Uptravi
(selexipag)Dosage & Administration
See Full Prescribing Information for instructions on preparation and administration. ( 2.3).
By using PrescriberAI, you agree to the AI Terms of Use.
Uptravi Prescribing Information
Pulmonary Arterial Hypertension
UPTRAVI is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.
Effectiveness of UPTRAVI tablets was established in a long-term study in PAH patients with WHO Functional Class II–III symptoms.
Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), PAH associated with congenital heart disease with repaired shunts (10%) [see Clinical Studies (14.1)] .
Recommended Dosage
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.
Preparation Instructions
Reconstitute and further dilute UPTRAVI for injection prior to intravenous infusion following aseptic procedures.
Determine the dose and total volume of reconstituted UPTRAVI solution required (see Table 1).
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.
| UPTRAVI tablets dose (mcg) for twice daily dosing | Corresponding IV UPTRAVI Dose (mcg) for twice daily dosing | Reconstituted transfer volume (mL) for dilution |
|---|---|---|
| 200 | 225 | 1.0 |
| 400 | 450 | 2.0 |
| 600 | 675 | 3.0 |
| 800 | 900 | 4.0 |
| 1000 | 1125 | 5.0 |
| 1200 | 1350 | 6.0 |
| 1400 | 1575 | 7.0 |
| 1600 | 1800 | 8.0 |
Administration Instructions
Administer by intravenous infusion over 80 minutes using an infusion set made of DEHP-free polyvinyl chloride (PVC), natural latex rubber-free microbore tubing protected from light.
Do not use a filter for administration.
Once the solution for infusion glass container is empty, continue the infusion at the same rate with 0.9% saline to empty the remaining solution for infusion in the IV line, to ensure that the entire solution for infusion has been administered.
Interruptions and Discontinuations
If a dose of UPTRAVI is missed, patients should take a missed dose as soon as possible unless the next dose is within the next 6 hours.
If treatment is missed for 3 days or more, restart UPTRAVI at a lower dose and then retitrate.
Dosage Adjustment in Patients with Hepatic Impairment
No dose adjustment of UPTRAVI is necessary for patients with mild hepatic impairment (Child-Pugh class A).
For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose of UPTRAVI tablets is 200 mcg once daily. Increase in increments of 200 mcg once daily at weekly intervals, as tolerated [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)] .
Avoid use of UPTRAVI in patients with severe hepatic impairment (Child-Pugh class C).
Dosage Adjustment with Co-administration of Moderate CYP2C8 Inhibitors
When co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox and teriflunomide), reduce the dosing of UPTRAVI to once daily [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)] .
UPTRAVI is available in the following presentations:
Film-Coated Tablets
- 200 mcg selexipag [Light yellow tablet debossed with 2]
- 400 mcg selexipag [Red tablet debossed with 4]
- 600 mcg selexipag [Light violet tablet debossed with 6]
- 800 mcg selexipag [Green tablet debossed with 8]
- 1000 mcg selexipag [Orange tablet debossed with 10]
- 1200 mcg selexipag [Dark violet tablet debossed with 12]
- 1400 mcg selexipag [Dark yellow tablet debossed with 14]
- 1600 mcg selexipag [Brown tablet debossed with 16]
UPTRAVI for Injection
- 1800 mcg selexipag [Lyophilized powder white to almost white broken cake or powdered material, supplied in a 10 mL single-dose glass vial]
Pregnancy
Risk Summary
There are no adequate and well-controlled studies with UPTRAVI in pregnant women. Animal reproduction studies performed with selexipag showed no clinically relevant effects on embryofetal development and survival. A slight reduction in maternal as well as in fetal body weight was observed when pregnant rats were administered selexipag during organogenesis at a dose producing an exposure to the active metabolite approximately 47 times that in humans at the maximum recommended human dose. No adverse developmental outcomes were observed with oral administration of selexipag to pregnant rabbits during organogenesis at exposures to the active metabolite up to 50 times the human exposure at the maximum recommended human dose.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Data
Animal Data
Pregnant rats were treated with selexipag using oral doses of 2, 6, and 20 mg/kg/day (up to 47 times the exposure to the active metabolite at the maximum recommended human oral dose of 1600 mcg twice daily on an area under the curve [AUC] basis) during the period of organogenesis (gestation days 7 to 17). Selexipag did not cause adverse developmental effects to the fetus in this study. A slight reduction in fetal body weight was observed in parallel with a slight reduction in maternal body weight at the high dose.
Pregnant rabbits were treated with selexipag using oral doses of 3, 10, and 30 mg/kg (up to 50 times the exposure to the active metabolite at the maximum recommended human oral dose of 1600 mcg twice daily on an AUC basis) during the period of organogenesis (gestation days 6 to 18). Selexipag did not cause adverse developmental effects to the fetus in this study.
In a pre- and post-natal development study, pregnant rats were treated with selexipag from gestation day 7 through lactation day 20 at oral doses of 2, 6, and 20 mg/kg/day (up to 35 times the exposure to the active metabolite at the maximum recommended human dose of 1600 mcg twice daily on an AUC basis). Treatment with selexipag did not cause adverse developmental effects in this study at any dose.
Lactation
It is not known if UPTRAVI is present in human milk. Selexipag or its metabolites were present in the milk of rats. Because many drugs are present in the human milk and because of the potential for serious adverse reactions in nursing infants, discontinue nursing or discontinue UPTRAVI.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Of the 1,368 subjects in clinical studies of UPTRAVI tablets, 248 subjects were 65 years of age and older, while 19 were 75 and older. No overall differences were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity cannot be ruled out.
Patients with Hepatic Impairment
No adjustment to the dosing regimen is needed in patients with mild hepatic impairment (Child-Pugh class A).
A once-daily regimen is recommended in patients with moderate hepatic impairment (Child-Pugh class B) due to the increased exposure to selexipag and its active metabolite. There is no experience with UPTRAVI in patients with severe hepatic impairment (Child-Pugh class C). Avoid use of UPTRAVI in patients with severe hepatic impairment [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)] .
Patients with Renal Impairment
No adjustment to the dosing regimen is needed in patients with estimated glomerular filtration rate >15 mL/min/1.73 m 2.
There is no clinical experience with UPTRAVI in patients undergoing dialysis or in patients with glomerular filtration rates <15 mL/min/1.73 m 2 [see Clinical Pharmacology (12.3)] .
Hypersensitivity to the active substance or to any of the excipients.
Concomitant use of strong inhibitors of CYP2C8 (e.g., gemfibrozil) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)] .
Pulmonary Edema with Pulmonary Veno-Occlusive Disease
Should signs of pulmonary edema occur, consider the possibility of associated pulmonary veno-occlusive disease. If confirmed, discontinue UPTRAVI.