Skip to Content
How to talk to a doctor about advanced ovarian cancer >>

Mechlorethamine (Systemic)

Pronunciation

(me klor ETH a meen)

Index Terms

  • Chlorethazine
  • Chlorethazine Mustard
  • HN2
  • Mechlorethamine Hydrochloride
  • Mustine
  • Nitrogen Mustard

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection, as hydrochloride:

Mustargen: 10 mg (1 ea)

Brand Names: U.S.

  • Mustargen

Pharmacologic Category

  • Antineoplastic Agent, Alkylating Agent
  • Antineoplastic Agent, Alkylating Agent (Nitrogen Mustard)

Pharmacology

Bifunctional alkylating agent that inhibits DNA and RNA synthesis via formation of carbonium ions; produces interstrand and intrastrand cross-links in DNA resulting in miscoding, breakage, and failure of replication. Although not cell phase-specific per se, mechlorethamine effect is most pronounced in the S phase, and cell proliferation is arrested in the G2 phase.

Metabolism

Rapid hydrolysis in the plasma to active metabolites (Perry, 2012)

Half-Life Elimination

15-20 minutes (Perry, 2012)

Use: Labeled Indications

Hodgkin lymphoma: Palliative treatment of Hodgkin lymphoma

Malignant effusion: Palliative treatment of effusions from metastatic carcinomas

Additional approved uses (manufacturer labeling): Treatment of lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia, polycythemia vera, mycosis fungoides, and bronchogenic carcinoma

Contraindications

Hypersensitivity to mechlorethamine or any component of the formulation; presence of known infection

Dosing: Adult

Dosage should be based on ideal dry weight (evaluate the presence of edema or ascites so that dosage is based on actual weight unaugmented by edema/ascites). Mechlorethamine is associated with a high emetic potential (Basch, 2011; Roila, 2010); antiemetics are recommended to prevent nausea and vomiting

Hodgkin lymphoma (off-label dosing): IV:

MOPP regimen: 6 mg/m2 on days 1 and 8 of a 28-day treatment cycle for 6 to 8 cycles (Canelos, 1992; DeVita, 1970)

Stanford V regimen: 6 mg/m2 as a single dose on day 1 in weeks 1, 5, and 9 (Horning, 2000; Horning, 2002)

Malignant effusion: Intracavitary: 0.4 mg/kg as a single dose; although 0.2 mg/kg (10-20 mg) as a single dose has been used by the intrapericardial route

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling.

The following have also been reported:

Mild-to-moderate impairment: No dosage adjustment necessary (Ecklund, 2005).

Severe liver impairment: No dosage adjustment necessary; concomitant chemotherapy may require alteration until improvement in hepatic function (Ecklund, 2005)

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: In general, utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012). Note: The manufacturer recommends dosing be based on ideal dry body weight and the presence of edema or ascites should be considered so the dose will be based on unaugmented weight.

Reconstitution

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). Must be prepared immediately before use; degradation begins shortly after dilution. Dilute powder with 10 mL SWFI or NS to a final concentration of 1 mg/mL. May be further diluted in 50-100 mL NS for intracavitary administration.

Administration

IV: Administer as a slow IV push over a few minutes into a free-flowing IV solution. Mechlorethamine is associated with a high emetic potential (Basch, 2011; Dupuis, 2011; Roila, 2010); antiemetics are recommended to prevent nausea and vomiting.

Intracavitary: May further dilute in 50-100 mL of normal saline prior to instillation; rotate patient position every 5-10 minutes for 1 hour after instillation to obtain uniform distribution.

Prepare immediately prior to administration.

Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.

Sodium thiosulfate 1/6 M solution: Inject subcutaneously into extravasation area using 2 mL for each mg of mechlorethamine suspected to have extravasated (Perez Fidalgo, 2012; Polovich, 2009). Apply ice for 6-12 hours after sodium thiosulfate administration (Mustargen prescribing information, 2013; Polovich, 2009) or may apply dry cold compresses for 20 minutes 4 times daily for 1-2 days (Perez Fidalgo, 2012).

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Compatibility

Stable in sterile water for injection, NS; incompatible with D5W.

Y-site administration: Incompatible with allopurinol, cefepime.

Storage

Store intact vials at room temperature of 15°C to 30°C (59°F to 86°F). Protect from light. Protect from humidity. Must be prepared immediately before use; degradation begins shortly after dilution.

Drug Interactions

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Adverse Reactions

Frequency not defined.

Cardiovascular: Local thrombophlebitis

Central nervous system: Brain disease (high dose), drowsiness, headache, lethargy, metallic taste, sedation, vertigo

Dermatologic: Alopecia, diaphoresis, erythema multiforme, maculopapular rash, skin rash

Endocrine & metabolic: Amenorrhea, hyperuricemia, oligomenorrhea

Gastrointestinal: Anorexia, diarrhea, mucositis, nausea, vomiting

Genitourinary: Inhibition of spermatogenesis

Hepatic: Jaundice

Hematologic & oncologic: Agranulocytosis, granulocytopenia (onset: 6 to 8 days; recovery: 10 to 21 days), hemolytic anemia, leukopenia, lymphocytopenia, pancytopenia, petechia, secondary leukemia, thrombocytopenia

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Infection: Herpes zoster

Neuromuscular & skeletal: Weakness

Ophthalmic: Lacrimation

Otic: Deafness, tinnitus

Miscellaneous: Fever, tissue necrosis (extravasation)

ALERT: U.S. Boxed Warning

Experienced physician:

Administer mechlorethamine injection only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.

Extravasation:

Extravasation of the drug into subcutaneous tissues results in a painful inflammation. The area usually becomes indurated and sloughing may occur. If leakage of drug is obvious, prompt infiltration of the area with sterile isotonic sodium thiosulfate (1/6 molar) and application of an ice compress for 6 to 12 hours may minimize the local reaction. For a 1/6 molar solution of sodium thiosulfate, use 4.14 g of sodium thiosulfate per 100 mL of sterile water for injection or 2.64 g of anhydrous sodium thiosulfate per 100 mL or dilute 4 mL of sodium thiosulfate injection (10%) with 6 mL of sterile water for injection.

Hazardous agent:

This drug is highly toxic, and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Due to the toxic properties of mechlorethamine (eg, corrosivity, carcinogenicity, mutagenicity, teratogenicity), review special handling procedures prior to handling and follow them diligently.

Pregnancy:

Avoid exposure during pregnancy.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: May cause lymphopenia, leukopenia, granulocytopenia, thrombocytopenia and anemia. Agranulocytopenia may occur (rare); persistent pancytopenia has been reported. Monitor blood counts. Bleeding due to thrombocytopenia may occur. Use with caution in patients where neoplasm has bone marrow involvement or in those who have received prior myelosuppressive chemotherapy; marrow function may be further compromised (possibly fatal). Bone marrow function should recover after mechlorethamine administration prior to initiating radiation therapy or other chemotherapy regimens.

• Extravasation: [U.S. Boxed Warning]: Mechlorethamine is a potent vesicant; extravasation results in painful inflammation with induration and sloughing. If extravasation occurs, promptly manage by infiltrating area with 1/6 molar sodium thiosulfate solution, followed by dry cold compresses for 6-12 hours. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.

• Fertility effects: Impaired spermatogenesis, azoospermia, and total germinal aplasia may occur in male patients treated with mechlorethamine, particularly when used in combination with other chemotherapy agents. Delayed menses, oligomenorrhea, or temporary or permanent amenorrhea may be observed in female patients treated with mechlorethamine.

• Gastrointestinal toxicities: Mechlorethamine is associated with a high emetic potential (Basch, 201; Dupuis, 2011; Roila, 2010); antiemetics are recommended to prevent nausea and vomiting.

• Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, have been reported.

• Immunosuppression: Mechlorethamine has immunosuppressant properties. May predispose patients to infections (bacterial, viral, or fungal).

• Secondary malignancies: Alkylating agents, including mechlorethamine, are associated with in increased incidence of secondary malignancies; concurrent radiation therapy or combination chemotherapy may increase the risk.

• Tumor lysis syndrome: Hyperuricemia may occur, especially with lymphomas; ensure adequate hydration; consider antihyperuricemic therapy if appropriate.

Disease-related concerns:

• Chronic lymphocytic leukemia (CLL): Bone marrow failure and other toxicities are more common in CLL; in general, mechlorethamine is no longer used in the treatment of CLL.

• Nonresponding tumors: Bone and nervous system tumors typically respond poorly to treatment with mechlorethamine. The routine use of mechlorethamine in widely disseminated tumors is discouraged.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pregnancy: [U.S. Boxed Warning]: Avoid exposure during pregnancy.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]). [U.S. Boxed Warning]: Mechlorethamine is a highly toxic nitrogen mustard; avoid inhalation of vapors or dust; review and follow special handling procedures. Avoid dust or vapor contact with skin or eyes. If accidental skin exposure occurs, wash/irrigate thoroughly with water for at least 15 minutes, followed by 2% sodium thiosulfate solution; remove and destroy any contaminated clothing. 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 ophthalmology consultation. The manufacturer recommends neutralizing remaining unused mechlorethamine, empty or partial vials, gloves, tubing, glassware, etc., after mechlorethamine administration; soak in an aqueous solution containing equal volumes of sodium thiosulfate (5%) and sodium bicarbonate (5%) for 45 minutes; rinse with water; dispose of properly.

Other warnings/precautions:

• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.

Monitoring Parameters

CBC with differential and platelet count; renal and hepatic function; signs/symptoms of hypersensitivity reactions, infection, and extravasation

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Women of childbearing potential are advised not to become pregnant during treatment. [U.S. Boxed Warning]: Avoid exposure during pregnancy.

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 lack of appetite. Have patient report immediately to prescriber signs of infection, severe nausea, vomiting, severe diarrhea, dark urine, jaundice, bruising, bleeding, loss of strength and energy, or severe pain or irritation at the injection site (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 healthcare 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.

Hide