Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.3 · PDF-Seite 3

HOS-113112 · Präparat HOS-093849

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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

Gegenanzeigen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.3 · PDF-Seite 3

HOS-113113 · Präparat HOS-093849

Mothers receiving nitisinone must not breast-feed (see sections 4.6 and 5.3).

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

Gegenanzeigen · Orfadin

Orfadin 4 mg/ml oral suspension · Abschnitt 4.3 · PDF-Seite 13

HOS-113125 · Präparat HOS-093849

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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

Gegenanzeigen · Orfadin

Orfadin 4 mg/ml oral suspension · Abschnitt 4.3 · PDF-Seite 13

HOS-113126 · Präparat HOS-093849

Mothers receiving nitisinone must not breast-feed (see sections 4.6 and 5.3).

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

Wechselwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.5 · PDF-Seite 4

HOS-113114 · Präparat HOS-093849

Nitisinone is metabolised in vitro by CYP 3A4 and dose-adjustment may therefore be needed when nitisinone is co-administered with inhibitors or inducers of this enzyme.

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

Wechselwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.5 · PDF-Seite 4

HOS-113115 · Präparat HOS-093849

Based on data from a clinical interaction study with 80 mg nitisinone at steady-state, nitisinone is a moderate inhibitor of CYP2C9 (2.3-fold increase in tolbutamide AUC), therefore nitisinone treatment may result in increased plasma concentrations of co-administered medicinal products metabolized primarily via CYP2C9 (see section 4.4). Nitisinone is a weak inducer of CYP2E1 (30% decrease in chlorzoxazone AUC) and a weak inhibitor of OAT1 and OAT3 (1.7-fold increase in AUC of furosemide), whereas nitisinone did not inhibit CYP2D6 (see section 5.2).

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): furosemide (HOS-089060) chlorzoxazone (HOS-112397) tolbutamide (HOS-086568)

Wechselwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.5 · PDF-Seite 4

HOS-113117 · Präparat HOS-093849

No formal food interactions studies have been performed with Orfadin hard capsules. However, nitisinone has been co-administered with food during the generation of efficacy and safety data. Therefore, it is recommended that if nitisinone treatment with Orfadin hard capsules is initiated with food, this should be maintained on a routine basis, see section 4.2.

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

Wechselwirkungen · Orfadin

Orfadin 4 mg/ml oral suspension · Abschnitt 4.5 · PDF-Seite 15

HOS-113127 · Präparat HOS-093849

Nitisinone is metabolised in vitro by CYP 3A4 and dose-adjustment may therefore be needed when nitisinone is co-administered with inhibitors or inducers of this enzyme.

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

Wechselwirkungen · Orfadin

Orfadin 4 mg/ml oral suspension · Abschnitt 4.5 · PDF-Seite 15

HOS-113128 · Präparat HOS-093849

Based on data from a clinical interaction study with 80 mg nitisinone at steady-state, nitisinone is a moderate inhibitor of CYP2C9 (2.3-fold increase in tolbutamide AUC), therefore nitisinone treatment may result in increased plasma concentrations of co-administered medicinal products metabolized primarily via CYP2C9 (see section 4.4). Nitisinone is a weak inducer of CYP2E1 (30% decrease in chlorzoxazone AUC) and a weak inhibitor of OAT1 and OAT3 (1.7-fold increase in AUC of furosemide), whereas nitisinone did not inhibit CYP2D6 (see section 5.2).

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): furosemide (HOS-089060) chlorzoxazone (HOS-112397) tolbutamide (HOS-086568)

Wechselwirkungen · Orfadin

Orfadin 4 mg/ml oral suspension · Abschnitt 4.5 · PDF-Seite 15

HOS-113129 · Präparat HOS-093849

Food does not influence the bioavailability of nitisinone oral suspension, but intake together with food decreases the absorption rate and consequently leads to lower fluctuations in serum concentrations within a dosage interval. Therefore, it is recommended that the oral suspension is taken with food, see section 4.2.

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

Nebenwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.8 · PDF-Seite 5

HOS-113118 · Präparat HOS-093849

Summary of the safety profile By its mode of action, nitisinone increases tyrosine levels in all nitisinone-treated patients. Eye-related adverse reactions, such as conjunctivitis, corneal opacity, keratitis, photophobia, and eye pain, related to elevated tyrosine levels are therefore common in both HT-1 and AKU patients. In the HT-1 population other common adverse reactions include thrombocytopenia, leucopenia, and granulocytopenia. Exfoliative dermatitis may occur uncommonly.

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

Nebenwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.8 · PDF-Seite 5

HOS-113119 · Präparat HOS-093849

Tabulated list of adverse reactions The adverse reactions listed below by MedDRA system organ class and absolute frequency, are based on data from clinical trials in patients with HT-1 and AKU and post-marketing use in HT-1. Frequency is defined as 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

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

Nebenwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.8 · PDF-Seite 5

HOS-113120 · Präparat HOS-093849

MedDRA system organ Frequency in HT-1 Frequency in AKU1 Adverse reaction class Infections and Common Bronchitis, pneumonia infestations Blood and lymphatic Common Thrombocytopenia, system disorders leucopenia, granulocytopenia Uncommon Leukocytosis Eye disorders Common Conjunctivitis, corneal opacity, keratitis, photophobia Very common2 Keratopathy Common Very common2 Eye pain Uncommon Blepharitis

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

Nebenwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.8 · PDF-Seite 5–6

HOS-113121 · Präparat HOS-093849

5  MedDRA system organ Frequency in HT-1 Frequency in AKU1 Adverse reaction class Skin and subcutaneous Uncommon Exfoliative dermatitis, tissue disorders erythematous rash Uncommon Common Pruritus, rash Investigations Very common Very common Elevated tyrosine levels 1 The frequency is based on one clinical study in AKU. 2 Elevated tyrosine levels are associated with eye-related adverse reaction. Patients in the AKU study did not have a diet restricted in tyrosine and phenylalanine.

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

Nebenwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.8 · PDF-Seite 6

HOS-113122 · Präparat HOS-093849

Description of selected adverse reactions Nitisinone treatment leads to elevated tyrosine levels. Elevated levels of tyrosine have been associated with eye-related adverse reactions, such as e.g. corneal opacities and hyperkeratotic lesions in HT-1 and AKU patients. Restriction of tyrosine and phenylalanine in the diet should limit the toxicity associated with this type of tyrosinemia by lowering tyrosine levels (see section 4.4). In clinical studies of HT-1, granulocytopenia was only uncommonly severe (<0.5x109/L) and not associated with infections. Adverse reactions affecting the MedDRA system organ class ‘Blood and lymphatic system disorders’ subsided during continued nitisinone treatment.

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

Nebenwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.8 · PDF-Seite 6

HOS-113123 · Präparat HOS-093849

Paediatric population The safety profile in HT-1 is mainly based on the paediatric population since nitisinone treatment should be started as soon as the diagnosis of hereditary tyrosinemia type 1 (HT-1) has been established. From clinical study and post-marketing data there are no indications that the safety profile is different in different subsets of the paediatric population or different from the safety profile in adult patients.

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

Nebenwirkungen · Orfadin

Orfadin 2 mg hard capsules Orfadin 5 mg hard capsules Orfadin 10 mg hard capsules Orfadin 20 mg hard capsules · Abschnitt 4.8 · PDF-Seite 6

HOS-113124 · Präparat HOS-093849

Reporting of suspected adverse reactions 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.

Nebenwirkungen · Orfadin

Orfadin 4 mg/ml oral suspension · Abschnitt 4.8 · PDF-Seite 15

HOS-113130 · Präparat HOS-093849

Summary of the safety profile By its mode of action, nitisinone increases tyrosine levels in all nitisinone-treated patients. Eye-related adverse reactions, such as conjunctivitis, corneal opacity, keratitis, photophobia, and eye pain, related to elevated tyrosine levels are therefore common in both HT-1 and AKU patients. In the HT-1 population other common adverse reactions include thrombocytopenia, leucopenia, and granulocytopenia. Exfoliative dermatitis may occur uncommonly.

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

Nebenwirkungen · Orfadin

Orfadin 4 mg/ml oral suspension · Abschnitt 4.8 · PDF-Seite 15

HOS-113131 · Präparat HOS-093849

Tabulated list of adverse reactions The adverse reactions listed below by MedDRA system organ class and absolute frequency, are based on data from clinical trials in patients with HT-1 and AKU and post-marketing use in HT-1. Frequency is defined as 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

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

Nebenwirkungen · Orfadin

Orfadin 4 mg/ml oral suspension · Abschnitt 4.8 · PDF-Seite 15–16

HOS-113132 · Präparat HOS-093849

15  MedDRA system organ Frequency in HT-1 Frequency in AKU1 Adverse reaction class Infections and infestations Common Bronchitis, pneumonia Blood and lymphatic Common Thrombocytopenia, leucopenia, system disorders granulocytopenia Uncommon Leukocytosis Eye disorders Common Conjunctivitis, corneal opacity, keratitis, photophobia Very common2 Keratopathy Common Very common2 Eye pain Uncommon Blepharitis Skin and subcutaneous Uncommon Exfoliative dermatitis, tissue disorders erythematous rash Uncommon Common Pruritus, rash Investigations Very common Very common Elevated tyrosine levels 1 The frequency is based on one clinical study in AKU. 2 Elevated tyrosine levels are associated with eye-related adverse reaction. Patients in the AKU study did not have a diet restricted in tyrosine and phenylalanine.

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