UPTRAVI Film-coated Tablets

The recommended starting dosage of UPTRAVI tablets is 200 micrograms (mcg) given twice daily. Tolerability may be improved when taken with food [see Clinical Pharmacology (12.3)] .

Increase the dose in increments of 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to

1600 mcg twice daily. If a patient reaches a dose that cannot be tolerated, the dose should be reduced to the previous tolerated dose.

Do not split, crush, or chew tablets.

UPTRAVI for Injection

Use UPTRAVI for injection in patients who are temporarily unable to take oral therapy.

Administer UPTRAVI for injection twice daily by intravenous infusion at a dose that corresponds to the patient's current dose of UPTRAVI tablets (see Table 1). Administer UPTRAVI for injection as an 80-minute intravenous infusion.

Reconstitution

• Remove the carton of UPTRAVI for injection from the refrigerator and allow to stand for approximately 30 to 60 minutes to reach room temperature (20°C to 25°C [68°F to 77°F]).
• The vial needs to be protected from light at all times. Ensure the protective wrap around label is covering the entire vial.
• Peel back light protective wrap on vial to inspect the contents in the vial. It should appear white to almost white broken cake or powdered material. Immediately close the light protective wrap on the vial.
• Reconstitute UPTRAVI for injection using a polypropylene syringe with 8.6 mL of 0.9% Sodium Chloride Injection, USP and slowly inject into the UPTRAVI vial with the stream directed toward the inside wall of the vial to obtain a concentration of 225 mcg/mL of selexipag.
• Document date and time of first puncture. Complete infusion within 4 hours of first puncture.
• Gently invert the vial and repeat until powder is completely dissolved. Do not shake.
• Inspect the vial by peeling back the light protective wrap around label for discoloration. The reconstituted solution should appear clear, colorless and free from foreign material. Do not use if the reconstituted solution is discolored, cloudy, or contains visible particles.

Dilution

• UPTRAVI for injection must be diluted in glass containers only.
• Withdraw 100 mL of 0.9% Sodium Chloride Injection, USP and transfer into an empty sterile glass container.
• Withdraw the required volume of reconstituted solution (see Table 1 for reconstituted transfer volume) from the UPTRAVI vial using a single, appropriately sized polypropylene syringe and dilute into the glass container containing 100 mL 0.9% Sodium Chloride Injection, USP to obtain the desired final dose.
• Mix the diluted UPTRAVI infusion solution by gentle inversion of the glass container 5 times. Do not shake.
• Protect diluted UPTRAVI infusion solution from light at all times. Assign a 4-hour expiry from the time of first vial puncture and wrap the glass container completely with light protective cover.
• The UPTRAVI infusion solution should be kept at room temperature (20°C–25°C [68°F–77°F]) and must be infused within 4 hours from the first puncture of the vial stopper (including infusion time).
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. The diluted UPTRAVI infusion solution should be clear and colorless. Discard if particulate matter is observed.

UPTRAVI for injection vials are single-dose, for single administration. All remaining reconstituted product must be discarded.