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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(me klor ETH a meen)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Hodgkin's disease; non-Hodgkin's lymphoma; intracavitary injection for treatment of metastatic tumors; pleural and other malignant effusions
Use: Unlabeled
Topical treatment of mycosis fungoides
Pregnancy Risk Factor
D
Pregnancy Considerations
Animal studies have demonstrated teratogenic effects. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential are advised not to become pregnant. Use only when potential benefit justifies potential risk to the fetus. [U.S. Boxed Warning]: Avoid exposure during pregnancy.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is not known if mechlorethamine is excreted in human breast milk. Due to the potential for serious adverse reactions in the nursing infant, breast-feeding is not recommended.
Contraindications
Hypersensitivity to mechlorethamine or any component of the formulation; presence of known infection
Warnings/Precautions
Boxed warnings:
• Experienced physician: See “Other warnings/precautions” below.
• Extravasation: See “Other warnings/precautions” below.
• Hazardous agent: See “Special handling” below.
• Pregnancy: See “Special populations” below.
Special handling:
• Hazardous agent: [U.S. Boxed Warning]: Use appropriate precautions for handling and disposal. Avoid contact with skin or eyes.
Concerns related to adverse effects:
• Bone marrow suppression: May cause lymphopenia, granulocytopenia, thrombocytopenia and anemia.
• Hyperuricemia: May occur, especially with lymphomas; ensure adequate hydration.
Special populations:
• Pregnancy: [U.S. Boxed Warning]: Avoid exposure during pregnancy.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• Extravasation: [U.S. Boxed Warning]: Mechlorethamine is a potent vesicant; if extravasation occurs, severe tissue damage (leading to ulceration and necrosis) and pain may occur. Sodium thiosulfate should be available for treatment of extravasation.
Adverse Reactions
>10%:
Dermatologic: Alopecia; hyperpigmentation of veins; contact and allergic dermatitis (50% with topical use)
Endocrine & metabolic: Chromosomal abnormalities, delayed menses, oligomenorrhea, amenorrhea, impaired spermatogenesis
Gastrointestinal: Nausea and vomiting (almost 100%), onset may be within minutes of drug administration
Genitourinary: Azoospermia
Hematologic: Myelosuppression, leukopenia, and thrombocytopenia
Onset: 4-7 days
Nadir: 14 days
Recovery: 21 days
1% to 10%:
Central nervous system: Fever
Gastrointestinal: Diarrhea, anorexia, metallic taste
Otic: Tinnitus
<1%: Vertigo, rash, hemolytic anemia, hepatotoxicity, weakness, peripheral neuropathy
Metabolism/Transport Effects
None known.
Drug Interactions
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: 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. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. 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. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (due to GI irritation).
Storage
Store intact vials at room temperature of 15°C to 30°C (59°F to 86°F). Protect from light. Solution is stable for only 15-60 minutes after dilution
Reconstitution
Must be prepared immediately before use. Use appropriate precautions for handling. Dilute powder with 10 mL SWFI or 0.9% sodium chloride to a final concentration of 1 mg/mL. May be diluted in up to 100 mL NS for intracavitary or topical administration.
Compatibility
Stable in sterile water for injection; incompatible with D5W, NS.
Y-site administration: Compatible: Amifostine, aztreonam, filgrastim, fludarabine, granisetron, melphalan, ondansetron, sargramostim, teniposide, vinorelbine. Incompatible: Allopurinol, cefepime.
Mechanism of Action
Bifunctional alkylating agent that inhibits DNA and RNA synthesis via formation of carbonium ions; cross-links strands of DNA, causing miscoding, breakage, and failure of replication; 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.
Pharmacodynamics/Kinetics
Duration: Unchanged drug is undetectable in blood within a few minutes
Absorption: Intracavitary administration: Incomplete secondary to rapid deactivation by body fluids
Metabolism: Rapid hydrolysis and demethylation, possibly in plasma
Half-life elimination: <1 minute
Excretion: Urine (50% as metabolites, <0.01% as unchanged drug)
Dosage
Details concerning dosing in combination regimens should also be consulted. 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).
Children and Adults (unlabeled dosing): Lymphoma: I.V.: 6 mg/m2 on days 1 and 8 of a 28-day cycle (MOPP regimen)
Adults:
I.V.: Lymphoma: 0.4 mg/kg as a single dose or in divided doses of 0.1 mg/kg/day (for 4 days) or 0.2 mg/kg/day (for 2 days) per treatment course; repeat treatment course after hematologic recovery
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
Topical (unlabeled use): 0.01% to 0.02% solution, lotion, or ointment
Hemodialysis: Not removed; supplemental dosing is not required.
Peritoneal dialysis: Not removed; supplemental dosing is not required.
Dosage: Combination Regimens
Brain tumors: MOPP (Medulloblastoma)
Lymphoma, Hodgkin:
MOPP/ABVD (Hodgkin)
MOPP/ABV Hybrid (Hodgkin)
MOPP (Hodgkin)
Stanford V (Hodgkin)
Administration: I.V.
Vesicant. Margin of error is very slight. Check dosage carefully before administration. Administer with caution. Administer I.V. push over a few minutes into a free-flowing I.V. solution. Must be prepared immediately prior to administration.
Administration: Other
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 administration to obtain uniform distribution.
Administration: I.V. Detail
Mechlorethamine may cause extravasation. Use within 1 hour of preparation. Avoid extravasation since mechlorethamine is a potent vesicant.
pH: 3-5
Monitoring Parameters
CBC with differential, hemoglobin, and platelet count
Patient Education
This medication can only be given by infusion. Report immediately any swelling, redness, pain, or burning at infusion site. Do not use alcohol during treatment; may increase gastric irritation. Maintain adequate nutrition and fluid balance unless instructed to restrict fluid intake. May cause discoloration (brown color) of veins used for infusion, hair loss (reversible), easy bleeding or bruising, or increased susceptibility to infection. This drug may cause menstrual irregularities, permanent sterility, and birth defects. Report changes in auditory or visual acuity; unusual bleeding or bruising; persistent fever or sore throat; blood in urine, stool, or vomitus; delayed healing of any wounds; skin rash; yellowing of skin or eyes; changes in color of urine of stool; acute or unresolved nausea or vomiting; diarrhea; or loss of appetite.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
Leukopenia is common; avoid use with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
This is a powerful vesicant. Premedication with antiemetic recommended (highly emetogenic; emesis may begin within minutes of starting infusion). Infusion site must be closely monitored; extravasation can cause severe sloughing or tissue necrosis. Patient must be monitored closely during infusion and between treatments (adverse reactions can be severe and involve several systems). Teach patient importance of adequate hydration.
Oncology: Emetic Potential
Very high (>90%)
Oncology: Vesicant
Vesicant
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as hydrochloride:
Mustargen®: 10 mg
References
Bonadonna G, Valagussa P, and Santoro A, “Alternating Non-Cross-Resistant Combination Chemotherapy or MOPP in Stage IV Hodgkin's Disease. A Report of 8-Year Results,” Ann Intern Med, 1986, 104(6):739-46.
DeVita VT, Serpick A, and Carbone PP, “Combination Chemotherapy in the Treatment of Advanced Hodgkin's Disease,” Ann Intern Med, 1970, 73:881-95.
Dorr RT, Soble M, and Alberts DS, “Efficacy of Sodium Thiosulfate as a Local Antidote to Mechlorethamine Skin Toxicity in the Mouse,” Cancer Chemother Pharmacol, 1988, 22(4):299-302.
Loutsidis A, Bellenis I, Argiriou M, et al, “Tetracycline Compared With Mechlorethamine in the Treatment of Malignant Pleural Effusions. A Randomized Trial,” Respir Med, 1994, 88(7):523-6.
Price NM, Hoppe RT, and Deneau DG, “Ointment Based Mechlorethamine Treatment for Mycosis Fungoides,” Cancer, 1983, 52:2214-9.
Taylor JR, Halprin KM, Levine V, et al, “Mechlorethamine Hydrochloride Solutions and Ointments,” Arch Dermatol, 1980, 116:783-5.
Vonderheid EC, “Topical Mechlorethamine Chemotherapy: Considerations on its Use in Mycosis Fungoides,” Int J Dermatol, 1984, 23(3):180-6.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
Content last modified February 2012
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