REVTORPYK Powder for solution for injection Ref.[116743] Active ingredients: Gedatolisib

2.1 Patient Selection

Select patients for treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer with REVTORPYK based on the absence of detected PIK3CA mutations in breast cancer [see Clinical Studies (14)].

An FDA-authorized test for the determination of PIK3CA mutation status in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer is not available.

2.2 Recommended Dosage and Administration

The recommended dosage of REVTORPYK is 180 mg as an intravenous infusion over 30 minutes once weekly on Days 1, 8, and 15 of every 28-day cycle, in combination with fulvestrant, with or without palbociclib, until disease progression or unacceptable toxicity.

If a planned dose is delayed or missed, administer as soon as possible thereafter. Do not wait until the next planned dose in the cycle. Adjust the timing of the subsequent dose to maintain the 3 weeks on followed by 1 week off schedule.

Refer to the Prescribing Information for fulvestrant and palbociclib administered in combination with REVTORPYK for additional dosing information.

2.3 Stomatitis Prophylaxis

Initiate steroid-containing alcohol-free mouthwash when starting REVTORPYK. Continue to administer steroid-containing alcohol-free mouthwash 4 times daily for the first 8 weeks of treatment and longer if needed [see Warnings and Precautions (5.1) and Patient Counseling Information (17)].

2.4 Dosage Modifications for Adverse Reactions

The recommended dosage reduction levels for adverse reactions are listed in Table 1.

Table 1. Recommended Dosage Reductions of REVTORPYK for Adverse Reactions:

Permanently discontinue REVTORPYK in patients who are unable to tolerate 130 mg intravenously once weekly on Days 1, 8, and 15 of every 28-day cycle.

The recommended dosage modifications for adverse reactions are described in Table 2.

Table 2. Recommended Dosage Modifications of REVTORPYK for Adverse Reactions:

Abbreviations: FBG, fasting blood glucose; FPG, fasting plasma glucose; ULN, upper limit of normal.
^a Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

2.5 Preparation and Administration

Reconstitute and further dilute REVTORPYK prior to intravenous infusion. Use appropriate aseptic technique.

Reconstitution:

• Add 20 mL of Sterile Water for Injection or 5% Dextrose Injection to the REVTORPYK vial.
• Swirl the vial until completely dissolved for up to 5 minutes. Minor foaming and opalescence may be observed.
• If not used immediately, store the reconstituted solution in the vial for up to 4 hours at room temperature at 20°C to 25°C (68°F to 77°F). Do not freeze or refrigerate.
• REVTORPYK does not contain a preservative. Discard unused reconstituted REVTORPYK vial after 4 hours.
• DO NOT use common chloride-containing infusion solutions (for example: normal saline, Ringer's solution, Lactated Ringer's solution).

Dilution:

• Withdraw the appropriate volume of the reconstituted solution from the REVTORPYK vial (See Table 3) using a sterile syringe. Inspect visually for particulate matter and discoloration prior to administration. The solution should be free of visible particulates, be clear (minor opalescence is acceptable) and colorless to pale yellow. Discard the vial if particles or discoloration are observed.

Table 3. Volume to Withdraw from Reconstituted Vial Based on Dose:

• Dilute the reconstituted REVTORPYK in an infusion bag containing 250 mL of 5% Dextrose Injection.
• Gently invert the infusion bag to thoroughly mix the solution. Do not shake.
• If not used immediately, store the diluted REVTORPYK infusion solution at room temperature at 20°C to 25°C (68°F to 77°F) for up to 24 hours. Do not freeze or refrigerate.
• Discard any unused portion left in the vial.

Administration:

• Flush the intravenous line with 5% Dextrose Injection before REVTORPYK administration.
• Administer REVTORPYK by intravenous infusion over 30 minutes through a dedicated infusion line equipped with a sterile, non-pyrogenic, in-line or add-on polyether sulfone filter (0.2- or 0.22-micron pore size) and catheter.
  • DO NOT administer any chloride-containing solutions (e.g., Sodium Chloride for Injection, Ringer's Injection, Lactated Ringer's Injection) or other medications concomitantly via the same intravenous line.
• Upon completion of the infusion, flush the intravenous line with 5% Dextrose Injection.
• Discard any unused portions left in the infusion set.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted 15°C to 30°C (59°F to 86°F). Store vial in original carton until time of reconstitution.