MITOMYCIN
Clinical safety rating: avoid
Contraindicated (not allowed)
Mitomycin is an alkylating agent that inhibits DNA synthesis by cross-linking DNA strands after undergoing enzymatic or chemical bioreduction. It produces oxygen radicals and causes DNA fragmentation, leading to cell cycle arrest and apoptosis.
| Metabolism | Mitomycin is extensively metabolized in the liver primarily by enzymatic reduction to active metabolites. The exact enzymes are not fully characterized, but NADPH-dependent reductases are involved. Metabolism is rapid, and metabolites are excreted in urine. |
| Excretion | Renal: ~10% unchanged; hepatic metabolism; biliary/fecal: 30-40% as metabolites. Total elimination: ~80% within 24h. |
| Half-life | Terminal elimination half-life: 23–78 min (mean ~50 min) in patients with normal renal function; prolonged in renal impairment. |
| Protein binding | ~90% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | 0.3–0.5 L/kg; reflects distribution into total body water with limited tissue binding. |
| Bioavailability | Intravenous: 100%; Intravesical: <1% systemic absorption. |
| Onset of Action | Intravenous: Within 30 min; Intravesical: Variable, typically within 1–2 hours. |
| Duration of Action | Intravenous: 3–4 weeks for myelosuppression recovery; Intravesical: 2–3 weeks for local effect. |
| Action Class | Alkaloids-cytotoxic agents |
| Brand Substitutes | Mitomycin C 40mg Injection, Mitocin 10mg Injection, Mitodus 10mg Injection, Oncocin 10mg Injection, Vesimycin 10mg Injection, Mitomycin C 10mg Injection |
20 mg/m2 IV as a single dose every 6-8 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: reduce dose by 50%; CrCl <10 mL/min: avoid use. |
| Liver impairment | No specific guidelines; use caution in severe impairment (Child-Pugh C). |
| Pediatric use | Not established; safety and efficacy not determined. |
| Geriatric use | No specific dose adjustment; monitor for nephrotoxicity and myelosuppression. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and hemolytic uremic syndrome.
| Breastfeeding | Contraindicated during breastfeeding. M/P ratio unknown; mitomycin is likely excreted into breast milk based on molecular weight (<500 Da) and may cause severe adverse effects in nursing infants, including myelosuppression and gastrointestinal toxicity. |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: high risk of teratogenicity (congenital anomalies including skeletal and visceral malformations). Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and neonatal myelosuppression; avoid use unless maternal benefit justifies fetal risk. |
■ FDA Black Box Warning
Hemolytic Uremic Syndrome (HUS): Mitomycin can cause HUS, a triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, which may lead to renal impairment and death. The risk correlates with cumulative doses >60 mg/m². Use with caution and monitor renal function and blood counts.
| Serious Effects |
["Absolute: Hypersensitivity to mitomycin or any component of the formulation.","Absolute: Severe thrombocytopenia, leukopenia, or bone marrow suppression.","Absolute: Active bleeding or hemorrhage.","Relative: Impaired renal function (risk of HUS increased).","Relative: Preexisting pulmonary disease (increased risk of pulmonary toxicity).","Relative: Concurrent use of live vaccines (risk of disseminated infection)."]
| Precautions | ["Bone marrow suppression: Dose-limiting myelosuppression with leukopenia and thrombocytopenia, typically occurring 2-3 weeks after administration.","Renal toxicity: Increased risk of HUS and renal failure, especially with cumulative doses >60 mg/m². Avoid in patients with pre-existing renal impairment.","Pulmonary toxicity: Interstitial pneumonitis and pulmonary fibrosis may occur, especially in patients receiving concurrent radiation or other pneumotoxic drugs.","Extravasation: Mitomycin is a vesicant; extravasation can cause severe tissue necrosis. Administer via a secure IV line.","Hemolytic uremic syndrome: Monitor for signs of HUS (e.g., microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure).","Carcinogenicity: May cause secondary malignancies, particularly acute leukemia.","Gastrointestinal effects: Nausea, vomiting, and diarrhea are common. Anorexia and stomatitis may occur.","Reproductive toxicity: Can cause fetal harm. Contraception recommended for both males and females during treatment."] |
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| Fetal Monitoring | Monitor maternal complete blood count (CBC) with differential, renal function, and hepatic function throughout therapy. Fetal monitoring includes ultrasound for growth and amniotic fluid volume, and nonstress test or biophysical profile in third trimester if used. |
| Fertility Effects | Mitomycin can cause amenorrhea, oligospermia, and azoospermia due to gonadal toxicity; may lead to irreversible infertility in both males and females. Risk is dose-dependent. |