Mitomycin is an antitumor antibiotic that acts as an alkylating agent and is derived from Streptomyces caespitosus. It is indicated intravenously for the treatment of metastatic stomach or pancreatic cancer in proven combinations with other chemotherapeutic agents. An ophthalmic solution is indicated as a topical adjunct to ab externo glaucoma surgery; this formulation is not intended for intraocular administration. Finally, a pyelocalyceal solution is indicated for the treatment of patients with low-grade upper tract urothelial cancer (LG-UTUC); this formulation appears as a semisolid gel at room temperature and must be chilled to become a viscous liquid for administration. Mitomycin can be associated neutropenia and thrombocytopenia; an interruption of therapy or discontinuation of therapy may be necessary if myelosuppression occurs.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 1
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
-Low
-Administer prn antiemetics as necessary.
Extravasation Risk
-Vesicant
-Administer drug through a central venous line.
Route-Specific Administration
Injectable Administration
Intravenous Administration
-Mitomycin for injection is administered intravenously. Because the drug is extremely irritating to tissues, it should not be administered intramuscularly or subcutaneously.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Mitomycin IV solutions are a blue-gray color.
-Monitor the patient closely for signs and symptoms of extravasation; cellulitis, ulceration, and sloughing may result if extravasation occurs.
Reconstitution:
-5 mg vial: Add 10 mL Sterile Water for Injection.
-20 mg vial: Add 40 mL Sterile Water for Injection.
-40 mg vial: Add 80 mL Sterile Water for Injection.
-Shake vial to dissolve the powder. If the powder for injection does not dissolve immediately, let stand at room temperature until completely dissolved.
-Storage after reconstitution: The reconstituted solution is stable for 7 days at room temperature or 14 days under refrigeration.
Dilution
-The solution may be further diluted in 0.9% Sodium Chloride for Injection (stable for 12 hours at room temperature) or Sodium Lactate Injection (stable for 24 hours at room temperature) to a final concentration of 20 to 40 mcg/mL.
Ophthalmic Administration
Reconstitution
-The non-sterile circulating nurse should open the outer pack of the Mitosol Kit and affect the sterile transfer of all contents to the sterile field.
-The sterile scrub technician should handle and open the sterile inner tray, and then assemble and dispense its contents as below.
-Remove the vial and vial adapter from the blue foam pouch. Screw the clear plunger rod to the rubber plunger of the pre-filled syringe.
-Rock the syringe cap sideways (do not twist) until it breaks free from the syringe collar.
-Attach the threaded end of the connector to the syringe, and then firmly attach the smaller threaded end of the vial adapter to the safety connector.
-Stand upright on a sturdy, flat surface and push on the vial lid until sealed and secure.
-Inject the entire contents of the syringe (1 mL Sterile Water for Injection) into the vial of mitomycin for a final concentration of 0.2 mg/mL; shake to dissolve.
-DO NOT force the plunger; the syringe will not operate if the vial adapter and syringe connector are not properly connected. Forcing the plunger may result in syringe leakage and exposure to mitomycin.
-If the product does not dissolve immediately, allow it to stand at room temperature until dissolution.
-Storage after reconstitution: After reconstitution, mitomycin is stable for 1 hour at room temperature.
Preparing Sponges
-Invert the mitomycin vial and syringe; draw the full volume of medication into the syringe.
-Remove all sponges from the sponge tray, and return to the tray only those sponges to be used.
-Unscrew the syringe with the safety connector from the vial and vial adaptor.
-DO NOT remove the safety connector from the syringe.
-Place the vial and vial adaptor in the chemotherapy waste disposal bag (yellow bag); set the bag aside, within the sterile field, for additional use.
-Remove the sponge container from the sterile inner tray.
-Screw both syringes into the sponge container: the TB syringe to one end, and the syringe with reconstituted mitomycin to the other.
-Inject the medication into the sponge container, fully saturating the sponges with the entire reconstituted contents of the vial.
-Leave reconstituted mitomycin undisturbed in the sponge container for 60 seconds. Do not force the syringe plunger. If any excess fluid remains, withdraw the plunger of the TB syringe to draw out excess fluid/air.
Administration
-NOTE: Mitomycin for solution (for ophthalmic use) is for topical application to the surgical site of glaucoma filtration surgery only; it is not intended for intraocular administration. Intraocular administration may result in cell death leading to corneal infarction, retinal infarction, and ciliary body atrophy.
-With both syringes connected, open the sponge container and offer the contents to the surgeon for placement.
-The treatment area should approximate 10 mm x 6 mm +/- 2 mm.
-Apply fully saturated sponges equally to the treatment area, in a single layer, with the use of surgical forceps.
-Keep the sponges on the treatment area for 2 minutes, then remove them and copiously irrigate the surgical site.
-Return the used sponges back into the sponge container for disposal. Close the container lid.
-With both syringes still connected, remove the entire assembly from the surgical field and place it in the Chemotherapy Waste Bag provided.
-The use of mitomycin ophthalmic solution in concentrations higher than 0.2 mg/mL or for use longer than 2 minutes may lead to unintended corneal and/or scleral damage including thinning or perforation. Direct contact with the corneal endothelium will result in cell death.
Other Administration Route(s)
Pyelocalyceal Administration
-Mitomycin for pyelocalyceal solution is for pyelocalyceal use only. It is NOT for intravenous use, topical use, or oral administration.
-Prior to every instillation, the patient should take sodium bicarbonate 1.3 g PO the evening prior to, the morning of, and 30 minutes prior to the instillation procedure (total, 3.9 g). If the patient is to be anesthetized, they should NOT take sodium bicarbonate within 30 minutes prior to treatment.
-General anesthesia, local anesthesia, sedation, prophylactic antibiotics, and/or antihistamines may be used at the discretion of the treating urologist.
-Consider holding diuretics one day prior to instillation until 4 hours post-instillation.
-Intravesical administration of mitomycin may discolor the urine to a violet to blue color following the instillation procedure. Patients should avoid contact with urine for at least 6 hours post-instillation, should void sitting on a toilet, and should flush the toilet several times after use.
-Mitomycin for pyelocalyceal solution must be prepared under chilled conditions. Once reconstituted, it will appear as a viscous liquid for instillation. If there is any difficulty pushing or withdrawing the solution during preparation, put the components back in the Chilling Block until it liquifies.
Preparation
-The day prior to preparation, put the Chilling Block upside down in the freezer at -20 to -12 degrees Celsius (-4 to 10.4 degrees Fahrenheit) overnight.
-Remove the Chilling Block from the freezer and disinfect it with 70% Isopropyl alcohol spray or equivalent. Allow the Chilling Block to air dry, and then place it upright inside the hood or isolator.
-Wait 20 minutes.
-Connect vial adaptors to all 3 vials. Connect a syringe adaptor to one of the 10 mL syringes and to the 20 mL syringe.
-Place the 3 vials (2 vials mitomycin, 1 vial sterile hydrogel), the 10 mL syringe, and the 20 mL syringe into the Chilling Block for at least 10 minutes.
-During this time, withdraw 2 mL of sterile water into the other 10 mL syringe and set aside for later use.
-Slowly fill the chilled 20 mL syringe with 14 mL of sterile hydrogel. Recap the syringe and place it in the Chilling Block.
-Slowly fill the chilled 10 mL syringe with 4 mL of sterile hydrogel. Discard the unused portion of sterile hydrogel.
-Replace the needle on the 2 mL sterile water syringe with the Luer Lock connector.
-Remove the syringe adaptor from the 4 mL sterile hydrogel syringe and connect it to the other side of the Luer Lock connector on the 2 mL sterile water syringe.
-Gently mix the sterile water with the sterile hydrogel by pushing the plungers back and forth at least 25 times to create the "pre-wetting solution" (PWS).
-Transfer the 6 mL PWS into one of the syringes. Replace the Luer Lock connector with a new syringe adaptor. Place the 6 mL PWS syringe in the Chilling Block.
Reconstitution
-Remove both mitomycin vials from the Chilling Block; gently tap the bottom of each vial on the table to ensure all powder is at the bottom of the vials.
-Remove the chilled 6 mL PWS syringe from the Chilling Block. Inject 3 mL PWS into each vial of mitomycin and discard the empty PWS syringe.
-NOTE: To ensure accurate dosing, the contents of each vial must be the same.
-Gently swirl each vial of mitomycin upright at least 15 times; ensure all powder and admixture remains at the bottom of the vial. DO NOT invert or shake.
-Immediately remove the chilled 14 mL syringe of sterile hydrogel from the Chilling Block and inject 7 mL into each vial of mitomycin.
-Gently swirl each vial of mitomycin upright at least 15 times; ensure all powder and admixture remains at the bottom of the vial. DO NOT invert or shake.
-Recap and place the 20 mL syringe in the Chilling Block.
-Recap and place both vials of mitomycin in the Chilling Block for 5 minutes; then remove the vials and vigorously swirl them upright at least 15 times, ensuring all admixture remains at the bottom of the vials. Return both vials to the Chilling Block. Repeat these steps every 5 minutes for 30 minutes (6 times). DO NOT invert or shake the vials.
-Remove 1 vial of mitomycin from the Chilling Block. After vigorously swirling upright at least 15 times, slowly withdraw the entire contents of the vial (7 mL) into the chilled 20 mL syringe. If it is difficult to withdraw the admixture, place the contents back into the Chilling Block until it liquifies again. Inject the contents of this syringe into the remaining chilled vial of mitomycin, so that all the admixture is in 1 vial.
-Recap the vial adaptor. Vigorously swirl the vial upright at least 15 minutes.
-Reconstituted mitomycin for pyelocalyceal solution has reverse thermal properties with a gelation point of approximately 19 degrees Celsius (66 degrees Fahrenheit).
-Storage after reconstitution: Instill mitomycin for pyelocalyceal solution as soon as possible after reconstitution. If immediate instillation is not possible, it may be stored at 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) for up to 8 hours protected from light; it will appear as a semisolid gel when stored under these conditions. The "Discard after" date and time is 8 hours from the completion of the preparation at room temperature; this should be documented on the admixture label and applied to the prepared vial.
Administration
-Once chilled at -3 to 5 degrees Celsius (27 to 41 degrees Farenheit), mitomycin for pyelocalyceal solution will convert to a viscous liquid for instillation and is stable for up to 1 additional hour.
-Reconstituted mitomycin for pyelocalyceal solution must be instilled within 1 hour after it is converted to a viscous liquid.
-Instill mitomycin for pyelocalyceal solution as a chilled solution using a Uroject12 Lever, a Luer lock syringe, and a ureteral catheter with molded Luer lock connector.
Cumulative bone marrow suppression is the most common and most serious toxicity reported in patients treated with systemic mitomycin (64.4%). Thrombocytopenia and leukopenia may occur anytime in the first 8 weeks of therapy (average, 4 weeks). Recovery typically occurs within 10 weeks after discontinuation of therapy; approximately 25% of leukopenic or thrombocytopenic episodes did not recover. Myelosuppression has also occurred in patients receiving pyelocalyceal administration of mitomycin including anemia (14% to 38%; grade 3 or 4, 1.4%), lymphopenia (21%; grade 3, 2.9%), and thrombocytopenia (21%; grade 3, 2.8%). Gross extravasation of pyelocalyceal mitomycin via urinary tract perforation or impaired mucosa was not observed in the patients with grade 3 thrombocytopenia and neutropenia.
Rash is rarely reported in patients treated with mitomycin for injection. Mild to moderate pruritus was reported in 13% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer.
Pulmonary toxicity has been infrequently reported with mitomycin injection but can be severe or life-threatening; symptoms may include dyspnea with a nonproductive cough and radiographic evidence of pulmonary infiltrates. If other etiologies are excluded, discontinue mitomycin therapy. While corticosteroids have been used as a treatment, their therapeutic value has not been determined. Additionally, cases of acute respiratory distress syndrome (ARDS) have been reported in patients receiving mitomycin in combination with other chemotherapy and maintained at FIO2 concentrations greater than 50% perioperatively. Acute shortness of breath and severe cases of acute bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin; the onset was minutes to hours after the vinca alkaloid injection.
Hemolytic-uremic syndrome (HUS) has been reported in patients receiving systemic mitomycin therapy, consisting primarily of microangiopathic hemolytic anemia (hematocrit, 25% or less), thrombocytopenia (platelets, 100,000 cells/mm3 or less), and irreversible renal failure (serum creatinine 1.6 mg/dL or more); the incidence of this syndrome has not been defined. Microangiopathic hemolysis with fragmented red blood cells on peripheral blood smears has occurred in 98% of patients with HUS; less frequent complications include pulmonary edema (65%), neurologic abnormalities (16%), and high blood pressure. Of 83 patients studied, 72 developed HUS at total doses exceeding 60 mg of mitomycin (approximately 87%); closely monitor patients receiving doses higher than 60 mg for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function. Blood product transfusion may exacerbate the symptoms. HUS has a mortality rate of 52%.
Headache, confusion, drowsiness, and syncope have occurred in patient treated with mitomycin for injection; they were not unequivocally drug-related reactions and may have been due to the primary or metastatic disease process.
Flank pain (including back pain) occurred in 41% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer in a single-arm, open-label study (grade 3 or 4, 2.8%). Additional urinary symptoms included hematuria (34%; grade 3 or 4, 2.8%), dysuria (23%), and pollakiuria (14%). Dysuria (33.3%), increased urinary frequency (24.3%), urinary urgency (21.6%), and hematuria (26.1%) were reported in 111 high-risk patients with transitional cell carcinoma of the bladder who received a 40-mg dose of mitomycin intravesically weekly for 6 weeks in a randomized, phase 3 study.
Congestive heart failure (CHF) has rarely been reported in patients receiving mitomycin for injection; it was often treated effectively with diuretics and cardiac glycosides. Most patients who developed CHF had received prior doxorubicin therapy.
Nausea and vomiting each occurred in less than 14% of patients treated with mitomycin for injection. Hematemesis has also been reported in these patients, although it was not unequivocally drug-related and may have been due to the primary or metastatic disease process. Nausea was reported in 25% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer (grade 3 or 4, 1.4%); vomiting occurred in 20% of patients in this trial (grade 3 or 4, 4.2%).
Fatigue including asthenia was reported in 27% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer in an open-label, single-agent trial (grade 3 or 4, 1.4%). Fatigue, asthenia, and malaise have also been reported in postmarketing experience with mitomycin for injection.
Abdominal pain was reported in 28% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer in a single-arm, open-label trial (grade 3 or 4, 1.4%). Nonspecific reports of pain have also occurred in patients receiving mitomycin for injection, although they were not unequivocally drug-related and may have been due to the primary or metastatic disease process.
The use of mitomycin topical solution in concentrations higher than 0.2 mg/mL or for longer than 2 minutes may result in corneal or scleral damage, including thinning or perforation. Direct contact with the corneal endothelium will result in cell death. The most frequent adverse reactions to mitomycin topical solution used in ocular surgery occur locally and include hypotony maculopathy, blebitis, endophthalmitis, vascular reactions, corneal reactions, and cataracts. Post-operative ocular hypotonia (hypotony) due to choroidal detachment, choroidal effusion, serous choroidal detachment, suprachoroidal hemorrhage, hypotony maculopathy, presence of supraciliochoroidal fluid, or hypoechogenic suprachoroidal effusion has also frequently been associated with the use of mitomycin topical solution. In phakic patients, the use of mitomycin topical solution has been associated with increased frequency of lenticular change and formation of cataracts. Other ophthalmic adverse reactions associated with the use of mitomycin topical solution include: bleb ulceration, chronic bleb leak, encapsulated or cystic bleb, bleb-related infection, wound dehiscence, conjunctival necrosis, thin-walled bleb, corneal endothelial damage, epithelial defect, anterior synechiae, superficial punctuate keratitis, Descemet's detachment, induced astigmatism, endophthalmitis, iritis, fibrin reaction, cataract development, cataract progression, capsule opacification, capsular constriction or capsulotomy rupture, posterior synechiae, retinal pigment epithelial tear, retinal detachment (serous and rhegmatogenous), scleritis, hyphema, central retinal vein occlusion, hemiretinal vein occlusion, retinal hemorrhage, ocular hemorrhage (i.e., vitreal hemorrhage and blood clot, subconjunctival hemorrhage, disk hemorrhage), macular edema, sclera thinning or ulceration, intraocular lens capture, papilledema, malignant glaucoma, lacrimal drainage system obstruction, ciliary block, corneal vascularization, cystic conjunctival degeneration, upper eyelid retraction, dislocated implants, and visual impairment including decreased visual acuity and severe vision loss. Blurred vision has occurred in patients treated with mitomycin for injection; however, it was not unequivocally drug-related and may have been due to the primary or metastatic disease process.
Renal dysfunction (including renal impairment, acute kidney injury, and renal failure (unspecified) occurred in 25% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer (grade 3 or 4, 2.8%); a mild (grade 1 or 2) increase in creatinine occurred in 34% of patients and a decrease in estimated glomerular filtration rate was reported in 38% (grade 3 or 4, 11%). Of patients treated with systemic mitomycin, 2% of 1,281 patients had a statistically significant rise in creatinine; there appeared to be no correlation between the total dose administered or duration of therapy and the degree of renal impairment.
Alopecia frequently occurs in patients treated with mitomycin for injection.
Urinary tract obstruction (including hydronephrosis, obstructive uropathy, pelvi-ureteric obstruction, ureteric obstruction, and ureteric stenosis) occurred in 58% of patients receiving mitomycin for pyelocalyceal use in an open-label, single-arm trial of patients with low-grade upper tract urothelial cancer (grade 3, 17%); in patients who only received mitomycin during the treatment phase (no maintenance therapy), the incidence was 40%. The median time to first onset was 72 days. Ureteric obstruction did not resolve or resolved with sequelae in 44% of these patients. In this trial, ureteric stenosis occurred in 44% (grade 3 or 4, 8%), hydronephrosis in 18% (grade 3 or 4, 6%), pelvi-ureteric obstruction in 6% (grade 3 or 4, 1.4%), urinary tract obstruction in 7% (grade 3 or 4, 1.4%), ureteric obstruction in 2.8% (grade 3 or 4, 1.4%), and obstructive uropathy in 1.4%; clinically relevant inflammation of the urinary tract and bladder spasm occurred in 2% up to 10% of patients. Bladder fibrosis and bladder contraction have been reported with intravesical administration of mitomycin, which in rare cases has required cystectomy.
Urinary tract infection (including pyelonephritis) occurred in 34% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer in a single-arm, open-label trial (grade 3 or 4, 4.2%); urosepsis occurred in 2% to up to 10% of patients in this study (grade 3 or higher, 3% or more). Fever occurred in 13% (grade 3 or 4, 1.4%) and chills in 11% of patients in this trial. Cellulitis has been reported in patients treated with mitomycin injection and is occasionally severe. Fever has been reported in less than 14% of patients receiving intravenous mitomycin.
Extravasation (injection site reaction) has been reported in patients treated with mitomycin injection, and may occur with or without an accompanying stinging or burning sensation and even if there is adequate blood return when the injection needle is aspirated; this may result in tissue necrosis and consequent sloughing of tissue. There have also been reports of delayed erythema and/or ulceration either at the injection site or distant from the site of injection, occurring weeks to months after administration; there may have been no obvious evidence of extravasation during administration of mitomycin. Skin grafting has been necessary in some of these cases. Instillation site pain occurred in 2% to up to 10% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer.
Stomatitis frequently occurs in patients treated with mitomycin for injection.
Anorexia was reported in less than 14% of patients treated with mitomycin for injection. Decreased appetite occurred in 10% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer.
Diarrhea has occurred in patients treated with mitomycin for injection; it was not unequivocally drug-related and may have been due to the primary or metastatic disease process.
Edema has occurred in patients treated with mitomycin for injection; it was not unequivocally drug-related and may have been due to the primary or metastatic disease process.
Thrombo-phlebitis has occurred in patients treated with mitomycin for injection; however, it was not unequivocally drug-related and may have been due to the primary or metastatic disease process.
Hypoalbuminemia occurred in 28% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer in a single-arm, open-label trial (grade 3 or 4, 2.8%).
Hypocalcemia (17%), hyperkalemia (13%; grade 3 or 4, 1.4%), and hypernatremia (11%) occurred in patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer in a single-arm, open-label trial.
Severe (grade 3 or 4) hyperuricemia occurred in 16% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer in a single-arm, open-label trial.
Hypertension occurred in 10% of patients receiving pyelocalyceal administration of mitomycin for the treatment of urothelial cancer (grade 3 or 4, 4.2%).
Mitomycin administration requires an experienced clinician familiar with the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is only possible when adequate diagnostic and treatment facilities are readily available.
Mitomycin for injection is contraindicated in patients with thrombocytopenia. Bone marrow suppression, notably thrombocytopenia and leukopenia, is the most common and severe adverse reaction associated with intravenous administration of mitomycin. Because of cumulative myelosuppression, a complete blood count with differential should be obtained repeatedly during intravenous therapy and for at least 8 weeks following therapy; dose reductions are based on nadir leukocyte and platelet counts of the previous cycle. Subsequent cycles of treatment should not begin until the leukocyte count is at least 4,000 cells/mm3 and the platelet count is at least 100,000 cells/mm3. Thrombocytopenia and neutropenia have also occurred in patients receiving pyelocalyceal mitomycin; there were no signs of gross extravasation via urinary tract perforation or impaired mucosa in these patients. Therefore, a complete blood count with differential should also be obtained prior to each dose. An interruption or discontinuation of therapy may be necessary if thrombocytopenia or neutropenia occur.
Mitomycin for injection is contraindicated in patients with a coagulopathy or an increased risk of bleeding due to other causes due to the risk associated with thrombocytopenia, which occurs commonly with treatment.
Mitomycin for pyelocalyceal use is contraindicated in patients with a bladder perforation or perforation of the upper urinary tract. Increased systemic absorption may occur, resulting in bone marrow suppression (particularly leukopenia, neutropenia, and thrombocytopenia).
Urinary tract obstruction, including ureteral stenosis and hydronephrosis, occurred commonly in patients treated with mitomycin for pyelocalyceal administration in clinical trials. The median time to first onset was 72 days; resolution occurred in approximately half of patients. Monitor patients for signs and symptoms of ureteric obstruction, including flank pain, fever, and changes in renal function; interrupt or permanently discontinue mitomycin based on the severity of ureteric obstruction. Patients who experience obstruction may require transient or long-term ureteral stents or alternative procedures including balloon dilatation, and nephroureterectomy. Bladder fibrosis/contraction has also been reported with intravesical administration (not an approved route of administration), which in rare cases has required cystectomy.
Mitomycin extravasation may occur with or without an accompanying stinging or burning sensation, and even if there is adequate blood return when the injection needle is aspirated. Delayed erythema and/or ulceration has been reported to occur either at or distant from the injection site, weeks to months after administration, even when no obvious evidence of extravasation was observed during administration; some cases have required skin grafting. Postmarketing surveillance suggests that geriatric patients may be more susceptible to injection site reactions and hypersensitivity reactions than younger patients.
Patients with renal impairment (serum creatinine greater than 1.7 mg/dL) should not be treated with systemic mitomycin; monitor patients for evidence of renal toxicity. Hemolytic-uremic syndrome (HUS) has been reported in patients receiving systemic mitomycin therapy, consisting primarily of microangiopathic hemolytic anemia, thrombocytopenia, and irreversible renal failure. Of 83 patients studied, 72 developed HUS at total doses exceeding 60 mg of mitomycin (approximately 87%); closely monitor patients receiving doses higher than 60 mg for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function. Blood product transfusion may exacerbate the symptoms associated with this syndrome.
Use systemic mitomycin with caution in patients with a history of chronic lung disease (CLD). Acute shortness of breath and severe cases of acute bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin; the onset was minutes to hours after the vinca alkaloid injection. A few cases of respiratory distress have been reported in patients receiving mitomycin in combination with other chemotherapy and maintained at FIO concentrations greater than 50% perioperatively; use only enough oxygen to provide adequate arterial saturation. Pay careful attention to fluid balance and avoid overhydration.
Use mitomycin ophthalmic solution with caution in patients with a history of cataracts. The use of mitomycin has been associated with an increased incidence of postoperative hypotony, which may lead to corneal decompensation, accelerated cataract formation, maculopathy, and discomfort. Use in phakic patients has been correlated to a higher incidence of lenticular change and cataract formation.
Pregnancy should be avoided by females of reproductive potential during mitomycin treatment. The manufacturer of mitomycin for pyelocalyceal administration recommends avoidance of pregnancy during treatment and for at least 6 months after the last dose. Although there are no adequately controlled studies in pregnant women, mitomycin can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving mitomycin should be apprised of the potential hazard to the fetus. When administered parenterally, mitomycin has been shown to be teratogenic in mice and rats when given at doses equivalent to the usual human intravenous dose. There are no available data on mitomycin for pyelocalyceal administration or ophthalmic administration to inform the drug-associated risk with these dosage forms.
Counsel patients about the reproductive risk and contraception requirements during mitomycin treatment. Mitomycin can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 6 months after treatment with mitomycin for pyelocalyceal use. Due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential should use effective contraception during treatment and for at least 3 months after the last dose with mitomycin for pyelocalyceal use. Specific contraception recommendations are unavailable for mitomycin injection and mitomycin ophthalmic solution. Females of reproductive potential should undergo pregnancy testing prior to initiation of mitomycin. Women who become pregnant while receiving mitomycin should be apprised of the potential hazard to the fetus.
Due to the potential for serious adverse reactions in nursing infants from mitomycin, advise women to discontinue breast-feeding during treatment; the manufacturers of mitomycin for pyelocalyceal administration and mitomycin ophthalmic solution additionally recommend avoidance of breast-feeding for 1 week after the final dose. It is not known whether mitomycin is present in human milk, although many drugs are excreted in human milk.
For treatment of gastric cancer:
Intravenous dosage:
Adults: 20 mg/m2 IV every 6 to 8 weeks in combination with other chemotherapeutic agents. A commonly used regimen is mitomycin 10 mg/m2 IV on day 1 plus 5-fluorouracil (600 mg/m2/day IV days 1, 8, 29, and 36) and doxorubicin (30 mg/m2/day IV days 1, and 29) (FAM regimen). Other combination regimens include: a) mitomycin 7 mg/m2 (max 14 mg) IV every 6 weeks for 4 doses, cisplatin (60 mg/m2 IV every 3 weeks for 8 doses) and 5-fluorouracil (300 mg/m2/day IV for up to 6 months); b) mitomycin 7 mg/m2 IV on day 2, cisplatin (50 mg/m2 IV on day 1 every 2 weeks), leucovorin (100 mg/m2 IV) then 5-fluorouracil (400 mg/m2 IV bolus then 600 mg/m2 IV over 22-hours on days 1 and 2) every 6 weeks; c) mitomycin 10 mg/m2 IV plus irinotecan (150 mg/m2 IV) every 2 weeks; or d) mitomycin 15 mg/m2 IV on day 1 every 7 weeks plus leucovorin (500 mg/m2 IV) and 5-fluorouracil (2600 mg/m2 IV) on days 1, 8, 15, 22, 29, and 36.
Intravenous dosage (Mitozytrex only):
Adults: 15 mg/m2 IV every 6 to 8 weeks in combination with other chemotherapy agents. If the disease continues to progress after 2 courses of Mitozytrex, the drug should be stopped since chances of response are minimal.
For the treatment of pancreatic cancer:
Intravenous dosage:
Adults: 20 mg/m2 IV every 6 to 8 weeks in combination with other chemotherapy agents. The addition of mitomycin 7 mg/m2 IV every 6 weeks for 4 courses to a protracted 5-fluorouracil (5-FU) regimen (i.e., 300 mg/m2/day IV for up to 24 weeks) resulted in an increased response rate compare to 5-FU alone, but did not translate into a survival advantage.
Intravenous dosage (Mitozytrex only):
Adults: 15 mg/m2 IV every 6 to 8 weeks in combination with other chemotherapy agents. If the disease continues to progress after 2 courses of Mitozytrex, the drug should be stopped since chances of response are minimal.
For the treatment of colorectal cancer*:
-for the treatment of liver metastases from colorectal cancer*:
Hepatic Intra-Arterial dosage*:
Adults: Mitomycin 10 mg in a chemo-emulsion with 5-fluorouracil 1,000 mg and 10 mL of ethiodol in a total volume of 30 mL, administered as an intra-arterial injection into the hepatic artery of the affected lobe. If the disease was present in more than 1 lobe, each lobe was treated on a separate occasion, with an interval of 4 weeks between the 2 procedures.
-for the treatment of peritoneal carcinomatosis of colorectal cancer*:
Intraperitoneal dosage*:
Adults: Perfusion was started with a minimum of 3 liters of isotonic dialysis fluid, at 1 to 2 liters/min,and an inflow temperature of 41 degrees C to 42 degrees C. As soon as the temperature in the abdomen was stable above 40 degrees C, MMC was added to the perfusate at a dose of 17.5 mg/m2 followed by 8.8 mg/m2 every 30 minutes. The total dose was limited to 70 mg. If the core temperature exceeded 39 degrees C, the inflow temperature was reduced. After 90 minutes, the perfusion fluid was drained from the abdomen, and bowel continuity was restored.
For the treatment of anal cancer* in combination with fluorouracil and radiation:
Intravenous dosage:
Adults: 10 mg/m2 IV bolus on days 1 and 29 in combination with 5-fluorouracil (5-FU) 1,000 mg/m2/day continuous IV for 4 days on days 1 through 4 and 29 through 32 and radiation therapy. A smaller phase III study has also considered mitomycin 15 mg/m2 IV on day 1 in combination with 5-FU 750 mg/m2 IV continuous infusion over 4 days on days 1 through 4 and 29 through 32 and radiotherapy in patients with locally advanced anal cancer.
For the treatment of advanced head and neck cancer* in combination with 5-fluorouracil and radiation therapy:
Intravenous dosage:
Adults: 10 mg/m2 IV as a bolus on days 5 and 36 in combination with 5-fluorouracil 600 mg/m2/day CIVI days 1 to 5 plus external beam radiation delivered over 6 weeks.
For the adjuvant treatment of superficial bladder cancer* in patients at high risk for recurrence:
Intravesical dosage*:
Adults: Doses of 20 to 60 mg diluted in sterile water to concentrations of 0.5 to 2 mg/mL weekly for 6 to 8 weeks as induction with or without maintenance for 1 year have been used. In a phase III trial using mitomycin 40 mg in 20 mL of sterile water weekly for 6 weeks, an ultrasound monitor was used to reposition the patient and catheter to reduce the amount of urine that came in contact with the drug. In this trial, patients also received sodium bicarbonate and were instructed to refrain from drinking fluids for 8 hours before and during the procedure.
For the treatment of cervical cancer* in combination with cisplatin:
Intravenous dosage:
Adults: 6 mg/m2 IV on day 1 in combination with cisplatin 50 mg/m2 IV on day 1, repeated every 4 weeks.
For the treatment of malignant mesothelioma*:
-for the treatment of malignant pleural mesothelioma administered locally in the pleural cavity in combination with cisplatin*:
Intrapleural dosage*:
Adults: 8 mg/m2 and cisplatin 100 mg/m2 mixed in 100 mL normal saline, instilled into the pleural space via 1 chest tube for 15 minutes. Position was changed every 30 minutes and after 4 hours, the chest tube was put back to suction.
-for the treatment of malignant peritoneal mesothelioma in combination with cisplatin*:
Intraperitoneal dosage:
Adults: 4 to 6 L of isotonic dialysis fluid was circulated at a flow rate of 500 to 700 mL/min and heated to achieve an intraperitoneal temperature between 42 to 45 degrees C. Intraperitoneal chemotherapy with mitomycin 0.5 mg/kg in combination with cisplatin 0.7 mg/kg was administered over 90 minutes. 5-year overall survival was 28.9% and median overall survival was 35.6 months.
For use as an adjunct to ab externo ocular surgery for glaucoma:
Topical dosage:
Adults: Saturate provided sponges with entire reconstituted contents of the vial. Apply fully saturated sponges equally to the treatment area, in a single layer, with the use of a surgical forceps. Treat an area of approximately 10 mm x 6 mm +/- 2 mm. Keep the sponges on the treatment area for 2 minutes, then remove and return to the provided tray for defined disposal in the chemotherapy waste bag provided.
For the treatment of biliary tract cancer*:
-for the treatment of unresectable intrahepatic cholangiocarcinoma in combination with cisplatin and doxorubicin*:
Intra-Arterial dosage:
Adults: Chemoembolization material consisted of mitomycin 10 mg, doxorubicin 50 mg, and cisplatin 100 mg dissolved in sterile contrast (8.5 mL) and diluted with 1.5 mL of sterile water. This was emulsified in a 1:1 ratio with ethiodol. The emulsion was instilled in 1- to 5-mL aliquots. Intra-arterial 1% lidocaine was administered in 1- to 3-mL boluses interleaved with the aliquots of chemoembolic emulsion. Added to the final aliquot of the emulsion or separately following administration of the emulsion was 0.2 mL of 150- to 250-l polyvinyl alcohol particles. In addition, 0.9% normal saline was administered at 200 to 300 mL/hour until the completion of the procedure, followed by 0.9% normal saline at 150 mL/hour for a total of 3 L. No diuretics were given. Prophylactic antiemetics (ondansetron 24 mg and dexamethasone 10 mg IV) and antibiotics (cefazolin 1 g and metronidazole 500 mg) were given.
-for the treatment of unresectable intrahepatic cholangiocarcinoma*:
Intra-Arterial dosage:
Adults: Mitomycin 2 mg and 300 mg degradable starch microspheres (DSM) mixed in 3 mL contrast media were infused within 30 seconds under fluoroscopic guidance via hepatic port. After a 1 minute pause between administrations, the process was repeated until reflux into the gastroduodenal artery or embolization of the hepatic artery was noted. Treatment was repeated weekly without the use of contrast media.
For the treatment of non-small cell lung cancer (NSCLC)*:
-for the first-line treatment of inoperable stage III or IV NSCLC, in combination with cisplatin and vinblastine (MVP regimen)*:
Intravenous dosage:
Adults: 6 or 8 mg/m2 IV on day 1, in combination with cisplatin (50 mg/m2 IV on day 1) and vinblastine (6 mg/m2 IV on day 1), every 3 weeks for 4 cycles has been studied in patients with inoperable stage III or IV non-small cell lung cancer (NSCLC) in randomized clinical studies. Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. There was no significant difference in the median overall survival (OS) time (8.7 vs 9.5 months), 1-year OS rate (35% vs 39%), or 2-year OS rate (13% vs 13%) in patients who received MVP or MIC compared with docetaxel plus carboplatin (DC regimen) in a multicenter, randomized, phase 3 trial. Serious toxicity, including grade 3 and 4 neutropenia and leukopenia, was reported significantly less often in the MVP/MIC arm compared with the DC arm (22% vs 41%); additionally, patients in the MVP/MIC arm had significantly less overnight hospital stays due to toxicity and antibiotic use. In another randomized, phase 3 trial, there was no significant difference in the median OS time (248 vs. 236 days), 1-year OS rate (32.5% vs. 33.2%), or 2-year OS rate (11.8% vs. 6.9%) in patients who received MVP or MIC compared with gemcitabine plus carboplatin (GC regimen). Significantly less grade 3 and 4 neutropenia and thrombocytopenia and antibiotic use were reported with MVP/MIC compared with GC; however, emergent overnight hospital stays occurred significantly more often in the MVP/MIC arm.
For the treatment of urothelial carcinoma:
NOTE: The FDA has designated mitomycin as an orphan drug for this indication.
-for the treatment of low-grade upper tract urothelial cancer (LG-UTUC):
Ureteral or Nephrostomy Tube dosage:
Adults: 4 mg/mL (maximum, 60 mg mitomycin or 15 mL) via ureteral catheter or a nephrostomy tube over 1 minute once weekly for 6 weeks; the total instillation volume is based on volumetric measurements using pyelography. Mitomycin instillations may continue once monthly for a maximum of 11 additional instillations for patients with a complete response after 3 months. Patients should take sodium bicarbonate 1.3 g PO the evening prior to, the morning of, and 30 minutes prior to each instillation (total, 3.9 g); if the patient will be anesthetized, do not give sodium bicarbonate within 30 minutes prior to the treatment. Consider holding diuretics 1 day prior to instillation and until 4 hours post-instillation. In a multicenter, noncomparative trial (the OLYMPUS trial; n = 71), intravesical administration of mitomycin resulted in a complete response rate of 58% in patients with treatment-naive or recurrent noninvasive low-grade upper tract urothelial cancer (LG-UTUC) with at least one measurable papillary tumor 5 to 15 mm located above the ureteropelvic junction; the median duration of response was not reached (range, up to 18.8+ months). At 12 months, 56% of patients remained in a complete response.
Therapeutic Drug Monitoring:
Dose Adjustments for Treatment-Related Toxicities
Mitomycin for Injection:
Leukopenia and/or Thrombocytopenia
-Nadir leukocyte count greater than 4,000 cells/mm3 and platelets greater than 100,000 cells/mm3: Administer 100% of the prior dose.
-Nadir leukocyte count 3,000 to 3,999 cells/mm3 or platelets 75,000 to 99,999 cells/mm3: Do not give the next dose of mitomycin until the leukocyte count has returned to 4,000 cells/mm3 and platelets to 100,000 cells/mm3. At that time, administer 100% of the prior dose.
-Nadir leukocyte count 2,000 to 2,999 cells/mm3 or platelets 25,000 to 74,999 cells/mm3: Do not give the next dose of mitomycin until the leukocyte count has returned to 4,000 cells/mm3 and platelets to 100,000 cells/mm3. At that time, administer 70% of the prior dose.
-Nadir leukocyte count less than 2,000 cells/mm3 or platelets less than 25,000 cells/mm3: Do not give the next dose of mitomycin until the leukocyte count has returned to 4,000 cells/mm3 and platelets to 100,000 cells/mm3. At that time, administer 50% of the prior dose.
Mitomycin for Pyelocalyceal Use:
Neutropenia and/or Thrombocytopenia
-Grade 2 thrombocytopenia or neutropenia: Hold mitomycin therapy.
-Grade 3 or higher thrombocytopenia or neutropenia: Permanently discontinue mitomycin therapy.
Ureteric Obstruction
-Hold or permanently discontinue mitomycin therapy, depending on the severity of obstruction.
Maximum Dosage Limits:
The suggested maximum tolerated dose (MTD) for mitomycin is dependent on type of mitomycin injection used, performance status, other chemotherapy agents or radiation given in combination, and disease state. Therefore, dosing may vary from protocol to protocol. If questions arise, clinicians should consult the appropriate references to verify the dose.
-Adults
Mitomycin for injection: 20 mg/m2 IV.
Mitomycin for ophthalmic use: topically applied to glaucoma surgery site for no longer than 2 minutes.
Mitomycin for pyelocalyceal solution: 60 mg (15 mL).
-Geriatric
Mitomycin for injection: 20 mg/m2 IV.
Mitomycin for ophthalmic use: topically applied to glaucoma surgery site for no longer than 2 minutes.
Mitomycin for pyelocalyceal solution: 60 mg (15 mL).
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
-CrCl less than 30 mL/min: Avoid the use of mitomycin for pyelocalyceal solution.
-SCr greater than 1.7 mg/dL: Do not administer mitomycin for injection.
*non-FDA-approved indication
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Vinblastine: (Moderate) Monitor for pulmonary toxicity if coadministration of mitomycin and vinca alkaloids is necessary. Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of acute respiratory distress occurred within minutes to hours after vinca alkaloid administration. Treatment with bronchodilators, steroids, and/or oxygen may provide symptomatic relief.
Vinca alkaloids: (Moderate) Monitor for pulmonary toxicity if coadministration of mitomycin and vinca alkaloids is necessary. Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of acute respiratory distress occurred within minutes to hours after vinca alkaloid administration. Treatment with bronchodilators, steroids, and/or oxygen may provide symptomatic relief.
Vincristine Liposomal: (Moderate) Monitor for pulmonary toxicity if coadministration of mitomycin and vinca alkaloids is necessary. Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of acute respiratory distress occurred within minutes to hours after vinca alkaloid administration. Treatment with bronchodilators, steroids, and/or oxygen may provide symptomatic relief.
Vincristine: (Moderate) Monitor for pulmonary toxicity if coadministration of mitomycin and vinca alkaloids is necessary. Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of acute respiratory distress occurred within minutes to hours after vinca alkaloid administration. Treatment with bronchodilators, steroids, and/or oxygen may provide symptomatic relief.
Vinorelbine: (Moderate) Monitor for pulmonary toxicity if coadministration of mitomycin and vinca alkaloids is necessary. Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of acute respiratory distress occurred within minutes to hours after vinca alkaloid administration. Treatment with bronchodilators, steroids, and/or oxygen may provide symptomatic relief.
Antineoplastic Activity:
Mitomycin is an alkylating agent that inhibits DNA synthesis; at high concentrations, cellular RNA and protein synthesis are also suppressed. The guanine and cytosine content correlate with the degree of mitomycin-induced cross-linking.
Activity in Ocular Surgery:
In glaucoma surgery, mitomycin is applied topically for a short period during the surgery. It inhibits the proliferative phase of the wound-healing pathway through inhibition of fibroblast as well asendothelial cell growth and replication. It is approximately 100-fold more potent than fluorouracil after a single topical intraoperative application. These antifibrotic actions of the drug prevent scarring of the tissue when surgeons create a flap in the eye to relieve the excess fluid buildup, reducing intraocular pressure following the surgery.
Mitomycin can be administered intravenously, topically, or by pyelocalyceal instillation, depending on the dosage form and indication; one dosage form should not be substituted for another. While systemic clearance is primarily affected by hepatic metabolism, metabolism occurs in other tissue as well. The rate of clearance is inversely proportional to the Cmax due to saturation of the degradative pathways. Approximately 10% of a dose of mitomycin is excreted unchanged in the urine; this percentage increases proportionally with dose due to saturation of metabolic pathways at low doses.
Affected cytochrome P450 isoenzymes and drug transporters: None.
-Route-Specific Pharmacokinetics
Intravenous Route
The Cmax of mitomycin after an intravenous injection of 30 mg was 2.4 mcg/mL; the Cmax after a 20 mg and 10 mg injection was 1.7 mcg/mL and 0.52 mcg/mL, respectively. After intravenous administration, mitomycin is rapidly cleared from the serum, with concentrations reduced by 50% in 17 minutes after a single bolus injection.
Topical Route
Ocular Administration
It is not known if mitomycin is systemically absorbed following topical ocular administration during surgery. The proposed dose of mitomycin used during glaucoma surgery (0.2 mg) is significantly lower than intravenous doses used for oncologic indications (up to 20 mg/m2); therefore, systemic concentrations after topical ocular administration would be expected to be multiple orders of magnitude lower than those achieved by IV administration. Mitomycin is cleared from ophthalmic tissue after intraoperative topical application and irrigation, as metabolism occurs in other affected tissues.
Other Route(s)
Pyelocalyceal Use
Plasma concentrations of mitomycin were variable after instillation of up to 60 mg of mitomycin into the pyelocalyceal system, ranging from 2.43 ng/mL to 12.8 ng/mL over the course of treatment. The mean Cmax of mitomycin was 6.24 ng/mL, which is estimated to be less than 1% of the expected Cmax after intravenous administration. After instillation into the pyelocalyceal system, mitomycin (Jelmyto) forms a semisolid gel which dissolves from normal kidney urine flow, releasing mitomycin for up to 4 to 6 hours; it is eliminated unchanged in the urine.
-Special Populations
Pediatrics
The excretion of intravenously administered mitomycin in children is similar to adults.