Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Zyprexa

ZYPREXA 10 mg powder for solution for injection · Abschnitt 4.5 · PDF-Seite 24

HOS-085983 · Präparat HOS-083234

Potential interactions affecting olanzapine Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine.

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

Wechselwirkungen · Zyprexa

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HOS-085984 · Präparat HOS-083234

Induction of CYP1A2 The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to reduced olanzapine concentrations. Only slight to moderate increase in olanzapine clearance has been observed. The clinical consequences are likely to be limited, but clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary (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): carbamazepine (HOS-085618) lead (HOS-085592)

Wechselwirkungen · Zyprexa

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HOS-085985 · Präparat HOS-083234

Inhibition of CYP1A2 Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of olanzapine. The mean increase in olanzapine Cmax following fluvoxamine was 54 % in female non- smokers and 77 % in male smokers. The mean increase in olanzapine AUC was 52 % and 108 % respectively. A lower starting dose of olanzapine should be considered in patients who are using fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin. A decrease in the dose of olanzapine should be considered if treatment with an inhibitor of CYP1A2 is initiated.

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): ciprofloxacin (HOS-085177) fluvoxamine (HOS-085908)

Wechselwirkungen · Zyprexa

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HOS-085986 · Präparat HOS-083234

Decreased bioavailability Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60 % and should be taken at least 2 hours before or after olanzapine.

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): activated charcoal (HOS-085944)

Wechselwirkungen · Zyprexa

ZYPREXA 10 mg powder for solution for injection · Abschnitt 4.5 · PDF-Seite 24

HOS-085987 · Präparat HOS-083234

Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.

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): cimetidine (HOS-085835) fluoxetine (HOS-085946) magnesium (HOS-085165)

Wechselwirkungen · Zyprexa

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HOS-085988 · Präparat HOS-083234

Potential for olanzapine to affect other medicinal products Olanzapine may antagonise the effects of direct and indirect dopamine agonists (see section 6.2).

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): dopamine (HOS-085948)

Wechselwirkungen · Zyprexa

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HOS-085989 · Präparat HOS-083234

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). Thus no particular interaction is expected as verified through in vivo studies where no inhibition of metabolism of the following active substances was found: tricyclic antidepressant (representing mostly CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 2C19).

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): theophylline (HOS-085910) diazepam (HOS-085904) warfarin (HOS-085950)

Wechselwirkungen · Zyprexa

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HOS-085990 · Präparat HOS-083234

Olanzapine showed no interaction when co-administered with lithium or biperiden.

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): biperiden (HOS-085953) lithium (HOS-085952)

Wechselwirkungen · Zyprexa

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HOS-085991 · Präparat HOS-083234

Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is required after the introduction of concomitant olanzapine.

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): valproate (HOS-085955)

Wechselwirkungen · Zyprexa

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HOS-085992 · Präparat HOS-083234

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with Parkinson's disease and dementia is not recommended (see section 4.4).

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

Wechselwirkungen · Zyprexa

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HOS-085993 · Präparat HOS-083234

QTc interval Caution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc interval (see section 4.4).

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

Nebenwirkungen · Zyprexa

ZYPREXA 2.5 mg coated tablets ZYPREXA 5 mg coated tablets ZYPREXA 7.5 mg coated tablets ZYPREXA 10 mg coated tablets ZYPREXA 15 mg coated tablets ZYPREXA 20 mg coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-085959 · Präparat HOS-083234

Summary of the safety profile

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

Nebenwirkungen · Zyprexa

ZYPREXA 2.5 mg coated tablets ZYPREXA 5 mg coated tablets ZYPREXA 7.5 mg coated tablets ZYPREXA 10 mg coated tablets ZYPREXA 15 mg coated tablets ZYPREXA 20 mg coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-085960 · Präparat HOS-083234

Adults The most frequently (seen in ≥ 1 % of patients) reported adverse reactions associated with the use of olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 4.4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma glutamyltransferase, high uric acid, high creatine phosphokinase and oedema.

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

Nebenwirkungen · Zyprexa

ZYPREXA 2.5 mg coated tablets ZYPREXA 5 mg coated tablets ZYPREXA 7.5 mg coated tablets ZYPREXA 10 mg coated tablets ZYPREXA 15 mg coated tablets ZYPREXA 20 mg coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-085961 · Präparat HOS-083234

Tabulated list of adverse reactions The following table lists the adverse reactions and laboratory investigations observed from spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency terms listed are defined as follows: 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 data available).

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

Nebenwirkungen · Zyprexa

ZYPREXA 2.5 mg coated tablets ZYPREXA 5 mg coated tablets ZYPREXA 7.5 mg coated tablets ZYPREXA 10 mg coated tablets ZYPREXA 15 mg coated tablets ZYPREXA 20 mg coated tablets · Abschnitt 4.8 · PDF-Seite 8

HOS-085962 · Präparat HOS-083234

Very Common Uncommon Rare Not common known Blood and the lymphatic system disorders Eosinophilia Thrombocytopenia11 Leukopenia10 Neutropenia10 Immune system disorders Hypersensitivity11

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

Nebenwirkungen · Zyprexa

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HOS-085963 · Präparat HOS-083234

8 Metabolism and nutrition disorders Weight Elevated cholesterol Development or Hypothermia12 gain1 levels2,3 exacerbation of Elevated glucose diabetes occasionally levels4 associated with Elevated triglyceride ketoacidosis or coma, levels2,5 including some fatal Glucosuria cases (see section Increased appetite 4.4) 11 Nervous system disorders Somnolence Dizziness Seizures where in Neuroleptic malignant Akathisia 6 most cases a history syndrome (see section Parkinsonism6 of seizures or risk 4.4)12 Dyskinesia6 factors for seizures Discontinuation were reported 11 symptoms7, 12 Dystonia (including oculogyration) 11 Tardive dyskinesia11 Amnesia 9 Dysarthria Stuttering11 Restless Legs Syndrome11 Cardiac disorders Bradycardia Ventricular QTc prolongation (see tachycardia/fibrillation, section 4.4) sudden death (see section 4.4)11 Vascular disorders Orthostatic Thromboembolism hypotension10 (including pulmonary embolism and deep vein thrombosis) (see section 4.4) Respiratory, thoracic and mediastinal disorders Epistaxis9 Gastrointestinal disorders Mild, transient Abdominal Pancreatitis11 anticholinergic distension9 effects including Salivary constipation and dry hypersecretion11 mouth Hepatobiliary disorders Transient, Hepatitis (including asymptomatic hepatocellular, elevations of hepatic cholestatic or mixed aminotransferases liver injury) 11 (ALT, AST), especially in early treatment (see section 4.4)

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

Nebenwirkungen · Zyprexa

ZYPREXA 2.5 mg coated tablets ZYPREXA 5 mg coated tablets ZYPREXA 7.5 mg coated tablets ZYPREXA 10 mg coated tablets ZYPREXA 15 mg coated tablets ZYPREXA 20 mg coated tablets · Abschnitt 4.8 · PDF-Seite 9–10

HOS-085964 · Präparat HOS-083234

9  Skin and subcutaneous tissue disorders Rash Photosensitivity reaction Alopecia Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Musculoskeletal and connective tissue disorders Arthralgia9 Rhabdomyolysis11 Renal and urinary disorders Urinary incontinence, urinary retention Urinary hesitation11 Pregnancy, puerperium and perinatal conditions Drug withdrawal syndrome neonatal (see section 4.6) Reproductive system and breast disorders Erectile dysfunction Amenorrhea Priapism12 in males Breast enlargement Decreased libido in Galactorrhea in males and females females Gynaecomastia/breast enlargement in males General disorders and administration site conditions Asthenia Fatigue Oedema Pyrexia10 Investigations Elevated Increased alkaline Increased total plasma phosphatase10 bilirubin prolactin High creatine levels8 phosphokinase11 High Gamma Glutamyltransferase10 High uric acid 10 1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. Following short term treatment (median duration 47 days), weight gain ≥ 7 % of baseline body weight was very common (22.2 %), ≥ 15 % was common (4.2 %) and ≥ 25 % was uncommon (0.8 %). Patients gaining ≥ 7 %, ≥ 15 % and ≥ 25 % of their baseline body weight with long-term exposure (at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively). 2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline. 3 Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (≥ 6.2 mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17 - < 6.2 mmol/l) to high (≥ 6.2 mmol/l) were very common.

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

Nebenwirkungen · Zyprexa

ZYPREXA 2.5 mg coated tablets ZYPREXA 5 mg coated tablets ZYPREXA 7.5 mg coated tablets ZYPREXA 10 mg coated tablets ZYPREXA 15 mg coated tablets ZYPREXA 20 mg coated tablets · Abschnitt 4.8 · PDF-Seite 10–11

HOS-085965 · Präparat HOS-083234

10 4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were very common. 5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (≥ 2.26 mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - < 2.26 mmol/l) to high (≥ 2.26 mmol/l) were very common. 6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo. Olanzapine-treated patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol. In the absence of detailed information on the pre-existing history of individual acute and tardive extrapyramidal movement disorders, it cannot be concluded at present that olanzapine produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly. 8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal range in approximately 30 % of olanzapine treated patients with normal baseline prolactin value. In the majority of these patients the elevations were generally mild, and remained below two times the upper limit of normal range. 9 Adverse event identified from clinical trials in the Olanzapine Integrated Database. 10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database. 11 Adverse event identified from spontaneous post-marketing reporting with frequency determined utilising the Olanzapine Integrated Database. 12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the upper limit of the 95 % confidence interval utilising the Olanzapine Integrated Database.

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

Nebenwirkungen · Zyprexa

ZYPREXA 2.5 mg coated tablets ZYPREXA 5 mg coated tablets ZYPREXA 7.5 mg coated tablets ZYPREXA 10 mg coated tablets ZYPREXA 15 mg coated tablets ZYPREXA 20 mg coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-085966 · Präparat HOS-083234

Long-term exposure (at least 48 weeks) The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9- 12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 6 months.

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

Nebenwirkungen · Zyprexa

ZYPREXA 2.5 mg coated tablets ZYPREXA 5 mg coated tablets ZYPREXA 7.5 mg coated tablets ZYPREXA 10 mg coated tablets ZYPREXA 15 mg coated tablets ZYPREXA 20 mg coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-085967 · Präparat HOS-083234

Additional information on special populations In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher incidence of death and cerebrovascular adverse reactions compared to placebo (see section 4.4). Very common adverse reactions associated with the use of olanzapine in this patient group were abnormal gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence were observed commonly.

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