WARNING: NEUTROPENIA AND DIARRHEA
- Severe neutropenia may occur. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay [see Warnings and Precautions (5.1)].
- Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide [see Warnings and Precautions (5.2)]. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses [see Dosage and Administration (2.3)].
1INDICATIONS AND USAGE
TRODELVY is indicated for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease.
This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
2DOSAGE AND ADMINISTRATION
2.1 Important Use Information
Do NOT substitute TRODELVY for or use with other drugs containing irinotecan or its active metabolite SN-38.
2.2 Recommended Dose and Schedule
The recommended dose of TRODELVY is 10 mg/kg administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles. Continue treatment until disease progression or unacceptable toxicity. Do not administer TRODELVY at doses greater than 10 mg/kg.
Administer TRODELVY as an intravenous infusion only. Do not administer as an intravenous push or bolus.
First infusion: Administer infusion over 3 hours. Observe patients during the infusion and for at least 30 minutes following the initial dose, for signs or symptoms of infusion-related reactions [see Warning and Precautions (5.3)].
Subsequent infusions: Administer infusion over 1 to 2 hours if prior infusions were tolerated. Observe patients during the infusion and for at least 30 minutes after infusion.
Prior to each dose of TRODELVY, premedication for prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting (CINV) is recommended.
- Premedicate with antipyretics, H1 and H2 blockers prior to infusion, and corticosteroids may be used for patients who had prior infusion reactions.
- Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist, as well as other drugs as indicated).
2.3 Dose Modifications for Adverse Reactions
Slow or interrupt the infusion rate of TRODELVY if the patient develops an infusion-related reaction. Permanently discontinue TRODELVY for life-threatening infusion-related reactions [see Warning and Precautions (5.3)]
Dose Modifications for Adverse Reactions
Withhold or discontinue TRODELVY to manage adverse reactions as described in Table 1. Do not re-escalate the TRODELVY dose after a dose reduction for adverse reactions has been made.
|Adverse Reaction||Occurrence||Dose Modification|
|Severe Neutropenia [see Warning and Precautions (5.1)]|
|Grade 4 neutropenia ≥7 days,|
Grade 3 febrile neutropenia
(absolute neutrophil count <1000/mm3 and fever ≥38.5°C),
At time of scheduled treatment, Grade 3-4 neutropenia which delays dosing by 2 or 3 weeks for recovery to ≤ Grade 1
|First||25% dose reduction and administer granulocyte-colony stimulating factor (G‑CSF)|
|Second||50% dose reduction|
|At time of scheduled treatment, Grade 3-4 neutropenia which delays dosing beyond 3 weeks for recovery to ≤ Grade 1||First||Discontinue treatment|
|Severe Non-Neutropenic Toxicity|
Grade 4 non-hematologic toxicity of any duration,OR
Other Grade 3-4 non-hematologic toxicity persisting >48 hours despite optimal medical management,OR
At time of scheduled treatment, Grade 3-4 non-neutropenic hematologic or non-hematologic toxicity, which delays dose by 2 or 3 weeks for recovery to ≤ Grade 1
|First||25% dose reduction|
|Second||50% dose reduction|
|In the event of Grade 3-4 non-neutropenic hematologic or non-hematologic toxicity, which does not recover to ≤ Grade 1 within 3 weeks||First||Discontinue treatment|
2.4 Preparation for Administration
- TRODELVY is a cytotoxic drug.
- Follow applicable special handling and disposal procedures1.
- Calculate the required dose (mg) of TRODELVY based on the patient’s body weight at the beginning of each treatment cycle (or more frequently if the patient’s body weight changed by more than 10% since the previous administration) [see Dosage and Administration (2.1)].
- Allow the required number of vials to warm to room temperature.
- Using a sterile syringe, slowly inject 20 mL of 0.9% Sodium Chloride Injection, USP, into each 180 mg TRODELVY vial. The resulting concentration will be 10 mg/mL.
- Gently swirl vials and allow to dissolve for up to 15 minutes. Do not shake. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be free of visible particulates, clear and yellow. Do not use the reconstituted solution if it is cloudy or discolored.
- Use immediately to prepare a diluted TRODELVY infusion solution.
- Calculate the required volume of the reconstituted TRODELVY solution needed to obtain the appropriate dose according to patient’s body weight. Withdraw this amount from the vial(s) using a syringe. Discard any unused portion remaining in the vial(s).
- Slowly inject the required volume of reconstituted TRODELVY solution into a polypropylene (PP) infusion bag, to minimize foaming. Do not shake the contents.
- Adjust the volume in the infusion bag as needed with 0.9% Sodium Chloride Injection, USP, to obtain a concentration of 1.1 mg/mL to 3.4 mg/mL (total volume should not exceed 500 mL). For patients whose body weight exceeds 170 kg, divide the total dosage of TRODELVY equally between two 500 mL infusion bags and infuse sequentially via slow infusion.
- Only 0.9% Sodium Chloride Injection, USP, should be used since the stability of the reconstituted product has not been determined with other infusion-based solutions. Use the diluted solution in the infusion bag immediately. If not used immediately, the infusion bag containing TRODELVY solution can be stored refrigerated 2°C to 8°C (36°F to 46°F) for up to 4 hours. After refrigeration, administer diluted solution within 4 hours (including infusion time).
Do Not Freeze or Shake. Protect from Light.
- Administer TRODELVY as an intravenous infusion. Protect infusion bag from light.
- An infusion pump may be used.
- Do not mix TRODELVY, or administer as an infusion, with other medicinal products.
- Upon completion of the infusion, flush the intravenous line with 20 mL 0.9% Sodium Chloride Injection, USP.
3DOSAGE FORMS AND STRENGTHS
For injection: 180 mg off-white to yellowish lyophilized powder in a single-dose vial.