Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Xagrid

Xagrid 0.5 mg hard capsules. · Abschnitt 4.3 · PDF-Seite 3

HOS-111699 · Präparat HOS-093587

Hypersensitivity to anagrelide or to any of the excipients listed in section 6.1. Patients with moderate or severe hepatic impairment. Patients with moderate or severe renal impairment (creatinine clearance <50 ml/min).

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): creatinine (HOS-086273)

Wechselwirkungen · Xagrid

Xagrid 0.5 mg hard capsules. · Abschnitt 4.5 · PDF-Seite 5

HOS-111700 · Präparat HOS-093587

Limited pharmacokinetic and/or pharmacodynamic studies investigating possible interactions between anagrelide and other medicinal products have been conducted.

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Wechselwirkungen · Xagrid

Xagrid 0.5 mg hard capsules. · Abschnitt 4.5 · PDF-Seite 5

HOS-111701 · Präparat HOS-093587

Effects of other active substances on anagrelide  In vivo interaction studies in humans have demonstrated that digoxin and warfarin do not affect the pharmacokinetic properties of anagrelide. CYP1A2 inhibitors  Anagrelide is primarily metabolised by CYP1A2. It is known that CYP1A2 is inhibited by several medicinal products, including fluvoxamine and enoxacin, and such medicinal products could theoretically adversely influence the clearance of anagrelide. CYP1A2 inducers  CYP1A2 inducers (such as omeprazole) could decrease the exposure of anagrelide (see section 5.2). The consequences on the safety and efficacy profile of anagrelide are not established. Therefore, clinical and biological monitoring is recommended in patients taking concomitant CYP1A2 inducers. If needed, anagrelide dose adjustment could be made.

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): enoxacin (HOS-111703) digoxin (HOS-086172) fluvoxamine (HOS-085908) warfarin (HOS-085950) omeprazole (HOS-085912)

Wechselwirkungen · Xagrid

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HOS-111704 · Präparat HOS-093587

Effects of anagrelide on other active substances  Anagrelide demonstrates some limited inhibitory activity towards CYP1A2 which may present a theoretical potential for interaction with other co-administered medicinal products sharing that clearance mechanism e.g., theophylline.  Anagrelide is an inhibitor of PDE III. The effects of medicinal products with similar properties such as the inotropes milrinone, enoximone, amrinone, olprinone and cilostazol may be exacerbated by anagrelide.

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): enoximone (HOS-111706) cilostazol (HOS-111550) theophylline (HOS-085910) milrinone (HOS-111705)

Wechselwirkungen · Xagrid

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HOS-111707 · Präparat HOS-093587

5  In vivo interaction studies in humans have demonstrated that anagrelide does not affect the pharmacokinetic properties of digoxin or warfarin.  At the doses recommended for use in the treatment of essential thrombocythaemia, anagrelide may potentiate the effects of other medicinal products that inhibit or modify platelet function e.g., acetylsalicylic acid.  A clinical interaction study performed in healthy subjects showed that co-administration of repeat-dose anagrelide 1 mg once daily and acetylsalicylic acid 75 mg once daily may enhance the anti-platelet aggregation effects of each active substance compared with administration of acetylsalicylic acid alone. In some patients with ET concomitantly treated by acetylsalicylic acid and anagrelide, major haemorrhages occurred. Therefore, the potential risks of the concomitant use of anagrelide with acetylsalicylic acid should be assessed, particularly in patients with a high-risk profile for haemorrhage before treatment is initiated.  Anagrelide may cause intestinal disturbance in some patients and compromise the absorption of hormonal oral contraceptives.

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) warfarin (HOS-085950)

Wechselwirkungen · Xagrid

Xagrid 0.5 mg hard capsules. · Abschnitt 4.5 · PDF-Seite 6

HOS-111708 · Präparat HOS-093587

Food interactions  Food delays the absorption of anagrelide, but does not significantly alter systemic exposure.  The effects of food on bioavailability are not considered clinically relevant to the use of anagrelide.

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

Wechselwirkungen · Xagrid

Xagrid 0.5 mg hard capsules. · Abschnitt 4.5 · PDF-Seite 6

HOS-111709 · Präparat HOS-093587

Paediatric population Interaction studies have only been performed in adults.

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

Nebenwirkungen · Xagrid

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HOS-111710 · Präparat HOS-093587

Summary of the safety profile The safety of anagrelide has been examined in 4 open label clinical studies. In 3 of the studies 942 patients who received anagrelide at a mean dose of approximately 2 mg/day were assessed for safety. In these studies, 22 patients received anagrelide for up to 4 years.

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

Nebenwirkungen · Xagrid

Xagrid 0.5 mg hard capsules. · Abschnitt 4.8 · PDF-Seite 7

HOS-111711 · Präparat HOS-093587

In the later study 3660 patients who received anagrelide at a mean dose of approximately 2 mg/day were assessed for safety. In this study 34 patients received anagrelide for up to 5 years.

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

Nebenwirkungen · Xagrid

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HOS-111712 · Präparat HOS-093587

The most commonly reported adverse reactions associated with anagrelide were headache occurring at approximately 14%, palpitations occurring at approximately 9%, fluid retention and nausea both occurring at approximately 6% and diarrhoea occurring at 5%. These adverse drug reactions are expected based on the pharmacology of anagrelide (inhibition of PDE III). Gradual dose titration may help diminish these effects (see section 4.2).

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

Nebenwirkungen · Xagrid

Xagrid 0.5 mg hard capsules. · Abschnitt 4.8 · PDF-Seite 7

HOS-111713 · Präparat HOS-093587

Tabulated list of adverse reactions Adverse reactions arising from clinical studies, post-authorisation safety studies and spontaneous reports are presented in the table below. Within the system organ classes they are listed under the following headings: 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 · Xagrid

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HOS-111714 · Präparat HOS-093587

MedDRA Frequency of adverse reactions System Organ Very Common Uncommon Rare Not known Class common Blood and Anaemia Pancytopenia lymphatic Thrombocytopenia system Haemorrhage disorders Ecchymosis Metabolism and Fluid Oedema Weight gain nutrition retention Weight loss disorders Nervous system Headache Dizziness Depression Migraine Cerebral disorders Amnesia Dysarthria infarction* Confusion Somnolence Insomnia Abnormal Paraesthesia coordination Hypoaesthesia Nervousness Dry mouth Eye disorders Diplopia Vision abnormal Ear and Tinnitus labyrinth disorders Cardiac Tachycardia Ventricular Myocardial Torsade de disorders Palpitations tachycardia infarction pointes Congestive heart Cardiomyopathy failure Cardiomegaly Atrial fibrillation Pericardial Supraventricular effusion tachycardia Angina pectoris Arrhythmia Postural Hypertension hypotension Syncope Vasodilatation

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

Nebenwirkungen · Xagrid

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HOS-111715 · Präparat HOS-093587

7 MedDRA Frequency of adverse reactions System Organ Very Common Uncommon Rare Not known Class common Prinzmetal angina Respiratory, Pulmonary Pulmonary Interstitial lung thoracic and hypertension infiltrates disease including mediastinal Pneumonia pneumonitis and disorders Pleural effusion allergic alveolitis Dyspnoea Epistaxis Gastrointestinal Diarrhoea Gastrointestinal Colitis disorders Vomiting haemorrhage Gastritis Abdominal Pancreatitis Gingival pain Anorexia bleeding Nausea Dyspepsia Flatulence Constipation Gastrointestinal disorder Hepatobiliary Hepatic enzymes Hepatitis disorders increased Skin and Rash Alopecia Dry skin subcutaneous Pruritus tissue disorders Skin discoloration Musculoskeletal Arthralgia and connective Myalgia tissue disorders Back pain Renal and Impotence Renal failure Tubulointerstitial urinary Nocturia nephritis disorders General Fatigue Chest pain Flu-like disorders and Fever syndrome administration Chills Pain site conditions Malaise Asthenia Weakness Investigations Blood creatinine increased * Cerebral infarction (see section 4.4 Thrombotic Risk)

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

Nebenwirkungen · Xagrid

Xagrid 0.5 mg hard capsules. · Abschnitt 4.8 · PDF-Seite 8

HOS-111716 · Präparat HOS-093587

Paediatric population 48 patients aged 6 through17 years (19 children and 29 adolescents) have received anagrelide for up to 6.5 years either in clinical studies or as part of a disease registry (see section 5.1). The majority of adverse events observed were among those listed in the SmPC. However, safety data are limited and do not allow a meaningful comparison between adult and paediatric patients to be made (see section 4.4).

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

Nebenwirkungen · Xagrid

Xagrid 0.5 mg hard capsules. · Abschnitt 4.8 · PDF-Seite 8

HOS-111717 · Präparat HOS-093587

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.