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Uptravi

Generic Name: Selexipag
Class: Vasodilating Agents
Chemical Name: 2-[4-[(5,6-diphenylpyrazin-2-yl)-propan-2-ylamino]butoxy]-N-methylsulfonylacetamide
Molecular Formula: C26H32N4O4S
CAS Number: 475086-01-2

Introduction

Selexipag is a vasodilator.

Uses for Uptravi

Selexipag has the following uses:

Selexipag is an oral prostacyclin receptor agonist indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.1

Uptravi Dosage and Administration

General

Selexipag is available in the following dosage form(s) and strength(s):

Tablets: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1000 mcg, 1200 mcg, 1400 mcg, and 1600 mcg.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

  • Starting dose: 200 mcg twice daily.1

  • Increase the dose by 200 mcg twice daily at weekly intervals to the highest tolerated dose up to 1600 mcg twice daily.1

  • Maintenance dose is determined by tolerability.1

  • Moderate hepatic impairment: Starting dose 200 mcg once daily, increase the dose by 200 mcg once daily at weekly intervals to the highest tolerated dose up to 1600 mcg.1

Cautions for Uptravi

Contraindications

None.1

Warnings/Precautions

Pulmonary Veno-Occlusive Disease (PVOD)

Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue selexipag.1

Specific Populations

Pregnancy

There are no adequate and well-controlled studies with selexipag 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 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 up to 50 times the human exposure at the maximum recommended human dose.1 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.1

Pregnant rats were treated with selexipag using oral doses of 2, 6, and 20 mg/kg/day (up to 47 times the exposure at the maximum recommended human 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.1 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 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.1

Lactation

It is not known if selexipag is present in human milk. Selexipag or its metabolites were present in the milk of rats. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants, discontinue nursing or discontinue selexipag.1

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.1

Geriatric Use

Of the 1368 subjects in clinical studies of selexipag, 248 subjects were 65 years of age and older while 19 were 75 years of age 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.1

Patients with Hepatic Impairment

No adjustment to the dosing regimen is needed in patients with mild hepatic impairment (Child-Pugh class A).1

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 selexipag in patients with severe hepatic impairment (Child-Pugh class C). Avoid use of selexipag in patients with severe hepatic impairment.1

Patients with Renal Impairment

No adjustment to the dosing regimen is needed in patients with estimated glomerular filtration rate > 15 mL/min/1.73 m2.1

There is no clinical experience with selexipag in patients undergoing dialysis or in patients with glomerular filtration rates < 15 mL/min/1.73 m2.1

Common Adverse Effects

Adverse reactions occurring more frequently (≥5%) on selexipag compared to placebo are headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, and flushing.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Strong CYP2C8 inhibitors: increased exposure to selexipag and its active metabolite. Avoid concomitant use.1

Actions

Mechanism of Action

Selexipag is a selective, nonprostanoid prostacyclin receptor (IP receptor) agonist that is structurally distinct from prostacyclin. Selexipag is hydrolyzed by carboxylesterase 1 to yield its active metabolite, which is approximately 37-fold as potent as selexipag. Selexipag and the active metabolite are selective for the IP receptor versus other prostanoid receptors (EP1-4, DP, FP and TP).1

Advice to Patients

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Package Insert).1

Inform patients what to do if they miss a dose. 1

Inform patients not to split, crush, or chew tablets. 1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Selexipag

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablet, Coated

200 mcg

Uptravi

Actelion Pharmaceuticals US Inc.

400 mcg

Uptravi

Actelion Pharmaceuticals US Inc.

600 mcg

Uptravi

Actelion Pharmaceuticals US Inc.

800 mcg

Uptravi

Actelion Pharmaceuticals US Inc.

1000 mcg

Uptravi

Actelion Pharmaceuticals US Inc.

1200 mcg

Uptravi

Actelion Pharmaceuticals US Inc.

1400 mcg

Uptravi

Actelion Pharmaceuticals US Inc.

1600 mcg

Uptravi

Actelion Pharmaceuticals US Inc.

Titration Pack (Tablet, Coated)

200 mcg (140 tablets) and 800 mcg (60 tablets)

Uptravi

Actelion Pharmaceuticals US Inc.

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Date published: September 16, 2016
Last reviewed: September 16, 2016
Date modified: October 12, 2016

References

1. Actelion Pharmaceuticals US, Inc. UPTRAVI (Selexipag) ORAL prescribing information. 2015 Dec.

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