New Drug Introduction: Uptravi®/ selexipag
Pharmacology
Prostacyclin (IP) receptor agonist that causes vasodilation of
pulmonary arteries
Manufacturer
Actelion Pharmaceuticals
Approval Date
December 21, 2015
Indications
Treatment of pulmonary arterial hypertension (PAH), WHO Group I, to
delay disease progression and reduce risk of hospitalization for PAH
Contraindications
None
Black Box Warnings None
Warnings &
If pulmonary edema occurs, consider pulmonary veno-occlusive
Precautions
disease (PVOD). If PVOD confirmed, discontinue use.
Pregnancy/Lactation Pregnancy: no adequate or well-controlled studies in pregnant women
Lactation Recommendation: Unknown if excreted in human breast
milk; recommend discontinuation of selexipag if nursing
Pharmacokinetics
A – Time to peak: (selexipag): 1-3 hours; (metabolite): 3-4 hours
~30% lower Cmax, and delayed time to Tmax in presence of food
D – Highly bound (~99%) to plasma proteins
M – Hydrolysis to yield active metabolite, then metabolism catalyzed
by CYP3A4 and CYP2C8
E – Terminal t ½ (selexipag): 0.8-2.5 hours; terminal t ½ (active
metabolite): 6.2-13.5 hours
Drug Interactions –
Avoid concomitant administration with strong inhibitors of CYP2C8
Precipitant/Object
(e.g. gemfibrozil) as this results in increased exposure to selexipag
and active metabolite
Adverse Effects
Headache (65%) [32%]
Nausea (33%) [18%]
(Treatment%) [Placebo%] Diarrhea (42%) [18%]
Myalgia (16%) [6%]
Jaw pain (26%) [6%]
Vomiting (18%) [9%]
Extremity pain (17%) [8%]
Flushing (12%) [5%]
Monitoring Efficacy
6-minute walk distance
WHO functional class
Dosing - Initial
200 mcg twice daily
Dosing - Usual
Increase dose by 200 mcg twice daily at weekly intervals to maximum
tolerated dose
Dosing - Max
1600 mcg twice daily
Renal Adjustment
No adjustment needed if eGFR > 15 mL/min/1.73 m 2
There is no clinical experience for dialysis or eGFR < 15 mL/min/1.73
m2
Hepatic Adjustment
Recommend a once daily regimen for those with moderate hepatic
impairment (Child-Pugh Class B)
There is no clinical experience in Child-Pugh Class C impairment
Avoid in severe hepatic impairment
Cost: Source: Medpagetoday.com 1/6/16
Dose(s)
Uptravi ® – selexipag
200, 400, 600, 800, 1000,
Uptravi (selexipag)
1200, 1400, and 1600 mcg
Tyvaso (orenitram)
0.125, 0.25, 1, and 2.5 mg
$ (30d) or (Tx course)
$13,000 per 30 days
$526-$7,020 per 30 days
Summary
 Uptravi®, selexipag, is an oral prostacyclin agonist indicated for pulmonary arterial
hypertension (PAH)
 Selexipag should not be used with other strong CYP2C8 inhibitors
 Administered at 200 mcg BID and titrated on a weekly basis to the highest tolerated
dose or the max dose of 1600 mcg BID
 Most common side effects include headache, diarrhea, jaw pain and nausea
 Selexipag can be used in combination with other classes of PAH medications (PDE-5
inhibitors and endothelin receptor antagonists)
References:
1. www.uptravi.com
2. Uptravi package insert. Actelion. Dec. 2015.
3. Sitbon O, Channick R, Chin KM, et al. Selexipag for the Treatment of Pulmonary
Arterial Hypertension. N Engl J Med. 2015;373(26):2522-33.
Date Prepared: December 27, 2015
Editor: Peter G. Koval, Pharm.D., BCPS
Author: Ruhaniyah Alam, Pharm.D. Candidate, UNC Eshelman School of Pharmacy