mitomycin pyelocalyceal (Rx)

>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%)

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

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.

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)

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