mechlorethamine; nitrogen mustard (Mustargen, Nor-mustard, Chlorethazine)

Introduction

Tradename: Mustargen.

Indications

• brain tumors
• Hodgkin's disease
• non-Hodgkin's lymphoma
• chronic leukemias
• malignant effusions (intracavitary injections)
  • malignant ascites
• mycosis fungoides
• palliative treatment of:
  • bronchogenic carcinoma
  • breast carcinoma
  • ovarian carcinoma
• polycythemia vera

Contraindications

• severe myelosuppression
• infection

pregnancy category = x

safety in lactation = -

Dosage

• Hodgkin's lymphoma: 6 mg/m2 IV on days 1 & 8, repeated monthly
• as single agent: 0.4 mg/kg/month
• intracavitary: 0.4 mg/kg
• topically: 0.17 mg/mL applied daily

Powder for injection: 10 mg.

Pharmacokinetics

• rapidly deactivated in blood
• 1/2life is 12-15 minutes

elimination via plasma

Adverse effects

• common (> 10%)
  • bone marrow suppression (dose-related)
    • leukopenia & thrombocytopenia may be severe
    • onset: 4-7 days
    • nadir: 14 days
    • recovery: 21 days
  • moderate to severe nausea/vomiting
  • reproductive dysfunction
    • amenorrhea (may be temporary or pemanent)
    • impaired spermatogenesis (may return to normal after several years)
      • chromosomal abnormalities
  • precipitation of Herpes zoster (shingles)
  • ototoxicity
• less common (1-10%)
  • thrombosis, diarrhea, anorexia, metallic taste, secondary malignancies*, thrombophlebitis, tissue necrosis with extravasation#
• uncommon (< 1%)
  • allergic reactions, hepatotoxicity, peptic ulcer, peripheral neuropathy, vertigo, tinnitus, rash, hemolytic anemia, weakness, hypersensitivity
• other
  • stomatitis

* secondary malignancies occur in 1-6% of patients after several years

# sodium thiosulfate is a specific antidote for nitrogen mustard extravasations

• drug adverse effects of alkylating agents

Test interactions

increases serum K+

Mechanism of action

• alkylating agent
• interferes with DNA & RNA synthesis

Mechanism of drug resistance:

• defective transport via the choline transporter

Notes

• not related to the mustard plant

More general terms

• alkylating agent nitrogen mustard

Additional terms

• choline transporter

Component of

• nitrogen mustard/vincristine (Oncovin)/prednisone/ procarbazine (MOPP)
• estramustine (Emcyt)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4033
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9533