Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.3 · PDF-Seite 5

HOS-131247 · Präparat HOS-097037

 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  Severe coronary heart disease or unstable angina.  Myocardial infarction within the last 6 months.  Decompensated cardiac failure if not under close medical supervision.  Severe arrhythmias.  Cerebrovascular events (e.g., transient ischaemic attack, stroke) within the last 3 months.  Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension.  Concomitant use of strong inhibitors of CYP2C8 (e.g., gemfibrozil; see section 4.5).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): gemfibrozil (HOS-088403)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-131248 · Präparat HOS-097037

Effect of other medicinal products on selexipag

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-131249 · Präparat HOS-097037

Selexipag is hydrolysed to its active metabolite by carboxylesterases (see section 5.2). Selexipag and its active metabolite both undergo oxidative metabolism mainly by CYP2C8 and to a smaller extent by CYP3A4. The glucuronidation of the active metabolite is catalysed by UGT1A3 and UGT2B7. Selexipag and its active metabolite are substrates of OATP1B1 and OATP1B3. Selexipag is a weak substrate of the P-gp efflux pump. The active metabolite is a weak substrate of the breast cancer resistance protein (BCRP).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 6–7

HOS-131250 · Präparat HOS-097037

6 The pharmacokinetics of selexipag and its active metabolite are not affected by warfarin.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): warfarin (HOS-085950)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-131251 · Präparat HOS-097037

Inhibitors of CYP2C8 In the presence of 600 mg gemfibrozil, twice a day, a strong inhibitor of CYP2C8, exposure to selexipag increased approximately 2-fold, whereas exposure to the active metabolite, the major contributor to efficacy, increased approximately 11-fold. Concomitant administration of Uptravi with strong inhibitors of CYP2C8 (e.g., gemfibrozil) is contraindicated (see section 4.3).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): gemfibrozil (HOS-088403)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-131252 · Präparat HOS-097037

Concomitant administration of Uptravi with clopidogrel (loading dose of 300 mg or maintenance dose of 75 mg once a day), a moderate inhibitor of CYP2C8, had no relevant effect on the exposure to selexipag but increased the exposure to the active metabolite approximately 2.2 and 2.7-fold following loading dose and maintenance dose, respectively. The total daily dose of Uptravi should be decreased by reducing each dose to half when co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox, teriflunomide). Alternatively, a once daily dosing frequency to achieve half of the daily dose of Uptravi may be continued in patients already well controlled on a once daily dosing regimen or may be applied in patients for whom the appropriate dose strength(s) supporting twice daily dosing with half the dose is not available. When co-administration of a moderate CYP2C8 inhibitor is stopped increase the total daily dose of Uptravi, as applicable. The maximum dose of 1 600 micrograms twice daily should not be exceeded (see section 4.2).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): deferasirox (HOS-088409) teriflunomide (HOS-089632) clopidogrel (HOS-087927)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-131254 · Präparat HOS-097037

Inducers of CYP2C8 In the presence of 600 mg rifampicin, once a day, an inducer of CYP2C8 (and UGT enzymes), the exposure to selexipag did not change, whereas exposure to the active metabolite was reduced by half. Dose adjustment of selexipag may be required with concomitant administration of inducers of CYP2C8 (e.g., rifampicin, carbamazepine, phenytoin).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): carbamazepine (HOS-085618) phenytoin (HOS-084531)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-131255 · Präparat HOS-097037

Inhibitors of UGT1A3 and UGT2B7 The effect of strong inhibitors of UGT1A3 and UGT2B7 (valproic acid, probenecid, and fluconazole) on the exposure to selexipag and its active metabolite has not been studied. Caution is required when administering these medicinal products concomitantly with Uptravi. A potential pharmacokinetic interaction with strong inhibitors of UGT1A3 and UGT2B7 cannot be excluded.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): valproic acid (HOS-088515) fluconazole (HOS-087945) probenecid (HOS-085208)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-131256 · Präparat HOS-097037

Inhibitors and inducers of CYP3A4 In the presence of 400 mg/100 mg lopinavir/ritonavir twice daily, a strong CYP3A4 inhibitor, exposure to selexipag increased approximately 2-fold, whereas the exposure to the active metabolite of selexipag did not change. Given the 37-fold higher potency of the active metabolite, this effect is not clinically relevant. Since a strong inhibitor of CYP3A4 did not affect the pharmacokinetics of the active metabolite, indicating that the CYP3A4 pathway is not important in the elimination of the active metabolite, no effect of inducers of CYP3A4 on the pharmacokinetics of the active metabolite is expected.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): lopinavir (HOS-086269) ritonavir (HOS-084521)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-131257 · Präparat HOS-097037

PAH-specific therapies In the phase 3 placebo-controlled trial in patients with PAH, the use of selexipag in combination with both an ERA and a PDE-5 inhibitor resulted in a 30% lower exposure to the active metabolite.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-131258 · Präparat HOS-097037

Transporter inhibitors (lopinavir/ritonavir) In the presence of 400 mg/100 mg lopinavir/ritonavir twice daily, a strong OATP (OATP1B1 and OATP1B3) and P-gp inhibitor, exposure to selexipag increased approximately 2-fold, whereas the exposure to the active metabolite of selexipag did not change. Given that the majority of the pharmacological effect is driven by the active metabolite, this effect is not clinically relevant.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): lopinavir (HOS-086269) ritonavir (HOS-084521)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-131259 · Präparat HOS-097037

Effect of selexipag on other medicinal products

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-131260 · Präparat HOS-097037

Selexipag and its active metabolite do not inhibit or induce cytochrome P450 enzymes and transport proteins at clinically relevant concentrations.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 7–8

HOS-131261 · Präparat HOS-097037

7 Anticoagulants or inhibitors of platelet aggregation Selexipag is an inhibitor of platelet aggregation in vitro. In the phase 3 placebo-controlled study in patients with PAH, no increased risk of bleeding was detected with selexipag compared to placebo, including when selexipag was administered with anticoagulants (such as heparin, coumarin-type anticoagulants) or inhibitors of platelet aggregation. In a study in healthy subjects, selexipag (400 micrograms twice daily) did not alter the exposure to S-warfarin (CYP2C9 substrate) or R-warfarin (CYP3A4 substrate) after a single dose of 20 mg warfarin. Selexipag did not influence the pharmacodynamic effect of warfarin on the international normalised ratio.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): placebo (HOS-088378) heparin (HOS-086930) warfarin (HOS-085950)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-131262 · Präparat HOS-097037

Midazolam At steady state after up-titration to 1 600 micrograms selexipag twice a day, no clinically relevant change in exposure to midazolam, a sensitive intestinal and hepatic CYP3A4 substrate, or its metabolite, 1-hydroxymidazolam, was observed. Concomitant administration of selexipag with CYP3A4 substrates does not require dose adjustment.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): midazolam (HOS-086167)

Wechselwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-131263 · Präparat HOS-097037

Hormonal contraceptives Specific drug-drug interaction studies with hormonal contraceptives have not been conducted. Since selexipag did not affect the exposure to the CYP3A4 substrates midazolam and R-warfarin or to the CYP2C9 substrate S-warfarin, reduced efficacy of hormonal contraceptives is not expected.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): warfarin (HOS-085950) midazolam (HOS-086167)

Nebenwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-131264 · Präparat HOS-097037

Summary of the safety profile

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-131265 · Präparat HOS-097037

The most commonly reported adverse reactions are headache, diarrhoea, nausea and vomiting, jaw pain, myalgia, pain in extremity, arthralgia, and flushing. These reactions are more frequent during the up-titration phase. The majority of these reactions are of mild to moderate intensity.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-131266 · Präparat HOS-097037

The safety of selexipag has been evaluated in a long-term, phase 3 placebo-controlled study enrolling 1 156 adult patients with symptomatic PAH (GRIPHON study). The mean treatment duration was 76.4 weeks (median 70.7 weeks) for patients receiving selexipag versus 71.2 weeks (median 63.7 weeks) for patients on placebo. The exposure to selexipag was up to 4.2 years.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Uptravi

Uptravi 100 microgram film-coated tablets Uptravi 200 microgram film-coated tablets Uptravi 400 microgram film-coated tablets Uptravi 600 microgram film-coated tablets Uptravi 800 microgram film-coated tablets Uptravi 1 000 microgram film-coated tablets Uptravi 1 200 microgram film-coated tablets Uptravi 1 400 microgram film-coated tablets Uptravi 1 600 microgram film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-131267 · Präparat HOS-097037

Tabulated list of adverse reactions

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.