Chlormethine

Registered South African indications:

• Topical treatment of mycosis fungoides-type cutaneous T-cell lymphoma (MF-type CTCL)

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy

Forms avail. in SA and covered in this monograph: gel

South African registered indications and dosages

Treatment should be initiated by an appropriately experienced doctor

Topical treatment of mycosis fungoides-type cutaneous T-cell lymphoma (MF-type CTCL)

• Topical (gel): Apply a thin layer to affected area, once dly, at least 4hrs before or 30 min. after showering or washing

Treatment should be stopped for any grade of skin ulceration or blistering, or moderately severe or severe dermatitis (e.g. marked skin redness with oedema)
Upon improvement, treatment can be restarted at a reduced frequency of once every 3 days. If reintroduction of treatment is tolerated for at least 1 week, the frequency of application can be increased to every other day for at least 1 week and then once daily application if tolerated

Method of administration
Chlormethine is for topical application to the skin. Chlormethine should be applied to completely dry skin at least 4 hours before or 30 minutes after showering or washing. The patient should allow treated areas to dry for 5 to 10 minutes after application before covering with clothing. Occlusive (air- or water-tight) dressings should not be used on areas of the skin where chlormethine was applied. See additional prescribing points for additional directions

Not established for use in children below 18 years

Pregnancy

South African recommendations

• Contraindicated
• Chlormethine is not recommended during pregnancy
• Based on case reports in humans, findings in animal reproduction studies, its mechanism of action, and genotoxicity findings, chlormethine may cause foetal harm
• There are case reports of children born with malformations in pregnant women systemically administered chlormethine
• Chlormethine was teratogenic and embryo-lethal after a single subcutaneous administration to animals
• Advise women to avoid becoming pregnant while using chlormethine. If this medicine is used during pregnancy or if the patient becomes pregnant while taking this medicine, the patient should be apprised of the potential hazard to a foetus
• Chlormethine has been shown to cause foetal malformations, embryofoetal lethality and foetal growth retardation in mice and rats after a single injection at 1 - 2.5mg/kg. Animal embryofoetal development studies involving topical administration of chlormethine have not been performed

Women of childbearing potential/ Contraception in males and females

• Chlormethine is not recommended in women of childbearing potential not using contraception

Breastfeeding

South African recommendations

• Caution; not recommended
• Breastfeeding during treatment with chlormethine is not recommended because of the potential for topical or systemic exposure to chlormethine through exposure to the mother's skin and the potential for serious adverse reactions in the breastfed child from chlormethine
• There are no data on the presence of chlormethine or its metabolites in human milk, the effects of the medicine on the breastfed child, or the effects of the medicine on milk production

Fertility

South African recommendations

• Female patients of reproductive potential should be advised to use effective contraception during treatment with chlormethine
• A barrier method of contraception should be used to avoid direct exposure of reproductive organs to chlormethine
• Males with female partners of reproductive potential should be advised to use effective contraception during treatment with chlormethine
• A barrier method of contraception should be used to avoid direct exposure of reproductive organs to chlormethine
• Adverse effects on fertility have been observed with chlormethine after systemic administration in animals
• Fertility was impaired in male rats with intravenous administration at doses ≥ 0.25mg/kg every 2 weeks, and in mice (treated males paired with treated females) with intraperitoneal administration at 0.5mg/kg/day for 4 days. The relevance to humans receiving topical chlormethine is unknown

South African recommendations

• Caution; no information available

South African recommendations

• Caution; no information available

South African recommendations

• No dose adjustment recommended

Skin and subcutaneous tissue disorders

Very common

• Skin irritation
• Pruritus
• Erythema
• Contact dermatitis

Common

• Skin hyperpigmentation

Respiratory, Thoracic and Mediastinal disorders

Very common

• Upper respiratory tract infection

Infections and infestations

Common

• Folliculitis

No information available

Observations

• Development of secondary skin cancers

The following instructions should be followed by patients or caregivers when applying chlormethine

• Wash hands thoroughly with soap and water immediately after handling or applying chlormethine
• Apply to affected areas of the skin. In case of chlormethine exposure to non-affected areas of the skin,  wash the exposed area with soap and water
• Caregivers must wear disposable nitrile gloves when applying to patients. Caregivers should remove gloves carefully (turning them inside out during the removal to avoid contact with chlormethine) and wash hands thoroughly with soap and water after removal of gloves. If there is accidental skin exposure to chlormethine, caregivers must immediately wash exposed areas thoroughly with soap and water for at least 15 minutes. Remove and wash contaminated clothing
• The opening of the tube is covered with a foil safety seal. The cap should be used to puncture the seal. The tube should not be used and the pharmacist should be contacted if the seal is missing, punctured, or lifted
• Chlormethine should be applied immediately or within 30 minutes after removal from the refrigerator. The tube should be returned to the refrigerator immediately after each use. With clean hands, the tube should be placed back into the original box and the box should be placed in the supplied transparent, sealable, plastic bag for storage in the refrigerator
• Chlormethine should be applied to completely dry skin at least 4 hours before or 30 minutes after showering or washing. The patient should allow treated areas to dry for 5 to 10 minutes after application before covering with clothing. Occlusive (air- or water-tight) dressings should not be used on areas of the skin where chlormethine was applied
• Emollients (moisturisers) or other topical products may be applied to the treated areas 2 hours before or 2 hours after application
• Fire, flame, and smoking must be avoided until chlormethine has dried

Chlormethine is a bifunctional alkylating agent that inhibits rapidly proliferating cells.