Uptravi Selexipag Tablets

1. Indications and Usage
Pulmonary Arterial Hypertension (PAH): Treatment of patients with PAH (WHO Group 1) to delay the progression of the disease and reduce the risk of hospitalization for worsening PAH.
It is used for the treatment of pulmonary arterial hypertension (PAH, WHO Group 1) to delay disease progression and reduce the risk of hospitalization due to the deterioration of PAH.
2. Dosage and Administration
Administration: Oral administration with food. Tablets must be swallowed whole and not broken, crushed, or chewed.
Dose Titration: Dosage must be individualized based on tolerability.
Starting Dose: 200 mcg (0.2 mg) twice daily (approx. 12 hours apart).
Titration: Increase by 200 mcg increments at weekly intervals until the maximum tolerated dose is reached.
Maximum Dose: 1600 mcg (1.6 mg) twice daily.
If a Dose is Missed: Take as soon as possible unless less than 6 hours remain until the next dose.
Interruption: If treatment is interrupted for ≥3 days, restart at the lowest dose (200 mcg twice daily) and re-titrate.
3. Mechanism of Action
Selective IP Receptor Agonist: Selexipag is the first oral, selective, small-molecule prostacyclin IP receptor agonist.
Active Metabolite: It is metabolized by CES1 into an active metabolite (ACT-333679) which is approximately 37 times more potent than the parent compound.
Pathway: Activation of the IP receptor increases intracellular cAMP, leading to pulmonary and systemic vasodilation, and inhibition of vascular smooth muscle cell proliferation.
4. Safety and Warnings
Contraindications:
Hypersensitivity to selexipag or any excipients.
Severe coronary artery disease or unstable angina.
Recent myocardial infarction (within 6 months) or cerebrovascular accident (within 3 months).
Uncontrolled heart failure or severe arrhythmias.
Concomitant use with strong CYP2C8 inhibitors (e.g., Gemfibrozil).
Pregnancy: Contraindicated due to potential fetal risk. Women of childbearing potential must use effective contraception.
Hypotension: May cause systemic hypotension; monitor blood pressure, especially during titration.
5. Adverse Reactions
Adverse reactions are often related to its prostacyclin-like activity and are most common during dose titration:
Very Common (≥10%): Headache, Diarrhea, Nausea, Vomiting,Jaw pain, Myalgia, Limb pain, Arthralgia, Flushing.
Common (1-10%): Anemia, Hypotension, Insomnia, Rash.
6. Drug Interactions
CYP2C8 Inhibitors:
Strong Inhibitors (e.g., Gemfibrozil): Contraindicated due to significantly increased exposure.
Moderate Inhibitors (e.g., Clopidogrel, Teriflunomide): Reduce dosing frequency to once daily during co-administration.
CYP2C8 Inducers: May decrease exposure; monitor efficacy (e.g., Rifampicin).
Antacids: No significant interaction, but take at different times if possible.
7. Pharmaceutical Information
Chemical Name: 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide.