Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.3 · PDF-Seite 6

HOS-118621 · Präparat HOS-094855

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 • Severe renal impairment (CrCL < 30 mL/min) in adult patients • eGFR < 50 mL/min/1.73 m2 in paediatric patients • Active clinically significant bleeding • Lesion or condition, if considered a significant risk factor for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities • Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin etc), heparin derivatives (fondaparinux etc), oral anticoagulants (warfarin, rivaroxaban, apixaban etc) except under specific circumstances. These are switching anticoagulant therapy (see section 4.2), when UFH is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fibrillation (see section 4.5) • Hepatic impairment or liver disease expected to have any impact on survival • Concomitant treatment with the following strong P-gp inhibitors: systemic ketoconazole, cyclosporine, itraconazole, dronedarone and the fixed-dose combination glecaprevir/pibrentasvir (see section 4.5) • Prosthetic heart valves requiring anticoagulant treatment (see section 5.1). 6

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): dronedarone (HOS-086144) ketoconazole (HOS-084513) pibrentasvir (HOS-086298) fondaparinux (HOS-110096) glecaprevir (HOS-086297) heparin (HOS-086930) rivaroxaban (HOS-086236) itraconazole (HOS-084516) apixaban (HOS-112091) cyclosporine (HOS-084512) enoxaparin (HOS-118623) dalteparin (HOS-118624) warfarin (HOS-085950)

Gegenanzeigen · Pradaxa

Pradaxa 110 mg hard capsules · Abschnitt 4.3 · PDF-Seite 38

HOS-118700 · Präparat HOS-094855

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 • Severe renal impairment (CrCL < 30 mL/min) in adult patients • eGFR < 50 mL/min/1.73 m2 in paediatric patients • Active clinically significant bleeding • Lesion or condition, if considered a significant risk factor for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of

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

Gegenanzeigen · Pradaxa

Pradaxa 110 mg hard capsules · Abschnitt 4.3 · PDF-Seite 38–39

HOS-118701 · Präparat HOS-094855

38  bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities • Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin etc), heparin derivatives (fondaparinux etc), oral anticoagulants (warfarin, rivaroxaban, apixaban etc) except under specific circumstances. These are switching anticoagulant therapy (see section 4.2), when UFH is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fibrillation (see section 4.5) • Hepatic impairment or liver disease expected to have any impact on survival • Concomitant treatment with the following strong P-gp inhibitors: systemic ketoconazole, cyclosporine, itraconazole, dronedarone and the fixed-dose combination glecaprevir/pibrentasvir (see section 4.5) • Prosthetic heart valves requiring anticoagulant treatment (see section 5.1).

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): dronedarone (HOS-086144) ketoconazole (HOS-084513) pibrentasvir (HOS-086298) fondaparinux (HOS-110096) glecaprevir (HOS-086297) heparin (HOS-086930) rivaroxaban (HOS-086236) itraconazole (HOS-084516) apixaban (HOS-112091) cyclosporine (HOS-084512) enoxaparin (HOS-118623) dalteparin (HOS-118624) warfarin (HOS-085950)

Gegenanzeigen · Pradaxa

Pradaxa 150 mg hard capsules · Abschnitt 4.3 · PDF-Seite 78

HOS-118788 · Präparat HOS-094855

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 • Severe renal impairment (CrCL < 30 mL/min) in adult patients • eGFR < 50 mL/min/1.73 m2 in paediatric patients • Active clinically significant bleeding • Lesion or condition, if considered a significant risk factor for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of

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

Gegenanzeigen · Pradaxa

Pradaxa 150 mg hard capsules · Abschnitt 4.3 · PDF-Seite 78–79

HOS-118789 · Präparat HOS-094855

78  bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities • Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin etc), heparin derivatives (fondaparinux etc), oral anticoagulants (warfarin, rivaroxaban, apixaban etc) except under specific circumstances. These are switching anticoagulant therapy (see section 4.2), when UFH is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fibrillation (see section 4.5) • Hepatic impairment or liver disease expected to have any impact on survival • Concomitant treatment with the following strong P-gp inhibitors: systemic ketoconazole, cyclosporine, itraconazole, dronedarone and the fixed-dose combination glecaprevir/pibrentasvir (see section 4.5) • Prosthetic heart valves requiring anticoagulant treatment (see section 5.1).

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): dronedarone (HOS-086144) ketoconazole (HOS-084513) pibrentasvir (HOS-086298) fondaparinux (HOS-110096) glecaprevir (HOS-086297) heparin (HOS-086930) rivaroxaban (HOS-086236) itraconazole (HOS-084516) apixaban (HOS-112091) cyclosporine (HOS-084512) enoxaparin (HOS-118623) dalteparin (HOS-118624) warfarin (HOS-085950)

Gegenanzeigen · Pradaxa

Pradaxa 20 mg coated granules Pradaxa 30 mg coated granules Pradaxa 40 mg coated granules Pradaxa 50 mg coated granules Pradaxa 110 mg coated granules Pradaxa 150 mg coated granules · Abschnitt 4.3 · PDF-Seite 113

HOS-118874 · Präparat HOS-094855

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 • eGFR < 50 mL/min/1.73 m2 in paediatric patients • Active clinically significant bleeding • Lesion or condition, if considered a significant risk factor for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent

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

Gegenanzeigen · Pradaxa

Pradaxa 20 mg coated granules Pradaxa 30 mg coated granules Pradaxa 40 mg coated granules Pradaxa 50 mg coated granules Pradaxa 110 mg coated granules Pradaxa 150 mg coated granules · Abschnitt 4.3 · PDF-Seite 113–114

HOS-118875 · Präparat HOS-094855

113  intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities • Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin etc), heparin derivatives (fondaparinux etc), oral anticoagulants (warfarin, rivaroxaban, apixaban etc) except under specific circumstances. These are switching anticoagulant therapy (see section 4.2) or when UFH is given at doses necessary to maintain an open central venous or arterial catheter (see section 4.5). • Hepatic impairment or liver disease expected to have any impact on survival • Concomitant treatment with the following strong P-gp inhibitors: systemic ketoconazole, cyclosporine, itraconazole, dronedarone and the fixed-dose combination glecaprevir/pibrentasvir (see section 4.5) • Prosthetic heart valves requiring anticoagulant treatment (see section 5.1).

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): dronedarone (HOS-086144) ketoconazole (HOS-084513) pibrentasvir (HOS-086298) fondaparinux (HOS-110096) glecaprevir (HOS-086297) heparin (HOS-086930) rivaroxaban (HOS-086236) itraconazole (HOS-084516) apixaban (HOS-112091) cyclosporine (HOS-084512) enoxaparin (HOS-118623) dalteparin (HOS-118624) warfarin (HOS-085950)

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-118626 · Präparat HOS-094855

Transporter interactions

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

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-118627 · Präparat HOS-094855

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of P-gp inhibitors (see table 7) is expected to result in increased dabigatran plasma concentrations.

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): dabigatran (HOS-112096)

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-118628 · Präparat HOS-094855

If not otherwise specifically described, close clinical surveillance (looking for signs of bleeding or anaemia) is required when dabigatran is co-administered with strong P-gp inhibitors. Dose reductions may be required in combination with some P-gp inhibitors (see sections 4.2, 4.3, 4.4 and 5.1).

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): dabigatran (HOS-112096)

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-118629 · Präparat HOS-094855

Table 7: Transporter interactions

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

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-118630 · Präparat HOS-094855

P-gp inhibitors

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

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-118631 · Präparat HOS-094855

Concomitant use contraindicated (see section 4.3)

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

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11

HOS-118632 · Präparat HOS-094855

Ketoconazole Ketoconazole increased total dabigatran AUC0-∞ and Cmax values by 2.38-fold and 2.35-fold, respectively, after a single oral dose of 400 mg, and by 2.53-fold and 2.49-fold, respectively, after multiple oral dosing of 400 mg ketoconazole once daily. Dronedarone When dabigatran etexilate and dronedarone were given at the same time total dabigatran AUC0-∞ and Cmax values increased by about 2.4-fold and 2.3-fold, respectively, after multiple dosing of 400 mg dronedarone bid, and about 2.1-fold and 1.9-fold, respectively, after a single dose of 400 mg. Itraconazole, Based on in vitro results a similar effect as with ketoconazole may be expected. cyclosporine Glecaprevir / The concomitant use of dabigatran etexilate with the fixed-dose combination of pibrentasvir the P-gp inhibitors glecaprevir/pibrentasvir has been shown to increase exposure of dabigatran and may increase the risk of bleeding.

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): dronedarone (HOS-086144) ketoconazole (HOS-084513) pibrentasvir (HOS-086298) glecaprevir (HOS-086297) dabigatran (HOS-112096) itraconazole (HOS-084516) cyclosporine (HOS-084512)

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 11–12

HOS-118633 · Präparat HOS-094855

11 Concomitant use not recommended

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

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 12

HOS-118634 · Präparat HOS-094855

Tacrolimus Tacrolimus has been found in vitro to have a similar level of inhibitory effect on P-gp as that seen with itraconazole and cyclosporine. Dabigatran etexilate has not been clinically studied together with tacrolimus. However, limited clinical data with another P-gp substrate (everolimus) suggest that the inhibition of P-gp with tacrolimus is weaker than that observed with strong P-gp inhibitors.

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): itraconazole (HOS-084516) tacrolimus (HOS-085202) everolimus (HOS-086310) cyclosporine (HOS-084512)

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 12

HOS-118635 · Präparat HOS-094855

Cautions to be exercised in case concomitant use (see sections 4.2 and 4.4)

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

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 12

HOS-118636 · Präparat HOS-094855

Verapamil When dabigatran etexilate (150 mg) was co-administered with oral verapamil, the Cmax and AUC of dabigatran were increased but the magnitude of this change differs depending on timing of administration and formulation of verapamil (see sections 4.2 and 4.4).

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): dabigatran (HOS-112096) verapamil (HOS-090602)

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 12

HOS-118637 · Präparat HOS-094855

The greatest elevation of dabigatran exposure was observed with the first dose of an immediate release formulation of verapamil administered one hour prior to the dabigatran etexilate intake (increase of Cmax by about 2.8-fold and AUC by about 2.5-fold). The effect was progressively decreased with administration of an extended release formulation (increase of Cmax by about 1.9-fold and AUC by about 1.7-fold) or administration of multiple doses of verapamil (increase of Cmax by about 1.6-fold and AUC by about 1.5-fold).

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): dabigatran (HOS-112096) verapamil (HOS-090602)

Wechselwirkungen · Pradaxa

Pradaxa 75 mg hard capsules · Abschnitt 4.5 · PDF-Seite 12

HOS-118638 · Präparat HOS-094855

There was no meaningful interaction observed when verapamil was given 2 hours after dabigatran etexilate (increase of Cmax by about 1.1-fold and AUC by about 1.2-fold). This is explained by completed dabigatran absorption after 2 hours. Amiodarone When dabigatran etexilate was co-administered with a single oral dose of 600 mg amiodarone, the extent and rate of absorption of amiodarone and its active metabolite DEA were essentially unchanged. The dabigatran AUC and Cmax were increased by about 1.6-fold and 1.5-fold, respectively. In view of the long half-life of amiodarone the potential for an interaction may exist for weeks after discontinuation of amiodarone (see sections 4.2 and 4.4). Quinidine Quinidine was given as 200 mg dose every 2nd hour up to a total dose of 1 000 mg. Dabigatran etexilate was given twice daily over 3 consecutive days, on the 3rd day either with or without quinidine. Dabigatran AUCτ,ss and Cmax,ss were increased on average by 1.53-fold and 1.56-fold, respectively with concomitant quinidine (see sections 4.2 and 4.4). Clarithromycin When clarithromycin (500 mg twice daily) was administered together with dabigatran etexilate in healthy volunteers, increase of AUC by about 1.19-fold and Cmax by about 1.15-fold was observed. Ticagrelor When a single dose of 75 mg dabigatran etexilate was coadministered simultaneously with a loading dose of 180 mg ticagrelor, the dabigatran AUC and Cmax were increased by 1.73-fold and 1.95-fold, respectively. After multiple doses of ticagrelor 90 mg b.i.d. the increase of dabigatran exposure is 1.56-fold and 1.46-fold for Cmax and AUC, respectively.

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): ticagrelor (HOS-112065) quinidine (HOS-085593) dabigatran (HOS-112096) clarithromycin (HOS-084517) amiodarone (HOS-085596) verapamil (HOS-090602)