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. |
| Molecular Weight | 334.33 |
| 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 | Contraindicated due to teratogenicity; high risk of fetal malformations. |
| 2nd trimester | Contraindicated due to fetal toxicity; may cause low birth weight and developmental abnormalities. |
| 3rd trimester | Contraindicated due to risk of neonatal myelosuppression and other adverse effects. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and hemolytic uremic syndrome.
| Placental transfer | Mitomycin crosses the placenta. Evidence demonstrates fetal exposure, with potential for teratogenicity and fetal toxicity. |
| Breastfeeding | Breastfeeding is contraindicated during mitomycin therapy. The drug is excreted in breast milk and may cause serious adverse effects in the nursing infant, including myelosuppression. A washout period after the last dose is recommended before resuming breastfeeding. |
■ 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 |
Hypersensitivity to mitomycinThrombocytopeniaCoagulation disordersActive infectionPregnancyBreastfeeding
| 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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| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
| Food/Dietary | Avoid alcohol due to potential hepatotoxicity and increased nausea. No specific food interactions known. |
| Clinical Pearls | Mitomycin is a potent alkylating agent, often used intravesically for superficial bladder cancer. It causes significant myelosuppression, especially thrombocytopenia, with nadir at 4-6 weeks. Extravasation causes severe tissue necrosis; administer through a running IV and avoid peripheral veins. Pulmonary toxicity (interstitial pneumonitis) is a rare but serious adverse effect, more common with cumulative doses >50 mg/m². Monitor renal function as it can cause hemolytic-uremic syndrome. |
| Patient Advice | This medication can lower your blood cell counts, increasing risk of infection, bleeding, and fatigue. Report fever, bruising, or unusual tiredness. · If you experience shortness of breath or a persistent cough, contact your doctor immediately, as this may indicate lung toxicity. · Mitomycin may cause kidney damage. Drink plenty of fluids and report changes in urination or swelling. · Nausea and vomiting are common; take antiemetics as prescribed. Avoid alcohol. · For bladder instillation: do not urinate for 2 hours after treatment. Drink fluids to flush the bladder. · Use effective contraception during treatment and for at least 3 months after. Do not breastfeed. · Your urine may turn blue-green; this is harmless. |