Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Apixaban Accord

Apixaban Accord 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 45

HOS-146685 · Präparat HOS-099542

In studies conducted in healthy subjects, as described below, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, or atenolol.

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): atenolol (HOS-087794) digoxin (HOS-086172) naproxen (HOS-087936)

Wechselwirkungen · Apixaban Accord

Apixaban Accord 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 45

HOS-146686 · Präparat HOS-099542

Digoxin Coadministration of apixaban (20 mg once a day) and digoxin (0.25 mg once a day), a P-gp substrate, did not affect digoxin AUC or Cmax. Therefore, apixaban does not inhibit P-gp mediated substrate transport.

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): digoxin (HOS-086172)

Wechselwirkungen · Apixaban Accord

Apixaban Accord 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 45

HOS-146687 · Präparat HOS-099542

Naproxen Coadministration of single doses of apixaban (10 mg) and naproxen (500 mg), a commonly used NSAID, did not have any effect on the naproxen AUC or Cmax.

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): naproxen (HOS-087936)

Wechselwirkungen · Apixaban Accord

Apixaban Accord 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 45

HOS-146688 · Präparat HOS-099542

Atenolol Coadministration of a single dose of apixaban (10 mg) and atenolol (100 mg), a common beta-blocker, did not alter the pharmacokinetics of atenolol.

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): atenolol (HOS-087794)

Wechselwirkungen · Apixaban Accord

Apixaban Accord 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 45

HOS-146689 · Präparat HOS-099542

Activated charcoal Administration of activated charcoal reduces apixaban exposure (see section 4.9).

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): activated charcoal (HOS-085944)

Wechselwirkungen · Apixaban Accord

Apixaban Accord 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 45

HOS-146690 · Präparat HOS-099542

Paediatric population

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

Wechselwirkungen · Apixaban Accord

Apixaban Accord 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 45

HOS-146691 · Präparat HOS-099542

Interaction studies have not been performed in paediatrics. The above mentioned interaction data was obtained in adults and the warnings in section 4.4 should be taken into account for the paediatric population.

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-146652 · Präparat HOS-099542

Summary of the safety profile In adults, the safety of apixaban has been investigated in 7 Phase III clinical studies including more than 21 000 patients: more than 5 000 patients in VTEp studies, more than 11 000 patients in NVAF studies and more than 4 000 patients in the VTE treatment (VTEt) studies, for an average total exposure of 20 days, 1.7 years and 221 days respectively (see section 5.1).

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-146653 · Präparat HOS-099542

Common adverse reactions were haemorrhage, contusion, epistaxis, and haematoma (see Table 3 for adverse reaction profile and frequencies by indication).

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-146654 · Präparat HOS-099542

In the VTEp studies, in total, 11% of the patients treated with apixaban 2.5 mg twice daily experienced adverse reactions. The overall incidence of adverse reactions related to bleeding with apixaban was 10% in the apixaban vs enoxaparin studies.

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-146655 · Präparat HOS-099542

In the NVAF studies, the overall incidence of adverse reactions related to bleeding with apixaban was 24.3% in the apixaban vs warfarin study and 9.6% in the apixaban vs acetylsalicylic acid study. In the apixaban vs warfarin study the incidence of ISTH major gastrointestinal bleeds (including upper GI, lower GI, and rectal bleeding) with apixaban was 0.76%/year. The incidence of ISTH major intraocular bleeding with apixaban was 0.18%/year.

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13–14

HOS-146656 · Präparat HOS-099542

13 In the VTEt studies, the overall incidence of adverse reactions related to bleeding with apixaban was 15.6% in the apixaban vs enoxaparin/warfarin study and 13.3% in the apixaban vs placebo study (see section 5.1).

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-146657 · Präparat HOS-099542

Tabulated list of adverse reactions Table 3 shows the adverse reactions ranked under headings of system organ class and frequency using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data) in aults for VTEp, NVAF, and VTEt and in paediatric patients from 28 days to < 18 years of age for VTEt and prevention of recurrent VTE.

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-146658 · Präparat HOS-099542

The frequencies of adverse reactions reported in Table 3 for paediatric patients are derived from study CV185325, in which they received apixaban for treatment of VTE and prevention of recurrent VTE.

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-146659 · Präparat HOS-099542

Table 3: Tabulated adverse reactions System organ class Prevention of Prevention of Treatment of Treatment of VTE in adult stroke and DVT and PE, VTE and patients who systemic and prevention prevention of have embolism in of recurrent recurrent undergone adult patients DVT and PE VTE in elective hip or with NVAF, (VTEt) in adult paediatric knee with one or patients patients from replacement more risk 28 days to surgery factors less than (VTEp) (NVAF) 18 years of age Blood and lymphatic system disorders Anaemia Common Common Common Common Thrombocytopenia Uncommon Uncommon Common Common Immune system disorders Hypersensitivity, allergic oedema Rare Uncommon Uncommon Common‡ and anaphylaxis Pruritus Uncommon Uncommon Uncommon* Common Angioedema Not known Not known Not known Not known Nervous system disorders Brain haemorrhage† Not known Uncommon Rare Not known Eye disorders Eye haemorrhage (including Rare Common Uncommon Not known conjunctival haemorrhage) Vascular disorders Haemorrhage, haematoma Common Common Common Common Hypotension (including Uncommon Common Uncommon Common procedural hypotension) Intra-abdominal haemorrhage Not known Uncommon Not known Not known Respiratory, thoracic and mediastinal disorders Epistaxis Uncommon Common Common Very common Haemoptysis Rare Uncommon Uncommon Not known Respiratory tract haemorrhage Not known Rare Rare Not known Gastrointestinal disorders Nausea Common Common Common Common Gastrointestinal haemorrhage Uncommon Common Common Not known Haemorrhoidal haemorrhage Not known Uncommon Uncommon Not known Mouth haemorrhage Not known Uncommon Common Not known

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14–15

HOS-146660 · Präparat HOS-099542

14 System organ class Prevention of Prevention of Treatment of Treatment of VTE in adult stroke and DVT and PE, VTE and patients who systemic and prevention prevention of have embolism in of recurrent recurrent undergone adult patients DVT and PE VTE in elective hip or with NVAF, (VTEt) in adult paediatric knee with one or patients patients from replacement more risk 28 days to surgery factors less than (VTEp) (NVAF) 18 years of age Haematochezia Uncommon Uncommon Uncommon Common Rectal haemorrhage, gingival Rare Common Common Common bleeding Retroperitoneal haemorrhage Not known Rare Not known Not known Hepatobiliary disorders Liver function test abnormal, Uncommon Uncommon Uncommon Common aspartate aminotransferase increased, blood alkaline phosphatase increased, blood bilirubin increased Gamma-glutamyltransferase Uncommon Common Common Not known increased Alanine aminotransferase Uncommon Uncommon Common Common increased Skin and subcutaneous tissue disorders Skin rash Not known Uncommon Common Common Alopecia Rare Uncommon Uncommon Common Erythema multiforme Not known Very rare Not known Not known Cutaneous vasculitis Not known Not known Not known Not known Musculoskeletal and connective tissue disorders Muscle haemorrhage Rare Rare Uncommon Not known Renal and urinary disorders Haematuria Uncommon Common Common Common Anticoagulant-related Not known Not known Not known Not known nephropathy Reproductive system and breast disorders Abnormal vaginal haemorrhage, Uncommon Uncommon Common Very urogenital haemorrhage common§ General disorders and administration site conditions Application site bleeding Not known Uncommon Uncommon Not known Investigations Occult blood positive Not known Uncommon Uncommon Not known Injury, poisoning and procedural complications Contusion Common Common Common Common

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15–16

HOS-146661 · Präparat HOS-099542

15  System organ class Prevention of Prevention of Treatment of Treatment of VTE in adult stroke and DVT and PE, VTE and patients who systemic and prevention prevention of have embolism in of recurrent recurrent undergone adult patients DVT and PE VTE in elective hip or with NVAF, (VTEt) in adult paediatric knee with one or patients patients from replacement more risk 28 days to surgery factors less than (VTEp) (NVAF) 18 years of age Post procedural haemorrhage Uncommon Uncommon Uncommon Common (including post procedural haematoma, wound haemorrhage, vessel puncture site haematoma and catheter site haemorrhage), wound secretion, incision site haemorrhage (including incision site haematoma), operative haemorrhage Traumatic haemorrhage Not known Uncommon Uncommon Not known * There were no occurrences of generalised pruritus in CV185057 (long term prevention of VTE). † The term “Brain haemorrhage” encompasses all intracranial or intraspinal haemorrhages (i.e., haemorrhagic stroke or putamen, cerebellar, intraventricular, or subdural haemorrhages). ‡ Includes anaphylactic reaction, drug hypersensitivity, and hypersensitivity. § Includes heavy menstrual bleeding, intermenstrual bleeding, and vaginal haemorrhage.

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 16

HOS-146662 · Präparat HOS-099542

The use of apixaban may be associated with an increased risk of occult or overt bleeding from any tissue or organ, which may result in posthaemorrhagic anaemia. The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding (see sections 4.4 and 5.1).

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 16

HOS-146663 · Präparat HOS-099542

Paediatric population

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

Nebenwirkungen · Apixaban Accord

Apixaban Accord 2.5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 16

HOS-146664 · Präparat HOS-099542

The safety of apixaban has been investigated in 1 Phase I and 3 Phase II/III clinical studies including 970 patients. Of these patients, 568 patients received one or more doses of apixaban for average total exposure of 1, 24, 331 and 80 days, respectively (see section 5.1). The patients received weight adjusted doses of an age-appropriate formulation of apixaban.

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