drug-monograph

mechlorethamine

Other Names

Mustargen®

Appearance

Clear, colorless solution

A - Drug Name

mechlorethamine

SYNONYM(S): HN2; Nitrogen Mustard

COMMON TRADE NAME(S): Mustargen® ()

B - Mechanism of Action and Pharmacokinetics

Mechlorethamine is an analogue of mustard gas, derived from toxic gas warfare research. The first clinical trials took place in the early 1940's. It is a polyfunctional alkylating agent which interferes with DNA replication and RNA transcription through alkylation. Alkylation produces breaks in the DNA molecule as well as cross-linking of its twin strands. Mechlorethamine is cell cycle phase non-specific and possesses weak immunosuppressive activity.

Absorption

Bioavailability

oral : Yes but extremely irritating to tissues

Distribution

Not elucidated, highly reactive drug which is cleared from the blood within minutes.

Cross blood brain barrier?

No information found

PPB

No information found

Metabolism

Ionizes in solution to active form and combines with reactive compounds.

Active metabolites

Yes, ethylene-immonium ion

Inactive metabolites

Yes

Elimination

No active drug recovered in urine

Urine

50% (as metabolites) within 24 hours, < 0.01% unchanged

Half-life

15 minutes

C - Indications and Status

Health Canada Approvals:

Palliative treatment of Hodgkin’s lymphoma (stages III and IV), as part of the MOPP regimen.

Other Uses:

Non Hodgkin’s lymphoma
Chronic lymphocytic leukemia
Chronic myelocytic leukemia
Polycythemia rubra vera
Malignant effusions (pleura, pericardium, ascites)
Mycosis fungoides

D - Adverse Effects

Emetogenic Potential:

High

Extravasation Potential: Vesicant

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Auditory	Hearing impaired (rare)	E
	Tinnitus (rare)	E
Dermatological	Alopecia (mild)	E
	Rash (rare, may be severe)	E
Gastrointestinal	Anorexia	E
	Diarrhea	E
	Dyspepsia	E
	GI hemorrhage	E
	GI ulcer (peptic)	E
	Mucositis (rare)	E
	Nausea (very common)	I
	Vomiting (very common)	I
General	Fatigue (or weakness)	E
Hematological	Hemolysis (rare)	E
	Immunosuppression	E
	Myelosuppression ± infection, bleeding	E
Hepatobiliary	Jaundice (rare)	E
Hypersensitivity	Anaphylaxis (Type I anaphylactoid- rare)	I
	Delayed hypersensitivity (allergic contact dermatitis: 10-20% with topical use)	E D
Injection site	Injection site reaction (pain)	I
	Phlebitis (thrombosis or chemical phlebitis)	I E
Metabolic / Endocrine	Hyperuricemia (during periods of active cell lysis)	I
Neoplastic	Amyloidosis	L
	Leukemia (secondary)	L
	Lymphoma (secondary)	L
	Secondary malignancy (skin cancer)	L
Nervous System	Depressed level of consciousness (coma - rare)	E
	Paresthesia	E
	Seizure (rare)	E
	Somnolence	I
	Vertigo (rare)	E
Renal	Azotemia (rare)	E
	Renal failure (rare)	E
Reproductive and breast disorders	Infertility	L
	Irregular menstruation	L
Urinary	Urine output decreased (rare)	E

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

The dose-limiting effect of mechlorethamine is myelosuppression; the risk is increased in debilitated patients and in heavily pre-treated patients. Irradiation of such areas as sternum, ribs, and vertebrae shortly after a course of nitrogen mustard may lead to increased myelosuppression. Myelosuppression may continue for 50 days or longer after starting therapy, but recovery is generally complete within 4-6 weeks after a mechlorethamine dose. Neither mechlorethamine following radiotherapy nor radiotherapy subsequent to the drug should be given until bone marrow recovery.

Extravasation into subcutaneous tissue causes painful inflammation, and can result in induration and sloughing. Application of ice compresses to patient tolerance for 6-12 hours will minimize local reaction. The tissue necrosis that happens with extravasation may happen days to weeks after the treatment. Patients must be observed for delayed reactions and prior injection sites carefully inspected.

Injection site problems include chemical phlebitis and pain of the injection site during or after injection. Mechlorethamine can cause significant sclerosing of the veins through which it is injected, resulting in pain and limitation of movement of the extremities. Application of ice compresses may provide symptomatic relief, and patients should be encouraged to mobilize their arm to avoid limitation of movement.

Hyperuricemia during periods of active cell lysis, which is caused by cytotoxic chemotherapy of highly proliferative tumours of massive burden (e.g. some leukemias and lymphomas), can be minimized with allopurinol and hydration. In hospitalized patients the urine may be alkalinized, by addition of sodium bicarbonate to the IV fluids, if tumour lysis is expected.

Serious neurotoxicity can occur with high doses. Neurotoxicity appeared to increase with age and occurred more frequently in patients who also received procarbazine or cyclophosphamide.

Reproductive effects include delayed menstruation, oligomenorrhea, temporary or permanent amenorrhea. In males, mechlorethamine may cause impaired spermatogenesis, azoospermia or total germinal aplasia. Although spermatogenesis may return in some cases, this may occur only several years after intensive chemotherapy has been discontinued.

Pain occurs with intrapleural use. It is common with intraperitoneal injection and is often associated with mild nausea, vomiting and diarrhea of 2-3 days duration. Transient cardiac arrhythmias may occur with intrapericardial injection. Myelosuppression is milder for intracavitary injection than when given IV.

E - Dosing

Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Dosage should be based on ideal dry body weight. Doses should not be repeated until toxicity has resolved. Since mechlorethamine is highly emetogenic, appropriate premedications should be administered to prevent nausea and vomiting.

Adults:

Intravenous: 0.4 mg/kg Every 3-6 weeks
(May be divided over 1, 2 or 4 days)

Intravenous: 6 mg/m² on days 1 and 8 (MOPP) Every 4 weeks

Intracavitary: 0.2-0.4 mg/kg
intrapleural, intraperitoneal, pericardial; refer to protocol by which patient is being treated.

Dosage with Toxicity:

Dosage in myelosuppression:

Subsequent doses should not be given until hematologic recovery has occurred.
Modify according to protocol by which patient is being treated; if no guidelines available, refer to Appendix 6 "Dosage Modification for Hematologic and Non-Hematologic Toxicities."

Suggested dose modifications for mechlorethamine in MOPP:

Platelets (x 10⁹/L)		Leukocytes (x 10⁹/L)	Dose (% of previous)
>100	and	>4	100%
>100	and	3 to <4	75%
>100	and	2 to <3	50%
50 to < 100	and/or	1 to <2	25%
<50	and/or	<1	OMIT

Dosage with Hepatic Impairment:

No information found; adjustment unlikely to be necessary.

Dosage with Renal Impairment:

No information found; adjustment unlikely to be necessary.

Dosage in the elderly:

Use with caution due to increased risk of toxicity. Consider dose modification.

Children:

Limited data in stages III and IV Hodgkin’s lymphoma (MOPP regimen). Safety and effectiveness have not been established by well-controlled studies.

F - Administration Guidelines

Solution should be prepared immediately prior to administration. Mechlorethamine is highly unstable in neutral or alkaline aqueous solutions.
Slow push over a few minutes through sidearm of free-flowing IV (Normal Saline); flush IV line with Normal Saline after the injection to clear any remaining drug from the tubing.
Protect from light.
Before disposal, equipment and unused injection solution should be neutralized with mixing an equal volume of sodium thiosulfate and sodium bicarbonate solutions. See product monograph for details.

G - Special Precautions

Other:

Mechlorethamine is contraindicated in patients with infectious diseases and in patients who have had previous anaphylactic reactions or who are hypersensitive to the drug or to any excipients in the formulation; use with caution in heavily pre-treated patients, debilitated patients and in the elderly. As nitrogen mustard therapy may contribute to extensive and rapid development of amyloidosis, mechlorethamine should be used only if foci of acute and chronic suppurative inflammation are absent.

Mechlorethamine is highly toxic; both powder and solution preparations must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes especially that of the eyes, must be avoided.

Mechlorethamine has mutagenic, teratogenic and carcinogenic properties in experimental models. It should not be used in pregnancy. Adequate contraception should be used during treatment and for at least 6 months after the last dose. Impaired fertility has been observed in animal studies. Breast feeding is not recommended since it is unknown whether mechlorethamine is secreted into breast milk.

H - Interactions

AGENT	EFFECT	MECHANISM	MANAGEMENT
Curcumin (termeric)	May ↓ mechlorethamine effect	Inhibits mechlorethamine induced apoptosis	Avoid concomitant use
Steroids (i.e., prednisone, dexamethasone, etc.)	↑ risk of bacterial, viral, or fungal infections	Additive immunosuppression	Caution

I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
CBC	Baseline and regular
Clinical assessment for nausea and vomiting, infection, bleeding, ototoxicity, hypersensitivity, and local toxicity.

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

Monitor Type	Monitor Frequency
Uric acid levels	Baseline and regular
Renal function tests	Baseline and regular
Liver function tests	Baseline and regular

K - References

Cancer Drug Manual (the Manual), 1994, British Columbia Cancer Agency (BCCA)

Longo DL, Young RC, Wesley M, et al. Twenty years of MOPP therapy for Hodgkin’s disease. J Clin Oncol, 1986; 4: 1295-1306.

McEvoy GK, editor. AHFS Drug Information 2009. Bethesda: American Society of Health-System Pharmacists, p. 1154-7.

Product Monograph: Mustagen® (mechlorethamine). Lundbeck Inc., Sep 11, 2009.

Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 2002 Jul 1; 62(13): 3868-75.

Revised January 2010

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Last Updated: July 27, 2026

The information on this website is intended for informational purposes only and is not a substitute for medical advice. Always consult your health care provider if you have questions or concerns. The use of the information on this website does not create a physician-patient relationship between Ontario Health and you.
Ontario Health is committed to ensuring accessible services and communications to individuals with disabilities. To receive any information on this website in an alternate format, please contact Ontario Health’s Communications Department at: 1-877-280-8538,TTY 1-800-855-0511, or by email at info@ontariohealth.ca.