Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 5

HOS-220227 · Präparat HOS-216571

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. - Severe hepatic impairment. - Narrow-angle glaucoma. - Pheochromocytoma. - Coadministration of Corbilta with non-selective monoamine oxidase (MAO-A and MAO-B) inhibitors (e.g. phenelzine, tranylcypromine). - Coadministration with a selective MAO-A inhibitor and a selective MAO-B inhibitor (see section 4.5). - A previous history of Neuroleptic Malignant Syndrome (NMS) and/or non-traumatic rhabdomyolysis.

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): phenelzine (HOS-087875) tranylcypromine (HOS-087876)

Wechselwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6–7

HOS-220230 · Präparat HOS-216571

6 Other antiparkinsonian medicinal products: To date there has been no indication of interactions that would preclude concurrent use of standard antiparkinsonian medicinal products with Corbilta therapy. Entacapone in high doses may affect the absorption of carbidopa. However, no interaction with carbidopa has been observed with the recommended treatment schedule (200 mg of entacapone up to 10 times daily). Interactions between entacapone and selegiline have been investigated in repeated dose studies in Parkinson's disease patients treated with levodopa/DDC inhibitor and no interaction was observed. When used with Corbilta, the daily dose of selegiline should not exceed 10 mg.

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): selegiline (HOS-086575)

Wechselwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-220232 · Präparat HOS-216571

Caution should be exercised when the following active substances are administered concomitantly with levodopa therapy.

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

Wechselwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-220233 · Präparat HOS-216571

Antihypertensives: Symptomatic postural hypotension may occur when levodopa is added to the treatment of patients already receiving antihypertensives. Dose adjustment of the antihypertensive agent may be required.

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

Wechselwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-220234 · Präparat HOS-216571

Antidepressants: Rarely, reactions including hypertension and dyskinesia have been reported with the concomitant use of tricyclic antidepressants and levodopa/carbidopa. Interactions between entacapone and imipramine and between entacapone and moclobemide have been investigated in single dose studies in healthy volunteers. No pharmacodynamic interactions were observed. A significant number of Parkinson's disease patients have been treated with the combination of levodopa, carbidopa and entacapone with several active substances including MAO-A inhibitors, tricyclic antidepressants, noradrenaline reuptake inhibitors such as desipramine, maprotiline and venlafaxine and medicinal products that are metabolised by COMT (e.g. catechol-structured compounds, paroxetine). No pharmacodynamic interactions have been observed. However, caution should be exercised when these medicinal products are used concomitantly with Corbilta (see sections 4.3 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): maprotiline (HOS-086572) paroxetine (HOS-086246) desipramine (HOS-086249) imipramine (HOS-085907) moclobemide (HOS-087879) venlafaxine (HOS-086573)

Wechselwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-220238 · Präparat HOS-216571

Other active substances: Dopamine receptor antagonists (e.g. some antipsychotics and antiemetics), phenytoin and papaverine may reduce the therapeutic effect of levodopa. Patients taking these medicinal products with Corbilta should be carefully observed for loss of therapeutic response.

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): dopamine (HOS-085948) papaverine (HOS-112321) phenytoin (HOS-084531)

Wechselwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-220241 · Präparat HOS-216571

Due to entacapone's affinity to cytochrome P450 2C9 in vitro (see section 5.2), Corbilta may potentially interfere with active substances whose metabolism is dependent on this isoenzyme, such as S-warfarin. However, in an interaction study with healthy volunteers, entacapone did not change the plasma levels of S-warfarin, while the AUC for R-warfarin increased on average by 18% [CI90 11– 26%]. The INR values increased on average by 13% [CI90 6–19%]. Thus, a control of INR is recommended when Corbilta is initiated for patients receiving warfarin.

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): warfarin (HOS-085950)

Wechselwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-220242 · Präparat HOS-216571

Other forms of interactions: Since levodopa competes with certain amino acids, the absorption of Corbilta may be impaired in some patients on high protein diet.

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

Wechselwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-220243 · Präparat HOS-216571

Levodopa and entacapone may form chelates with iron in the gastrointestinal tract. Therefore, Corbilta and iron preparations should be taken at least 2–3 hours apart (see section 4.8).

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): iron (HOS-085656)

Wechselwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-220244 · Präparat HOS-216571

In vitro data: Entacapone binds to human albumin binding site II which also binds several other medicinal products, including diazepam and ibuprofen. According to in vitro studies, significant displacement is not anticipated at therapeutic concentrations of the medicinal products. Accordingly, to date there has been no indication of such interactions.

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): ibuprofen (HOS-087884) diazepam (HOS-085904)

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-220245 · Präparat HOS-216571

a. Summary of the safety profile

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

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-220246 · Präparat HOS-216571

The most frequently reported adverse reactions with Corbilta are dyskinesias occurring in approximately 19% of patients; gastrointestinal symptoms including nausea and diarrhoea occurring in approximately 15% and 12% of patients, respectively; muscle, musculoskeletal and connective tissue pain occurring in approximately 12% of patients; and harmless reddish-brown discolouration of urine (chromaturia) occurring in approximately 10% of patients. Serious events of gastrointestinal haemorrhage (uncommon) and angioedema (rare) have been identified from the clinical trials with Corbilta or entacapone combined with levodopa/DDC inhibitor. Serious hepatitis with mainly cholestatic features, rhabdomyolysis and neuroleptic malignant syndrome may occur with Corbilta although no cases have been identified from the clinical trial data.

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

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-220247 · Präparat HOS-216571

b. Tabulated list of adverse reactions

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

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-220248 · Präparat HOS-216571

The following adverse reactions, listed in Table 1, have been accumulated both from a pooled data of eleven double-blind clinical trials consisting of 3 230 patients (1 810 treated with Corbilta or entacapone combined with levodopa/DDC inhibitor, and 1 420 treated with placebo combined with levodopa/DDC inhibitor or cabergoline combined with levodopa/ DDC inhibitor), and from the post- marketing data since the introduction of entacapone into the market for the combination use of entacapone with levodopa/DDC inhibitor.

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

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-220249 · Präparat HOS-216571

Adverse reactions are ranked under headings of frequency, the most frequent first, 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, since no valid estimate can be derived from clinical trials or epidemiological studies).

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

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-220250 · Präparat HOS-216571

Table 1. Adverse reactions

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

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-220251 · Präparat HOS-216571

Blood and lymphatic system disorders Common: Anaemia Uncommon: Thrombocytopenia

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

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-220252 · Präparat HOS-216571

Metabolism and nutrition disorders Common: Weight decreased*, decreased appetite*

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

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 8–9

HOS-220253 · Präparat HOS-216571

8 Psychiatric disorders Common: Depression, hallucination, confusional state*, abnormal dreams*, anxiety, insomnia Uncommon: Psychosis, agitation* Not known: Suicidal behaviour, Dopamine dysregulation syndrome

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

Nebenwirkungen · Corbilta (previously Levodopa/Carbidopa/Entacapone Sandoz)

Corbilta 50 mg/12.5 mg/200 mg film-coated tablets Corbilta 75 mg/18.75 mg/200 mg film-coated tablets Corbilta 100 mg/25 mg/200 mg film-coated tablets Corbilta 125 mg/31.25 mg/200 mg film-coated tablets Corbilta 150 mg/37.5 mg/200 mg film-coated tablets Corbilta 175 mg/43.75 mg/200 mg film-coated tablets Corbilta 200 mg/50 mg/200 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-220254 · Präparat HOS-216571

Nervous system disorders Very common: Dyskinesia* Common: Parkinsonism aggravated (e.g. bradykinesia)*, tremor, on and off phenomenon, dystonia, mental impairment (e.g. memory impairment, dementia), somnolence, dizziness*, headache Not known: Neuroleptic malignant syndrome*

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