selexipag (Rx)

Brand and Other Names:Uptravi
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

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

Pulmonary Arterial Hypertension (PAH) Disease Progression

To delay disease and reduce risk of hospitalization for PAH (WHO Group I): 200 mcg PO BID, initially

Increase dose by 200 mcg BID, at weekly intervals (usually), to highest tolerated dose; not to exceed 1600 mcg BID

If dose not tolerated, reduce to the previous tolerated dose

Dosage Modifications

Renal impairment

  • eGFR >15 mL/min/1.73 m2: No dosage adjustment required
  • eGFR <15 mL/min/1.73 m2 or patients undergoing dialysis: No clinical experience

Hepatic impairment

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

Coadministration with moderate CYP2C8 inhibitors

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

Coadministration with CYP2C8 inducers

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

Dosage Considerations

Effectiveness was established in a long-term study in patients with PAH with WHO Functional Class II-III symptoms

Patients had idiopathic and heritable PAH (58%), PAH associated with connective-tissue disease (29%), or PAH associated with congenital heart disease with repaired shunts (10%)

Chronic Thromboembolic Pulmonary Hypertension (Orphan)

Orphan designation for chronic thromboembolic pulmonary hypertension

Orphan sponsor

  • Janssen Research & Development LLC; 1820 Chapel Ave West, Suite 300; Cherry Hill, New Jersey 08002

Safety and efficacy not established

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Interactions

Interaction Checker

and selexipag

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Headache (65%)

            Diarrhea (42%)

            Jaw pain (26%)

            Nausea (33%)

            Vomiting (18%)

            Pain in extremity (17%)

            Myalgia (16%)

            Flushing (12%)

            Arthralgia (11%)

            Rash (11%)

            1-10%

            Hemoglobin decreased below 10 g/dL (8.6%)

            Anemia (8%)

            Decreased appetite (6%)

            Frequency Not Defined

            TSH reduced (up to −0.3 MU/L from a baseline of 2.5 MU/L)

            Symptomatic hypotension

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            Warnings

            Contraindications

            Concomitant use of strong CYP2C8 inhibitors (eg, gemfibrozil)

            Cautions

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

            Drug interaction overview

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

            Pregnancy

            No adequate and well-controlled studies with selexipag exist in pregnant women

            Animal studies

            • Reproduction studies performed with selexipag showed no clinically relevant effects on embryofetal development and survival
            • A slight reduction in maternal as well as in fetal body weight was observed when pregnant rats were administered selexipag during organogenesis at a dose producing an exposure ~47 times that in humans at the maximum recommended human dose

            Lactation

            Unknown if distributed in human breast milk

            Selexipag or its metabolites were present in the milk of rats

            Because many drugs are present in the human milk and because of the potential for serious adverse reactions in nursing infants, discontinue nursing or discontinue selexipag

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Selectively activates the prostacyclin receptor (ie, IP-receptor), one of 5 types of prostanoid receptors

            Unlike prostacyclin analogs, selexipag is selective for the IP receptor over other prostanoid receptors (ie, EP1-4, DP, FP, TP)

            Activating the IP receptor induces vasodilation and inhibits proliferation of vascular smooth muscle cells

            Absorption

            Peak plasma time: 1-3 hr; 3-4 hr (active metabolite)

            Distribution

            Protein bound: ~99% (albumin and alpha1-acid glycoprotein)

            Metabolism

            Undergoes enzymatic hydrolysis of the acylsulfonamide by hepatic carboxylesterase 1, to yield the active metabolite, which is ~37-fold as potent as selexipag

            Elimination

            Half-life: 0.8-2.5 hr; 6.2-13.5 hr (active metabolite)

            Oral clearance: 35 L/hr

            Excretion: 93% in feces; neither selexipag nor its metabolite were found in urine

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            Administration

            Oral Administration

            Swallow tablet whole; do not split, crush, or chew

            Tolerability may be improved when taken with food

            Dose interruptions and discontinuations

            • If a dose is missed, patients should take a missed dose as soon as possible unless the next dose is within the next 6 hr
            • If treatment is missed for ≥3 days, restart selexipag at a lower dose and then titrate to desired effect and tolerance

            Storage

            Store at 20-25ºC (68-77ºF)

            Excursions permitted between 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.