Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.3 · PDF-Seite 5

HOS-114898 · Präparat HOS-094185

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

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Wechselwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.5 · PDF-Seite 7

HOS-114899 · Präparat HOS-094185

Daptomycin undergoes little to no Cytochrome P450 (CYP450)-mediated metabolism. It is unlikely that daptomycin will inhibit or induce the metabolism of medicinal products metabolised by the P450 system.

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Wechselwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.5 · PDF-Seite 7

HOS-114900 · Präparat HOS-094185

Interaction studies for Cubicin were performed with aztreonam, tobramycin, warfarin and probenecid. Daptomycin had no effect on the pharmacokinetics of warfarin or probenecid, nor did these medicinal products alter the pharmacokinetics of daptomycin. The pharmacokinetics of daptomycin were not significantly altered by aztreonam.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): aztreonam (HOS-114901) tobramycin (HOS-114902) probenecid (HOS-085208) warfarin (HOS-085950)

Wechselwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.5 · PDF-Seite 7

HOS-114903 · Präparat HOS-094185

Although small changes in the pharmacokinetics of daptomycin and tobramycin were observed during co-administration by intravenous infusion over a 30-minute period using a Cubicin dose of 2 mg/kg, the changes were not statistically significant. The interaction between daptomycin and tobramycin with an approved dose of Cubicin is unknown. Caution is warranted when Cubicin is co-administered with tobramycin.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tobramycin (HOS-114902)

Wechselwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.5 · PDF-Seite 7–8

HOS-114904 · Präparat HOS-094185

7 Experience with the concomitant administration of Cubicin and warfarin is limited. Studies of Cubicin with anticoagulants other than warfarin have not been conducted. Anticoagulant activity in patients receiving Cubicin and warfarin should be monitored for the first several days after therapy with Cubicin is initiated.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): warfarin (HOS-085950)

Wechselwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.5 · PDF-Seite 8

HOS-114905 · Präparat HOS-094185

There is limited experience regarding concomitant administration of daptomycin with other medicinal products that may trigger myopathy (e.g. HMG-CoA reductase inhibitors). However, some cases of marked rises in CPK levels and cases of rhabdomyolysis occurred in adult patients taking one of these medicinal products at the same time as Cubicin. It is recommended that other medicinal products associated with myopathy should if possible be temporarily discontinued during treatment with Cubicin unless the benefits of concomitant administration outweigh the risk. If co-administration cannot be avoided, CPK levels should be measured more frequently than once weekly and patients should be closely monitored for any signs or symptoms that might represent myopathy. See sections 4.4, 4.8 and 5.3.

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Wechselwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.5 · PDF-Seite 8

HOS-114906 · Präparat HOS-094185

Daptomycin is primarily cleared by renal filtration and so plasma levels may be increased during co-administration with medicinal products that reduce renal filtration (e.g. NSAIDs and COX-2 inhibitors). In addition, there is a potential for a pharmacodynamic interaction to occur during co-administration due to additive renal effects. Therefore, caution is advised when daptomycin is co-administered with any other medicinal product known to reduce renal filtration.

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Wechselwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.5 · PDF-Seite 8

HOS-114907 · Präparat HOS-094185

During post–marketing surveillance, cases of interference between daptomycin and particular reagents used in some assays of prothrombin time/international normalised ratio (PT/INR) have been reported. This interference led to a false prolongation of PT and elevation of INR. If unexplained abnormalities of PT/INR are observed in patients taking daptomycin, consideration should be given to a possible in vitro interaction with the laboratory test. The possibility of erroneous results may be minimised by drawing samples for PT or INR testing near the time of trough plasma concentrations of daptomycin (see section 4.4).

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): prothrombin (HOS-085093)

Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 9

HOS-114908 · Präparat HOS-094185

Summary of the safety profile In clinical studies, 2,011 adult subjects received Cubicin. Within these trials, 1,221 subjects received a daily dose of 4 mg/kg, of whom 1,108 were patients and 113 were healthy volunteers; 460 subjects received a daily dose of 6 mg/kg, of whom 304 were patients and 156 were healthy volunteers. In paediatric studies, 372 patients received Cubicin, of whom 61 received a single dose and 311 received a therapeutic regimen for cSSTI or SAB (daily doses ranged from 4 mg/kg to 12 mg/kg). Adverse reactions (i.e. considered by the investigator to be possibly, probably, or definitely related to the medicinal product) were reported at similar frequencies for Cubicin and comparator regimens.

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Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 9

HOS-114909 · Präparat HOS-094185

The most frequently reported adverse reactions (frequency common (≥ 1/100 to < 1/10)) are: Fungal infections, urinary tract infection, candida infection, anaemia, anxiety, insomnia, dizziness, headache, hypertension, hypotension, gastrointestinal and abdominal pain, nausea, vomiting, constipation, diarrhoea, flatulence, bloating and distension, liver function tests abnormal (increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP)), rash, pruritus, limb pain, serum creatine phosphokinase (CPK) increased, infusion site reactions, pyrexia, asthenia.

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Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 9

HOS-114910 · Präparat HOS-094185

Less frequently reported, but more serious, adverse reactions include hypersensitivity reactions, eosinophilic pneumonia (occasionally presenting as organising pneumonia), drug reaction with eosinophilia and systemic symptoms (DRESS), angioedema and rhabdomyolysis.

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Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 9

HOS-114911 · Präparat HOS-094185

Tabulated list of adverse reactions The following adverse reactions were reported during therapy and during follow-up with frequencies corresponding to 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):

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Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 9

HOS-114912 · Präparat HOS-094185

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

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Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 9

HOS-114913 · Präparat HOS-094185

Table 1 Adverse reactions from clinical studies and post-marketing reports

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Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 9

HOS-114914 · Präparat HOS-094185

System organ class Frequency Adverse reactions Infections and infestations Common: Fungal infections, urinary tract infection, candida infection Uncommon: Fungaemia Not known*: Clostridioides difficile-associated diarrhoea** Blood and lymphatic system Common: Anaemia disorders Uncommon: Thrombocythaemia, eosinophilia, international normalised ratio (INR) increased, leukocytosis Rare: Prothrombin time (PT) prolonged Not known*: Thrombocytopaenia Immune system disorders Not known*: Hypersensitivity**, manifested by isolated spontaneous reports including, but not limited to angioedema, pulmonary eosinophilia, sensation of oropharyngeal swelling, anaphylaxis**, infusion reactions including the following symptoms: tachycardia, wheezing, pyrexia, rigors, systemic flushing, vertigo, syncope and metallic taste Metabolism and nutrition Uncommon: Decreased appetite, hyperglycaemia, electrolyte disorders imbalance Psychiatric disorders Common: Anxiety, insomnia

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Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 9–10

HOS-114915 · Präparat HOS-094185

9 System organ class Frequency Adverse reactions Nervous system disorders Common: Dizziness, headache Uncommon: Paraesthesia, taste disorder, tremor, eye irritation Not known*: Peripheral neuropathy** Ear and labyrinth disorders Uncommon: Vertigo Cardiac disorders Uncommon: Supraventricular tachycardia, extrasystole Vascular disorders Common: Hypertension, hypotension Uncommon: Flushes Respiratory, thoracic and Not known*: Eosinophilic pneumonia1**, cough mediastinal disorders Gastrointestinal disorders Common: Gastrointestinal and abdominal pain, nausea, vomiting, constipation, diarrhoea, flatulence, bloating and distension Uncommon: Dyspepsia, glossitis Hepatobiliary disorders Common: Liver function tests abnormal2 (increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP)) Rare: Jaundice Skin and subcutaneous tissue Common: Rash, pruritus disorders Uncommon: Urticaria Not known*: Acute generalised exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS)**, vesiculobullous rash with or without mucous membrane involvement (SJS or TEN)** Musculoskeletal and Common: Limb pain, serum creatine phosphokinase (CPK) 2 connective tissue disorders increased Uncommon: Myositis, increased myoglobin, muscular weakness, muscle pain, arthralgia, serum lactate dehydrogenase (LDH) increased, muscle cramps Not known*: Rhabdomyolysis3 ** Renal and urinary disorders Uncommon: Renal impairment, including renal failure and renal insufficiency, serum creatinine increased Not known*: Tubulointerstitial nephritis (TIN)** Reproductive system and Uncommon: Vaginitis breast disorders General disorders and Common: Infusion site reactions, pyrexia, asthenia administration site conditions Uncommon: Fatigue, pain * Based on post-marketing reports. Since these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorised as not known. ** See section 4.4. 1 While the exact incidence of eosinophilic pneumonia associated with daptomycin is unknown, to date the reporting rate of spontaneous reports is very low (< 1/10,000). 2 In some cases of myopathy involving raised CPK and muscle symptoms, the patients also presented with elevated transaminases. These transaminase increases were likely to be related to the skeletal muscle effects. The majority of transaminase elevations were of Grade 1-3 toxicity and resolved upon discontinuation of treatment. 3 When clinical information on the patients was available to make a judgement, approximately 50 % of the cases occurred in patients with pre-existing renal impairment, or in those receiving concomitant medicinal products known to cause rhabdomyolysis.

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Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 10

HOS-114916 · Präparat HOS-094185

The safety data for the administration of daptomycin via 2-minute intravenous injection are derived from two pharmacokinetic studies in healthy adult volunteers. Based on these study results, both methods of daptomycin administration, the 2-minute intravenous injection and the 30-minute intravenous infusion, had a similar safety and tolerability profile. There was no relevant difference in local tolerability or in the nature and frequency of adverse reactions.

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Nebenwirkungen · Cubicin

Cubicin 350 mg powder for solution for injection or infusion Cubicin 500 mg powder for solution for injection or infusion · Abschnitt 4.8 · PDF-Seite 10–11

HOS-114917 · Präparat HOS-094185

10 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.

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