Multidisciplinary Cutaneous Lymphoma Group

Topical Nitrogen Mustard (Mustargen)

What is topical nitrogen mustard?

Manufactured by Merck & Co., topical nitrogen mustard (mechlorethamine), also called Mustargen™ or NM, is a commonly used topical chemotherapy agent that is prescribed to patients with mycosis fungoides (MF). It is efficient in treating patches or plaques. Since its discovery of use in 1959, NM has been the most widely used topical (applied to the skin) chemotherapy in treating MF. Topical NM may be used as an aqueous (water) or ointment based preparation (mixed with Aquaphor), though the results are the same. It may also be used in propylene glycol, though the effectiveness of this method in comparison to the other two methods are still not completely known.

Recent clinical evidence for topical mechlorethamine in mycosis fungoides - Valchlor - 2014

How does nitrogen mustard work?

When nitrogen mustard is administered systemically, it acts as an alkylating agent with an anti-mitotic effect. The NM used in medicine include mechlorethamine, cyclophosphamide, ifosfamide, melphalan, and chlorambucil. Mechlorethamine is the only NM used as a topical agent in the management of cutaneous lymphomas. The alkylating agents have a common property of becoming strong electrophiles which then result in formation of covalent linkages by alkylation of various nucleophilic moieties. The cytotoxic effects are directly related to the alkylation of DNA. Mechlorethamine is a bifunctional alkylating agent with two 2-chlorethyl side chains. The 7 nitrogen atom of guanine residues in DNA is highly susceptible to the formation of a covalent bond with bifunctional alkylating agents such as NM. The modified guanine leads to DNA damage and ultimately causes cell death.The mechanism of action of topical NM is still uncertain. One theory suggests that NM has a unique effect on the immune mechanisms (e.g. immunostimulation) against MF.

How long does the treatment take?

Topical NM should be applied on a daily basis until complete skin clearance which should be followed by a time of maintenance therapy for about one to two months.

Does topical nitrogen mustard have any risks?

Patients who use topical NM alone and not in combination with other therapies do not have a risk of developing melanoma or non-melanoma skin cancers. This risk has been primarily for patients who are receiving multiple skin treatments (such as phototherapy or radiation) in addition to topical NM. Also, the risk is higher for those patients who use the aqueous preparation rather than the ointment. There is no systemic (internal) absorption of topical NM, thus no organs or bone marrow are at risk from using this medication. Patients should not apply topical NM to sensitive areas (such as the face and genitals) to decrease the chance of risk. Patients should notify their doctor if they are pregnant or breast-feeding because of the potential side effects that may get in the way. In studies of the use of topical nitrogen mustard amongst children, there was no increase in risk found.

What are the side effects of using topical NM?

The most common side effect found amongst patients who use topical nitrogen mustard is an allergic reaction that results usually in itching, rash, or redness—this is especially in more sensitive areas such as skin folds. Patients should test for any allergies by applying NM to only a small patch and waiting to see if an allergic reaction occurs. Patients who use the aqueous solution are more prone to developing an allergic reaction than those who use the ointment preparation. Acute allergic reactions could be treated by a topical steroid. Patients are usually advised to decrease the frequency of the NM application when there is a mild reaction or irritation to the medication. In most cases, patients are able to continue the medicine with a decrease in frequency or concentration, and eventually the irritant reactions improve and allow for the patient to increase the strength and frequency of the medication. Another potential side effect is hyper-pigmentation (darkening of skin) in the area where NM was applied. However, this side effect is reversible once the medication is discontinued.

Instructions for Patient Use

Topical nitrogen mustard (Mustargen, mechlorethamine) can be used either mixed in Aquaphor or propylene glycol by a trained pharmacist or made up fresh in water by you prior to application. The water preparation of NM is unstable and needs to be used immediately, whereas the ointment preparation of NM is stable for at least a few months. The following instructions apply to either forms of preparation with minor differences that are noted below (*). There is a higher risk of allergic reactions on the skin with the water preparation.

In order to check for any allergic reactions, we start you off by applying the medicine to a test patch.

  1. Apply a small amount of the nitrogen mustard (NM) preparation to a selected test-patch on your skin, once a day, for 7-10 days. The test-patch can be a palm-sized patch on your arm, leg, or trunk.
    If there is no significant irritation, new rash, or increased redness or itching, you may go ahead and apply the NM preparation to all the areas that you were instructed to do so. Patients who have specific patches or plaques should apply NM only to the localized affected skin area. Patients with patches or plaques spread out all over the body or scattered should apply NM generally all over the skin. Usually, we have you apply the NM only once a day, either after showering or in the evening, unless you were given instructions to apply a second time. If you are concerned about a possible allergic reaction, please discontinue the application and call us, so that we can advise you appropriately.
  2. Please apply only a very thin film of NM preparation on your skin with each application; there is no need to leave large amounts of residue on your skin. The topical NM is maximally absorbed usually within the first hour after application.
  3. You can wear disposable gloves or simply wash your hands after applying the NM. As you were informed, the topical preparations of NM do NOT get absorbed into your blood, therefore, it does NOT result in systemic toxicity. If someone else helps apply the NM, they should probably wear disposable gloves. If the medicine gets on the skin of other people, just have them wash with soap and water; it will not affect them adversely.
  4. In the initial month of NM application, you may see new areas of mycosis fungoides patches showing up, since the NM can bring out faint, subtle lesions that will be made more visible. Please continue the application to these ‘new' areas until you are seen for a follow-up visit.
  5. Please use additional moisturizing lotions or creams throughout the day as needed. (*This is especially important if you are using the water preparation, since the skin will be left very dry without moisturizing supplements.)
  6. Always, feel free to call us if you have any questions.

Contact Information:

Los Altos Pharmacy
225 2nd Street
Los Altos, CA 94022
(650) 948-1212 / (650) 949-8662

Santa Clara Drug Pharmacy
2453 Forest Ave.
Santa Clara, CA 95051
(408) 296-5015
Fax: (408) 248-2790

For information on the propylene glycol mixture of NM, please contact (866) 275-9484, or send your physician's prescription to:

Converse Care Pharmacy
720 E. Market Street
Suite 155
West Chester, PA 19382

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