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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

UPTRAVI® (selexipag)

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UPTRAVI - Alternative Dosing and Titration Schedule

Last Updated: 11/28/2024

SUMMARY

In the pivotal phase 3 study, GRIPHON (Prostacyclin [PGI₂] Receptor agonist In Pulmonary arterial HypertensiON), UPTRAVI was initiated at 200 mcg twice daily (BID) and increased weekly in increments of 200 mcg BID, as tolerated, up to a maximum dose of 1600 mcg BID.¹
SPHERE (SelexiPag: tHe usErs dRug rEgistry) registry study showed that the median maintenance dose of UPTRAVI was 1100 mcg BID in 729 of 759 patients with pulmonary arterial hypertension (PAH). In the overall PAH population (n=759), the median duration of UPTRAVI titration was 8.1 weeks, with 671 (88.4%) patients titrating at speeds slower than 200 mcg BID per week and 88 (11.6%) patients titrating at speeds equal to or faster than 200 mcg BID per week; 97 (12.8%) patients received a different or an unrecorded UPTRAVI dose, the specific outcomes of which are not available.²^,³
EXPOSURE (EXPloratory Observational Study of Uptravi in Real-lifE) is an ongoing, Europe and Canada-based, multicenter, prospective, observational study of PAH patients initiating PAH-specific therapy. Three dose groups were defined (low, medium, and high) in the study based on patients’ individualized dose (ID) at the end of titration. Overall, 6% (n=36) of patients received doses outside of the defined groups, for reasons that were not captured in EXPOSURE.⁴^,⁵
Doses of UPTRAVI of up to 1800 mcg BID were administered to healthy adult patients in the phase 1 study AC-065-101, which was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple-ascending doses of UPTRAVI administered orally BID in healthy male patients. The study was terminated in compliance with the protocol after uptitration to 1800 mcg BID because more than 50% of patients who were still on active treatment (7 out of 9) showed moderate drugrelated adverse events (AEs) at 1800 mcg BID, which, in some cases, required treatment.⁶
A search of the scientific literature retrieved 2 articles⁷^,⁸ and 2 congress abstracts⁹^,¹⁰ describing patients who were administered UPTRAVI at doses exceeding 1600 mcg BID. Relevant information from these publications is summarized in Table: Published Literature Describing the Administration of UPTRAVI at Doses Exceeding 1600 mcg BID in the Treatment of PAH.
A real-world, retrospective, observational cohort study evaluating adult patient outcomes across UPTRAVI dose ranges in the United States (US) using the Komodo closed-claims database reported the UPTRAVI dosage adjustments in varied patterns, across all the ID strata. Increase in maintenance dose by ≥200 mcg occurred ≥1 time in 112 (67.1%) patients in the low-ID group, 91 (48.1%) in the medium-ID group, and 75 (27.0%) in the high-ID group (standardized mean difference [SMD], 0.69). Decrease in the maintenance dose by ≥200 mcg occurred ≥1 time in 93 (55.7%) patients in the low-ID group, 79 (41.8%) in the medium-ID group, and 58 (20.9%) in the high-ID group (SMD, 0.46).¹¹
A retrospective study examining real-world dosing patterns of UPTRAVI, and the effect of prior prostacyclin pathway agent (PPA) use on UPTRAVI dosing and discontinuation reported that the mean time to reach the individualized maintenance dose was 14 weeks (greater than that specified in the protocol outlined in the GRIPHON study [12 weeks]). The median time to reach the individualized maintenance dose was 56 days in the ≤weekly cohort and 86 days in the >weekly cohort.¹²
Another retrospective study examining real-world dosing patterns of UPTRAVI reported that the overall median time to reach the maintenance dose was 83 days, suggesting that clinicians may be titrating UPTRAVI slower than on a weekly basis.¹³
Administration of doses not specified in the UPTRAVI product label is not recommended.

CLINICAL DATA

GRIPHON Study

In the pivotal phase 3 study, GRIPHON, UPTRAVI was initiated at 200 mcg BID and increased weekly in increments of 200 mcg BID, as tolerated, up to a maximum dose of 1600 mcg BID. This dose adjustment phase spanned the first 12 weeks of treatment. To determine the highest tolerable dose, the dose was reduced by 200 mcg BID when an intolerable dose was reached.¹

Alternative Dosing and Titration Schedule

SPHERE Registry

SPHERE (SelexiPag: tHe usErs dRug rEgistry) is a US-based, multicenter, prospective, observational, real-world registry. Adult patients (≥18 years of age) receiving UPTRAVI in routine clinical practice were enrolled from November 2016 to March 2020 and followed for up to 18 months. The study provided data on the realworld outcomes of UPTRAVI treatment in the US along with information regarding patient demographics and disease characteristics in the enrolled population.²

Of the total 829 patients with pulmonary hypertension (PH; World Health Organization [WHO] group I-V) enrolled in SPHERE, 759 had PAH (WHO group I), of whom 387 and 372 were newly (starting UPTRAVI ≤60 days before enrollment) and previously (starting UPTRAVI >60 days before enrollment) initiated on UPTRAVI, respectively.²

In 729 of 759 patients, the median maintenance dose of UPTRAVI was 1100 mcg BID (range, 100-3200 mcg). In the overall PAH population (n=759), the median duration of UPTRAVI titration was 8.1 weeks (range, 1.1-26.9 weeks), with 671 (88.4%) patients (newly initiated, n=338 [87.3%]; previously initiated, n=333 [89.5%]) titrating at speeds slower than 200 mcg BID per week and 88 (11.6%) patients (newly initiated, n=49 [12.7%]; previously initiated, n=39 [10.5%]) titrating at speeds equal to or faster than 200 mcg BID per week. One hundred and fourteen (15.0%), 238 (31.4%), and 310 (40.8%) patients received a BID maintenance dose of UPTRAVI 200-400 mcg, 6001000 mcg, and >1200 mcg, respectively, whereas 97 (12.8%) patients received a different or an unrecorded UPTRAVI dose, the specific outcomes of which are not available.²^,³

Four-Strata Risk Assessment of EXPOSURE Study

EXPOSURE (EXPloratory Observational Study of Uptravi in Real-lifE) is an ongoing, Europe and Canada-based, multicenter, prospective, observational study of PAH patients initiating PAH-specific therapy. Adult patients with Group I PH initiating a new PAH-specific therapy within 1 month of or at enrollment were enrolled from September 2017 to November 2022 and followed for up to 3 years. This study provided data on real-world characteristics, treatment patterns, and outcomes of patients with PAH, categorized by risk status when initiated with UPTRAVI.⁴

Of the 698 patients enrolled with PAH, 163 did not have sufficient data to allow for risk evaluation, leaving 535 patients for baseline risk assessment calculations. Patients with available baseline data were grouped into low (n=76), intermediate-low (n=168), intermediate-high (n=182), or high risk (n=109) of 1-year mortality according to the European Society of Cardiology and the European Respiratory Society (ESC/ERS) 4-strata method.⁴^,⁵

There were 3 defined dose groups based on patients’ ID at the end of titration: low (200 or 400 mcg BID), medium (600, 800 or 1000 mcg BID), and high dose (1200, 1400, or 1600 mcg BID). A total of 36 patients received doses outside of the defined dose groups for reasons not captured in EXPOSURE: 9 patients in the low risk group received alternative doses (50 mcg [n=1], 300 mcg [n=5], 500 mcg [n=2], and 2000 mcg [n=1] BID); 6 in the intermediate-low risk group (300 mcg [n=3] and 700 mcg [n=3] BID); 7 in the intermediate-high risk group (300 mcg [n=1], 500 mcg [n=2], 700 mcg [n=3], and 1500 mcg [n=1] BID); 4 in the high risk group (100 mcg [n=2], 300 mcg [n=1], and 700 mcg [n=1] BID). Overall, patients received 50 mcg (n=1), 100 mcg (n=5), 300 mcg (n=12), 500 mcg (n=6), 700 mcg (n=9), 900 mcg (n=1), 1500 mcg (n=1), and 2000 mcg (n=1) BID.⁴^,⁵

Alternative Dosing

Phase 1 Study

Bruderer et al (2014)⁶ described a single-center, randomized, placebo-controlled, doubleblind, multiple-period, multiple-ascending-dose phase 1 study designed to evaluate the safety, tolerability, PK and PD of multiple-ascending doses of UPTRAVI administered orally BID in healthy male patients. In this study, 16 healthy male patients received increasing oral doses of UPTRAVI (400-1800 mcg; n=12) or placebo (n=4) BID, with each dose being administered for up to 3 days. The maximum dose of 1800 mcg BID was administered for 2.5 days.

The study was terminated in compliance with the protocol after uptitration to 1800 mcg BID because more than 50% of patients who were still on active treatment (7/9) showed moderate drug-related AEs at 1800 mcg BID which, in some cases, required treatment; specifically, 3 patients receiving UPTRAVI at 1800 mcg BID received paracetamol for headache or myalgia. Concomitant medication for the treatment of AEs was received by 2 patients in the placebo group (a combination of anthraquinone glycosides and topical salicylic acid to treat mouth ulcerations). At the end of the study, all AEs had resolved without sequelae.

Concerning PK, with increasing UPTRAVI doses (up to the maximum of 1800 mcg BID), the values for maximum concentration (C_max) and area under the curve for dosing interval (AUC_τ) increased for both UPTRAVI and ACT-333679. These increases were dose proportional for UPTRAVI and slightly less than dose proportional for ACT333679.

Overview of Identified Information From Other Studies

Relevant information identified from 2 articles and 2 congress abstracts is summarized in Table: Published Literature Describing the Administration of UPTRAVI at Doses Exceeding 1600 mcg BID in the Treatment of PAH.

Published Literature Describing the Administration of UPTRAVI at Doses Exceeding 1600 mcg BID in the Treatment of PAH

Reference	Patient History	UPTRAVI Treatment	Efficacy and Safety Outcomes
Parikh et al (2020)⁷	Fourteen patients (11 female) with PAH (WHO group I PH) FC II symptoms, who were selected to be transitioned from parenteral prostanoid therapy to UPTRAVI using a protocol including clinic visits and RHC assessments At the time of the switch, participants had a median (Q1Q3) age of 53.5 (48.559.0) years and BMI of 30.1 kg/m² The median (Q1-Q3) time from diagnosis of PAH to initiation of parenteral therapy was 1.3 (014.5) months, and from initiation of parenteral therapy to initiation of UPTRAVI was 5.6 (3.08.8) years Over 80% of patients were on combination therapy (no details reported)	Conversion was individualized for each participant but followed the same general principles: initiation with UPTRAVI 200 mcg BID followed by weekly dose increases in BID increments of 200 mcg The dose of parenteral drug was decreased by ≥1 ng/kg/min with initiation of UPTRAVI based on patients’ prior tolerability with prostanoid titration With every uptitration of UPTRAVI, 3 days were allowed to reach the steady state and then the dose of parenteral therapy was reduced by 1/8 over that week In case of increased PAH symptoms prior to the next scheduled increase of UPTRAVI, the dose of parenteral prostanoid therapy was increased by 13 ng/kg/min per day. If the patient was still experiencing PAH symptoms at a dose of UPTRAVI 1600 mcg BID, further titration up to 3200 mcg BID was considered	The median total daily UPTRAVI dose achieved was 3200 mcg, and 6/15 patients were taking >3200 mcg total daily dose Two patients required an additional oral agent (PDE-5i and/or ERA) during the transition period. Repeat assessments of PAH severity and functional capacity revealed stability in hemodynamics, NTproBNP, and functional capacity. RV function remained stable except in 1 patient who only could tolerate 1200 mcg total daily dose of UPTRAVI. This patient’s RV function worsened from normal to mild dysfunction in the setting of stable symptoms and other assessed surrogate markers All but 1 patient remained on UPTRAVI, and none required reinitiation of parenteral therapy (median [Q1Q3], 23.7 [20.328.6] months). One death occurred in a patient with PoPH^a who died from worsening liver failure after the switch. No other patients experienced hospitalization or death
Verlinden et al (2019)⁸	34-year-old female patient diagnosed with PAH secondary to SLE Prior treatment with sildenafil 20 mg TID, bosentan 125 mg BID, and treprostinil 2.5 mg TID for 2 years (mPAP=56 mmHg, PVR=869 dynes·s·cm⁵; CI (assessed by the Fick method)=3.0 L/min/m², 6MWD=522 m)	Patient was switched from oral treprostinil to UPTRAVI, initially at 600 mcg BID and uptitrated to 1600 mcg BID Ten months after the transition, patient had improved NYHA FC I symptoms and an increase in 6MWD; however, RHC showed worsening hemodynamics (mPAP=58 mmHg, PVR=1253 dynes·s·cm^-5; CI=2.2 L/min/m², 6MWD=558 m) UPTRAVI 1600 mcg BID was further uptitrated to 1800 mcg BID, and bosentan was transitioned to macitentan 10 mg daily	Patient showed improved hemodynamics while on 1800 mcg BID at 6month follow-up (mPAP=44 mmHg, PVR=496 dynes·s·cm^-5; CI=4.1 L/min/m², 6MWD=523 m) and was clinically stable on a regimen of UPTRAVI 1800 mcg BID, macitentan 10 mg daily, and sildenafil 20 mg TID at 2-year followup
MoralesEstrella et al (2018)⁹	72-year-old female patient diagnosed with PVOD Prior treatment with sildenafil 20 mg TID and IV epoprostenol at 6 ng/kg/min	Patient was transitioned to sildenafil and UPTRAVI 1400 mcg TID due to her preference for nonparenteral agents	Patient was hospitalized with decompensated right heart failure after 3 months of transitioning from IV epoprostenol to UPTRAVI 1400 mcg TID (mPAP=42 mmHg, mRAP=10 mmHg, mPCWP=14 mmHg, PVR=8 WU; thermodilution CI=2.37 L/min/m²,assumed Fick CI=1.40 L/min/m²) UPTRAVI was discontinued without weaning (the last dose was given 9.5 hours before the initiation of IV epoprostenol), followed by a rapid titration of IV epoprostenol by 1 ng/kg/min every 30 minutes until the goal rate of 6 ng/kg/min No medicationrelated AEs were reported
Habib and Feldman (2018)¹⁰ Case series (N=3)	Case 1: 26-year-old male patient with a history of familial PAH Prior treatment with sildenafil and SC, IV, and then oral treprostinil. ambrisentan was subsequently added Patient reported to have “declined” on above treatment	Patient was switched to UPTRAVI^b, initially at 1600 mcg BID After 3 months, patient remained in FC III UPTRAVI dose was then increased to 1600 mcg TID	After 3 months, patient improved to FC II No specific safety outcomes related to UPTRAVI are reported
	Case 2: 71-year-old female patients with a history of BOOP and MCTD, diagnosed with PAH (mPAP=58 mmHg, CO=5.3^c; CI=2.94^c, 6MWD=400^d) Initial treatment with sildenafil and SC treprostinil with good response Subsequently transitioned to oral treprostinil and tadalafil; after 2 years, patient experienced gradual decline	Patient was switched to UPTRAVI^b 1600 mcg TID	The authors report that “side-effects” improved greatly 6MWD at last followup was 1050 ft No specific safety outcomes related to UPTRAVI are reported
	Case 3: 60-year-old female patient with history of scleroderma, CREST, and DVT, diagnosed with PAH (mPAP=68 mmHg, CO=4.6) Initial treatment with tadalafil and SC treprostinil with good response Ambrisentan was added and was subsequently transitioned to oral treprostinil Hemodynamics deteriorated over 2 years	Patient was transitioned to UPTRAVI^b 1600 mcg BID Repeat RHC after 9 months showed inadequate response UPTRAVI dose was then increased to 1600 mcg TID	Highest 6MWD (1630^b) was achieved while on UPTRAVI 1600 mcg TID No specific safety outcomes related to UPTRAVI are reported
Note: Data are given as number of patients (n=) or mean±standard deviation, unless otherwise stated.Abbreviations: 6MWD, 6-minute walk distance; AE, adverse effect; BID, twice daily; BMI, body mass index; BOOP, bronchiolitis obliterans with organizing pneumonia; CI, cardiac index; CO, cardiac output; CREST, calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia; DVT, deep vein thrombosis; ERA, endothelin receptor antagonist; FC, functional class; IV, intravenous; MCTD, mixed connective tissue disease; mPAP, mean pulmonary arterial pressure; mPCWP, mean pulmonary capillary wedge pressure; mRAP, mean right atrial pressure; NTproBNP, N-terminal pro b-type natriuretic peptide; NYHA, New York Heart Association; PAH, pulmonary arterial hypertension; PDE-5i, phosphodiesterase-5 inhibitor; PH, pulmonary hypertension; PoPH, portopulmonary hypertension; PVOD, pulmonary venoocclusive disease; PVR, pulmonary vascular resistance; Q, quartile; RHC, right heart catheterization; RV, right ventricle; SC, subcutaneous; SLE, systemic lupus erythematosus; TID, 3 times daily; WHO, World Health Organization; WU, Wood units. ^aOff-label usage of UPTRAVI for PoPH; not recommended. ^bThe abstract does not specify the protocols used to switch/transition treatment to UPTRAVI, nor does it confirm the PAH-specific concomitant therapies being used with UPTRAVI. ^cUnit of measure is not specified in the abstract. ^dUnit of measure is not specified in the abstract (presumed to be feet).

Alternative Titration Schedule

Real-World Evidence

Burger et al (2024)¹¹ conducted a real-world, retrospective, observational cohort study to evaluate patient outcomes across UPTRAVI dose ranges in the US using the Komodo closed-claims database between December 15, 2015, and June 30, 2022. Eligibility criteria included adult patients treated with UPTRAVI during the study period and had ≥1 inpatient or 2 outpatient records with an International Classification of Diseases, Ninth or Tenth Revision (ICD-9/ ICD-10) diagnosis code for PH (on separate days, with ≥1 PH diagnosis prior to UPTRAVI initiation). The index date was UPTRAVI ID date defined as receipt of the first maintenance UPTRAVI dose pack used for >60 consecutive days.

A total of 1186 eligible patients with PAH were included in the study, of whom 634 (53.5%) completed the titration phase and reached their UPTRAVI ID, and categorized into high- (43.8%), medium- (29.8%), and low- (26.3%) ID strata. Across all ID strata, adjustments in UPTRAVI dosing occurred in varied patterns. In the high-ID group, a higher proportion of patients remained at their initial ID with fewer dose adjustments over time compared with the low- and medium-ID groups. The UPTRAVI maintenance dose was adjusted in 121 (72.5%), 117 (61.9%), and 96 (34.5%) patients in the low-, medium-, and high-ID group patients, respectively (SMD, 0.63). An increase in the maintenance dose by ≥200 mcg occurred ≥1 time in 112 (67.1%) patients in the low-ID group, 91 (48.1%) patients in the medium-ID group, and 75 (27.0%) patients in the high-ID group (SMD, 0.69). A decrease in maintenance dose by ≥200 mcg occurred ≥1 time in 93 (55.7%) patients in the low-ID group, 79 (41.8%) patients in the medium-ID group, and 58 (20.9%) patients in the high-ID group (SMD, 0.46).¹¹ The details on UPTRAVI dose adjustments are summarized in the Table: UPTRAVI Dose Adjustments - Overall and According to Initial ID Reached.

UPTRAVI Dose Adjustments - Overall and According to Initial ID Reached¹¹

Parameter	All Patients Reaching UPTRAVI ID (N=634)	Low ID (UPTRAVI 200-400 mcg BID) (n=167)	Medium ID (UPTRAVI 600-1000 mcg BID) (n=189)	High ID (UPTRAVI 1200-1600 mcg BID) (n=278)	SMD^a
Number of times maintenance dose was adjusted, n (%)
None	300 (47.3)	46 (27.5)	72 (38.1)	182 (65.5)	0.63
1	135 (21.3)	32 (19.2)	51 (27.0)	52 (18.7)
≥2	199 (31.4)	89 (53.3)	66 (34.9)	44 (15.8)
Number of times maintenance dose was increased by 200 mcg, n (%)
None	514 (81.1)	119 (71.3)	133 (70.4)	262 (94.2)	0.46
1	78 (12.3)	28 (16.8)	39 (20.6)	11 (4.0)
≥2	42 (6.6)	20 (12.0)	17 (9.0)	5 (1.8)
Number of times dose was decreased by 200 mcg, n (%)
None	516 (81.4)	124 (74.3)	144 (76.2)	248 (89.2)	0.31
1	83 (13.1)	26 (15.6)	30 (15.9)	27 (9.7)
≥2	35 (5.5)	17 (10.2)	15 (7.9)	3 (1.1)
Number of times dose was increased by ≥200 mcg, n (%)
None	356 (56.2)	55 (32.9)	98 (51.9)	203 (73.0)	0.69
1	157 (24.8)	43 (25.7)	55 (29.1)	59 (21.2)
≥2	121 (19.1)	69 (41.3)	36 (19.0)	16 (5.8)
Number of times dose was decreased by ≥200 mcg, n (%)
None	404 (63.7)	74 (44.3)	110 (58.2)	220 (79.1)	0.46
1	129 (20.3)	33 (19.8)	52 (27.5)	44 (15.8)
≥2	101 (15.9)	60 (35.9)	27 (14.3)	14 (5.0)
Abbreviations: BID, twice daily; ID, individualized dose; SMD, standardized mean difference.^aSMD <0.1 predefined as indicating covariate balance between the cohorts.

Palevsky et al (2020)¹² conducted a retrospective study using de-identified specialty pharmacy data from January 01, 2016 to March 29, 2019, to examine real-world dosing patterns of UPTRAVI and the effect of prior PPA use on UPTRAVI dosing and discontinuation. Adult patients (≥18 years old) who attained their individualized maintenance doses were included. These patients were further categorized into 2 cohorts (based on dosing pattern and PPA use), which each had 2 subcategories ([≤weekly cohort: patients who received titration ≤8 days/200 mcg BID; >weekly cohort: patients who received titration >8 days/200 mcg BID] and [prior-use cohort: patients with a history of PPA use; naïve cohort: patients without a history of PPA use]).

Of the 3931 patients who attained their individualized maintenance doses, 2869 (73.0%) were female, and the mean (±standard deviation [SD]) age was 57.9 (±14.8) years. The mean time to reach the individualized maintenance dose was 14 weeks (greater than that specified in the protocol outlined in the GRIPHON study [12 weeks]).

The ≤weekly and >weekly cohorts included 550 (14.0%) and 3381 (86.0%) patients, respectively. The median time to reach the individualized maintenance dose was 56 days in the ≤weekly cohort and 86 days in the >weekly cohort. The median time to reach the individualized maintenance dose for patients on low, medium, and high individualized maintenance doses were 73, 83, and 89 days, respectively. Results pertaining to patients with (n=523; 13.3%) and without (n=3408; 86.7%) a history of PPA use are presented in Table: Outcomes in Patients With and Without a History of PPA Use.

Outcomes in Patients With and Without a History of PPA Use¹²

Parameter	Prior-Use Cohort^a (n=523; 13.3%)	Naïve Cohort^b (n=3,408; 86.7%)	P-Value^c
Maximum dose achieved at first individualized maintenance dose (mcg BID), median	1600	1200	<0.001
Speed of titration, n (%)
Patients who had ≤weekly titration (fast)	110 (21.0)	440 (12.9)	<0.001
Patients who had >weekly titration (slow)	413 (79.0)	2968 (87.1)	<0.001
Abbreviations: BID, twice daily; PPA, prostacyclin pathway agent.^aPrior-use cohort consists of patients with a history of PPA use. ^bNaïve cohort consists of patients without a history of PPA use. ^cP-Value <0.05 is considered significant.

The lack of information on whether PAH was incident or prevalent, the status of existing comorbidities, whether patients were on concomitant mediations, and if the medication was taken as prescribed was a set of limitations of this study. Additionally, the inability to identify if patients started the maintenance phase with a titration package and the context of treatment discontinuation were also noted as the study limitations.

Kung et al (2018)¹³ conducted a retrospective study using dosing and shipment records from specialty pharmacies to examine the real-world dosing patterns of UPTRAVI. Patients with ≥6 months of exposure to UPTRAVI and 6 shipments were included.

At the time of analysis, 2490 patients were exposed to UPTRAVI for ≥6 months and had corresponding shipment data. The overall median time to reach the maintenance dose was 83 days, suggesting that clinicians may be titrating UPTRAVI slower than on a weekly basis.

LiTERATURE Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 18 November 2024.

References

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2	McLaughlin V, Farber HW, Highland KB, et al. Disease characteristics, treatments, and outcomes of patients with pulmonary arterial hypertension treated with selexipag in real-world settings from the SPHERE registry (SelexiPag: tHe usErs dRug rEgistry). J Heart Lung Transplant. 2024;43(2):272-283.
3	McLaughlin V, Farber H, Highland K. Supplement to: Disease characteristics, treatments, and outcomes of patients with pulmonary arterial hypertension treated with selexipag in real-world settings from the SPHERE registry (SelexiPag: tHe usErs dRug rEgistry). J Heart Lung Transplant. 2024;43(2):272-283.
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7	Parikh K, Doerfler S, Shelburne N, et al. Experience in transitioning from parenteral prostacyclins to selexipag in pulmonary arterial hypertension. J Cardiovasc Pharmacol. 2020;75:299-304.
8	Verlinden N, Walter C, Kanwar M, et al. Transition from oral treprostinil to selexipag in a patient with pulmonary arterial hypertension. Ann Pharmacother. 2019;53:764-765.
9	Morales-Estrella J, Chen A, Heresi G. Successful transition from oral selexipag to intravenous epoprostenol [abstract]. Am J Respir Crit Care Med. 2018;197:A3695.
10	Habib N, Feldman J. Three-a-day dosing of selexipag in the treatment of pulmonary arterial hypertension: a case series [abstract]. Am J Respir Crit Care Med. 2018;197:Abstract A3719.
11	Burger CD, Tang W, Tsang Y, et al. Impact of selexipag maintenance dose on persistence, adherence, and hospitalization in US patients with pulmonary arterial hypertension. Pulm Circ. 2024;14(3):e12415.
12	Palevsky H, Pruett J, Ogbomo A, et al. Examining dosing patterns for selexipag in real-world practice using US specialty pharmacy data. Poster presented at: Academy of Managed Care Pharmacy (AMCP); April 21-24, 2020; Houston, TX.
13	Kung T, Archer-Chicko C, Raspa S, et al. Dosing trends for UPTRAVI (selexipag) in real-world practice: a review of specialty pharmacy data. Abstract presented at: Annual Meeting of the American College of Chest Physicians (CHEST); October 6-10, 2018; San Antonio, TX.