Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8–9

HOS-126673 · Präparat HOS-096301

8 There was an increase in mean rosuvastatin Cmax and AUC (2.65- and 2.51-fold, respectively), following repeated doses of teriflunomide. However, there was no apparent impact of this increase in plasma rosuvastatin exposure on the HMG-CoA reductase activity. For rosuvastatin, a dose reduction by 50% is recommended for coadministration with teriflunomide. For other substrates of BCRP (e.g., methotrexate, topotecan, sulfasalazine, daunorubicin, doxorubicin) and the OATP family especially HMG-Co reductase inhibitors (e.g., simvastatin, atorvastatin, pravastatin, methotrexate, nateglinide, repaglinide, rifampicin) concomitant administration of teriflunomide should also be undertaken with caution. Patients should be closely monitored for signs and symptoms of excessive exposure to the medicinal products and reduction of the dose of these medicinal products should be considered.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): daunorubicin (HOS-089674) sulfasalazine (HOS-089673) atorvastatin (HOS-086304) simvastatin (HOS-086158) rosuvastatin (HOS-086307) nateglinide (HOS-089675) topotecan (HOS-086047) doxorubicin (HOS-084538) repaglinide (HOS-086935) pravastatin (HOS-086306) methotrexate (HOS-087522)

Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-126674 · Präparat HOS-096301

Summary of the safety profile

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Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-126675 · Präparat HOS-096301

The most frequently reported adverse reactions in the teriflunomide treated (7 mg and 14 mg) patients were: headache (17.8%, 15.7%), diarrhoea (13.1%, 13.6%) increased ALT (13%, 15%), nausea (8%, 10.7%), and alopecia (9.8%, 13.5%). In general, headache, diarrhoea, nausea and alopecia, were mild to moderate, transient and infrequently led to treatment discontinuation.

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Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-126676 · Präparat HOS-096301

Teriflunomide is the main metabolite of leflunomide. The safety profile of leflunomide in patients suffering from rheumatoid arthritis or psoriatic arthritis may be pertinent when prescribing teriflunomide in MS patients.

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Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-126677 · Präparat HOS-096301

Tabulated list of adverse reactions Teriflunomide was evaluated in a total of 2,267 patients exposed to teriflunomide (1,155 on teriflunomide 7 mg and 1,112 on teriflunomide 14 mg) once daily for a median duration of about 672 days in four placebo-controlled studies (1,045 and 1,002 patients for teriflunomide 7 mg and 14 mg, respectively) and one active comparator study (110 patients in each of the teriflunomide treatment groups) in adult patients with relapsing forms of MS (Relapsing Multiple Sclerosis, RMS).

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Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-126678 · Präparat HOS-096301

Listed below are the adverse reactions reported with AUBAGIO in placebo-controlled studies in adult patients, reported for teriflunomide 7 mg or 14 mg from clinical studies in adult patients. Frequencies were defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10);

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Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10–11

HOS-126679 · Präparat HOS-096301

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). Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.

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Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-126680 · Präparat HOS-096301

System organ Very Common Uncommon Rare Very Not known class common rare Infections and Influenza, Upper Severe infections infestations respiratory tract including sepsisa infection, Urinary tract infection, Bronchitis, Sinusitis, Pharyngitis, Cystitis, Gastroenteritis viral, Herpes virus infectionsb, Tooth infection, Laryngitis, Tinea pedis Blood and Neutropeniab, Mild lymphatic Anaemia thrombocytopenia system disorders (platelets <100G/l) Immune system Mild allergic Hyper-sensitivity disorders reactions reactions (immediate or delayed) including anaphylaxis and angioedema Psychiatric Anxiety disorders Nervous system Headache Paraesthesia, Hyperaesthesia, disorders Sciatica, Neuralgia, Carpal tunnel Peripheral syndrome neuropathy

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Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-126681 · Präparat HOS-096301

Cardiac Palpitations disorders Vascular Hypertensionb disorders Respiratory, Interstitial lung Pulmonary thoracic and disease hypertension mediastinal disorders Gastrointestinal Diarrhoea, Pancreatitisb,c , Stomatitis disorders Nausea Abdominal pain Colitis upper, Vomiting, Toothache Hepatobiliary Alanine Gamma- Acute Drug-induced disorders aminotrans glutamyltransfera hepatiti liver injury ferase se (GGT) s (DILI) (ALT) increaseb, increaseb Aspartate aminotransferase increaseb Metabolism and Dyslipidaemia nutrition disorders

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Nebenwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11–12

HOS-126682 · Präparat HOS-096301

11  System organ Very Common Uncommon Rare Very Not known class common rare Skin and Alopecia Rash, Acne Nail disorders, subcutaneous Psoriasis tissue disorders (including pustular)a,b Severe skin reactionsa Musculoskeletal Musculoskeletal and connective pain, tissue disorders Myalgia, Arthralgia Renal and Pollakiuria urinary disorders Reproductive Menorrhagia system and breast disorders General Pain, Astheniaa disorders and administration site conditions Investigations Weight decrease, Neutrophil count decreaseb, White blood cell count decreaseb, Blood creatine phosphokinase increased Injury, Post-traumatic poisoning and pain procedural complications

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Nebenwirkungen · Aubagio

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

HOS-126683 · Präparat HOS-096301

a : please refer to the detailed description section b : see section 4.4 c : frequency is “common” in children based on a controlled clinical study in paediatrics; frequency is “uncommon” in adults

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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

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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:

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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%)

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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.

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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.

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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.

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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.

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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.