Selexipag (Uptravi) is a pulmonary arterial vasodilator that is used to treat patients with primary (WHO Group 1) pulmonary arterial hypertension in symptomatic patients. Bosentan is another orally available medicine used in the treatment of pulmonary arterial hypertension.

Indications of Selexipag (Uptravi):

• Pulmonary arterial hypertension:

  • It is approved for the treatment of patients with moderate to severe symptom limitations who have WHO Group 1 pulmonary arterial hypertension (Class II or Class III dyspnea).
  • Selexipag reduces the risk of hospitalization and delays the progression of the disease.

Selexipag (Uptravi) Dose in Adults

Selexipag (Uptravi) Dose in the treatment of pulmonary arterial hypertension:

• 200 mcg orally two times a day.
• Up until the maximum acceptable dose, the dose is raised by 200 mcg twice daily at weekly intervals.
• The maximum dose is 1,600 mcg two times a day.
• Patients who do not tolerate an escalated dose may be switched back to the previously tolerated dose.

• If a dose is missed:

  • Unless the following dose is planned within six hours, a missing dose should be taken as soon as possible.
  • It should be reintroduced at a reduced dose and titrated upwards if doses are missed for three or more days.

Selexipag (Uptravi) dose in Children:

The drug's effectiveness and safety in children have not been shown.

Selexipag (Uptravi) Pregnancy Risk Category: U

• It has not yet been tested in pregnant women.
• It is advisable for females with pulmonary hypertension to delay pregnancy and utilise reliable contraception.

Selexipag use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• Manufacturers recommend weighing the benefits and risks of drug exposure for the mother against the risks to the infant.

Dose in Renal Disease:

• eGFR (Estimated Glomerular filtration rate) ≥ 15 mL/minute/1.73m²:

  • Adjustment in the dose is not necessary.

• eGFR (Estimated Glomerular filtration rate) < 15 mL/minute/1.73m²:

  • It has not been studied in patients with an eGFR of less than 15 ml/minute/1.73m².
  • The manufacturer has not provided any adjustments in the dose in these patients.

• Dialysis:

  • It has not been studied in dialysis patients. The manufacturer has not provided any adjustments in the dose in these patients.

Dose in Liver disease:

• Mild hepatic impairment (Child-Pugh class A):

  • Adjustment in the dose is not necessary.

• Moderate hepatic impairment (Child-Pugh class B):

  • Start with a daily dose of 200 mcg.
  • If tolerated, the dose may be increased once a day by 200 mcg at weekly intervals.

• Severe hepatic impairment (Child-Pugh class C):

  • Avoid using it.

Common Side Effects of Selexipag:

• Cardiovascular:

  • Flushing

• Central Nervous System:

  • Headache

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Vomiting

• Neuromuscular & Skeletal:

  • Jaw Pain
  • Limb Pain
  • Myalgia
  • Arthralgia

Less Common Side Effects of Selexipag (Uptravi):

• Endocrine & Metabolic:

  • Hyperthyroidism

• Gastrointestinal:

  • Decreased Appetite

• Hematologic & Oncologic:

  • Anemia

Contraindications to Selexipag (Uptravi):

• It is contraindicated for patients allergic to the drug or any of its components, as well as those who are taking strong CYP2C8 inhibitors such gemfibrozil.

Warnings and precautions

• Pulmonary edema

  • Patients with pulmonary edema should be aware that there may be pulmonary-veno-occlusive diseases.
  • Treatment must be stopped if the diagnosis of pulmonary venoocclusive disease has been confirmed.

• Hepatic impairment

  • Since this hasn't been researched in patients with severe hepatic impairment, it should be avoided.
  • A reduction in dose may be necessary for moderate hepatic impairment.

Selexipag: Drug Interaction

Monitor:

• Monitor the patient for improvement
  • monitor pulmonary function tests
  • exercise tolerance
  • quality of life
• Monitor for features of pulmonary edema.
• Liver function tests.

How to administer Selexipag (Uptravi)?

It can be taken with or without food and is taken orally. Taking a medication with food may make it more tolerable. The tablets shouldn't be chewed and swallowed whole, nor should they be broken or crushed.

Mechanism of action of Selexipag (Uptravi):

• A selective prostacyclin receptor agonist called selexipag dilates the blood vessels in the lungs.
• Patients with pulmonary hypertension have a dysregulation of the metabolic pathways responsible for Prostacyclin production. 
• Prostacyclin is found in healthy people. It prevents platelet accumulation and induces vasodilation.

AbsorptionRapid

Protein binding99% It is mostly bound to alpha-1 and albumin glycoproteins.

Metabolism It is metabolized in the liver by CYP3A4, CYP2C8, UGT1A3 or UGT2B7. It is then hydrolyzed by carboxylesterase to its active metabolite ACT-333679. The active metabolite then becomes glucuronidated.

Bioavailability: About 49%

Half-life elimination: The Terminal half-life of selexipag: 0.8 to 2.5 hours; The Terminal half-life of the active metabolite: 6.2 to 13.5 hours

The time to reach peak plasma concentration: Selexipag: 1 to 3 hours; Active metabolite: 3 to 4 hours; Delayed with food

Excretion: It is mostly excreted in the feces (~93%) and urine (12%; as inactive metabolites)

International Brands of Selexipag:

• Uptravi

Selexipag Brand Names in Pakistan:

No Brands Available in Pakistan.