No

Antineoplastic Agent, Alkylating Agent

Combination therapy of Hodgkin's disease and malignant lymphomas; non-Hodgkin's lymphoma; palliative treatment of bronchogenic, breast and ovarian carcinoma; may be used by intracavitary injection for treatment of metastatic tumors; pleural and other malignant effusions; topical treatment of mycosis fungoides

D

Hypersensitivity to mechlorethamine or any component; pre-existing profound myelosuppression or infection

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Extravasation of the drug into subcutaneous tissues results in painful inflammation and induration; sloughing may occur. Patients with lymphomas should receive prophylactic allopurinol 2-3 days prior to therapy to prevent complications resulting from tumor lysis.

>10%:

Gastrointestinal: Nausea and vomiting usually occur in nearly 100% of patients and onset is within 30 minutes to 2 hours after administration

Emetic potential: High (>90%)

Time course of nausea/vomiting: Onset: 1-3 hours; duration 2-8 hours

Hematologic: Myelosuppressive: Leukopenia and thrombocytopenia can be severe; caution should be used with patients who are receiving radiotherapy, secondary leukemia

WBC: Severe

Platelets: Severe

Onset (days): 4-7

Nadir (days): 14

Recovery (days): 21

Endocrine & metabolic: Delayed menses, oligomenorrhea, temporary or permanent amenorrhea, impaired spermatogenesis; spermatogenesis may return in patients in remission several years after the discontinuation of chemotherapy, chromosomal abnormalities

Genitourinary: Azoospermia

Otic: Ototoxicity

Miscellaneous: Precipitation of herpes zoster

1% to 10%:

Central nervous system: Fever, vertigo

Dermatologic: Alopecia

Endocrine & metabolic: Hyperuricemia

Gastrointestinal: Diarrhea, anorexia, metallic taste

Local: Thrombophlebitis/extravasation: May cause local vein discomfort which may be relieved by warm soaks and pain medication. A brown discoloration of veins may occur. Mechlorethamine is a strong vesicant and can cause tissue necrosis and sloughing.

Vesicant chemotherapy

Secondary malignancies: Have been reported after several years in 1% to 6% of patients treated

Neuromuscular & skeletal: Weakness

Otic: Tinnitus

Miscellaneous: Hypersensitivity, anaphylaxis

<1%: Vertigo, rash, peptic ulcer, myelosuppression, hemolytic anemia, hepatotoxicity, peripheral neuropathy

Suppression of all formed elements of the blood, uric acid crystals, nausea, vomiting, diarrhea

Sodium thiosulfate is the specific antidote for nitrogen mustard extravasations; treatment of systemic overdose is supportive

Patients may experience impaired immune response to vaccines; possible infection after administration of live vaccines in patients receiving immunosuppressants

Store intact vials at room temperature.

Dilute powder with 10 mL SWI to a final concentration of 1 mg/mL; solution is highly unstable - should be administered within 15 minutes of dilution

May be diluted in up to 100 mL NS for intracavitary administration

Standard I.V. dilution:

I.V. push: Dose/syringe (concentration is 1 mg/mL)

Maximum syringe for IVP is 30 mL and syringe should be less than or equal to 75% full

Must be prepared fresh; solution is stable for only 1 hour after dilution and must be administered within that time period

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

Absorption: Incomplete absorption into bloodstream following intracavitary administration secondary to rapid deactivation by body fluids

Metabolism: Following I.V. administration, drug undergoes rapid chemical transformation; unchanged drug is undetectable in the blood within a few minutes

Half-life: <1 minute

Elimination: <0.01% of unchanged drug is recovered in urine

Refer to individual protocols. Dosage should be based on ideal dry weight; the presence of edema or ascites must be considered so that dosage will be based on actual weight unaugmented by these conditions

Adults:

I.V.: 0.4 mg/kg OR 12-16 mg/m² for one dose OR divided into 0.1 mg/kg/day for 4 days, repeated at 4- to 6-week intervals

Intracavitary: 10-20 mg diluted in 10 mL of SWI or 0.9% sodium chloride

Intrapericardially: 0.2-0.4 mg/kg diluted in up to 100 mL of 0.9% sodium chloride

Hemodialysis: Not removed; supplemental dosing is not required

Peritoneal dialysis: Not removed; supplemental dosing is not required

Topical mechlorethamine has been used in the treatment of cutaneous lesions of mycosis fungoides. A skin test should be performed prior to treatment with the topical preparation to detect sensitivity and possible irritation (use fresh mechlorethamine 0.1 mg/mL and apply over a 3 x 5 cm area of normal skin).

CBC with differential, hemoglobin, and platelet count

May cause dizziness

Leukopenia is common; avoid use with clozapine and carbamazepine

This medication can only be given by infusion, usually in cycles of therapy. You will need frequent laboratory and medical monitoring during treatment. Do not use alcohol, aspirin or aspirin-containing medications, and OTC medications without consulting prescriber. Maintain adequate fluid balance (2-3 L/day of fluids unless instructed to restrict fluid intake) and adequate nutrition (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may reduce anorexia and nausea). May cause discoloration (brown color) of veins used for infusion, hair loss (reversible); easy bleeding or bruising (use soft toothbrush or cotton swabs and frequent mouth care, use electric razor, avoid sharp knives or scissors); increased susceptibility to infection (avoid crowds or exposure to infection - do not have any vaccinations unless approved by prescriber). This drug may cause menstrual irregularities, permanent sterility, and birth defects. Report changes in auditory or visual acuity; unusual bleeding or bruising or 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. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to become pregnant. Male/female: Consult prescriber for instruction on appropriate barrier contraceptive measures. This drug may cause severe fetal defects. Breast-feeding is not recommended.

Use within 1 hour of preparation; avoid extravasation since mechlorethamine is a potent vesicant

Powder for injection, as hydrochloride: 10 mg

Akintonwa A, "Potentiation of Nitrogen Mustard Toxicity by Narcotic Analgesics," Clin Toxicol, 1981, 18:451-8.

Berg SL, Grisell DL, DeLaney TF, et al, "Principles of Treatment of Pediatric Solid Tumors," Pediatr Clin North Am, 1991, 38(2):249-67.

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.

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.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

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.

Vonderheid EC, "Topical Mechlorethamine Chemotherapy: Considerations on its Use in Mycosis Fungoides ," Int J Dermatol, 1984, 23(3):180-6.