Dosing and uses of Mitomycin (Mitomycin C, Mutamycin)
Adult dosage forms and strengths
powder for injection
- 5mg
- 20mg
- 40mg
Stomach Cancer, Pancreas Cancer
20 mg/m² IV q6-8Weeks
Anal Carcinoma (Off-label)
10 mg/m² as IV bolus days 1-29; not to exceed 20 mg/dose
Dosage modification
for SI units: count in US units x10^6/L
Full dose if
- Leukocytes >3000/mm³
- Platelets >75 x 10^3/mm³
Give 70% if
- Leukocytes: 2000-2999/mm³
- Platelets: 25-74.999 x 10^3/mm³
Give 50% if
- Leukocytes <2000/mm³
- Platelets <25 x 10^3/mm³
Renal Impairment
Serum creatinine >1.7 mg/dL: Avoid use
CrCl <10 mL/min: Decrease dose by 25%
CAPD: Decrease dose by 25%
Monitor
CBC, LFTs, renal function
Do not repeat dose until WBC >4000/mm³ and Plts >100,000/mm³
Administration
Always use in combo with other antineoplastics
Discontinue if progression continues after two courses
Pediatric dosage forms and strengths
Safety and efficacy not established
Mitomycin (Mitomycin C, Mutamycin) adverse (side) effects
>10%
Hemolytic uremic syndrome (≤15%)
Myelosuppression (64%)
Nausea/vomiting (14%)
Fever (14%)
1-10%
Stomatitis (4%)
Increased serum creatinine (2%)
Mucous membrane toxicity (4%)
Frequency not defined
Fatigue
Pulmonary toxicity
Dyspnea
Cystitis
Interstitial fibrosis
Nephrotoxicity
Amenorrhea
Alopecia
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to manage complications
Bone marrow suppression, notably thrombocytopenia and leucopenia, may contribute to overwhelming infections in an already compromised patient
Hemolytic uremic syndrome may occur with monotherapy or combination therapy and usually occurs with doses >60 mg. Blood product transfusion may exacerbate symptoms.
Contraindications
Hypersensitivity
Thrombocytopenia, coagulation disorders, bleeding diathesis
Cautions
Vesicant
Avoid use in renal impairment (SCr >1.7 mg/dL [150.3 umol/L])
Chicken pox, recent
Bladder fibrosis/contraction reported
Herpes zoster
Acute respiratory distress syndrome reported when used in combination with other types of chemotherapy maintained at FIO2 concentrations >50% preoperatively
Avoid pregnancy
Increased prevalence of Heart Failure observed when used in conjunction with anthracyclines
Pregnancy and lactation
Pregnancy category: d
Lactation: Not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Mitomycin (Mitomycin C, Mutamycin)
Mechanism of action
Crosslinks DNA, preventing replication & transciption
Pharmacokinetics
Half-life: 48 min
Vd: 16-56 L/m²
Metabolism: Liver
Clearance: 201-810 mL/min/m²
Excretion: Urine (10%)
Administration
IV Incompatibilities
Solution: D5W
Additive: bleomycin
Y-site: aztreonam, cefepime, etoposide PO4, filgrastim, gemcitabine, piperacillin/tazobactam, sargramostim, topotecan, vinorelbine
IV Compatibilities
Solution: LR, Ns
Additive: dexamethasone Na-phosphate, heparin, hydrocortisone Na-succinate
Syringe: bleomycin, cisplatin, cyclophosphamide, doxorubicin, droperidol, fluorouracil, furosemide, heparin, leucovorin, methotrexate, metoclopramide, vinblastine, vincristine
Y-site: amifostine, bleomycin, cisplatin, cyclophosphamide, doxorubicin, droperidol, fluorouracil, furosemide, granisetron, heparin, leucovorin, melphalan, methotrexate, metoclopramide, ondansetron, teniposide, thiotepa, vinblastine, vincristine
IV Preparation
Reconstitute with SWI to a concentration of 0.5 mg/mL
Standard dilution
- IV push: dose/syringe (concentration is 0.5 mg/mL); maximum syringe size for IVP is a 30 mL syringe & syringe should be <75% full
- IVPB: dose/100 mL NS
IV Administration
Vesicant
Administer slow IV push by central line only
Flush with 5-10 mL of IV solution before & after drug administration
IVPB infusion should be closely monitored for adequate vein patency
Extravasation Management
Frequently causes necrosis
Plastic surgeon may be required
Storage
Store intact vials of lyophilized powder at Rt
