Portrazza Solution for injection Ref.[11133] Active ingredients: Human normal immunoglobulin G

2.1 Recommended Dose and Schedule

The recommended dose of PORTRAZZA is 800 mg administered as an intravenous infusion over 60 minutes on Days 1 and 8 of each 3-week cycle prior to gemcitabine and cisplatin infusion. Continue PORTRAZZA until disease progression or unacceptable toxicity.

2.2 Premedication

• For patients who have experienced a previous Grade 1 or 2 infusion-related reaction (IRR), pre-medicate with diphenhydramine hydrochloride (or equivalent) prior to all subsequent PORTRAZZA infusions [see Dosage and Administration (2.3)].
• For patients who have experienced a second Grade 1 or 2 occurrence of IRR, pre-medicate for all subsequent infusions, with diphenhydramine hydrochloride (or equivalent), acetaminophen (or equivalent), and dexamethasone (or equivalent) prior to each PORTRAZZA infusion [see Dosage and Administration (2.3)].

2.3 Dose Modifications

Infusion-Related Reactions (IRR):

• Reduce the infusion rate of PORTRAZZA by 50% for Grade 1 IRR [see Dosage and Administration (2.2) and Warnings and Precautions (5.5)].
• Stop the infusion for Grade 2 IRR until signs and symptoms have resolved to Grade 0 or 1; resume PORTRAZZA at 50% reduced rate for all subsequent infusions [see Dosage and Administration (2.2) and Warnings and Precautions (5.5)].
• Permanently discontinue PORTRAZZA for Grade 3 or 4 IRR [see Dosage and Administration (2.2) and Warnings and Precautions (5.5)].

Dermatologic Toxicity:

• Withhold PORTRAZZA for Grade 3 rash or acneiform rash until symptoms resolve to Grade ≤2, then resume PORTRAZZA at reduced dose of 400 mg for at least 1 treatment cycle. If symptoms do not worsen, may increase dose to 600 mg and 800 mg in subsequent cycles.
• Permanently discontinue PORTRAZZA if:
  • Grade 3 rash or acneiform rash do not resolve to Grade ≤2 within 6 weeks,
  • Reactions worsen or become intolerable at a dose of 400 mg
  • Patient experiences Grade 3 skin induration/fibrosis [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)] or
  • Grade 4 dermatologic toxicity [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].

2.4 Preparation for Administration

Inspect vial contents for particulate matter and discoloration prior to dilution [see Description (11)]. Discard the vial if particulate matter or discoloration is identified. Store vials in a refrigerator at 2° to 8°C (36˚ to 46˚F) until time of use. Keep the vial in the outer carton in order to protect from light [see How Supplied/Storage and Handling (16.2)].

• Dilute the required volume of PORTRAZZA with 0.9% Sodium Chloride Injection, USP in an intravenous infusion container to a final volume of 250 mL. Do not use solutions containing dextrose.
• Gently invert the container to ensure adequate mixing.
• DO NOT FREEZE OR SHAKE the infusion solution. DO NOT dilute with other solutions or co-infuse with other electrolytes or medication.
• Store diluted infusion solution for no more than 24 hours at 2° to 8°C (36° to 46°F), or no more than 4 hours at room temperature (up to 25°C [77°F]).
• Discard vial with any unused portion of PORTRAZZA.

2.5 Administration

Visually inspect the diluted solution for particulate matter and discoloration prior to administration. If particulate matter or discoloration is identified, discard the solution.

Administer diluted PORTRAZZA infusion via infusion pump over 60 minutes through a separate infusion line. Flush the line with 0.9% Sodium Chloride Injection, USP at the end of the infusion.

There has been limited experience with PORTRAZZA overdose in human clinical trials.

The highest dose of PORTRAZZA studied clinically in a human dose-escalation Phase 1 study was 1000 mg once a week and once every other week. Two out of 9 patients in the every other week cohort experienced dose-limiting toxicities (e.g., a combination of Grade 3 headache, vomiting, and nausea). There is no known antidote for PORTRAZZA overdose.

Store vials in a refrigerator at 2° to 8°C (36° to 46°F) until time of use. Keep the vial in the outer carton in order to protect from light. DO NOT FREEZE OR SHAKE the vial.