Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-126684 · Präparat HOS-096301

Description of selected adverse reactions

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-126685 · Präparat HOS-096301

Alopecia Alopecia was reported as hair thinning, decreased hair density, hair loss, associated or not with hair texture change, in 13.9% of patients treated with 14 mg teriflunomide versus 5.1% in patients treated with placebo. Most cases were described as diffuse or generalised over the scalp (no complete hair loss reported) and occurred most often during the first 6 months and with resolution in 121 of 139 (87.1%) patients treated with teriflunomide 14 mg. Discontinuation because of alopecia was 1.3% in the teriflunomide 14 mg teriflunomide group, versus 0.1% in the placebo group.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-126686 · Präparat HOS-096301

Hepatic effects During placebo-controlled studies in adult patients the following was detected:

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12–13

HOS-126687 · Präparat HOS-096301

ALT increase (based on laboratory data) according to baseline status - Safety population in placebo-controlled studies Placebo Teriflunomide 14 mg (N=997) (N=1002) >3 ULN 66/994 (6.6%) 80/999 (8.0%) >5 ULN 37/994 (3.7%) 31/999 (3.1%) >10 ULN 16/994 (1.6%) 9/999 (0.9%) 12  ALT increase (based on laboratory data) according to baseline status - Safety population in placebo-controlled studies Placebo Teriflunomide 14 mg (N=997) (N=1002) >20 ULN 4/994 (0.4%) 3/999 (0.3%) ALT >3 ULN and TBILI >2 ULN 5/994 (0.5%) 3/999 (0.3%)

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-126688 · Präparat HOS-096301

Mild increases in transaminase, ALT below or equal to 3-fold ULN were more frequently seen in teriflunomide-treated groups as compared to placebo. The frequency of elevations above 3-fold ULN and higher was balanced across treatment groups. These elevations in transaminase occurred mostly within the first 6 months of treatment and were reversible after treatment cessation. The recovery time varied between months and years.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-126689 · Präparat HOS-096301

Blood pressure effects In placebo-controlled studies in adult patients the following was established: - systolic blood pressure was >140 mm Hg in 19.9% of patients receiving 14 mg/day teriflunomide as compared to 15.5% receiving placebo; - systolic blood pressure was >160 mm Hg in 3.8% of patients receiving 14 mg/day teriflunomide as compared to 2.0% receiving placebo; - diastolic blood pressure was >90 mm Hg in 21.4% of patients receiving 14 mg/day teriflunomide as compared to 13.6% receiving placebo.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-126690 · Präparat HOS-096301

Infections In placebo-controlled studies in adult patients, no increase in serious infections was observed with teriflunomide 14 mg (2.7%) as compared to placebo (2.2%). Serious opportunistic infections occurred in 0.2% of each group. Severe infections including sepsis, sometimes fatal have been reported post- marketing.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-126691 · Präparat HOS-096301

Haematological effects A mean decrease affecting white blood cell (WBC) count (<15% from baseline levels, mainly neutrophil and lymphocytes decrease) was observed in placebo-controlled trials with AUBAGIO in adult patients, although a greater decrease was observed in some patients. The decrease in mean count from baseline occurred during the first 6 weeks then stabilised over time while on-treatment but at decreased levels (less than a 15% decrease from baseline). The effect on red blood cell (RBC) (<2%) and platelet counts (<10%) was less pronounced.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-126692 · Präparat HOS-096301

Peripheral neuropathy In placebo-controlled studies in adult patients, peripheral neuropathy, including both polyneuropathy and mononeuropathy (e.g., carpal tunnel syndrome), was reported more frequently in patients taking teriflunomide than in patients taking placebo. In the pivotal, placebo-controlled studies, the incidence of peripheral neuropathy confirmed by nerve conduction studies was 1.9% (17 patients out of 898) on 14 mg of teriflunomide, compared with 0.4% (4 patients out of 898) on placebo. Treatment was discontinued in 5 patients with peripheral neuropathy on teriflunomide 14 mg. Recovery following treatment discontinuation was reported in 4 of these patients.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-126693 · Präparat HOS-096301

Neoplasms benign, malignant and unspecified (incl. cysts and polyps) There does not appear to be an increased risk of malignancy with teriflunomide in the clinical trial experience. The risk of malignancy, particularly lymphoproliferative disorders, is increased with use of some other agents that affect the immune system (class effect).

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-126694 · Präparat HOS-096301

Severe skin reactions Cases of severe skin reactions have been reported with teriflunomide post-marketing (see section 4.4).

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-126695 · Präparat HOS-096301

Asthenia In placebo-controlled studies in adult patients, frequencies for asthenia were 2.0%, 1.6% and 2.2% in the placebo, teriflunomide 7 mg and teriflunomide 14 mg group, respectively.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13–14

HOS-126696 · Präparat HOS-096301

13 Psoriasis In placebo-controlled studies, frequencies for psoriasis were 0.3%, 0.3% and 0.4% in the placebo, teriflunomide 7 mg and teriflunomide 14 mg group, respectively.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-126697 · Präparat HOS-096301

Gastrointestinal disorders Pancreatitis has been reported infrequently in the post-marketing setting with teriflunomide in adults, including cases of necrotising pancreatitis and pancreatic pseudocyst. Pancreatic events may occur at any time during treatment with teriflunomide, which may lead to hospitalisation and/or require corrective treatment.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-126698 · Präparat HOS-096301

Paediatric population

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-126699 · Präparat HOS-096301

The observed safety profile in paediatric patients (from 10 to 17 years-old) receiving teriflunomide daily was overall similar to that seen in adult patients. However, in the paediatric study (166 patients: 109 in the teriflunomide group and 57 in the placebo group), cases of pancreatitis were reported in 1.8% (2/109) of the teriflunomide-treated patients compared to none in the placebo group, in the double-blind phase. One of these events led to hospitalisation and required corrective treatment. In paediatric patients treated with teriflunomide in the open-label phase of the study, 2 additional cases of pancreatitis (one was reported as a serious event, the other was a nonserious event of mild intensity) and one case of serious acute pancreatitis (with pseudo-papilloma), were reported. In two of these 3 patients, pancreatitis led to hospitalisation. Clinical symptoms included abdominal pain, nausea and/ or vomiting and serum amylase and lipase were elevated in these patients. All patients recovered after treatment discontinuation and accelerated elimination procedure (see section 4.4) and corrective treatment.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-126700 · Präparat HOS-096301

The following adverse reactions were more frequently reported in the paediatric population than in the adult population: • Alopecia was reported in 22.0% of patients treated with teriflunomide versus 12.3% in patients treated with placebo. • Infections were reported in 66.1% of patients treated with teriflunomide versus 45.6% in patients treated with placebo. Among them, nasopharyngitis and upper respiratory tract infections were more frequently reported with teriflunomide. • CPK increase was reported in 5.5% of patients treated with teriflunomide versus 0% in patients treated with placebo. The majority of the cases were associated with documented physical exercise. • Paraesthesia was reported in 11.0% of patients treated with teriflunomide versus 1.8% in patients treated with placebo. • Abdominal pain was reported in 11.0% of patients treated with teriflunomide versus 1.8% in patients treated with placebo.

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-126701 · Präparat HOS-096301

Reporting of suspected adverse reactions

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

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-126702 · Präparat HOS-096301

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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-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)