Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Cymbalta

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HOS-113273 · Präparat HOS-093901

CNS medicinal products: The risk of using duloxetine in combination with other CNS-active medicinal products has not been systematically evaluated, except in the cases described in this section. Consequently, caution is advised when Cymbalta is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products (e.g. benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines).

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): phenobarbital (HOS-085617)

Wechselwirkungen · Cymbalta

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HOS-113274 · Präparat HOS-093901

Serotonergic agents: In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable if Cymbalta is used concomitantly with serotonergic agents like SSRIs, SNRIs, tricyclic antidepressants like clomipramine or amitriptyline, MAOIs like moclobemide or linezolid, St John’s wort (Hypericum perforatum) or triptans, tramadol, pethidine and tryptophan (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): amitriptyline (HOS-085911) tryptophan (HOS-112872) moclobemide (HOS-087879) serotonin (HOS-085477) clomipramine (HOS-085906) linezolid (HOS-112865) tramadol (HOS-112871)

Wechselwirkungen · Cymbalta

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HOS-113275 · Präparat HOS-093901

Effect of duloxetine on other medicinal products Medicinal products metabolised by CYP1A2: The pharmacokinetics of theophylline, a CYP1A2

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)

Wechselwirkungen · Cymbalta

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HOS-113276 · Präparat HOS-093901

7 substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily).

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

Wechselwirkungen · Cymbalta

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HOS-113277 · Präparat HOS-093901

Medicinal products metabolised by CYP2D6: Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered at a dose of 60 mg twice daily with a single dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold. The co-administration of duloxetine (40 mg twice daily) increases steady state AUC of tolterodine (2 mg twice daily) by 71 %, but does not affect the pharmacokinetics of its active 5-hydroxyl metabolite and no dosage adjustment is recommended. Caution is advised if Cymbalta is co-administered with medicinal products that are predominantly metabolised by CYP2D6 (risperidone, tricyclic antidepressants [TCAs] such as nortriptyline, amitriptyline, and imipramine) particularly if they have a narrow therapeutic index (such as flecainide, propafenone and metoprolol).

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): nortriptyline (HOS-086245) propafenone (HOS-084530) tolterodine (HOS-087792) amitriptyline (HOS-085911) desipramine (HOS-086249) flecainide (HOS-086203) imipramine (HOS-085907) risperidone (HOS-086280) metoprolol (HOS-090094)

Wechselwirkungen · Cymbalta

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HOS-113278 · Präparat HOS-093901

Oral contraceptives and other steroidal agents: Results of in vitro studies demonstrate that duloxetine does not induce the catalytic activity of CYP3A. Specific in vivo drug interaction studies have not been performed.

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

Wechselwirkungen · Cymbalta

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HOS-113279 · Präparat HOS-093901

Anticoagulants and antiplatelet agents: Caution should be exercised when duloxetine is combined with oral anticoagulants or antiplatelet agents due to a potential increased risk of bleeding attributable to a pharmacodynamic interaction. Furthermore, increases in INR values have been reported when duloxetine was co-administered to patients treated with warfarin. However, concomitant administration of duloxetine with warfarin under steady state conditions, in healthy volunteers, as part of a clinical pharmacology study, did not result in a clinically significant change in INR from baseline or in the pharmacokinetics of R- or S-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 · Cymbalta

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HOS-113280 · Präparat HOS-093901

Effects of other medicinal products on duloxetine Antacids and H2 antagonists: Co-administration of duloxetine with aluminium- and magnesium- containing antacids or duloxetine with famotidine had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose.

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): famotidine (HOS-112087)

Wechselwirkungen · Cymbalta

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HOS-113281 · Präparat HOS-093901

Inducers of CYP1A2: Population pharmacokinetic analyses have shown that smokers have almost 50% lower plasma concentrations of duloxetine compared with non-smokers.

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

Nebenwirkungen · Cymbalta

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HOS-113282 · Präparat HOS-093901

a. Summary of the safety profile The most commonly reported adverse reactions in patients treated with Cymbalta were nausea, headache, dry mouth, somnolence, and dizziness. However, the majority of common adverse reactions were mild to moderate, they usually started early in therapy, and most tended to subside even as therapy was continued.

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

Nebenwirkungen · Cymbalta

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HOS-113283 · Präparat HOS-093901

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 · Cymbalta

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HOS-113284 · Präparat HOS-093901

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 · Cymbalta

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HOS-113285 · Präparat HOS-093901

Within each frequency grouping, undesirable effects 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 · Cymbalta

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HOS-113286 · Präparat HOS-093901

Very Common Uncommon Rare Very rare Not known common Infections and infestations Laryngitis Immune system disorders Anaphylactic reaction Hyper- sensitivity disorder

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

Nebenwirkungen · Cymbalta

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HOS-113287 · Präparat HOS-093901

9  Very Common Uncommon Rare Very rare Not known common Endocrine disorders Hypo- thyroidism Metabolism and nutrition disorders Decreased Hyperglycaemia Dehydration Appetite (reported Hyponatraemia especially in SIADH6 diabetic patients) Psychiatric disorders Insomnia Suicidal Suicidal Agitation ideation5,7 behaviour5,7 Libido Sleep disorder Mania decreased Bruxism Hallucinations Anxiety Disorientation Aggression and Orgasm Apathy anger4 abnormal Abnormal dreams Nervous system disorders Headache Dizziness Myoclonus Serotonin Somnolence Lethargy Akathisia7 syndrome6 Tremor Nervousness Convulsion1 Paraesthesi Disturbance in Psychomotor a attention restlessness6 Dysgeusia Extra-pyramidal Dyskinesia symptoms6 Restless legs syndrome Poor quality sleep Eye disorders Blurred Mydriasis Glaucoma vision Visual impairment Ear and labyrinth disorders Tinnitus1 Vertigo Ear pain Cardiac disorders Palpitation Tachycardia Stress s Supra- cardiomyopathy ventricular (Takotsubo arrhythmia, cardiomyopathy) mainly atrial fibrillation Vascular disorders Blood Syncope2 Hypertensive pressure Hypertension3,7 crisis3,6 increase 3 Orthostatic Flushing hypotension2 Peripheral coldness

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

Nebenwirkungen · Cymbalta

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HOS-113288 · Präparat HOS-093901

10  Very Common Uncommon Rare Very rare Not known common Respiratory, thoracic and mediastinal disorders Yawning Throat tightness Interstitial lung Epistaxis disease10 Eosinophilic pneumonia6 Gastrointestinal disorders Nausea Constipatio Gastrointestinal Stomatitis Dry mouth n haemorrhage7 Haematochezia Diarrhoea Gastroenteritis Breath odour Abdominal Eructation Microscopic pain Gastritis colitis9 Vomiting Dysphagia Dyspepsia Flatulence Hepato-biliary disorders Hepatitis3 Hepatic failure6 Elevated liver Jaundice6 enzymes (ALT, AST, alkaline phosphatase) Acute liver injury Skin and subcutaneous tissue disorders Sweating Night sweats Stevens-Johnson Cutaneous increased Urticaria Syndrome6 vasculitis Rash Dermatitis Angio-neurotic contact oedema6 Cold sweat Photo- sensitivity reactions Increased tendency to bruise Musculoskeletal and connective tissue disorders Musculo- Muscle tightness Trismus skeletal Muscle pain twitching Muscle spasm Renal and urinary disorders Dysuria Urinary Urine odour Pollakiuria retention abnormal Urinary hesitation Nocturia Polyuria Urine flow decreased Reproductive system and breast disorders Erectile Gynaecological Menopausal dysfunctio haemorrhage symptoms n Menstrual Galactorrhoea disorder

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

Nebenwirkungen · Cymbalta

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HOS-113289 · Präparat HOS-093901

11  Very Common Uncommon Rare Very rare Not known common Ejaculation Sexual Hyperprolactina disorder dysfunction emia Ejaculation Testicular pain Postpartum delayed haemorrhage6 General disorders and administration site conditions Falls8 Chest pain7 Fatigue Feeling abnormal Feeling cold Thirst Chills Malaise Feeling hot Gait disturbance Investigations Weight Weight increase Blood decrease Blood creatine cholesterol phosphokinase increased increased Blood potassium increased

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

Nebenwirkungen · Cymbalta

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HOS-113290 · Präparat HOS-093901

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 · Cymbalta

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HOS-113291 · Präparat HOS-093901

c. Description of selected adverse reactions 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 · Cymbalta

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HOS-113292 · Präparat HOS-093901

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.