Selexipag

Selexipag is used to treat pulmonary arterial hypertension (PAH).

Selexipag is available under the following different brand names: Uptravi.

Dosages of Selexipag:

Dosage Forms and Strengths

Tablets

• 200 mcg
• 400 mcg
• 600 mcg
• 800 mcg
• 1000 mcg
• 1200 mcg
• 1400 mcg
• 1600 mcg

Dosage Considerations – Should be Given as Follows:

Pulmonary Arterial Hypertension (PAH) Disease Progression

• To delay disease and reduce risk of hospitalization for PAH (WHO Group I): 200 mcg orally twice daily, initially
• Increase dose by 200 mcg twice daily, at weekly intervals (usually), to highest tolerated dose; not to exceed 1600 mcg twice daily
• If dose not tolerated, reduce to the previously tolerated dose

Dosage Modifications

Renal impairment

• eGFR greater than 15 mL/min/1.73 m2: No dosage adjustment required
• eGFR less than 15 mL/min/1.73 m2 or patients undergoing dialysis: No clinical experience

Hepatic impairment

• Mild (Child-Pugh A): No dosage adjustment required
• Moderate (Child-Pugh B): Starting dose is 200 mcg once daily; increase by increments of 200 mcg/day at weekly intervals, as tolerated
• Severe (Child-Pugh C): Avoid use

Coadministration with moderate CYP2C8 inhibitors

• Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors (eg, clopidogrel, deferasirox, teriflunomide)
• Revert to selexipag twice-daily dosing when moderated CYP2C8 inhibitor discontinued

Coadministration with CYP2C8 inducers

• Increase selexipag dose (up to 2-fold) if coadministered with rifampin

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%)
• Safety and efficacy not established in pediatric patients

Common side effects of Selexipag include:

• Headache
• Diarrhea
• Jaw pain
• Nausea
• Vomiting
• Pain in extremities
• Muscle pain
• Flushing
• Joint pain
• Rash

Less common side effects of selexipag include:

• Hemoglobin decreased below 10 g/dL
• Anemia
• Decreased appetite

Other side effects of selexipag include:

• TSH reduced (up to −0.3 MU/L from a baseline of 2.5 MU/L)
• Symptomatic low blood pressure (hypotension)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Severe interactions of selexipag include:
  • gemfibrozil
• Serious interactions of selexipag include:
  • darolutamide
  • lasmiditan
• Selexipag has moderate interactions with at least 59 different drugs.
• Mild interactions of selexipag include:
  • lopinavir
  • ritonavir

Warnings

• This medication contains selexipag. Do not take Uptravi if you are allergic to selexipag or any ingredients contained in this drug.

Contraindications

• Concomitant use of strong CYP2C8 inhibitors (e.g., gemfibrozil)

Effects of Drug Abuse

• No information is available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Selexipag?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Selexipag?"

Cautions

• If signs of pulmonary edema occur, consider the possibility of associated pulmonary veno-occlusive disease (PVOD); if PVOD is confirmed, discontinue selexipag

Drug interactions overview

• Contraindicated with strong CYP2C8 inhibitors; coadministration with strong CYP2C8 inhibitors may result in significantly increased exposure to selexipag and its active metabolite
• Concomitant administration with an inducer of CYP2C8 and UGT 1A3 and 2B7 enzymes (rifampin) halved exposure to active metabolite; increase the dose up to twice of the normal dose when coadministered with rifampin; reduce therapy dose when rifampin is stopped
• An increased selexipag dose (up to 2-fold) may be necessary if coadministered with strong CYP2C8 inducers

Pregnancy and Lactation

• No adequate and well-controlled studies with selexipag exist in pregnant women. Consult your doctor. Reproduction studies in animals 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.
• It is unknown if selexipag is 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.
  • In embryo-fetal studies in mice and rats, selexipag was shown to produce fetal developmental toxicities in mice and maternal toxicity and fetal developmental toxicities in rats
  • Selexipag administered orally during organogenesis to pregnant animals was associated with reduced fetal weights and an increased incidence of costal cartilage anomalies in the absence of maternal toxicity in mice; and maternal toxicity decreased fetal weights, and increased skeletal variations in rats at plasma exposures approximately 4- and 6-times respectively, the human plasma exposure at the maximum recommended human dose (MRHD) of 200 mg/day
  • In female rats, d selexipag administered during organogenesis through lactation did not show evidence of fetal toxicity, developmental delays, or impaired reproduction in offspring at plasma exposures approximately equivalent to the human plasma exposure at the MRHD
• Selexipag is excreted in the breast milk of rats. When the drug is present in animal milk, the drug will likely be present in human milk. It is unknown whether selexipag is excreted in human milk. Exercise caution when administering to a nursing woman. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on a breastfed child from selexipag or the underlying maternal condition.