Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Herceptin

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

HOS-090955 · Präparat HOS-084155

By comparison of simulated serum trastuzumab concentrations after Herceptin monotherapy (4 mg/kg loading/2 mg/kg q1w IV) and observed serum concentrations in Japanese women with HER2- positive MBC (study JP16003) no evidence of a PK effect of concurrent administration of docetaxel on the pharmacokinetics of trastuzumab was found.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): docetaxel (HOS-084505)

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.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): cyclophosphamide (HOS-084539) paclitaxel (HOS-087959) doxorubicin (HOS-084538)

Wechselwirkungen · Herceptin

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

HOS-090957 · Präparat HOS-084155

Pharmacokinetic data from Study H4613g/GO01305 suggested that carboplatin had no impact on the PK of trastuzumab.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): carboplatin (HOS-084540)

Wechselwirkungen · Herceptin

Herceptin 600 mg solution for injection in vial · Abschnitt 4.5 · PDF-Seite 40–41

HOS-090958 · Präparat HOS-084155

40 The administration of concomitant anastrozole did not appear to influence the pharmacokinetics of trastuzumab.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): anastrozole (HOS-090912)

Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-090913 · Präparat HOS-084155

Summary of the safety profile

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-090914 · Präparat HOS-084155

Amongst the most serious and/or common adverse reactions reported in Herceptin usage (intravenous and subcutaneous formulations) to date are cardiac dysfunction, infusion-related reactions, haematotoxicity (in particular neutropenia), infections and pulmonary adverse reactions.

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-090915 · Präparat HOS-084155

Tabulated list of adverse reactions

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-090916 · Präparat HOS-084155

In this section, the following categories of frequency have been used: 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-090917 · Präparat HOS-084155

Presented in Table 1 are adverse reactions that have been reported in association with the use of intravenous Herceptin alone or in combination with chemotherapy in pivotal clinical trials and in the post-marketing setting.

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-090918 · Präparat HOS-084155

All the terms included are based on the highest percentage seen in pivotal clinical trials. In addition, terms reported in the post marketing setting are included in Table 1.

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-090919 · Präparat HOS-084155

Table 1 Undesirable Effects Reported with Intravenous Herceptin Monotherapy or in Combination with Chemotherapy in Pivotal Clinical Trials (N = 8386) and in Post-Marketing

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11

HOS-090920 · Präparat HOS-084155

System organ class Adverse reaction Frequency Infections and infestations Infection Very common Nasopharyngitis Very common Neutropenic sepsis Common Cystitis Common Influenza Common Sinusitis Common Skin infection Common Rhinitis Common Upper respiratory tract infection Common Urinary tract infection Common Pharyngitis Common Neoplasms benign, Malignant neoplasm progression Not known malignant and unspecified Neoplasm progression Not known (incl. Cysts and polyps) Blood and lymphatic Febrile neutropenia Very common system disorders Anaemia Very common Neutropenia Very common White blood cell count Very common decreased/leukopenia

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

Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 11–12

HOS-090921 · Präparat HOS-084155

11 System organ class Adverse reaction Frequency Thrombocytopenia Very common Hypoprothrombinaemia Not known Immune thrombocytopenia Not known Immune system disorders Hypersensitivity Common + Anaphylactic reaction Rare + Anaphylactic shock Rare Metabolism and nutrition Weight decreased/Weight loss Very common disorders Anorexia Very common Tumour lysis syndrome Not known Hyperkalaemia Not known Psychiatric disorders Insomnia Very common Anxiety Common Depression Common 1 Nervous system disorders Tremor Very common Dizziness Very common Headache Very common Paraesthesia Very common Dysgeusia Very common Peripheral neuropathy Common Hypertonia Common Somnolence Common Eye disorders Conjunctivitis Very common Lacrimation increased Very common Dry eye Common Papilloedema Not known Retinal haemorrhage Not known Ear and labyrinth Deafness Uncommon disorders 1 Cardiac disorders Blood pressure decreased Very common 1 Blood pressure increased Very common 1 Heart beat irregular Very common 1 Cardiac flutter Very common Ejection fraction decreased* Very common + Cardiac failure (congestive) Common +1 Supraventricular tachyarrhythmia Common Cardiomyopathy Common 1 Palpitation Common Pericardial effusion Uncommon Cardiogenic shock Not known Gallop rhythm present Not known Vascular disorders Hot flush Very common +1 Hypotension Common Vasodilatation Common + Respiratory, thoracic and Dyspnoea Very common mediastinal disorders Cough Very common Epistaxis Very common Rhinorrhoea Very common + Pneumonia Common Asthma Common Lung disorder Common + Pleural effusion Common +1 Wheezing Uncommon Pneumonitis Uncommon

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

Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 12–13

HOS-090922 · Präparat HOS-084155

12 System organ class Adverse reaction Frequency + Pulmonary fibrosis Not known + Respiratory distress Not known + Respiratory failure Not known + Lung infiltration Not known + Acute pulmonary oedema Not known + Acute respiratory distress syndrome Not known + Bronchospasm Not known + Hypoxia Not known + Oxygen saturation decreased Not known Laryngeal oedema Not known Orthopnoea Not known Pulmonary oedema Not known Interstitial lung disease Not known Gastrointestinal disorders Diarrhoea Very common Vomiting Very common Nausea Very common 1 Lip swelling Very common Abdominal pain Very common Dyspepsia Very common Constipation Very common Stomatitis Very common Haemorrhoids Common Dry mouth Common Hepatobiliary disorders Hepatocellular injury Common Hepatitis Common Liver tenderness Common Jaundice Rare Skin and subcutaneous Erythema Very common tissue disorders Rash Very common 1 Swelling face Very common Alopecia Very common Nail disorder Very common Palmar-plantar erythrodysaesthesia Very common syndrome Acne Common Dry skin Common Ecchymosis Common Hyperhydrosis Common Maculopapular rash Common Pruritus Common Onychoclasis Common Dermatitis Common Urticaria Uncommon Angioedema Not known Musculoskeletal and Arthralgia Very common 1 connective tissue Muscle tightness Very common disorders Myalgia Very common Arthritis Common Back pain Common Bone pain Common Muscle spasms Common Neck Pain Common

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

Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 13–14

HOS-090923 · Präparat HOS-084155

13  System organ class Adverse reaction Frequency Pain in extremity Common Renal and urinary Renal disorder Common disorders Glomerulonephritis membranous Not known Glomerulonephropathy Not known Renal failure Not known Pregnancy, puerperium Oligohydramnios Not known and perinatal conditions Renal hypoplasia Not known Pulmonary hypoplasia Not known Reproductive system and Breast inflammation/mastitis Common breast disorders General disorders and Asthenia Very common administration site Chest pain Very common conditions Chills Very common Fatigue Very common Influenza-like symptoms Very common Infusion related reaction Very common Pain Very common Pyrexia Very common Mucosal inflammation Very common Peripheral oedema Very common Malaise Common Oedema Common Injury, poisoning and Contusion Common procedural complications + Denotes adverse reactions that have been reported in association with a fatal outcome. 1 Denotes adverse reactions that are reported largely in association with Infusion-related reactions. Specific percentages for these are not available. * Observed with combination therapy following anthracyclines and combined with taxanes

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 14

HOS-090924 · Präparat HOS-084155

Description of selected adverse reactions

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 14

HOS-090925 · Präparat HOS-084155

Cardiac dysfunction

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 14

HOS-090926 · Präparat HOS-084155

Congestive heart failure (NYHA Class II – IV) is a common adverse reaction associated with the use of Herceptin and has been associated with a fatal outcome (see section 4.4). Signs and symptoms of cardiac dysfunction such as dyspnoea, orthopnoea, increased cough, pulmonary oedema, S3 gallop, or reduced ventricular ejection fraction, have been observed in patients treated with Herceptin (see section 4.4).

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 14

HOS-090927 · Präparat HOS-084155

In 3 pivotal clinical trials of adjuvant Herceptin given in combination with chemotherapy, the incidence of grade 3/4 cardiac dysfunction (specifically symptomatic Congestive Heart Failure) was similar in patients who were administered chemotherapy alone (ie did not receive Herceptin) and in patients who were administered Herceptin sequentially after a taxane (0.3-0.4 %). The rate was highest in patients who were administered Herceptin concurrently with a taxane (2.0 %). In the neoadjuvant setting, the experience of concurrent administration of Herceptin and low dose anthracycline regimen is limited (see section 4.4).

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Nebenwirkungen · Herceptin

Herceptin 150 mg powder for concentrate for solution for infusion · Abschnitt 4.8 · PDF-Seite 14

HOS-090928 · Präparat HOS-084155

When Herceptin was administered after completion of adjuvant chemotherapy NYHA Class III-IV heart failure was observed in 0.6 % of patients in the one-year arm after a median follow-up of 12 months. In study BO16348, after a median follow-up of 8 years the incidence of severe CHF (NYHA Class III & IV) in the Herceptin 1 year treatment arm was 0.8 %, and the rate of mild symptomatic and asymptomatic left ventricular dysfunction was 4.6 %.

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