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  • CLASSES

    Prostacyclin Analogs/Receptor Agonists for PAH

    DEA CLASS

    Rx

    DESCRIPTION

    Selective prostacyclin receptor agonist
    For treatment of pulmonary arterial hypertension (WHO Group I)
    Delays disease progression and reduces risk of hospitalization

    COMMON BRAND NAMES

    UPTRAVI

    HOW SUPPLIED

    Selexipag Intravenous Inj Pwd: 1800mcg
    UPTRAVI Oral Tab: 200mcg, 400mcg, 600mcg, 800mcg, 1000mcg, 1200mcg, 1400mcg, 1600mcg, 200-800mcg

    DOSAGE & INDICATIONS

    For the treatment of pulmonary hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization.
    For use in patients temporarily unable to take oral therapy.
    Intravenous dosage
    Adults

    Intravenous dose corresponds to patient's current oral selexipag dose. For patients taking 200 mcg PO twice daily, give 225 mcg IV twice daily. For patients taking 400 mcg PO twice daily, give 450 mcg IV twice daily. For patients taking 600 mcg PO twice daily, give 675 mcg IV twice daily. For patients taking 800 mcg PO twice daily, give 900 mcg IV twice daily. For patients taking 1,000 mcg PO twice daily, give 1,125 mcg IV twice daily. For patients taking 1,200 mcg PO twice daily, give 1,350 mcg IV twice daily. For patients taking 1,400 mcg PO twice daily, give 1,575 mcg IV twice daily. For patients taking 1,600 mcg PO twice daily, give 1,800 mcg IV twice daily. Administer the IV infusion over 80 minutes.

    Oral dosage
    Adults

    200 mcg PO twice daily. Increase the dose by 200 mcg PO twice daily at weekly intervals to the highest tolerated dose up to 1600 mcg PO twice daily. If the patient reaches a dose that cannot be tolerated, reduce the dose to the previously tolerated 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.

    MAXIMUM DOSAGE

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    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.

    Renal Impairment

    CrCl more than 15 mL/min/1.73 m2: No dosage adjustments needed.
    CrCl less than 15 mL/min/1.73 m2: There are no data.
     
    Intermittent hemodialysis
    There are no data in patients undergoing dialysis.

    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.

    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.

    STORAGE

    UPTRAVI:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion 4 hours after initial puncture of container
    - Discard unused portion. Do not store for later use.
    - Protect from direct sunlight
    - Protect from heat
    - See package insert for detailed storage information
    - Store in a cool, well ventilated, dry place
    - Store in refrigerator at 2 to 8 degrees C (36 to 46 degrees F)
    - Store in the original carton to protect from light

    CONTRAINDICATIONS / PRECAUTIONS

    Pregnancy

    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.

    Breast-feeding

    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.

    Hepatic disease

    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.

    ADVERSE REACTIONS

    Severe

    veno-occlusive disease (VOD) / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known

    Moderate

    anemia / Delayed / 8.6-8.6
    hyperthyroidism / Delayed / 1.0-1.0
    hypotension / Rapid / Incidence not known
    erythema / Early / Incidence not known

    Mild

    headache / Early / 65.0-65.0
    diarrhea / Early / 42.0-42.0
    nausea / Early / 33.0-33.0
    vomiting / Early / 18.0-18.0
    myalgia / Early / 16.0-16.0
    flushing / Rapid / 12.0-12.0
    arthralgia / Delayed / 11.0-11.0
    rash / Early / 11.0-11.0
    anorexia / Delayed / 6.0-6.0
    injection site reaction / Rapid / Incidence not known

    DRUG INTERACTIONS

    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; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (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; Dichloralphenazone; Isometheptene: (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; 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; Carbetapentane; 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; 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; Hydrocodone; 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; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; Phenylephrine; Pyrilamine: (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.
    Carbetapentane; 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.
    Carbinoxamine; 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.
    Carbinoxamine; Hydrocodone; 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.
    Carbinoxamine; Hydrocodone; 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.
    Carbinoxamine; 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.
    Carbinoxamine; 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.
    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.
    Chlophedianol; 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.
    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; Dihydrocodeine; 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; Dihydrocodeine; 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; Guaifenesin; Hydrocodone; 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; Hydrocodone; 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; Hydrocodone; 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 selexipag dose to once daily when coadministered with clopidogrel due to increased exposure to the active metabolite of selexipag, which may cause side effects. Selexipag is a CYP2C8 substrate, and clopidogrel is a CYP2C8 inhibitor.
    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.
    Dihydrocodeine; 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.
    Diphenhydramine; Hydrocodone; 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.
    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; Hydrocodone; 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.
    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.
    Hydrocodone; 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.
    Hydrocodone; Potassium Guaiacolsulfonate; 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.
    Hydrocodone; 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.
    Mepivacaine; Levonordefrin: (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.
    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.
    Pemoline: (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.
    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.
    Ritodrine: (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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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, neither selexipag nor its active metabolite was found in urine.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8, CYP3A4, UGT1A3, UGT2B7, OATP1B1, OATP1B3, 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-glycoprotein (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.

    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.