Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, External:
Valchlor: 0.016% (60 g) [contains edetate disodium, isopropyl alcohol, menthol, propylene glycol]
Pharmacology
Mechanism of Action
Mechlorethamine is a nitrogen mustard alkylating agent which forms inter- and intra-strand DNA cross-links, resulting in inhibition of DNA synthesis. Topical application allows for skin-directed treatment while minimizing systemic nitrogen mustard exposure (Lessin 2013).
Pharmacokinetics/Pharmacodynamics
Absorption
Topical: None detected (Lessin 2013)
Distribution
Topical: No detectable systemic exposure in a clinical study (Lessin 2013)
Use: Labeled Indications
Cutaneous T-cell lymphoma: Topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy
Contraindications
Known severe hypersensitivity to mechlorethamine or any component of the formulation
Dosage and Administration
Dosing: Adult
Cutaneous T-cell lymphoma (mycosis fungoides-type): Topical: Apply a thin film once daily to affected areas of skin. In the clinical study, treatment was continued for 1 year and concurrent use of topical or systemic corticosteroids was not allowed (Lessin 2013).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Adjustment for Toxicity
Skin ulceration (any grade), blistering, or dermatitis (moderately severe-to-severe): Withhold treatment; upon improvement, may reinitiate treatment with a reduced frequency of once every 3 days; if every 3-day application is tolerated for at least 1 week, may increase to every other day for at least 1 week, then (if tolerated) may increase to once daily.
Administration
Apply a thin film topically to affected area. Apply immediately (or within 30 minutes) after removal from refrigerator; return to refrigerator promptly after each use. Apply to completely dry skin at least 4 hours before or 30 minutes after showering/washing. Allow treated area(s) to dry for 5 to 10 minutes after application before covering with clothing. May apply emollients (moisturizers) to treated area 2 hours before or 2 hours after mechlorethamine application. Do not use occlusive dressings over treatment areas. Avoid fire, flame, and smoking until mechlorethamine has dried.
Caregivers should wear nitrile gloves when applying to patients. Wash hands thoroughly with soap and water after handling/application. If accidental skin exposure occurs, wash thoroughly for at least 15 minutes with soap and water; remove any contaminated clothing.
Storage
Prior to dispensing, store in freezer at -25°C to -15°C (-13°F to 5°F). After dispensing, refrigerate at 2°C to 8°C (36°F to 46°F); apply immediately (or within 30 minutes) after removal from refrigerator; return to refrigerator promptly after each use.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
>10%:
Dermatologic: Dermatitis (56%; moderately severe or severe: 23%), pruritus (20%), bacterial skin infection (11%)
Hematologic & oncologic: Hematologic abnormality (decreased hemoglobin, neutrophils, or platelets; 13%)
1% to 10%:
Dermatologic: Dermal ulcer (6%), skin hyperpigmentation (5%)
Hematologic & oncologic: Malignant neoplasm (nonmelanoma skin cancer; 2%)
Postmarketing and/or case reports: Anaphylaxis, hypersensitivity reaction
Warnings/Precautions
Concerns related to adverse effects:
- Accidental exposure: Eye exposure may result in pain, burning, inflammation, photophobia, and blurred vision. Blindness and severe anterior eye injury (irreversible) may occur. If exposure to eye(s) occurs, promptly irrigate for at least 15 minutes with copious amounts of water, normal saline, or balanced salt ophthalmic irrigating solution; obtain immediate medical care, including ophthalmology consultation. Exposure to mucous membranes may cause pain, redness, and ulceration; may be severe. If mucosal contact occurs, irrigate promptly for at least 15 minutes with copious amounts of water and obtain medical consultation.
- Dermatitis: Dermatitis commonly occurs; may be moderately severe or severe. Monitor for redness, swelling, itching, blistering, ulceration, and secondary skin infections. Facial, genitalia, anus and intertriginous skin areas are at increased risk for dermatitis. Dermatitis may require dosage reduction.
- Hypersensitivity: Hypersensitivity reactions (including anaphylaxis) have occurred with topical mechlorethamine application.
- Secondary exposure: Avoid direct contact with mechlorethamine (other than intended treatment areas for the patient). Secondary exposure risks include dermatitis, mucosal injury, and secondary malignancies. To prevent secondary exposure, follow recommended application procedures.
- Secondary malignancy: In a clinical study, non-melanoma skin cancers developed during or within 1 year following treatment. Some instances occurred in patients who had received previous treatments that were associated with non-melanoma skin cancer. Monitor for non-melanoma skin cancers during and following treatment; may occur anywhere on the skin, including untreated areas.
Other warnings/precautions:
- Flammable gel: Mechlorethamine gel contains alcohol and is flammable; follow recommended application procedures and avoid fire, flame, and smoking until mechlorethamine has dried.
Monitoring Parameters
Monitor for dermatologic toxicity (skin ulcers, blistering, dermatitis, secondary skin infections), and signs/symptoms of nonmelanoma skin cancer or hypersensitivity reactions.
Pregnancy
Pregnancy Risk Factor
D
Pregnancy Considerations
Based on the mechanism of action, case reports in humans, and data from animal reproduction studies, in utero exposure to mechlorethamine may cause fetal harm. There have been case reports of teratogenic events following administration of systemic mechlorethamine in humans.
Females of reproductive potential are advised not to become pregnant during mechlorethamine treatment. Impaired male and female fertility has been reported following systemic mechlorethamine therapy (refer to Mechlorethamine [Systemic] monograph for additional information).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience itching or skin discoloration. Have patient report immediately to prescriber skin sores, blisters, redness, edema, signs of skin infection, skin ulcers, mole changes, or skin growths (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
