Dosing and uses of Uptravi (selexipag)
Adult dosage forms and strengths
tablet
- 200mcg
- 400mcg
- 600mcg
- 800mcg
- 1000mcg
- 1200mcg
- 1400mcg
- 1600mcg
Pulmonary Arterial Hypertension
Indicated for pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH
Starting dose: 200 mcg PO BId
Increase dose by increments of 200 mcg BID, usually at weekly intervals, to the highest tolerated dose; not to exceed 1600 mcg BId
If a patient reaches a dose that cannot be tolerated, the dose should be reduced to the previous tolerated dose
Also see Administration section
Dosage modifications
Renal impairment: No dosage adjustment required
Hepatic impairment
- Mild (Child-Pugh A): No dosage adjustment required
- Moderate (Child-Pugh B): Starting dose is 200 mcg qDay; increase by increments of 200 mcg/day at weekly intervals, as tolerated
- Severe (Child-Pugh C): Avoid use
Dosage considerations
Effectiveness was established in a long-term study in patients with PAH with WHO Functional Class II-III symptoms
Patients had idiopathic and heritable PAH (58%), PAH associated with connective-tissue disease (29%), or PAH associated with congenital heart disease with repaired shunts (10%)
Pediatric dosage forms and strengths
Safety and efficacy not established
Uptravi (selexipag) adverse (side) effects
>10%
Headache (65%)
Diarrhea (42%)
Jaw pain (26%)
Nausea (33%)
Vomiting (18%)
Pain in extremity (17%)
Myalgia (16%)
Flushing (12%)
Arthralgia (11%)
Rash (11%)
1-10%
Hemoglobin decreased below 10 g/dL (8.6%)
Anemia (8%)
Decreased appetite (6%)
Frequency not defined
TSH reduced (up to −0.3 MU/L from a baseline of 2.5 MU/L)
Warnings
Contraindications
None
Cautions
If signs of pulmonary edema occur, consider the possibility of associated pulmonary veno-occlusive disease (PVOD); if PVOD is confirmed, discontinue selexipag
Drug interaction overview
- Coadministration with strong CYP2C8 inhibitors may result in a significant increase in exposure to selexipag and its active metabolite
- Avoid concomitant administration with strong inhibitors of CYP2C8
Pregnancy
Pregnancy
No adequate and well-controlled studies with selexipag exist in pregnant women
Animal studies
- 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 ~47 times that in humans at the maximum recommended human dose
Lactation
Unknown if distributed in human breast 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 selexipag
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Uptravi (selexipag)
Mechanism of action
Selectively activates the prostacyclin receptor (ie, IP-receptor), one of 5 types of prostanoid receptors
Unlike prostacyclin analogs, selexipag is selective for the IP receptor over other prostanoid receptors (ie, EP1-4, DP, FP, TP)
Activating the IP receptor induces vasodilation and inhibits proliferation of vascular smooth muscle cells
Absorption
Peak plasma time: 1-3 hr; 3-4 hr (active metabolite)
Distribution
Protein bound: ~99% (albumin and alpha1-acid glycoprotein)
Metabolism
Undergoes enzymatic hydrolysis of the acylsulfonamide by hepatic carboxylesterase 1, to yield the active metabolite, which is ~37-fold as potent as selexipag
Elimination
Half-life: 0.8-2.5 hr; 6.2-13.5 hr (active metabolite)
Oral clearance: 35 L/hr
Excretion: 93% in feces; neither selexipag nor its metabolite were found in urine
Administration
Oral Administration
Swallow tablet whole; do not split, crush, or chew
Tolerability may be improved when taken with food
Dose interruptions and discontinuations
- If a dose is missed, patients should take a missed dose as soon as possible unless the next dose is within the next 6 hr
- If treatment is missed for ≥3 days, restart selexipag at a lower dose and then titrate to desired effect and tolerance
Storage
Store at 20-25ºC (68-77ºF)
Excursions permitted between 15-30°C (59-86°F)
