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mitomycin C (Mutamycin, Mitomycinum, Ametycin)

Tradename: Mutamycin. Indications: - gastrointestinal adenocarcinoma - gastric cancer, pancreatic cancer, colorectal carcinoma - advanced breast cancer - head & neck cancer - cancer of the lung - squamous cell carcinoma of the anus - bladder cancer - intraepithelial neoplasia [3] Contraindications: 1) thrombocytopenia < 75,000/mm3 2) leukopenia < 3000/mm3 3) serum creatinine > 1.7 mg/dL 4) coagulation disorder Dosage: 1) 10-20 mg/m2 IV every 6-8 weeks 2) bladder irrigation: 20-40 mg in 40 mL of normal saline or sterile water every 1-2 weeks Powder for injection: 5 mg, 20 mg. Stability: Reconstituted is stable: 1) in sterile water for 7 days & 14 days if refrigerated 2) 3 hours in D5W at room temperature 3) 12 hours in normal saline at room temperature 4) 24 hours in lactated ringers (LR) at room temperature 5) mitomycin 5-15 mg + heparin 1000-10,000 units in normal saline stable for 48 hours at room temperature Pharmacokinetics: 1) well distributed 2) no CSF penetration 3) inactivated by hepatic microsomal enzymes 4) further degraded by kidney & spleen 5) elimination 1/2life 1 hour 6) not removed by dialysis Adverse effects: 1) common (> 10%) a) nausea/vomiting (mild to moderate, 10%) - begins 1-2 hours after treatment - lasts 3-4 days b) myelosuppression - WBC (moderate) - platelets (severe) - onset 21 days - nadir 36 days - recovery 42-56 days c) extravasation with tissue necrosis 2) less common (1-10%) a) stomatitis, discolored fingernails (violet), paresthesias of extremities, alopecia b) pulmonary fibrosis (7%)* - independent of dosing - manifest as dry cough with progressive dyspnea - generally responsive to steroid therapy c) renal toxicity* - elevation of serum creatinine (2%) - hemolytic uremic syndrome (generally, doses > 30 mg) 3) uncommon (< 1%) - thrombophlebitis, weakness, paresthesias, fever, pruritus, microangiopathic hemolytic anemia, malaise, rash, - cardiomyopathy, heart failure (generally, doses > 30 mg) [4] 4) other - diarrhea, hepatotoxicity, headache, confusion * pneumonitis/nephrotoxicity with cumulative doses of 60 mg/m2 Drug interactions: vinca alkaloids Test interactions: increases serum K+ Mechanism of action: 1) antitumor antibiotic 2) inhibits DNA synthesis 3) at high concentrations, inhibits RNA synthesis

Interactions

drug interactions

General

antibiotic antineoplastic agent

Properties

MISC-INFO: elimination route LIVER 1/2life 1 HOUR elimination by hemodialysis - pregnancy-category X safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Deprecated Reference
  4. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015