mechlorethamine hydrochloride (nitrogen mustard)
Mustargen

Available forms
Available by prescription only
Injection: 10-mg vials

Indications and dosages
  Dosages and indications may vary. Check current literature for recommended protocols.
 Hodgkin’s disease, bronchogenic carcinoma, chronic lymphocytic leukemia, chronic myelocytic leukemia, lymphosarcoma, polycythemia vera. Adults: 0.4 mg/kg I.V. per course of therapy as a single dose or 0.1 to 0.2 mg/kg on 2 to 4 successive days q 3 to 6 weeks. Give through running I.V. infusion. Dose reduced in prior radiation therapy or chemotherapy to 0.2 to 0.4 mg/kg. Dose based on ideal or actual body weight, whichever is less.
 Intracavitary doses for neoplastic effusions. Adults: 0.2 to 0.4 mg/kg.
 Treatment of advanced Hodgkin’s disease (MOPP regimen). Adults: 6 mg/m² given I.V. on days 1 and 8 of 28-day cycle. In subsequent cycles, dose is based on leukocyte count.

Pharmacodynamics
Antineoplastic action: Mechlorethamine exerts its cytotoxic activity through the basic processes of alkylation. Drug causes cross-linking of DNA strands, single-strand breakage of DNA, abnormal base pairing, and interruption of other intracellular processes, resulting in cell death.

Pharmacokinetics
Absorption: Well absorbed after oral administration; however, because drug is very irritating to tissue, it must be given I.V. After intracavitary administration, mechlorethamine is absorbed incompletely, probably from deactivation by body fluids in the cavity.
Distribution: Doesn’t cross the blood-brain barrier.
Metabolism: Undergoes rapid chemical transformation and reacts quickly with various cellular components before being deactivated.
Excretion: Metabolites are excreted in urine. Less than 0.01% of an I.V. dose is excreted unchanged in urine.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with infectious diseases. Use cautiously in patients with severe anemia or depressed neutrophil or platelet count and in those who have recently undergone chemotherapy or radiation therapy.

Interactions
None reported.

Adverse reactions
CNS: weakness, vertigo.
CV: thrombophlebitis.
EENT: tinnitus, deafness.
GI: nausea, vomiting, anorexia.
GU: menstrual irregularities, impaired spermatogenesis.
Hematologic: thrombocytopenia, lymphocytopenia, agranulocytosis, nadir of myelosuppression occurring by days 4 to 10 and lasting 10 to 21 days; mild anemia begins in 2 to 3 weeks.
Hepatic: jaundice.
Metabolic: hyperuricemia.
Skin: alopecia, rash, sloughing, severe irritation (if drug extravasates or touches skin).
Other: precipitation of herpes zoster, anaphylaxis, amyloidosis.

Effects on lab test results
• May increase nitrogenous compound (urea) level.
• May decrease hemoglobin and granulocyte, lymphocyte, RBC, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include severe leukopenia, anemia, thrombocytopenia, and a hemorrhagic diathesis with subsequent delayed bleeding. Death may follow.
 Treatment is usually supportive and includes transfusion of blood components and antibiotic treatment of complicating infections.

Special considerations
• To prevent hyperuricemia with resulting uric acid nephropathy, allopurinol may be given; keep patient well hydrated.
• Drug has been used topically to treat mycosis fungoides.
 ALERT Avoid contact with skin or mucous membranes. Wear gloves when preparing solution and during administration to prevent accidental skin contact. If contact occurs, wash with copious amounts of water.
• To reconstitute powder, use 10 ml of sterile water for injection or normal saline solution to give a concentration of 1 mg/ml.
• When reconstituted, drug is a clear colorless solution. Don’t use if solution is discolored or if droplets of water are visible within vial before reconstitution.
• Solution is very unstable. Prepare immediately before infusion and use within 15 minutes. Discard unused solution.
• Dilution of drug into a large volume of I.V. solution isn’t recommended because it may react with the diluent and isn’t stable for a prolonged period.
• Drug may be given I.V. push over a few minutes into the tubing of a freely flowing I.V. infusion. Following administration, flush vein for 2.5 minutes with running I.V. solution or inject 5 to 10 ml of solution into sidearm.
• Treatment of extravasation includes local injections of a 1/6 M sodium thiosulfate solution. Prepare solution by mixing 4 ml of sodium thiosulfate 10% with 6 ml of sterile water for injection. Also, apply ice packs for 6 to 12 hours to minimize local reactions.
• During intracavitary administration, turn patient from side to side every 15 minutes for 1 hour to distribute drug.
• Avoid all I.M. injections when platelet count is low.
• Monitor uric acid levels, CBC, and liver function tests.
• Use anticoagulants cautiously. Watch closely for signs of bleeding.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. However, because of the potential for serious adverse reactions, mutagenicity, and carcinogenicity in the infant, breast-feeding isn’t recommended.

Patient education
• Tell patient to avoid exposure to people with infections.
• Advise patient that adequate fluid intake is very important to facilitate excretion of uric acid.
• Reassure patient that hair should grow back after treatment has ended.
• Tell patient to promptly report signs or symptoms of bleeding or infection.
• Advise patient to use contraception while using drug.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use