Dosing & Uses
Dosage Forms & Strengths
pyelocalyceal solution
- Kit contains: Two 40-mg single-dose vials plus 20-mL vial sterile hydrogel for reconstitution
Urothelial Cancer
Indicated for low-grade upper tract urothelial cancer (LG-UTUC)
Instill 4 mg/mL via ureteral catheter or a nephrostomy tube, with total instillation volume based on volumetric measurements using pyelography; not to exceed 15 mL (60 mg of mitomycin)
Instill qWeek x6 weeks
Patient achieving complete response 3 months after initial 6 weeks: May continue administration once monthly for maximum of 11 additional instillations
Dosage Modifications
Renal impairment
- GFR <30 mL/min: Avoid use; data are not available with severe renal impairment
Dosing Considerations
Verify pregnancy status in females of reproductive potential before initiating
Laboratory tests obtained before each treatment
- Platelet count
- WBC count (with differential)
- Hemoglobin
Safety and efficacy not established
Adverse Effects
>10% All Grades
Ureter stenosis (44%)
Flank pain (39%)
Urinary tract infection (34%)
Hematuria (32%)
Renal dysfunction (25%)
Nausea (24%)
Fatigue (24%)
Abdominal pain (23%)
Dysuria (21%)
Vomiting (20%)
Hydronephrosis (18%)
Pollakiuria (13%)
Anemia (13%)
Pruritus (13%)
Chills (11%)
Pyrexia (11%)
Laboratory abnormalities worsening from baseline
- Anemia (37%)
- eGFR (37%)
- Increased creatinine (32%)
- Hypoalbuminemia (30%)
- Lymphopenia (21%)
- Thrombocytopenia (21%)
- Hypocalcemia (17%)
- Hyperuricemia (16%)
- Hyperkalemia (13%)
>10% Grades 3-4
Laboratory abnormalities worsening from baseline
- Hyperuricemia (16%)
- 1-10% All Grades H3
- Ureteropelvic obstruction (6%)
- Urinary tract obstruction (6%)
- Ureteric obstruction (2.8%)
- Obstructive uropathy (1.4%)
1-10% Grades 3-4
Ureteric stenosis (8%)
Hydronephrosis (6%)
Urinary tract infection (4.2%)
Vomiting (4.2%)
Flank pain (2.8%)
Hematuria (2.8%)
Renal dysfunction (2.8%)
Ureteropelvic obstruction (1.4%)
Urinary tract obstruction (1.4%)
Ureteric obstruction (1.4%)
Nausea (1.4%)
Abdominal pain (1.4%)
Fatigue (1.4%)
Laboratory abnormalities worsening from baseline
- eGFR (10%)
- Lymphopenia (2.9%)
- Thrombocytopenia (2.8%)
- Hypoalbuminemia (2.8%)
- Hyperkalemia (1.4%)
Warnings
Contraindications
Perforation of bladder or upper urinary tract
Cautions
Ureteric obstruction, including ureteral stenosis, and hydronephrosis reported; monitor for signs and symptoms of ureteric obstruction, including flank pain, fever, and renal function changes; withhold or permanently discontinue mitomycin pyelocalyceal based on severity of ureteric obstruction
May cause bone marrow suppression, particularly thrombocytopenia and neutropenia; monitor laboratory tests before each dose; withhold mitomycin pyelocalyceal for Grade 2 thrombocytopenia or neutropenia; permanently discontinue for ≥Grade 3
Can cause fetal harm
Pregnancy & Lactation
Pregnancy
Based on animal studies and mechanism of action, can cause fetal harm
Advise pregnant females of potential risk to fetus
Animal studies
- Teratological changes observed in animal studies
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 6 months after last dose
- Males with female partners of reproductive potential: Use effective contraception during treatment and for 3 months after last dose
Lactation
Data are not available on presence in human milk, effects on breastfed children, or effects on milk production
Advise women not to breastfeed during treatment and for 1 week following the last dose
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
Mechanism of Action
Inhibits DNA synthesis; guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking; at high drug concentrations, cellular RNA and protein synthesis are also suppressed
Absorption
Peak plasma concentration: 6.24 ng/mL (range: 2.43-12.8 ng/mL)
Metabolism
Metabolized primarily in the liver
Elimination
Forms semisolid gel, which dissolves from normal kidney urine flow over 4-6 hr
Excretion: Urine (10%, unchanged)
Administration
Pyelocalyceal Preparation
Follow applicable special handling and disposal procedures
Prepared only under chilled conditions
Once reconstituted, admixture is 4 mg/mL and appears as a viscous liquid for instillation
Reconstituted mitomycin pyelocalyceal has reverse thermal properties with a gelation point of ~19ºC (66ºF)
Instill as soon as possible after reconstitution; if immediate instillation not possible, may store at controlled room temperature for up to 96 hr (4 days)
Pyelocalyceal Administration
Not for IV, topical, or oral administration
Before every instillation, instruct patient to take 1.3 g of sodium bicarbonate orally the evening prior to, the morning of, and 30 min prior to instillation
Instill as a chilled solution using an Uroject12 Lever, a Luer lock syringe, and a ureteral catheter with molded Luer lock connector
Once chilled at -3ºC to 5C (27-41ºF), it will convert to a viscous liquid for instillation and is stable for up to 1 additional hr
Instill within 1 hr after it is converted to a viscous liquid
Storage
Unopened vials
Store in carton at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Avoid excessive heat over 40ºC (104ºF)
After reconstitution
If immediate instillation is not possible, store at 20-25ºC (68-77ºF) for up to 96 hr (4 days)
Appears as a semisolid gel when stored under these conditions
Protect from light
Images
Formulary
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