MITOZYTREX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MITOZYTREX (MITOZYTREX).
Mitomycin C is an antibiotic that inhibits DNA synthesis by cross-linking DNA strands via alkylation, preferentially at guanine-cytosine sequences. It is bioreduced to an active form that generates oxygen radicals and causes DNA strand scission.
| Metabolism | Primarily metabolized in the liver by enzymatic reduction via NADPH-dependent cytochrome P450 reductase and DT-diaphorase (NQO1). Minor pathways include conjugation with glutathione and further metabolism to inactive products. |
| Excretion | Renal excretion is the primary route of elimination, with approximately 10-30% of the dose excreted unchanged in urine. Biliary/fecal excretion accounts for a minor fraction (<10%). |
| Half-life | Terminal elimination half-life is approximately 1.5-2.5 hours for the initial phase, followed by a prolonged terminal half-life of 20-40 hours due to extensive tissue binding. Clinically, this long terminal half-life indicates potential for cumulative toxicity with repeated doses. |
| Protein binding | Approximately 50-70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is large, approximately 0.5-1.5 L/kg, indicating extensive tissue distribution and binding. |
| Bioavailability | Bioavailability via IV is 100%; not administered orally due to poor oral bioavailability (<10%) and gastrointestinal toxicity. |
| Onset of Action | Intravenous administration: clinical effect (antitumor activity) typically observed within 1-2 hours after infusion; peak plasma levels achieved by end of infusion. |
| Duration of Action | Duration of antineoplastic effect is variable, typically lasting several days to weeks; myelosuppression (nadir at 2-3 weeks) and other toxicities may persist for 2-4 weeks due to prolonged drug retention in tissues. |
20 mg/m² intravenous injection once every 3 weeks for advanced gastric cancer; 15 mg/m² intravenous injection once every 3 weeks for metastatic breast cancer.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-59 mL/min: reduce dose to 15 mg/m² every 3 weeks; GFR 15-29 mL/min: reduce dose to 10 mg/m² every 3 weeks; GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 15 mg/m² every 3 weeks; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no standard dosing available. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor renal function and adjust accordingly; increased susceptibility to myelosuppression. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MITOZYTREX (MITOZYTREX).
| Breastfeeding | Contraindicated; possible distribution into breast milk. M/P ratio unknown. Potential severe adverse effects in nursing infant (immunosuppression, neutropenia). |
| Teratogenic Risk | First trimester: High risk of major congenital malformations (neural tube defects, craniofacial defects, limb abnormalities) and spontaneous abortion. Second/third trimester: Increased risk of intrauterine growth restriction, preterm birth, and fetal myelosuppression. |
| Fetal Monitoring |
■ FDA Black Box Warning
Mitomycin C should be administered under the supervision of a qualified physician experienced in cancer chemotherapy. Hemolytic Uremic Syndrome (HUS), a syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and irreversible renal failure, has been reported in patients receiving mitomycin C. The syndrome may occur at any time during treatment, but is most common with cumulative doses >60 mg/m². Cases of adult respiratory distress syndrome have been reported. Extravasation during injection can cause severe local tissue necrosis.
| Serious Effects |
Hypersensitivity to mitomycin C; thrombocytopenia and/or coagulation disorders with increased bleeding risk; severe leukopenia with risk of infection; compromised renal function (creatinine clearance <10 mL/min). Breastfeeding; concurrent use with live vaccines.
| Precautions | Bone marrow suppression (especially thrombocytopenia and leukopenia), hemolytic uremic syndrome (HUS), pulmonary toxicity (interstitial pneumonitis, fibrosis), renal toxicity, cardiac toxicity (congestive heart failure), extravasation leading to tissue necrosis, and carcinogenicity (secondary malignancies). Monitor complete blood counts, renal function, and pulmonary function. Reduce dose in patients with renal impairment. Administer with antiemetics due to high emetic risk. |
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| Complete blood count weekly; liver and renal function tests every 2 weeks; ultrasound every 4 weeks for fetal growth and anomalies; fetal echocardiography at 18-22 weeks. |
| Fertility Effects | Gonadal toxicity: May cause amenorrhea, premature ovarian failure, and azoospermia; risk depends on cumulative dose and age. Reversible in some cases. |