Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.3 · PDF-Seite 3

HOS-115813 · Präparat HOS-094361

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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Wechselwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 3

HOS-115814 · Präparat HOS-094361

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.

Wechselwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 3

HOS-115815 · Präparat HOS-094361

Pharmacokinetic interactions

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Wechselwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 3

HOS-115816 · Präparat HOS-094361

 Melatonin has been observed to induce CYP3A in vitro at supra-therapeutic concentrations. The clinical relevance of the finding is unknown. If induction occurs, this can give rise to reduced plasma concentrations of concomitantly administered medicinal products.  Melatonin does not induce CYP1A enzymes in vitro at supra-therapeutic concentrations. Therefore, interactions between melatonin and other active substances as a consequence of melatonin’s effect on CYP1A enzymes are not likely to be significant.  Melatonin’s metabolism is mainly mediated by CYP1A enzymes. Therefore, interactions between melatonin and other active substances as a consequence of their effect on CYP1A enzymes is possible.  Caution should be exercised in patients on fluvoxamine, which increases melatonin levels (by 17-fold higher AUC and a 12-fold higher serum Cmax) by inhibiting its metabolism by hepatic cytochrome P450 (CYP) isozymes CYP1A2 and CYP2C19. The combination should be avoided.  Caution should be exercised in patients on 5- or 8-methoxypsoralen (5 and 8-MOP), which increases melatonin levels by inhibiting its metabolism.  Caution should be exercised in patients on cimetidine a CYP2D inhibitor, which increases plasma melatonin levels, by inhibiting its metabolism.  Cigarette smoking may decrease melatonin levels due to induction of CYP1A2.  Caution should be exercised in patients on oestrogens (e.g. contraceptive or hormone replacement therapy), which increase melatonin levels by inhibiting its metabolism by CYP1A1 and CYP1A2.  CYP1A2 inhibitors such as quinolones may give rise to increased melatonin exposure.  CYP1A2 inducers such as carbamazepine and rifampicin may give rise to reduced plasma concentrations of melatonin.  There is a large amount of data in the literature regarding the effect of adrenergic agonists/antagonists, opiate agonists/antagonists, antidepressant medicinal products, prostaglandin inhibitors, benzodiazepines, tryptophan and alcohol, on endogenous melatonin secretion. Whether or not these active substances interfere with the dynamic or kinetic effects of Circadin or vice versa has not been studied.

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) carbamazepine (HOS-085618) tryptophan (HOS-112872) fluvoxamine (HOS-085908)

Wechselwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 3–4

HOS-115820 · Präparat HOS-094361

3 Pharmacodynamic interactions

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Wechselwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.5 · PDF-Seite 4

HOS-115821 · Präparat HOS-094361

 Alcohol should not be taken with Circadin, because it reduces the effectiveness of Circadin on sleep.  Circadin may enhance the sedative properties of benzodiazepines and non-benzodiazepine hypnotics, such as zaleplon, zolpidem and zopiclone. In a clinical trial, there was clear evidence for a transitory pharmacodynamic interaction between Circadin and zolpidem one hour following co-dosing. Concomitant administration resulted in increased impairment of attention, memory and co-ordination compared to zolpidem alone.  Circadin has been co-administered in studies with thioridazine and imipramine, active substances which affect the central nervous system. No clinically significant pharmacokinetic interactions were found in each case. However, Circadin co-administration resulted in increased feelings of tranquility and difficulty in performing tasks compared to imipramine alone, and increased feelings of “muzzy- headedness” compared to thioridazine alone.

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): imipramine (HOS-085907) thioridazine (HOS-086281) zolpidem (HOS-086327) zaleplon (HOS-115822) zopiclone (HOS-115824)

Nebenwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 4

HOS-115826 · Präparat HOS-094361

Summary of the safety profile In clinical trials (in which a total of 1,931 patients were taking Circadin and 1,642 patients were taking placebo), 48.8% of patients receiving Circadin reported an adverse reaction compared with 37.8% taking placebo. Comparing the rate of patients with adverse reactions per 100 patient weeks, the rate was higher for placebo than Circadin (5.743– placebo vs. 3.013– Circadin). The most common adverse reactions were headache, nasopharyngitis, back pain, and arthralgia, which were common, by MedDRA definition, in both the Circadin and placebo treated groups.

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

Nebenwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 4

HOS-115827 · Präparat HOS-094361

Tabulated list of adverse reactions The following adverse reactions were reported in clinical trials and from post-marketing spontaneous reporting. In clinical trials a total of 9.5% of patients receiving Circadin reported an adverse reaction compared with 7.4% of patients taking placebo. Only those adverse reactions reported during clinical trials occurring in patients at an equivalent or greater rate than placebo have been included below.

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Nebenwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 4–5

HOS-115828 · Präparat HOS-094361

4 Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

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Nebenwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 5

HOS-115829 · Präparat HOS-094361

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 established from the available data).

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

Nebenwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 5

HOS-115830 · Präparat HOS-094361

System Organ Very Common Uncommon Rare Not known: Class Common (Cannot be established from the available data) Infections and Herpes zoster infestations Blood and Leukopenia, lymphatic thrombocytopenia system disorders Immune system Hyper- disorders sensitivity reaction Metabolism and Hypertriglyceridaemia, nutrition hypocalcaemia, disorders hyponatraemia Psychiatric Irritability, Mood altered, disorders nervousness, aggression, agitation, restlessness, crying, stress insomnia, abnormal symptoms, dreams, nightmares, disorientation, early anxiety morning awakening, libido increased, depressed mood, depression Nervous system Migraine, headache, Syncope, memory disorders lethargy, impairment, psychomotor disturbance in hyperactivity, attention, dreamy state, dizziness, restless legs syndrome, somnolence poor quality sleep, paraesthesia Eye disorders Visual acuity reduced, vision blurred, lacrimation increased Ear and Vertigo positional, labyrinth vertigo disorders Cardiac Angina pectoris, disorders palpitations Vascular Hypertension Hot flush disorders

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Nebenwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 5–6

HOS-115831 · Präparat HOS-094361

5  System Organ Very Common Uncommon Rare Not known: Class Common (Cannot be established from the available data) Gastrointestinal Abdominal pain, Gastro-oesophageal disorders abdominal pain reflux disease, upper, dyspepsia, gastrointestinal mouth ulceration, disorder, oral mucosal dry mouth, nausea blistering, tongue ulceration, gastrointestinal upset, vomiting, bowel sounds abnormal, flatulence, salivary hypersecretion, halitosis, abdominal discomfort, gastric disorder, gastritis Hepatobiliary Hyperbilirubinaemia disorders Skin and Dermatitis, night Eczema, erythema, Angioedema, subcutaneous sweats, pruritus, hand dermatitis, oedema of tissue disorders rash, pruritus psoriasis, rash mouth, tongue generalised, dry skin generalised, rash oedema pruritic, nail disorder Musculoskeletal Pain in extremity Arthritis, muscle and connective spasms, neck pain, tissue disorders night cramps Renal and Glycosuria, Polyuria, haematuria, urinary disorders proteinuria nocturia Reproductive Menopausal Priapism, prostatitis Galactorrhoea system and symptoms breast disorders General Asthenia, chest pain Fatigue, pain, thirst disorders and administration site conditions Investigations Liver function test Hepatic enzyme abnormal, weight increased, blood increased electrolyes abnormal, laboratory test abnormal

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Nebenwirkungen · Circadin

Circadin 2 mg prolonged-release tablets · Abschnitt 4.8 · PDF-Seite 6

HOS-115832 · Präparat HOS-094361

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.