Should mucosal contact occur, immediately irrigate for at least 15 minutes with copious amounts of water, followed by immediate medical consultation.

• Secondary Exposure to VALCHLOR

• Avoid direct skin contact with VALCHLOR in individuals other than the patient. Risks of secondary exposure include dermatitis, mucosal injury, and secondary cancers. Follow recommended application instructions to prevent secondary exposure [see Dosage and Administration (2.2)].

• Dermatitis

• The most common adverse reaction was dermatitis, which occurred in 56% of the patients [see Adverse Reactions (6.1)]. Dermatitis was moderately severe or severe in 23% of patients. Monitor patients for redness, swelling, inflammation, itchiness, blisters, ulceration, and secondary skin infections. The face, genitalia, anus, and intertriginous skin are at increased risk of dermatitis. Follow dose modification instructions for dermatitis [see Dosage and Administration (2.1)].

• Non-Melanoma Skin Cancer

• Four percent (4%, 11/255) of patients developed a non-melanoma skin cancer during the clinical trial or during one year of post-treatment follow-up: 2% (3/128) of patients receiving VALCHLOR, and 6% (8/127) of patients receiving the mechlorethamine ointment comparator. Some of these non-melanoma skin cancers occurred in patients who had received prior therapies known to cause non-melanoma skin cancer. Monitor patients for non-melanoma skin cancers during and after treatment with VALCHLOR. Non-melanoma skin cancer may occur on any area of the skin, including untreated areas.

• Embryo-fetal Toxicity

• Based on its mechanism of action, case reports in humans, and findings in animals, VALCHLOR can cause fetal harm when administered to a pregnant woman. There are case reports of children born with malformations in pregnant women systemically administered mechlorethamine. Mechlorethamine was teratogenic and embryo-lethal after a single subcutaneous administration to animals. Advise women to avoid becoming pregnant while using VALCHLOR. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1)].

• Flammable Gel

• Alcohol-based products, including VALCHLOR, are flammable. Follow recommended application instructions

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

• No drug interaction studies have been performed with VALCHLOR. Systemic exposure has not been observed with topical administration of VALCHLOR; therefore, systemic drug interactions are not likely.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category D
• Risk Summary

• Mechlorethamine can cause fetal harm when administered to a pregnant woman. There are case reports of children born with malformations in pregnant women systemically administered mechlorethamine. Mechlorethamine was teratogenic in animals after a single subcutaneous administration. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Warnings and Precautions (5.5)].

• Animal Data

• Mechlorethamine caused fetal malformations in the rat and ferret when given as single subcutaneous injections of 1 mg/kg. Other findings in animals included embryolethality and growth retardation when administered as a single subcutaneous injection.

Pregnancy Category (AUS): 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

• It is not known if mechlorethamine is excreted in human milk. Due to the potential for topical or systemic exposure to VALCHLOR through exposure to the mother's skin, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Pediatric Use

• Safety and effectiveness in pediatric patients have not been established.

Geriatic Use

• A total of 79 patients age 65 and older (31% of the clinical trial population) were treated with either VALCHLOR or the comparator in the clinical trial. Forty-four percent (44%) of patients age 65 or older treated with VALCHLOR achieved a CAILS response compared to 66% of patients below the age of 65. Seventy percent (70%) of patients age 65 and older experienced cutaneous adverse reactions and 38% discontinued treatment due to adverse reactions, compared to 58% and 14% in patients below the age of 65, respectively. Similar differences in discontinuation rates between age subgroups were observed in the comparator group.

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

• Mechlorethamine, also known as nitrogen mustard, is an alkylating agent which inhibits rapidly proliferating cells.

Structure

• VALCHLOR is a topical product that contains mechlorethamine HCl, an alkylating drug. Mechlorethamine HCl is a white to off white solid that is very soluble in water and methanol, partially soluble in acetone, and generally not soluble in organic solvents.

• Mechlorethamine HCl is designated chemically as 2-chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride. The molecular weight is 192.52 and the melting point is 108-111°C. The empirical formula is C5H11Cl2N•HCl, and the structural formula is: CH3N(CH2CH2Cl)2•HCl.

• Each tube of VALCHLOR contains 60g of a gel containing 0.016% w/w of mechlorethamine (equivalent to 0.02% mechlorethamine HCl) in a base of the following inactive ingredients: diethylene glycol monoethyl ether, propylene glycol, isopropyl alcohol, glycerin, lactic acid, hydroxypropylcellulose, sodium chloride, menthol, edetate disodium, butylated hydroxytoluene.

Pharmacodynamics

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

Pharmacokinetics

• Systemic exposure was undetectable after topical administration of VALCHLOR to patients. Blood samples were analyzed from 16 and 15 patients following treatment with VALCHLOR (mechlorethamine gel 0.016%) and an identical formulation consisting of mechlorethamine 0.032% w/w, respectively. For patients who received mechlorethamine 0.016%, samples were collected to measure mechlorethamine concentrations prior to dosing, on day 1, and at the first month visit. Following the topical administration of mechlorethamine 0.016%, there were no detectable plasma mechlorethamine concentrations observed in any of the patients. Patients who received mechlorethamine 0.032% had no measurable concentrations of mechlorethamine or half-mustard after 2, 4, or 6 months of treatment.

Nonclinical Toxicology

• Carcinogenesis, Mutagenesis, Impairment of Fertility

• Mechlorethamine is a probable carcinogen in humans. There are reports of non-melanoma skin cancer with the use of topical mechlorethamine in patients [see Warnings and Precautions (5.4)]. Mechlorethamine was carcinogenic in mice when injected intravenously with four doses of 2.4 mg/kg (0.1% solution) at 2-week intervals with observations for up to 2 years. An increased incidence of thymic lymphomas and pulmonary adenomas was observed. Painting mechlorethamine on the skin of mice at a dose of 4 mg/kg for periods of up to 33 weeks resulted in squamous cell tumors in 9 of 33 mice.

• Mechlorethamine was genotoxic in multiple genetic toxicology studies, which included mutations in the bacterial reverse mutation assay (Ames test) and chromosome aberrations in mammalian cells. Dominant lethal mutations were produced in ICR/Ha Swiss mice.

• The reproductive effects of VALCHLOR have not been studied; however, published literature indicates that fertility may be impaired by systemically administered mechlorethamine. Mechlorethamine impaired fertility in the rat at a daily dose of 500 mg/kg intravenously for two weeks. Treatment with intravenous mechlorethamine has been associated with delayed catamenia, oligomenorrhea, and temporary or permanent amenorrhea.

• Animal Toxicology and/or Pharmacology

• Animal studies have shown mechlorethamine to be corrosive to skin and eyes, a powerful vesicant, irritating to the mucous membranes of the respiratory tract, and highly toxic by the oral route.

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

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Package and Label Display Panel

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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

• A® — B®

Drug Shortage Status

Price

References

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

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