MECHLORETHAMINE HYDROCHLORIDE

MECHLORETHAMINE HYDROCHLORIDE
(me-klor-eth'a-meen)
Mustargen
Classifications: antineoplastic; alkylating agent; nitrogen mustard;
Therapeutic: antineoplastic; nitrogen mustard
Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

10 mg powder for injection

Action

Analog of mustard gas and standard of reference for nitrogen mustards. Forms highly reactive carbonium ion, which causes cross-linking and abnormal base-pairing in DNA, thereby interfering with DNA replication and RNA and protein synthesis. Cell-cycle nonspecific inhibitor of DNA and RNA synthesis.

Therapeutic Effect

Antineoplastic agent that simulates actions of x-ray therapy, but nitrogen mustards produce more acute tissue damage and more rapid recovery.

Uses

Generally confined to nonterminal stages of neoplastic disease. Employed as single agent or in combination with other agents in palliative treatment of Hodgkin's disease (stages III and IV), lymphosarcoma, mycosis fungoides, polycythemia vera, bronchogenic carcinoma, chronic myelocytic or chronic lymphocytic leukemia. Also for intrapleural, intrapericardial, and intraperitoneal palliative treatment of metastatic carcinoma resulting in effusion.

Contraindications

Myelosuppression; infectious granuloma; known infectious diseases, acute herpes zoster; intracavitary use with other systemic bone marrow suppressants; pregnancy (category D), lactation.

Cautious Use

Bone marrow infiltration with malignant cells, chronic lymphocytic leukemia; men or women in childbearing age; use with x-ray treatment or other chemotherapy in alternating courses.

Route & Dosage

Advanced Hodgkin's Disease
Adult: IV 6 mg/m² on day 1 and 8 of a 28-d cycle

Other Neoplasms
Adult: IV 0.4 mg/kg given as a single dose or in divided doses of 0.1–0.2 mg/kg/d, may repeat course in 3–6 wk

Administration

Intravenous

Wear surgical gloves during preparation and administration of solution.
Avoid inhalation of vapors and dust and contact of drug with eyes and skin.
Flush contaminated area immediately if drug contacts the skin. Use copious amounts of water for at least 15 min, followed by 2% sodium thiosulfate solution. Irritation may appear after a latent period.
Irrigate immediately if eye contact occurs. Use copious amounts of NS followed by ophthalmologic examination as soon as possible.

PREPARE: Direct: Reconstitute immediately before use by adding 10 mL sterile water for injection or NS injection to vial to yield 1 mg/mL. With needle still in stopper, shake vial several times to dissolve. Discard colored solution or contents of any vial which has drops of moisture.

ADMINISTER: Direct: To reduce risk of severe infections from extravasation or high concentration of the drug, inject slowly over 3–5 min into tubing or sidearm of freely flowing IV infusion. Flush vein with running IV solution for 2–5 min to clear tubing of any remaining drug.

INCOMPATIBILITIES Solution/additive: D5W, methohexital. Y-site: Allopurinol, cefepime.

Be alert for extravasation. Treat promptly with subcutaneous or intradermal injection with isotonic sodium thiosulfate solution (1/6 molar) and application of ice compresses intermittently for a 6–12 h period to reduce local tissue damage and discomfort. Tissue induration and tenderness may persist 4–6 wk, and tissue may slough.

Adverse Effects (≥1%)

CNS: Neurotoxicity: vertigo, tinnitus, headache, drowsiness, peripheral neuropathy, light-headedness, paresthesias, cerebral deterioration, coma. GI: Stomatitis, xerostomia, anorexia, nausea, vomiting, diarrhea. Hematologic: Leukopenia, thrombocytopenia, lymphocytopenia, agranulocytosis, anemia, hyperheparinemia. Skin: Pruritus, hyperpigmentation, herpes zoster, alopecia. Urogenital: Amenorrhea, azoospermia, chromosomal abnormalities, hyperuricemia. Body as a Whole: Weakness, hypersensitivity reactions. With extravasation: painful inflammatory reaction, tissue sloughing, thrombosis, thrombophlebitis.

Interactions

Drug: Mechlorethamine (nitrogen mustards) may reduce effectiveness of antigout agents by raising serum uric acid levels; dosage adjustments may be necessary; may prolong neuromuscular blocking effects of succinylcholine; may potentiate bleeding effects of anticoagulants, salicylates, nsaids, platelet inhibitors.

Pharmacokinetics

Metabolism: Rapid hydrolysis and demethylation. Elimination: In urine. Half-Life: <1 min.

Nursing Implications

Assessment & Drug Effects

Establish baseline data for body weight, I&O ratio and pattern, and blood labs as reference for design of drug and care regimens.
Lab tests: Monitor CBC with differential and platelet count. Periodic serum uric acid levels.
Record daily weight. Alert physician to sudden or slow, steady weight gain.
Monitor and record patient's fluid losses carefully. Prolonged vomiting and diarrhea can produce volume depletion.
Report immediately petechiae, ecchymoses, or abnormal bleeding from intestinal and buccal membranes. Keep injections and other invasive procedures to a minimum during period of thrombocytopenia.
Report symptoms of agranulocytosis (e.g., unexplained fever, chills, sore throat, tachycardia, and mucosal ulceration).
Prevent exposure to people with infection, especially upper respiratory tract infections.
Note and record state of hydration of oral mucosa, condition of gingiva, teeth, tongue, mucosa, and lips.

Patient & Family Education

Report any signs of bleeding immediately.
Use caution to prevent falls or other traumatic injuries, especially during periods of low platelet counts.
Increase fluid intake up to 3000 mL/d if allowed to minimize risk of kidney stones. Report promptly all symptoms, including flank or joint pain, swelling of lower legs and feet, changes in voiding pattern.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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