Usual Adult Dose for Breast Cancer

10 mg/kg IV once a week on Days 1 and 8 of 21-day treatment cycles
Maximum dose: 10 mg/kg per dose
Duration of therapy: Until disease progression or unacceptable toxicity

Use: For the treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received 2 or more prior systemic therapies, at least 1 of them for metastatic disease

Usual Adult Dose for Urothelial Carcinoma

10 mg/kg IV once a week on Days 1 and 8 of 21-day treatment cycles
Maximum dose: 10 mg/kg per dose
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• This indication is approved under accelerated approval based on tumor response rate and duration of response; continued approval may be contingent on verification and description of clinical benefit in a confirmatory trial.

Use: For the treatment of patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Starting dose:

• Mild liver dysfunction (bilirubin up to 1.5 times the upper limit of normal [1.5 x ULN] and AST/ALT less than 3 x ULN): No adjustment recommended.
• Moderate or severe liver dysfunction: Data not available

Comments:

• Safety has not been established in patients with moderate or severe liver dysfunction; this drug has not been tested in patients with serum bilirubin greater than 1.5 x ULN, or AST and ALT greater than 3 x ULN, or AST and ALT greater than 5 x ULN and associated with liver metastases.
• No dedicated trial investigated the tolerability in patients with moderate or severe liver dysfunction; no recommendations can be made for the starting dose in these patients.

Dose Adjustments

INFUSION-RELATED REACTIONS:

• The infusion rate should be slowed or interrupted if the patient develops an infusion-related reaction.
• This drug should be permanently discontinued for life-threatening infusion-related reactions.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:

• This drug should be withheld or discontinued to manage adverse reactions (as described below).
• The dose should not be re-escalated after it has been reduced for adverse reactions.

Severe Neutropenia:

• Grade 4 neutropenia for at least 7 days, OR Grade 3 febrile neutropenia (absolute neutrophil count less than 1000/mm3 and fever at least 38.5C), OR at time of scheduled therapy, Grade 3 to 4 neutropenia which delays dosing by 2 or 3 weeks for recovery to Grade 1 or less:
• First occurrence: Dose should be reduced 25% and granulocyte-colony stimulating factor (G-CSF) should be administered.
• Second occurrence: Dose should be reduced 50%.
• Third occurrence: Therapy should be discontinued.
• At time of scheduled therapy, Grade 3 to 4 neutropenia which delays dosing beyond 3 weeks for recovery to Grade 1 or less:
• First occurrence: Therapy should be discontinued.

Severe Nonneutropenic Toxicity:

• Grade 4 nonhematologic toxicity of any duration, OR any Grade 3 to 4 nausea, vomiting, or diarrhea due to therapy that is not controlled with antiemetics and antidiarrheal agents, OR other Grade 3 to 4 nonhematologic toxicity persisting beyond 48 hours despite optimal medical management, OR at time of scheduled therapy, Grade 3 to 4 nonneutropenic hematologic or nonhematologic toxicity, which delays dose by 2 or 3 weeks for recovery to Grade 1 or less:
• First occurrence: Dose should be reduced 25%.
• Second occurrence: Dose should be reduced 50%.
• Third occurrence: Therapy should be discontinued.
• In the event of Grade 3 to 4 nonneutropenic hematologic or nonhematologic toxicity, which does not recover to Grade 1 or less within 3 weeks:
• First occurrence: Therapy should be discontinued.

Precautions

US BOXED WARNINGS:

• NEUTROPENIA: Severe or life-threatening neutropenia may occur. This drug should be withheld for absolute neutrophil count below 1500/mm3 or neutropenic fever. Blood cell counts should be monitored periodically during therapy. G-CSF should be considered for secondary prophylaxis. Anti-infective treatment should be started in patients with febrile neutropenia without delay.
• DIARRHEA: Severe diarrhea may occur. Patients with diarrhea should be monitored and given fluid and electrolytes as needed. Atropine should be administered (if not contraindicated) for early diarrhea of any severity. At the onset of late diarrhea, evaluation for infectious causes is recommended and, if negative, loperamide should be started promptly. If severe diarrhea occurs, this drug should be withheld until resolved to Grade 1 or less and subsequent doses should be reduced.

CONTRAINDICATIONS:
History of severe hypersensitivity reaction to the active component or any of the ingredients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Do NOT substitute this drug for or use with other drugs containing irinotecan or its active metabolite SN-38.
• Prior to each dose, premedication for prevention of infusion reactions and chemotherapy-induced nausea and vomiting (CINV) is recommended.
• Prevention of infusion reactions: Premedicate with antipyretics, H1 blockers, and H2 blockers prior to infusion; corticosteroids may be used for patients who had prior infusion reactions.
• Prevention of CINV: Premedicate with a 2 or 3 drug combination regimen (e.g., dexamethasone with either a 5-hydroxytryptamine type 3 [5-HT3] receptor antagonist or a neurokinin 1 [NK1] receptor antagonist, as well as other drugs as indicated).
• Administer this drug as an IV infusion only; do not administer as an IV push or bolus.
• First infusion: Administer infusion over 3 hours.
• Subsequent infusions: If prior infusions were tolerated, administer infusion over 1 to 2 hours.
• Protect infusion bag from light.
• An infusion pump may be used.
• Do not administer as an infusion with other medicinal products.
• When the infusion is complete, flush the IV line with 20 mL 0.9% Sodium Chloride Injection, USP.
• Closely monitor patients for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion.

Storage requirements:

• Do not freeze or shake; protect from light.
• Unopened vials: Store in a refrigerator at 2C to 8C (36F to 46F) in the original carton to protect from light until time of reconstitution; do not freeze.
• Before reconstitution, allow the required number of vials to warm to room temperature.
• Reconstituted solution: Use immediately to prepare the diluted infusion solution.
• Diluted solution: Use immediately; if not used immediately, store refrigerated 2C to 8C (36F to 46F) for up to 4 hours; after refrigeration, administer within 4 hours (including infusion time).

Reconstitution/preparation techniques:

• This drug requires reconstitution followed by dilution prior to administration; only 0.9% Sodium Chloride Injection, USP should be used for reconstitution and dilution.
• A polyvinyl chloride, polypropylene, or ethylene/propylene copolymer infusion bag should be used.
• The manufacturer product information should be consulted.

IV compatibility:

• Compatible: 0.9% Sodium Chloride Injection, USP
• This drug should not be mixed with other medicinal products.

General:

• This drug is cytotoxic; applicable special handling and disposal procedures should be followed.

Monitoring:

• General: For adverse reactions in patients with known reduced UGT1A1 activity

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Contact health care provider immediately if fever, chills, or other signs of infection occur.
• Contact health care provider immediately if you have diarrhea for the first time during therapy, black/bloody stools, symptoms of dehydration (e.g., lightheadedness, dizziness, faintness), inability to take fluids by mouth due to nausea/vomiting, or inability to get diarrhea under control within 24 hours.
• Contact health care provider immediately if facial/lip/tongue/throat swelling, urticaria, difficulty breathing, lightheadedness, dizziness, chills, rigors, wheezing, pruritus, flushing, rash, hypotension, or fever occurs during or within 24 hours after the infusion.
• Contact health care provider immediately if you have uncontrolled nausea or vomiting.
• Female patients of childbearing potential: Contact health care provider if you are pregnant or become pregnant; use effective contraception during therapy and for 6 months after the last dose.
• Male patients with female partners of childbearing potential: Use effective contraception during therapy and for 3 months after the last dose.
• Do not breastfeed during therapy and for 1 month after the last dose.