Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 8

HOS-112882 · Präparat HOS-093777

a. Summary of the safety profile The most commonly reported adverse events in patients treated with YENTREVE in clinical trials in SUI and other lower urinary tract disorders were nausea, dry mouth fatigue and constipation. The data analysis of four 12-week, placebo-controlled clinical trials in patients with SUI, including 958 duloxetine-treated and 955 placebo-treated patients, showed that the onset of the reported adverse events typically occurred in the first week of therapy. However, the majority of the most frequent adverse events were mild to moderate and resolved within 30 days of occurrence (e.g. nausea).

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 8

HOS-112883 · Präparat HOS-093777

b. Tabulated summary of adverse reactions Table 1 gives the adverse reactions observed from spontaneous reporting and in placebo-controlled clinical trials.

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 8

HOS-112884 · Präparat HOS-093777

Table 1: Adverse reactions Frequency estimate: 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).

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 8–9

HOS-112885 · Präparat HOS-093777

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 8  Very Common Uncommon Rare Very rare Not known common Infections and infestations Laryngitis Immune system disorders Hyper- Anaphylactic sensitivity reaction disorder Endocrine disorders Hypo- thyroidism Metabolism and nutrition disorders Appetite Dehydration Hyperglycaemi decreased a (reported especially in diabetic patients) Hyponatraemia SIADH6 Psychiatric disorders Insomnia Bruxism Suicidal Agitation Disorientation behaviour5,6 Libido Apathy Suicidal decreased Orgasm ideation5,7 Anxiety abnormal Mania6 Sleep Abnormal Hallucinations disorder dreams Aggression and anger4,6 Nervous system disorders Headache Nervousness Serotonin Dizziness Disturbance syndrome6 Lethargy in attention Convulsions1,6 Somnolence Dysgeusia Myoclonus Tremor Poor quality Akathisia6 Paraesthesia sleep Psychomotor restlessness6 Extra- pyramidal symptoms6 Dyskinesia Restless legs syndrome Eye disorders Blurred Mydriasis Glaucoma vision Visual impairment Dry eye Ear and labyrinth disorders Vertigo Tinnitus1 Ear pain Cardiac disorders Palpitations Supra- Stress Tachycardia ventricular cardiomyopathy arrhythmia, (Takotsubo cardiomyopathy)

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 9–10

HOS-112886 · Präparat HOS-093777

9  Very Common Uncommon Rare Very rare Not known common mainly atrial fibrillation6 Vascular disorders Hypertensio Syncope2 Hypertensive n3,7 Blood crisis3 Flushing pressure Orthostatic increase3 hypotension2 Peripheral coldness Respiratory, thoracic and mediastinal disorders Yawning Throat tightness Epistaxis Interstitial lung disease10 Eosinophilic pneumonia6 Gastrointestinal disorders Nausea Diarrhoea Gastrointestin Haematochezia Dry mouth Abdominal al Microscopic Constipation pain haemorrhage7 colitis9 Vomiting Gastroenteriti Dyspepsia s Stomatitis Eructation Gastritis Dysphagia Flatulence Breath odour Hepato-biliary disorders Hepatitis3 Hepatic failure6 Elevated liver Jaundice6 enzymes (ALT, AST, alkaline phosphatase) Acute liver injury Skin and subcutaneous tissue disorders Sweating Rash Stevens- Cutaneous increased Night sweats Johnson vasculitis Urticaria Syndrome6 Dermatitis Angio-neurotic contact oedema6 Cold sweat Photo- Increased sensitivity tendency to reactions bruise Musculoskeletal and connective tissue disorders Musculo- Muscle skeletal pain twitching Muscle tightness Muscle spasm

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 10–11

HOS-112887 · Präparat HOS-093777

10  Very Common Uncommon Rare Very rare Not known common Trismus Renal and urinary disorders Urinary Urinary hesitation retention6 Dysuria Polyuria Nocturia Urine flow Pollakiuria decreased Urine odour abnormal Reproductive system and breast disorders Gynaecologic Menstrual al disorder haemorrhage Galactorrhoea Menopausal Hyperprolactin symptoms aemia Postpartum haemorrhage6 General disorders and administration site conditions Fatigue Asthenia Chest pain7 Gait Chills Falls 8 disturbance Feeling abnormal Feeling cold Thirst Malaise Feeling hot Investigations Weight Blood decrease potassium Weight increased increase Blood cholesterol increased Blood creatine phosphokinas e increased 1 Cases of convulsion and cases of tinnitus have also been reported after treatment discontinuation. 2 Cases of orthostatic hypotension and syncope have been reported especially at the initiation of treatment. 3 See section 4.4. 4 Cases of aggression and anger have been reported particularly early in treatment or after treatment discontinuation. 5 Cases of suicidal ideation and suicidal behaviours have been reported during duloxetine therapy or early after treatment discontinuation (see section 4.4). 6 Estimated frequency of post-marketing surveillance reported adverse reactions; not observed in placebo-controlled clinical trials. 7 Not statistically significantly different from placebo. 8 Falls were more common in the elderly (≥65 years old). 9 Estimated frequency based on all clinical trial data. 10 Estimated frequency based on placebo-controlled clinical trials.

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 11–12

HOS-112888 · Präparat HOS-093777

c. Description of selected adverse reactions 11 Discontinuation of duloxetine (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia or electric shock-like sensations, particularly in the head), sleep disturbances (including insomnia and intense dreams), fatigue, somnolence, agitation or anxiety, nausea and/or vomiting, tremor, headache, myalgia, irritability, diarrhoea, hyperhydrosis and vertigo are the most commonly reported reactions.

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 12

HOS-112889 · Präparat HOS-093777

Generally, for SSRIs and SNRIs, these events are mild to moderate and self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when duloxetine treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 12

HOS-112890 · Präparat HOS-093777

The heart rate-corrected QT interval in duloxetine-treated patients did not differ from that seen in placebo-treated patients. No clinically significant differences were observed for QT, PR, QRS, or QTcB measurements between duloxetine-treated and placebo-treated patients.

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 12

HOS-112891 · Präparat HOS-093777

In the 12 week acute phase of three clinical trials of duloxetine in patients with diabetic neuropathic pain, small but statistically significant increases in fasting blood glucose were observed in duloxetine- treated patients. HbA1c was stable in both duloxetine-treated and placebo-treated patients. In the extension phase of these studies, which lasted up to 52 weeks, there was an increase in HbA1c in both the duloxetine and routine care groups, but the mean increase was 0.3% greater in the duloxetine- treated group. There was also a small increase in fasting blood glucose and in total cholesterol in duloxetine-treated patients while those laboratory tests showed a slight decrease in the routine care group.

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

Nebenwirkungen · Yentreve

YENTREVE 20 mg hard gastro-resistant capsules YENTREVE 40 mg hard gastro-resistant capsules · Abschnitt 4.8 · PDF-Seite 12

HOS-112892 · Präparat HOS-093777

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.

Gegenanzeigen · Cymbalta

Cymbalta 30 mg hard gastro-resistant capsules Cymbalta 60 mg hard gastro-resistant capsules · Abschnitt 4.3 · PDF-Seite 4

HOS-113264 · Präparat HOS-093901

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 · Cymbalta

Cymbalta 30 mg hard gastro-resistant capsules Cymbalta 60 mg hard gastro-resistant capsules · Abschnitt 4.3 · PDF-Seite 4

HOS-113265 · Präparat HOS-093901

Concomitant use of Cymbalta with nonselective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated (see section 4.5).

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

Gegenanzeigen · Cymbalta

Cymbalta 30 mg hard gastro-resistant capsules Cymbalta 60 mg hard gastro-resistant capsules · Abschnitt 4.3 · PDF-Seite 4

HOS-113266 · Präparat HOS-093901

Liver disease resulting in hepatic impairment (see section 5.2).

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

Gegenanzeigen · Cymbalta

Cymbalta 30 mg hard gastro-resistant capsules Cymbalta 60 mg hard gastro-resistant capsules · Abschnitt 4.3 · PDF-Seite 4

HOS-113267 · Präparat HOS-093901

Cymbalta should not be used in combination with fluvoxamine, ciprofloxacin or enoxacin (i.e. potent CYP1A2 inhibitors) since the combination results in elevated plasma concentrations of duloxetine (see section 4.5).

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) enoxacin (HOS-111703) fluvoxamine (HOS-085908)

Gegenanzeigen · Cymbalta

Cymbalta 30 mg hard gastro-resistant capsules Cymbalta 60 mg hard gastro-resistant capsules · Abschnitt 4.3 · PDF-Seite 4

HOS-113268 · Präparat HOS-093901

Severe renal impairment (creatinine clearance <30 ml/min) (see section 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): creatinine (HOS-086273)

Gegenanzeigen · Cymbalta

Cymbalta 30 mg hard gastro-resistant capsules Cymbalta 60 mg hard gastro-resistant capsules · Abschnitt 4.3 · PDF-Seite 4

HOS-113269 · Präparat HOS-093901

The initiation of treatment with Cymbalta is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis (see sections 4.4 and 4.8).

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

Wechselwirkungen · Cymbalta

Cymbalta 30 mg hard gastro-resistant capsules Cymbalta 60 mg hard gastro-resistant capsules · Abschnitt 4.5 · PDF-Seite 7

HOS-113270 · Präparat HOS-093901

Monoamine oxidase inhibitors (MAOIs): Due to the risk of serotonin syndrome, duloxetine should not be used in combination with non-selective irreversible monoamine oxidase inhibitors (MAOIs), or within at least 14 days of discontinuing treatment with an MAOI. Based on the half-life of duloxetine, at least 5 days should be allowed after stopping Cymbalta before starting an MAOI (see section 4.3).

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): serotonin (HOS-085477)

Wechselwirkungen · Cymbalta

Cymbalta 30 mg hard gastro-resistant capsules Cymbalta 60 mg hard gastro-resistant capsules · Abschnitt 4.5 · PDF-Seite 7

HOS-113271 · Präparat HOS-093901

The concomitant use of Cymbalta with selective, reversible MAOIs, like moclobemide, is not recommended (see section 4.4). The antibiotic linezolid is a reversible non-selective MAOI and should not be given to patients treated with Cymbalta (see section 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): moclobemide (HOS-087879) linezolid (HOS-112865)

Wechselwirkungen · Cymbalta

Cymbalta 30 mg hard gastro-resistant capsules Cymbalta 60 mg hard gastro-resistant capsules · Abschnitt 4.5 · PDF-Seite 7

HOS-113272 · Präparat HOS-093901

Inhibitors of CYP1A2: Because CYP1A2 is involved in duloxetine metabolism, concomitant use of duloxetine with potent inhibitors of CYP1A2 is likely to result in higher concentrations of duloxetine. Fluvoxamine (100 mg once daily), a potent inhibitor of CYP1A2, decreased the apparent plasma clearance of duloxetine by about 77% and increased AUCo-t 6-fold. Therefore Cymbalta should not be administered in combination with potent inhibitors of CYP1A2 like fluvoxamine (see section 4.3).

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): fluvoxamine (HOS-085908)