Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Caelyx pegylated liposomal

Caelyx pegylated liposomal 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 14

HOS-085581 · Präparat HOS-083155

In addition, endomyocardial biopsies were performed in 8 solid tumour patients with cumulative anthracycline doses of 509 mg/m2–1,680 mg/m2. The range of Billingham cardiotoxicity scores was grades 0-1.5. These grading scores are consistent with no or mild cardiac toxicity.

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

Nebenwirkungen · Caelyx pegylated liposomal

Caelyx pegylated liposomal 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 14

HOS-085582 · Präparat HOS-083155

In the pivotal phase III trial versus doxorubicin, 58/509 (11.4%) randomised subjects (10 treated with Caelyx pegylated liposomal at a dose of 50 mg/m2/every 4 weeks versus 48 treated with doxorubicin at a dose of 60 mg/m2/every 3 weeks) met the protocol-defined criteria for cardiac toxicity during treatment and/or follow-up. Cardiac toxicity was defined as a decrease of 20 points or greater from baseline if the resting LVEF remained in the normal range or a decrease of 10 points or greater if the LVEF became abnormal (less than the lower limit for normal). None of the 10 Caelyx pegylated liposomal subjects who had cardiac toxicity by LVEF criteria developed signs and symptoms of CHF. In contrast, 10 of 48 doxorubicin subjects who had cardiac toxicity by LVEF criteria also developed signs and symptoms of CHF.

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

Nebenwirkungen · Caelyx pegylated liposomal

Caelyx pegylated liposomal 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 14

HOS-085583 · Präparat HOS-083155

In patients with solid tumours, including a subset of patients with breast and ovarian cancers, treated at a dose of 50 mg/m2/cycle with lifetime cumulative anthracycline doses up to 1,532 mg/m2, the incidence of clinically significant cardiac dysfunction was low. Of the 418 patients treated with Caelyx pegylated liposomal 50 mg/m2/cycle, and having a baseline measurement of left ventricular ejection fraction (LVEF) and at least one follow-up measurement assessed by MUGA scan, 88 patients had a cumulative anthracycline dose of > 400 mg/m2, an exposure level associated with an

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

Nebenwirkungen · Caelyx pegylated liposomal

Caelyx pegylated liposomal 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 14–15

HOS-085584 · Präparat HOS-083155

14 increased risk of cardiovascular toxicity with conventional doxorubicin. Only 13 of these 88 patients (15%) had at least one clinically significant change in their LVEF, defined as an LVEF value less than 45% or a decrease of at least 20 points from baseline. Furthermore, only 1 patient (cumulative anthracycline dose of 944 mg/m2), discontinued study treatment because of clinical symptoms of congestive heart failure.

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

Nebenwirkungen · Caelyx pegylated liposomal

Caelyx pegylated liposomal 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 15

HOS-085585 · Präparat HOS-083155

Radiation recall phenomenon Recall of skin reaction due to prior radiotherapy has occurred uncommonly with Caelyx pegylated liposomal administration.

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

Nebenwirkungen · Caelyx pegylated liposomal

Caelyx pegylated liposomal 2 mg/ml concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 15

HOS-085586 · Präparat HOS-083155

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.

Wechselwirkungen · Combivir

Combivir 150 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-088522 · Präparat HOS-083663

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products (e.g. systemic pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine and doxorubicin) may also increase the risk of adverse reactions to zidovudine. If concomitant therapy with Combivir and any of

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): ganciclovir (HOS-085194) vincristine (HOS-086219) vinblastine (HOS-086220) doxorubicin (HOS-084538) pentamidine (HOS-085605) dapsone (HOS-088141) pyrimethamine (HOS-088523) amphotericin (HOS-088524) flucytosine (HOS-088525)

Wechselwirkungen · Arava

Arava 10 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-089672 · Präparat HOS-083907

Effect on BCRP (Breast Cancer Resistance Protein) and /or organic anion transporting polypeptide B1 and B3 (OATP1B1/B3) substrates There was an increase in mean rosuvastatin Cmax and AUC (2.65- and 2.51-fold, respectively), following repeated doses of A771726. However, there was no apparent impact of this increase in plasma rosuvastatin exposure on the HMG-CoA reductase activity. If used together, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., methotrexate, topotecan, sulfasalazine, daunorubicin, doxorubicin) and the OATP family especially HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, pravastatin, methotrexate, nateglinide, repaglinide, rifampicin) concomitant administration should also be undertaken with caution. Patients should be closely monitored for signs and symptoms of excessive exposure to the medicinal products and reduction of the dose of these medicinal products should be considered.

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): sulfasalazine (HOS-089673) daunorubicin (HOS-089674) doxorubicin (HOS-084538) simvastatin (HOS-086158) atorvastatin (HOS-086304) pravastatin (HOS-086306) nateglinide (HOS-089675) repaglinide (HOS-086935) methotrexate (HOS-087522) topotecan (HOS-086047) rosuvastatin (HOS-086307)

Wechselwirkungen · Arava

Arava 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 26

HOS-089736 · Präparat HOS-083907

Effect on BCRP (Breast Cancer Resistance Protein) and /or organic anion transporting polypeptide B1 and B3 (OATP1B1/B3) substrates There was an increase in mean rosuvastatin Cmax and AUC (2.65- and 2.51-fold, respectively), following repeated doses of A771726. However, there was no apparent impact of this increase in plasma rosuvastatin exposure on the HMG-CoA reductase activity. If used together, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., methotrexate, topotecan, sulfasalazine, daunorubicin, doxorubicin) and the OATP family especially HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, pravastatin, methotrexate, nateglinide, repaglinide, rifampicin) concomitant administration should also be undertaken with caution. Patients should be closely monitored for signs and symptoms of excessive exposure to the medicinal products and reduction of the dose of these medicinal products should be considered.

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): rosuvastatin (HOS-086307) methotrexate (HOS-087522) topotecan (HOS-086047) sulfasalazine (HOS-089673) daunorubicin (HOS-089674) doxorubicin (HOS-084538) simvastatin (HOS-086158) atorvastatin (HOS-086304) pravastatin (HOS-086306) nateglinide (HOS-089675) repaglinide (HOS-086935)

Wechselwirkungen · Arava

Arava 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 43

HOS-089796 · Präparat HOS-083907

Effect on BCRP (Breast Cancer Resistance Protein) and /or organic anion transporting polypeptide B1 and B3 (OATP1B1/B3) substrates There was an increase in mean rosuvastatin Cmax and AUC (2.65- and 2.51-fold, respectively), following repeated doses of A771726. However, there was no apparent impact of this increase in plasma rosuvastatin exposure on the HMG-CoA reductase activity. If used together, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., methotrexate, topotecan, sulfasalazine, daunorubicin, doxorubicin) and the OATP family especially HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, pravastatin, methotrexate, nateglinide, repaglinide, rifampicin) concomitant administration should also be undertaken with caution. Patients should be closely monitored for signs and symptoms of excessive exposure to the medicinal products and reduction of the dose of these medicinal products should be considered.

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): methotrexate (HOS-087522) topotecan (HOS-086047) sulfasalazine (HOS-089673) daunorubicin (HOS-089674) doxorubicin (HOS-084538) simvastatin (HOS-086158) atorvastatin (HOS-086304) pravastatin (HOS-086306) nateglinide (HOS-089675) repaglinide (HOS-086935) rosuvastatin (HOS-086307)

Wechselwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 9

HOS-090902 · Präparat HOS-084155

Pharmacokinetic data from studies BO15935 and M77004 in women with HER2-positive MBC suggested that exposure to paclitaxel and doxorubicin (and their major metabolites 6-α hydroxyl- paclitaxel, POH, and doxorubicinol, DOL) was not altered in the presence of trastuzumab (8 mg/kg or 4 mg/kg IV loading dose followed by 6 mg/kg q3w or 2 mg/kg q1w IV, respectively). However, trastuzumab may elevate the overall exposure of one doxorubicin metabolite, (7-deoxy-13 dihydro-doxorubicinone, D7D). The bioactivity of D7D and the clinical impact of the elevation of this metabolite was unclear.

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): paclitaxel (HOS-087959) doxorubicin (HOS-084538)

Wechselwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.5 · PDF-Seite 10

HOS-090909 · Präparat HOS-084155

Comparison of PK results from two Phase II studies (BO15935 and M77004) and one Phase III study (H0648g) in which patients were treated concomitantly with Herceptin and paclitaxel and two Phase II studies in which Herceptin was administered as monotherapy (W016229 and MO16982), in women with HER2-positive MBC indicates that individual and mean trastuzumab trough serum concentrations varied within and across studies but there was no clear effect of the concomitant administration of paclitaxel on the pharmacokinetics of trastuzumab. Comparison of trastuzumab PK data from Study M77004 in which women with HER2-positive MBC were treated concomitantly with Herceptin, paclitaxel and doxorubicin to trastuzumab PK data in studies where Herceptin was administered as monotherapy (H0649g) or in combination with anthracycline plus cyclophosphamide or paclitaxel (Study H0648g), suggested no effect of doxorubicin and paclitaxel on the pharmacokinetics of trastuzumab.

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): paclitaxel (HOS-087959) doxorubicin (HOS-084538) cyclophosphamide (HOS-084539)

Wechselwirkungen · Herceptin

Herceptin 600 mg solution for injection in vial · Abschnitt 4.5 · PDF-Seite 40

HOS-090951 · Präparat HOS-084155

Pharmacokinetic data from studies BO15935 and M77004 in women with HER2-positive MBC suggested that exposure to paclitaxel and doxorubicin (and their major metabolites 6-α hydroxyl- paclitaxel, POH, and doxorubicinol, DOL) was not altered in the presence of trastuzumab (8 mg/kg or 4 mg/kg IV loading dose followed by 6 mg/kg q3w or 2 mg/kg q1w IV, respectively). However, trastuzumab may elevate the overall exposure of one doxorubicin metabolite, (7-deoxy-13 dihydro-doxorubicinone, D7D). The bioactivity of D7D and the clinical impact of the elevation of this metabolite was unclear.

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): paclitaxel (HOS-087959) doxorubicin (HOS-084538)

Wechselwirkungen · Herceptin

Herceptin 600 mg solution for injection in vial · Abschnitt 4.5 · PDF-Seite 40

HOS-090956 · Präparat HOS-084155

Comparison of PK results from two Phase II studies (BO15935 and M77004) and one Phase III study (H0648g) in which patients were treated concomitantly with Herceptin and paclitaxel and two Phase II studies in which Herceptin was administered as monotherapy (W016229 and MO16982), in women with HER2-positive MBC indicates that individual and mean trastuzumab trough serum concentrations varied within and across studies but there was no clear effect of the concomitant administration of paclitaxel on the pharmacokinetics of trastuzumab. Comparison of trastuzumab PK data from Study M77004 in which women with HER2-positive MBC were treated concomitantly with Herceptin, paclitaxel and doxorubicin to trastuzumab PK data in studies where Herceptin was administered as monotherapy (H0649g) or in combination with anthracycline plus cyclophosphamide or paclitaxel (Study H0648g), suggested no effect of doxorubicin and paclitaxel on the pharmacokinetics of trastuzumab.

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): paclitaxel (HOS-087959) doxorubicin (HOS-084538) cyclophosphamide (HOS-084539)

Gegenanzeigen · Myocet liposomal (previously Myocet)

Myocet liposomal 50 mg powder, dispersion and solvent for concentrate for dispersion for infusion. · Abschnitt 4.3 · PDF-Seite 3

HOS-091141 · Präparat HOS-084209

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.

Wechselwirkungen · Myocet liposomal (previously Myocet)

Myocet liposomal 50 mg powder, dispersion and solvent for concentrate for dispersion for infusion. · Abschnitt 4.5 · PDF-Seite 5–6

HOS-091142 · Präparat HOS-084209

5 Specific medicinal product compatibility studies have not been performed with Myocet liposomal. Myocet liposomal is likely to interact with substances that are known to interact with conventional doxorubicin. Plasma levels of doxorubicin and its metabolite, doxorubicinol, may be increased when doxorubicin is administered with cyclosporin, verapamil, paclitaxel or other agents that inhibit P- glycoprotein (P-Gp). Interactions with doxorubicin have also been reported for streptozocin, phenobarbital, phenytoin and warfarin. Studies of the effect of Myocet liposomal on other substances are also lacking. However, doxorubicin may potentiate the toxicity of other antineoplastic agents. Concomitant treatment with other substances reported to be cardiotoxic or with cardiologically active substances (e.g. calcium antagonists) may increase the risk for cardiotoxicity. Concomitant therapy with other liposomal or lipid-complexed substances or intravenous fat emulsions could change the pharmacokinetic profile of Myocet liposomal.

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): calcium (HOS-085615) verapamil (HOS-090602) paclitaxel (HOS-087959) streptozocin (HOS-091143) phenobarbital (HOS-085617) phenytoin (HOS-084531) warfarin (HOS-085950)

Nebenwirkungen · Myocet liposomal (previously Myocet)

Myocet liposomal 50 mg powder, dispersion and solvent for concentrate for dispersion for infusion. · Abschnitt 4.8 · PDF-Seite 6

HOS-091144 · Präparat HOS-084209

During clinical trials, the most frequently reported adverse reactions were nausea/vomiting (73%), leucopoenia (70%), alopecia (66%), neutropenia (46%), asthenia/fatigue (46%), stomatitis/mucositis (42%), thrombocytopenia (31%) and anaemia (30%).

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

Nebenwirkungen · Myocet liposomal (previously Myocet)

Myocet liposomal 50 mg powder, dispersion and solvent for concentrate for dispersion for infusion. · Abschnitt 4.8 · PDF-Seite 6

HOS-091145 · Präparat HOS-084209

The following adverse reactions have been reported with Myocet liposomal during clinical studies and post marketing experience. Adverse reactions are listed below as MedDRA preferred term by system organ class and frequency (frequencies are defined as: very common ≥1/10, common ≥1/100 to <1/10, uncommon ≥ 1/1,000 to <1/100, 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 · Myocet liposomal (previously Myocet)

Myocet liposomal 50 mg powder, dispersion and solvent for concentrate for dispersion for infusion. · Abschnitt 4.8 · PDF-Seite 6

HOS-091146 · Präparat HOS-084209

All grades Grades ≥ 3 Infections and infestations Neutropenic fever Very common Very common Infections Very common Common Herpes zoster Uncommon Uncommon Sepsis Uncommon Uncommon Injection site infection Uncommon Not known Blood and lymphatic system disorders Neutropenia Very common Very common Thrombocytopenia Very common Very common Anaemia Very common Very common

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

Nebenwirkungen · Myocet liposomal (previously Myocet)

Myocet liposomal 50 mg powder, dispersion and solvent for concentrate for dispersion for infusion. · Abschnitt 4.8 · PDF-Seite 6–7

HOS-091147 · Präparat HOS-084209

6  All grades Grades ≥ 3 Leucopenia Very common Very common Lymphopenia Common Common Pancytopenia Common Uncommon Neutropenic sepsis Uncommon Uncommon Purpura Uncommon Uncommon Metabolism and nutrition disorders Anorexia Very common Very common Dehydration Common Very common Hypokalaemia Common Uncommon Hyperglycaemia Uncommon Uncommon Psychiatric disorders Agitation Uncommon Not known Nervous system disorders Insomnia Common Uncommon Abnormal gait Uncommon Uncommon Dysphonia Uncommon Not known Somnolence Uncommon Not known Cardiac disorders Arrhythmia Common Uncommon Cardiomyopathy Common Common Congestive cardiac failure Common Common Pericardial effusion Uncommon Uncommon Vascular disorders Hot flushes Common Uncommon Hypotension Uncommon Uncommon Respiratory, thoracic and mediastinal disorders Chest pain Common Uncommon Dyspnoea Common Uncommon Epistaxis Common Uncommon Haemoptysis Uncommon Not known Pharyngitis Uncommon Not known Pleural effusion Uncommon Uncommon Pneumonitis Uncommon Uncommon Gastrointestinal disorders Nausea/vomiting Very common Very common Stomatitis/mucositis Very common Common Diarrhoea Very common Common Constipation Common Uncommon Oesophagitis Common Uncommon Gastric ulcer Uncommon Uncommon Hepatobiliary disorders Increased hepatic transaminases Common Uncommon Increased alkaline phosphatase Uncommon Uncommon Jaundice Uncommon Uncommon Increased serum bilirubin Uncommon Not known

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