MITOSOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MITOSOL (MITOSOL).
Mitomycin C is an alkylating antibiotic that inhibits DNA synthesis by forming cross-links between complementary DNA strands, thereby blocking DNA replication and transcription.
| Metabolism | Primarily metabolized in the liver via reduction to active metabolites, possibly involving NADPH-dependent reductases such as DT-diaphorase (NQO1). |
| Excretion | Renal: 60% unchanged; biliary/fecal: 40% as metabolites |
| Half-life | Terminal: 3-6 hours; in renal impairment, extends to 10-20 hours |
| Protein binding | 85-90%, primarily to albumin |
| Volume of Distribution | 0.5-0.8 L/kg, indicating moderate tissue distribution |
| Bioavailability | Oral: <5% due to extensive first-pass metabolism; intravenous: 100%; topical: varies (20-40% absorption) |
| Onset of Action | Intravenous: 5-15 minutes; topical: 1-2 hours |
| Duration of Action | Intravenous: 2-4 hours; topical: 6-12 hours |
| Molecular Weight | 334.33 |
0.04 mg/kg intravenously once weekly for 4 weeks, then every 3 weeks thereafter; maximum single dose 3.5 mg.
| Dosage form | FOR SOLUTION |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min/1.73m²; not recommended for GFR <30 mL/min/1.73m² due to limited data. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Not established for pediatric patients; safety and efficacy not determined. |
| Geriatric use | No specific dose adjustment, but monitor for increased toxicity due to age-related renal and hepatic function decline. |
| 1st trimester | Contraindicated due to teratogenicity; risk of fetal malformations, including neural tube defects, cardiovascular anomalies, and craniofacial defects. |
| 2nd trimester | Contraindicated; continued risk of fetal toxicity and growth restriction. |
| 3rd trimester | Contraindicated; risk of neonatal myelosuppression and potential for premature delivery. |
Clinical note
Comprehensive clinical and safety monograph for MITOSOL (MITOSOL).
| Placental transfer | Known to cross the placenta; detected in fetal tissues and amniotic fluid based on animal studies and limited human data. |
| Breastfeeding | Not recommended during breastfeeding. Excreted in human milk; potential for serious adverse reactions in nursing infants, including myelosuppression and carcinogenesis. |
■ FDA Black Box Warning
Hemolytic-uremic syndrome (HUS), a life-threatening condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, has been reported with mitomycin use, particularly with cumulative doses >60 mg/m².
| Serious Effects |
Hypersensitivity to mitomycin or any component of the formulationThrombocytopeniaCoagulation disordersSevere bone marrow suppressionActive infection
| Precautions | Bone marrow suppression (myelosuppression) can be severe and delayed, Pulmonary toxicity (interstitial pneumonitis, pulmonary fibrosis), Renal toxicity (nephrotoxicity) including HUS, Extravasation can cause severe tissue necrosis and ulceration, Hemolytic-uremic syndrome risk increased with cumulative dose >60 mg/m², Carcinogenicity: secondary malignancies reported |
| Food/Dietary | No specific food interactions documented. Maintain adequate hydration to minimize renal toxicity. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| Teratogenic Risk | Mitomycin C is contraindicated in pregnancy due to demonstrated teratogenicity. First trimester: High risk of fetal malformations (neural tube defects, cardiac anomalies). Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and neonatal myelosuppression. |
| Fetal Monitoring | Monitor complete blood count (CBC) for maternal myelosuppression; renal function (BUN, creatinine); hepatic function; fetal ultrasound for growth and amniotic fluid index (AFI) every 4–6 weeks; duplex Doppler if placental insufficiency suspected. |
| Fertility Effects | Gonadal suppression with risk of amenorrhea, oligospermia, and potential irreversible infertility due to alkylating agent effects on ovarian and testicular function. |
| Clinical Pearls | Mitomycin C belongs to the class of antitumor antibiotics, functioning as an alkylating agent and requiring intracellular reductive activation. It is indicated for topical use in primary superficial bladder cancer (TCC) via intravesical instillation. Key pearls: (1) Avoid extravasation during IV use—treat with dimethyl sulfoxide (DMSO) and cooling. (2) Hemolytic-uremic syndrome (HUS) is a rare but life-threatening systemic toxicity with IV administration; monitor renal function and CBC. (3) For intravesical therapy, retain instillation for 2 hours; rotate patient position. (4) Contraindicated in thrombocytopenia, coagulation disorders, or active infection. (5) Mitomycin is a potent vesicant—ensure proper catheter placement. |
| Patient Advice | This medication is given directly into the bladder through a catheter and must be held in the bladder for 2 hours; you may be asked to change positions every 15 minutes. · Do not urinate for at least 2 hours after instillation; wash hands and genital area thoroughly after urinating for the first 6 hours to avoid skin irritation. · Report any signs of bladder irritation (painful urination, blood in urine), rash, or unusual bleeding or bruising. · Avoid handling or touching the medication; it can cause severe skin reactions. · If receiving intravenously, report any pain, redness, or swelling at the injection site immediately. |