Selexipag is a selective prostacyclin receptor (IP receptor) agonist for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH. Current pharmacologic options for the treatment of PAH are targeted to specific pathways involved in the disease process; many patients require combination therapy with agents from different classes. In a Phase II study, selexipag was shown to reduce pulmonary vascular resistance after 17 weeks of treatment in patients on stable therapy with an endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor. Results from a Phase III study of patients with PAH not currently being treated or on stable treatment with an endothelin receptor antagonist and/or phosphodiesterase type-5 inhibitor showed that patients treated with selexipag had a reduced risk of disease progression and hospitalization. Selexipag was FDA-approved in December 2015.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Administer with or without food. Administration with food may improve tolerability. Do not split, crush, or chew the tablets.
-Missed dose: If a dose is missed, administer as soon as possible unless the next dose is within the next 6 hours. If treatment is missed for 3 days or more, reinitiate treatment at a lower dose and retitrate.
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution:
-Remove the selexipag vial from the refrigerator approximately 30 to 60 minutes prior to reconstitution to allow it to reach room temperature of 20 to 25 degrees C (68 to 77 degrees F).
-To inspect the contents in the vial, peel back the light protective wrap. The contents should appear as a white to almost white broken cake or powdered material. Immediately close the light protective wrap on the vial.
-Protect the vial from light at all times and ensure that the protective wrap is covering the entire vial.
-Reconstitute selexipag using a polypropylene syringe containing 8.6 mL of 0.9% Sodium Chloride Injection.
-Slowly inject the 0.9% Sodium Chloride Injection into the vial as a stream directed toward the inside wall of the vial. Gently invert the vial and repeat gently inversion until the powder is completely dissolved. Do not shake.
-The final concentration of the reconstituted solution is 225 mcg/mL.
-Peal back the light protective wrap to inspect for solution discoloration. The reconstituted solution should appear clear, colorless, and free from foreign material. Do not use the reconstituted solution if discolored, cloudy, or contains visible particles.
-Storage of reconstituted solution: Document data and time of first puncture. Complete infusion within 4 hours of first puncture.
Dilution:
-Selexipag must be diluted in glass containers only.
-Withdraw 100 mL of 0.9% Sodium Chloride Injection and transfer into an empty sterile glass container.
-Withdraw the required volume of selexipag reconstituted solution from the vial using a single, appropriately sized polypropylene syringe and dilute in the 0.9% Sodium Chloride Injection to obtain the desired final dose. Discard any unused selexipag solution that remains in the vial; vials are single-use only.
--For a 225 mcg dose, withdrawal 1 mL of the reconstituted solution for further dilution
-For a 450 mcg dose, withdrawal 2 mL of the reconstituted solution for further dilution
-For a 675 mcg dose, withdrawal 3 mL of the reconstituted solution for further dilution
-For a 900 mcg dose, withdrawal 4 mL of the reconstituted solution for further dilution
-For a 1,125 mcg dose, withdrawal 5 mL of the reconstituted solution for further dilution
-For a 1,350 mcg dose, withdrawal 6 mL of the reconstituted solution for further dilution
-For a 1,575 mcg dose, withdrawal 7 mL of the reconstituted solution for further dilution
-For a 1,800 mcg dose, withdrawal 8 mL of the reconstituted solution for further dilution
-Mix the diluted solution by gentle inversion of the glass container 5 times. Do not shake. The diluted solution should be clear and colorless.
-Storage of diluted solution: Protect dilute solution from light at all times; completely wrap the glass container with a light protective cover. Keep the diluted solution at a room temperature of 20 to 25 degrees C (68 to 77 degrees F) and infuse within 4 hours from the first puncture of the vial stopper; this includes infusion time.
Intravenous Infusion:
-Infuse selexipag intravenously over 80 minutes using an infusion set made of DEHP-free polyvinyl chloride (PVC), natural latex rubber-free microbore tubing that is protected from light.
-Do not use a filter for administration.
-Following completion of the infusion, infuse 0.9% Sodium Chloride Injection at the same rate to empty any remaining solution in the IV line and ensure that the entire solution for infusion has been administered.
Reported adverse reactions occurred more frequently during the dose titration phase of treatment.
During selexipag clinical trials, headache was the most commonly reported adverse reaction (65% vs. 32% placebo).
Gastrointestinal adverse reactions reported during selexipag clinical trials include diarrhea (42% vs. 18% placebo), nausea (33% vs. 18% placebo), vomiting (18% vs. 9% placebo), and anorexia (decreased appetite, 6% vs. 3% placebo).
Musculoskeletal adverse reactions reported with the use of selexipag during clinical trials include jaw pain (26% vs. 6% placebo), myalgia (16% vs. 6% placebo), pain in extremity (17% vs. 8% placebo), and arthralgia (11% vs. 8% placebo).
During selexipag clinical trials, flushing was reported in 12% of patients receiving selexipag compared to 5% of those in the placebo group. Rash (unspecified) was reported in 11% of patients in the selexipag group (vs. 8% placebo).
During clinical trials of selexipag, anemia, defined as a decrease in hemoglobin concentration to below 10 g/dL, was reported in 8.6% of patients treated with selexipag and 5% of those in the placebo group. The mean absolute changes in hemoglobin at regular visits compared to baseline ranged from -0.34 to -0.02 g/dL in the selexipag group compared to -0.05 to 0.25 g/dL in the placebo group.
During selexipag clinical trials, hyperthyroidism was reported in 1% of patients receiving selexipag compared to no patients in the placebo group. A reduction of up to -0.3 MU/L from a baseline median of 2.5 MU/L in median thyroid-stimulating hormone was observed at most visits in the selexipag group compared to little change in the placebo group. No mean changes in triiodothyronine or thyroxine were observed in either group.
If signs of pulmonary edema occur during therapy with selexipag, consider the possibility of pulmonary veno-occlusive disease (VOD). Discontinue use of selexipag if pulmonary VOD is confirmed.
Symptomatic hypotension has been reported with the postmarketing use of selexipag.
Injection site reactions, such as infusion-site erythema/redness, pain, and swelling, have been reported with intravenous infusions of selexipag.
There are no adequate and well-controlled studies with the administration of selexipag in human pregnancy. Animal studies involving rats and rabbits showed no clinically relevant effects on embryofetal development and survival with oral selexipag doses that produced active metabolite exposures of up to 35 to 50 times the maximum recommended human dose (MRHD) of 1600 mcg PO twice daily. In one of the studies involving pregnant rats, slight reductions in both maternal and fetal body weights were observed.
It is unknown whether selexipag is present in human milk. Selexipag or its metabolites were present in rat milk. Due to the potential for serious adverse reactions in a nursing infant, the decision should be made to discontinue breast-feeding or discontinue selexipag. Eproprostenol may be a reasonable alternative in nursing women.
Use selexipag with caution in patients with hepatic disease or hepatic impairment. Following administration of selexipag to patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment, exposure was increased by 2- and 4-fold, respectively, of that seen in healthy patients. Compared to healthy patients, the active metabolite was similar in patients with mild hepatic impairment, but doubled in patients with moderate hepatic impairment. Based on pharmacokinetic modeling, the selexipag dose should be reduced to a once daily regimen, which is predicted to result in steady-state selexipag exposures 2-fold that seen with twice daily dosing in healthy patients. Due to the lack of experience in patients with severe hepatic impairment (Child-Pugh class C), avoid use of selexipag in this patient population.
For the treatment of pulmonary hypertension to delay disease progression and reduce the risk of hospitalization in persons with WHO Group 1 pulmonary hypertension:
Oral dosage:
Adults: 200 mcg PO twice daily, initially. Increase dose by 200 mcg twice daily at weekly intervals to the highest tolerated dose up to 1,600 mcg PO twice daily. If a dose cannot be tolerated, reduce the dose to the previously tolerated dose.
Intravenous dosage (substituting for oral selexipag therapy):
Adults: 225 mcg IV twice daily for 200 mcg PO twice daily; 450 mcg IV twice daily for 400 mcg PO twice daily; 675 mcg IV twice daily for 600 mcg PO twice daily; 900 mcg IV twice daily for 800 mcg PO twice daily; 1,125 mcg IV twice daily for 1,000 mcg PO twice daily; 1,350 mcg IV twice daily for 1,200 mcg PO twice daily; 1,575 mcg IV twice daily for 1,400 mcg PO twice daily; and 1,800 mcg IV twice daily for 1,600 mcg PO twice daily.
Maximum Dosage Limits:
-Adults
3200 mcg/day PO; 3,600 mcg/day IV.
-Geriatric
3200 mcg/day PO; 3,600 mcg/day IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Mild hepatic impairment (Child-Pugh class A): No dosage adjustments needed.
Moderate hepatic impairment (Child-Pugh class B): Initiate therapy with 200 mcg PO once daily and increase by weekly increments of 200 mcg once daily, as tolerated.
Severe hepatic impairment (Child-Pugh class C): Avoid use.
Patients with Renal Impairment Dosing
eGFR more than 15 mL/minute/1.73 m2: No dosage adjustments needed.
eGFR less than 15 mL/minute/1.73 m2: No data are available.
Intermittent hemodialysis
There are no data in patients undergoing dialysis. Dialysis is unlikely to remove selexipag and its active metabolite because they are highly protein-bound.
*non-FDA-approved indication
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acetaminophen; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acetaminophen; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Acrivastine; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Amphetamine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Amphetamine; Dextroamphetamine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Articaine; Epinephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Benzphetamine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Brompheniramine; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Brompheniramine; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Bupivacaine; Epinephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Cannabidiol: (Moderate) Consider a dose reduction of selexipag as clinically appropriate if adverse reactions occur when administered with cannabidiol. Increased exposure to the active metabolite of selexipag is possible. Selexipag is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Cetirizine; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Chlorpheniramine; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Chlorpheniramine; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Clopidogrel: (Major) Reduce the selexipag dose to once daily if coadministered with clopidogrel. Concomitant use may increase selexipag exposure and the risk of adverse effects. Selexipag is a CYP2C8 substrate and clopidogrel is a moderate CYP2C8 inhibitor. Coadministration has been observed to increase exposure to the active selexipag metabolite by approximately 2.7-fold.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Codeine; Phenylephrine; Promethazine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Deferasirox: (Major) Reduce selexipag dose to once daily when coadministered with deferasirox due to increased exposure to the active metabolite of selexipag, which may cause side effects. Selexipag is a CYP2C8 substrate, and deferasirox is a moderate CYP2C8 inhibitor.
Desloratadine; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Dexbrompheniramine; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Dexmethylphenidate: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Dextroamphetamine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Diethylpropion: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Diphenhydramine; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Dobutamine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Dopamine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Doxapram: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. It is advisable to monitor blood pressure if the combination is necessary.
Elbasvir; Grazoprevir: (Major) Administering selexipag with elbasvir may result in elevated selexipag plasma concentrations. Selexipag is a substrate of CYP3A and the active metabolite is a substrate for breast cancer resistance protein (BCRP). Elbasvir is an inhibitor of BCRP. If these drugs are used together, closely monitor for signs of adverse events. (Major) Administering selexipag with grazoprevir may result in elevated selexipag plasma concentrations. Selexipag is a substrate of CYP3A and the active metabolite is a substrate for breast cancer resistance protein (BCRP). Grazoprevir is an inhibitor of BCRP, and also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Ephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Ephedrine; Guaifenesin: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Epinephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Fexofenadine; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Gemfibrozil: (Contraindicated) Coadministration of selexipag and gemfibrozil is contraindicated due to doubled exposure to selexipag and approximately 11-fold increased exposure to the selexipag active metabolite, which may cause side effects. Selexipag is a CYP2C8 substrate, and gemfibrozil is a strong CYP2C8 inhibitor.
Guaifenesin; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Guaifenesin; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Ibuprofen; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Increase the dose of selexipag up to twice when coadministering with rifampin. Reduce the selexipag dose when rifampin is stopped. Coadministration of selexipag and rifampin resulted in halved exposure to the selexipag active metabolite. Selexipag is a substrate of CYP2C8, UGT1A3, and UGT2B7; rifampin is an inducer of CYP2C8, UGT1A3, and UGT2B7.
Isoniazid, INH; Rifampin: (Major) Increase the dose of selexipag up to twice when coadministering with rifampin. Reduce the selexipag dose when rifampin is stopped. Coadministration of selexipag and rifampin resulted in halved exposure to the selexipag active metabolite. Selexipag is a substrate of CYP2C8, UGT1A3, and UGT2B7; rifampin is an inducer of CYP2C8, UGT1A3, and UGT2B7.
Isoproterenol: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Leflunomide: (Major) Reduce selexipag dose to once daily when coadministered with leflunomide due to increased exposure to the active metabolite of selexipag, which may cause side effects. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Selexipag is a CYP2C8 substrate. Teriflunomide is an inhibitor of CYP2C8.
Letermovir: (Moderate) Increased exposure to the active metabolite of selexipag may occur when administered concurrently with letermovir. In vitro data suggests letermovir is a CYP2C8 inhibitor; however, the magnitude of inhibition is unknown. According to the selexipag manufacturer, strong CYP2C8 inhibitors are contraindicated with selexipag, a CYP2C8 substrate, and a dosage reduction should be considered with moderate CYP2C8 inhibitors. Specifically, consider a less frequent dosing regimen (e.g., once daily) when initiating selexipag in patients on a moderate CYP2C8 inhibitor. Reduce selexipag dose when a moderate CYP2C8 inhibitor is initiated.
Lidocaine; Epinephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Lisdexamfetamine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Lopinavir; Ritonavir: (Moderate) Concurrent use of lopinavir with selexipag may result in elevated selexipag serum concentrations. Selexipag is a substrate for the drug transporter organic anion transporting polypeptide (OATP1B1/1B3); lopinavir is an OATP1B1 inhibitor. Monitor for increased toxicities if these drugs are given together.
Loratadine; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Methamphetamine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Methylphenidate: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Midodrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Naproxen; Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Nicardipine: (Moderate) Consider a dose reduction of selexipag to once daily dosing as clinically appropriate if adverse reactions occur when administered with nicardipine. Increased exposure to the active metabolite of selexipag is possible. Selexipag is a CYP2C8 substrate and nicardipine is a CYP2C8 inhibitor.
Norepinephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Phendimetrazine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Phentermine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Phentermine; Topiramate: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Pirtobrutinib: (Major) Reduce the selexipag dose to once daily if coadministered with pirtobrutinib. Concomitant use may increase selexipag exposure and the risk of adverse effects. Selexipag is a CYP2C8 substrate and pirtobrutinib is a moderate CYP2C8 inhibitor. Coadministration with another moderate CYP2C8 inhibitor increased exposure to the active selexipag metabolite by approximately 2.7-fold.
Prilocaine; Epinephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Promethazine; Phenylephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Pseudoephedrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Pseudoephedrine; Triprolidine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Racepinephrine: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Rifampin: (Major) Increase the dose of selexipag up to twice when coadministering with rifampin. Reduce the selexipag dose when rifampin is stopped. Coadministration of selexipag and rifampin resulted in halved exposure to the selexipag active metabolite. Selexipag is a substrate of CYP2C8, UGT1A3, and UGT2B7; rifampin is an inducer of CYP2C8, UGT1A3, and UGT2B7.
Selpercatinib: (Major) Reduce selexipag dose to once daily when coadministered with selpercatinib due to increased exposure to the active metabolite of selexipag, which may cause side effects. Selexipag is a CYP2C8 substrate and selpercatinib is a moderate CYP2C8 inhibitor.
Serdexmethylphenidate; Dexmethylphenidate: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concurrent administration of voxilaprevir with selexipag. Taking these medications together may increase selexipag plasma concentrations, potentially increasing the risk for adverse events. Selexipag is a substrate for the drug transporters P-glycoprotein (P-gp), Organic Anion Transporting Polypeptides 1B1/1B3 (OATP1B1/1B3), and Breast Cancer Resistance Protein (BCRP). Voxilaprevir is a P-gp, OATP1B1/1B3, and BCRP inhibitor.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Consider a less frequent dosing regimen (e.g., once daily) when initiating selexipag in patients receiving trimethoprim. Reduce the selexipag dose when trimethoprim is initiated in patients already taking selexipag. Coadministration can be expected to increase exposure to selexipag and its active metabolite. Selexipag is a substrate of CYP2C8; trimethoprim is a moderate CYP2C8 inhibitor.
Sympathomimetics: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications.
Tedizolid: (Moderate) If possible, stop use of selexipag temporarily during treatment with oral tedizolid. If coadministration cannot be avoided, closely monitor for selexipag-associated adverse events. Concentrations of the selexipag active metabolite may be increased when selexipag is administered concurrently with oral tedizolid. The active metabolite of selexipag is a substrate of the Breast Cancer Resistance Protein (BCRP); oral tedizolid inhibits BCRP in the intestine.
Teriflunomide: (Major) Reduce selexipag dose to once daily when coadministered with teriflunomide due to increased exposure to the active metabolite of selexipag, which may cause side effects. Selexipag is a substrate of CYP2C8 and teriflunomide is a moderate CYP2C8 inhibitor.
Trimethoprim: (Major) Consider a less frequent dosing regimen (e.g., once daily) when initiating selexipag in patients receiving trimethoprim. Reduce the selexipag dose when trimethoprim is initiated in patients already taking selexipag. Coadministration can be expected to increase exposure to selexipag and its active metabolite. Selexipag is a substrate of CYP2C8; trimethoprim is a moderate CYP2C8 inhibitor.
Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and selexipag is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.
Prostacyclin synthase is reduced in patients with pulmonary arterial hypertension, resulting in reduced production of prostacyclin, a potent vasodilator with antiproliferative effects. Selexipag is an oral selective prostacyclin receptor (IP receptor) agonist that is structurally distinct from prostacyclin. Activation of the prostacyclin receptor produces cyclic adenosine monophosphate, which induces vascular smooth muscle relaxation and produces decreases in vascular pressure and pulmonary vascular resistance and an increase in cardiac index.
Selexipag is administered orally and intravenously. Selexipag and its active metabolite are highly bound (approximately 99%) to plasma protein. Selexipag is hydrolyzed by carboxylesterase 1 to yield its active metabolite, which is approximately 37-fold as potent as selexipag. The exposure at steady-state to the active metabolite is approximately 3- to 4-fold that of selexipag. The volume of distribution of selexipag at steady state is 11.7 L. Elimination of selexipag is predominantly via metabolism. The terminal half-life of selexipag is 0.8 to 2.5 hours, and the terminal half-life of the active metabolite is 6.2 to 13.5 hours. Minimal accumulation of the active metabolite was noted upon twice daily administration, suggesting that the effective half-life is in the range of 3 to 4 hours. In a study of radiolabeled selexipag administered to healthy individuals, approximately 93% of radioactive medication material was found in the feces and 12% in the urine. Neither selexipag nor its active metabolite were found in urine.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8, CYP3A4, UGT1A3, UGT2B7, OATP1B1, OATP1B3, P-glycoprotein (P-gp), BCRP.
Selexipag and its metabolite both undergo oxidative metabolism mainly by CYP2C8 and to a smaller extent by CYP3A4. Glucuronidation of the active metabolite is catalyzed by UGT1A3 and UGT2B7. Selexipag and its metabolite are substrates of OATP1B1 and OATP1B3. Selexipag is a substrate of P-gp, and the active metabolite is a substrate of the breast cancer resistance protein (BCRP). At clinically relevant concentrations, selexipag and its active metabolite do not inhibit or induce cytochrome P450 isoenzymes or hepatic or renal transport proteins.
-Route-Specific Pharmacokinetics
Oral Route
After oral administration, the maximum plasma concentration of selexipag and its active metabolite are reached in approximately 1 to 3 hours and 3 to 4 hours, respectively. The absolute bioavailability of orally administered selexipag is approximately 49%. The absorption of selexipag is prolonged in the presence of food, resulting in a delayed time to peak plasma concentration and a lower (approximately 30%) peak plasma concentration. The exposure to selexipag and the active metabolite did not change significantly in the presence of food.
Intravenous Route
The corresponding oral and intravenous doses provide similar exposure to the active metabolites; however, selexipag exposure is twice as high following intravenous administration compared to oral administration.
-Special Populations
Hepatic Impairment
In patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, the exposure to selexipag was 2- and 4-fold that seen in healthy subjects, respectively. Exposure to the active metabolite was unchanged in patients with mild hepatic impairment and doubled in patients with moderate hepatic impairment. At steady state, the exposure to the active metabolite in patients with moderate hepatic impairment after once daily dosing is expected to be similar to that in healthy subjects receiving twice daily selexipag. The exposure to selexipag at steady state is predicted to be 2-fold higher in patients with moderate hepatic impairment treated with a once daily regimen as compared to healthy subjects and a twice daily regimen.
Renal Impairment
In patients with severe renal impairment (estimated glomerular filtration rate between 15 and 29 mL/minute/m2), a 40 to 70% increase in exposure to selexipag and its active metabolite was observed.
Geriatric
Age has no effect on the pharmacokinetic parameters of selexipag and the active metabolite in patients with pulmonary arterial hypertension. Pharmacokinetic variables were similar in adult and elderly patients up to 75 years of age.
Gender Differences
Gender has no effect on the pharmacokinetic parameters of selexipag and the active metabolite in healthy subjects or patients with pulmonary arterial hypertension.
Ethnic Differences
Race has no effect on the pharmacokinetic parameters of selexipag and the active metabolite in healthy subjects or patients with pulmonary arterial hypertension.
Obesity
Weight has no effect on the pharmacokinetic parameters of selexipag and the active metabolite in healthy subjects or patients with pulmonary arterial hypertension.