Mechlorethamine (Monograph)

Brand name: Valchlor
Drug class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical name: 2-Chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride
Molecular formula: CH₃N(CH₂CH₂Cl)₂•HCl
CAS number: 55-86-7

Medically reviewed by Drugs.com on Feb 23, 2024. Written by ASHP.

Introduction

Antineoplastic agent; nitrogen mustard-derivative alkylating agent.

Uses for Mechlorethamine

Mycosis Fungoides-type Cutaneous T-cell Lymphoma (CTCL)

Topical treatment of cutaneous lesions in patients with early (stage IA and IB) mycosis fungoides-type CTCL who have received prior skin-directed therapy. Designated an orphan drug by FDA for use in this condition.

Expert treatment guidelines include topical mechlorethamine as one of several recommended treatment options for patients with early stages of mycosis fungoides-type CTCL.

Mechlorethamine Dosage and Administration

Administration

Topical Administration

Apply to skin as commercially available 0.016% mechlorethamine gel.

Has been applied to skin as aqueous solution or ointment-based preparation compounded extemporaneously using mechlorethamine hydrochloride for injection.

For topical dermatologic use only. Do not use near or in the eyes, nose, or mouth. (See Mucosal or Eye Injury under Cautions.)

Wash hands thoroughly with soap and water after handling or applying the drug. (See Warnings/Precautions under Cautions.)

Application by Caregiver

Manufacturer states caregiver must wear disposable nitrile gloves during application and wash hands thoroughly with soap and water after removing the gloves.

In case of accidental skin exposure, immediately wash exposed areas thoroughly with soap and water for ≥15 minutes and remove contaminated clothing.

In case of accidental exposure to eyes, mouth, or nose, immediately irrigate exposed area for ≥15 minutes with copious amounts of water.

Gel

Apply gel immediately (or within 30 minutes) after removal from refrigerator; return gel to refrigerator immediately after each use.

Apply gel to completely dry skin ≥4 hours before or ≥30 minutes after showering or washing affected areas. After application, allow treated areas to dry for 5–10 minutes before covering with clothing.

May apply emollients (moisturizers) to treated areas 2 hours before or 2 hours after application of the gel.

Do not use occlusive dressings on treated areas.

Avoid fire, flame, and smoking until gel has dried.

Extemporaneously Compounded Ointment

Usually prepared by dissolving mechlorethamine hydrochloride in dehydrated alcohol, filtering the solution to remove insoluble sodium chloride present in the commercial preparation (although filtration may not be necessary), and mixing the drug-alcohol solution into petrolatum or another anhydrous ointment base (e.g., hydrophilic petrolatum). Usual mechlorethamine hydrochloride concentration is 0.01 or 0.02%. Consult specialized references for detailed information on preparation of topical ointments.

Extemporaneously Compounded Solution

Usually prepared by dissolving 10 mg of mechlorethamine hydrochloride in 50–100 mL of water. Consult specialized references for detailed information on preparation of topical solutions.

Because of limited stability, prepare solution immediately before use.

Dosage

Available as mechlorethamine hydrochloride; dosage of gel expressed in terms of mechlorethamine.

Adults

Mycosis Fungoides-type CTCL

Topical

Apply thin film of mechlorethamine 0.016% gel to affected areas once daily.

Interrupt treatment if any skin ulceration or blistering, or moderately severe or severe dermatitis (i.e., marked erythema with edema), occurs.

Upon improvement, may resume with reduced frequency of once every 3 days. If reintroduction tolerated for ≥1 week, may increase application frequency to every other day for ≥1 week and then to once daily if tolerated.

Concentration of mechlorethamine hydrochloride in topical solutions and ointments, frequency of application, and duration of treatment have been based on dermatologic response and tolerance. Usual ointment concentration is 0.01 or 0.02%; may use lower concentrations initially in patients with dermatitis or history of hypersensitivity reactions to the topically applied drug, or use higher concentrations in patients with extensive or resistant lesions.

Topical applications of mechlorethamine preparations generally are repeated once daily until the lesions disappear. Optimal duration of therapy following clinical remission not fully established.

Special Populations

No special population dosage recommendations at this time.

Cautions for Mechlorethamine

Contraindications

• Known severe hypersensitivity to mechlorethamine.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, reported following exposure to topical formulations of mechlorethamine.

Desensitization using topical mechlorethamine has been used with some success to prevent allergic contact dermatitis with additional therapy.

Mucosal or Eye Injury

Eye exposure causes pain, burns, inflammation, photophobia, and blurred vision, and possibly blindness and severe irreversible anterior eye injury.

If eye exposure occurs, immediately irrigate affected eye(s) with copious amounts of water, 0.9% sodium chloride, or balanced salt ophthalmic irrigating solution for ≥15 minutes and obtain immediate medical care, including ophthalmologic consultation.

Mucosal exposure causes pain, erythema, and ulceration, which may be severe.

If mucosal exposure occurs, immediately irrigate affected area with copious amounts of water for ≥15 minutes and seek immediate medical consultation.

Secondary Exposure to Topical Mechlorethamine

Secondary exposure may cause dermatitis, mucosal injury, and secondary cancers.

Avoid direct skin contact with gel by anyone other than patient. Follow application instructions carefully to prevent secondary exposure (see Topical Administration under Dosage and Administration).

Dermatitis

The most common adverse effect of topical mechlorethamine. Reported in 56% of patients receiving the gel; was moderately severe or severe in 23% of patients.

Monitor patients for erythema, swelling, inflammation, pruritus, blisters, ulceration, and secondary skin infections. Face, genitalia, anus, and intertriginous areas associated with increased risk.

May require treatment interruption or dosage adjustment (see Dosage under Dosage and Administration). Topical emollients, oral antihistamines, and topical corticosteroids have been used to treat dermatitis.

Nonmelanoma Skin Cancer

Nonmelanoma skin cancer reported during clinical trial or one year of posttreatment follow-up in 4% of patients receiving mechlorethamine gel or an extemporaneously compounded ointment (2 or 6% of patients, respectively). Some patients previously had received therapies known to cause such cancers.

May occur on any area of the skin, including untreated areas.

Monitor patients for nonmelanoma skin cancer during and after treatment.

Fetal/Neonatal Morbidity and Mortality

Mechlorethamine can cause fetal harm. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

Systemic mechlorethamine associated with malformations in children exposed to the drug in utero; single sub-Q dose in animals associated with growth retardation, teratogenicity, and embryolethality.

Flammable Gel

Gel is alcohol based and flammable. Carefully follow application instructions (see Topical Administration under Dosage and Administration).

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether mechlorethamine is distributed into human milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Among patients receiving mechlorethamine gel for mycosis fungoides-type CTCL in a clinical trial, response rate appeared to be lower (44 versus 66%) and rates of adverse cutaneous reactions (70 versus 58%) and discontinuance due to adverse effects (38 versus 14%) higher in patients ≥65 years of age compared with younger patients.

Common Adverse Effects

Dermatitis, pruritus, laboratory abnormalities (anemia, neutropenia, thrombocytopenia), bacterial skin infection, skin ulceration or blistering, skin hyperpigmentation.

Drug Interactions

Drug interaction studies not performed to date. Systemic drug interactions unlikely.

Mechlorethamine Pharmacokinetics

Absorption

Bioavailability

Mechlorethamine was undetectable in plasma following topical administration of mechlorethamine 0.016% gel once daily for one month.

Mechlorethamine and half-mustard were undetectable in plasma after 2, 4, or 6 months of treatment with mechlorethamine 0.032% gel once daily.

Distribution

Extent

Not known whether distributed into milk.

Stability

Storage

Topical

Gel

Prior to dispensing: -25 to -15°C.

After dispensing: 2–8°C (in original box). Discard any unused gel after 60 days.

Actions

• Mechanism of action of topical mechlorethamine uncertain. May not be related solely to alkylating action; immune mechanisms may be involved.

Advice to Patients

• Importance of reading manufacturer's patient information (e.g., medication guide) before starting mechlorethamine gel therapy and reviewing this information each time prescription is renewed.

• Importance of storing mechlorethamine gel in original box in refrigerator out of reach of children and away from food. Contact pharmacist before use if gel is left at room temperature for >1 hour per day. Discard any unused gel after 60 days.

• Importance of strict adherence to recommended instructions for use and administration precautions.

• Importance of washing hands thoroughly with soap and water after handling or applying the drug.

• Risk of adverse effects (e.g., dermatitis, mucosal injury, secondary cancers) from secondary exposure; avoid direct skin contact in individuals other than the patient. Importance of caregivers wearing disposable nitrile gloves while applying mechlorethamine to patients and washing hands thoroughly with soap and water after removal of gloves. Importance of caregivers taking appropriate measures if accidental skin exposure occurs (see Application by Caregiver under Dosage and Administration). Dispose of used gloves and unneeded or used containers of the drug in a manner that prevents exposure of others.

• Risk of adverse ocular effects (e.g., pain, burns, inflammation, photophobia, blurred vision, blindness, severe irreversible injury) if eye exposure occurs; avoid eye contact and take appropriate measures if accidental eye contact occurs (see Mucosal or Eye Injury under Cautions).

• Risk of adverse effects (e.g., pain, erythema, ulceration), possibly severe, if contact with mucous membranes occurs; avoid mucosal contact and take appropriate measures if accidental mucosal contact occurs (see Mucosal or Eye Injury under Cautions).

• Risk of dermatitis, including increased risk on face, genitalia, anus, and intertriginous areas. Contact clinician if symptoms of dermatitis occur.

• Risk of nonmelanoma skin cancer. Notify clinician of any new skin lesions and undergo periodic assessments for signs and symptoms of skin cancer.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Necessity of advising women to avoid pregnancy and not to breast-feed during therapy.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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