Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.3 · PDF-Seite 3

HOS-140272 · Präparat HOS-098490

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Pregnancy and lactation (see section 4.6). Severe hepatic impairment (see sections 4.4 and 5.2).

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Wechselwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.5 · PDF-Seite 4

HOS-140273 · Präparat HOS-098490

A clinical interaction study with midazolam (substrate of CYP3A4) demonstrated that fulvestrant does not inhibit CYP3A4. Clinical interaction studies with rifampicin (inducer of CYP3A4) and ketoconazole (inhibitor of CYP3A4) showed no clinically relevant change in fulvestrant clearance. Dose adjustment is therefore not necessary in patients who are receiving fulvestrant and CYP3A4 inhibitors or inducers concomitantly.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): ketoconazole (HOS-084513) midazolam (HOS-086167)

Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 5

HOS-140276 · Präparat HOS-098490

Summary of the safety profile

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 5

HOS-140277 · Präparat HOS-098490

Monotherapy This section provides information based on all adverse reactions from clinical studies, post-marketing studies or spontaneous reports. In the pooled dataset of fulvestrant monotherapy, the most frequently reported adverse reactions were injection site reactions, asthenia, nausea, and increased hepatic enzymes (ALT, AST, ALP).

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 5

HOS-140278 · Präparat HOS-098490

In table 1, the following frequency categories for adverse drug reactions (ADRs) were calculated based on the fulvestrant 500 mg treatment group in pooled safety analyses of studies that compared fulvestrant 500 mg with fulvestrant 250 mg [CONFIRM (Study D6997C00002), FINDER 1 (Study D6997C00004), FINDER 2 (Study D6997C00006), and NEWEST (Study D6997C00003) studies], or from FALCON (Study D699BC00001) alone that compared fulvestrant 500 mg with anastrozole 1 mg. Where frequencies differ between the pooled safety analysis and FALCON, the highest frequency is presented. The frequencies in Table 1 were based on all reported adverse drug reactions, regardless of the investigator assessment of causality. The median duration of fulvestrant 500 mg treatment across the pooled dataset (including the studies mentioned above plus FALCON) was 6.5 months.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 5

HOS-140279 · Präparat HOS-098490

Tabulated list of adverse reactions

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 5

HOS-140280 · Präparat HOS-098490

Adverse reactions listed below are classified according to frequency and System Organ Class (SOC). Frequency groupings are defined according to the following convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100). Within each frequency grouping adverse reactions are reported in order of decreasing seriousness.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 5–6

HOS-140281 · Präparat HOS-098490

5 Table 1 Adverse drug reactions reported in patients treated with fulvestrant monotherapy

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 6

HOS-140282 · Präparat HOS-098490

Adverse reactions by system organ class and frequency Infections and infestations Common Urinary tract infections Blood and lymphatic system disorders Common Reduced platelet counte Immune system disorders Very common Hypersensitivity reactionse Uncommon Anaphylactic reactions Metabolism and nutrition disorders Common Anorexiaa Nervous system disorders Common Headache Vascular disorders Very common Hot flushese Common Venous thromboembolisma Gastrointestinal disorders Very common Nausea Common Vomiting, diarrhoea Hepatobiliary disorders Very common Elevated hepatic enzymes (ALT, AST, ALP) a Common Elevated bilirubina Uncommon Hepatic failurec,f, hepatitis f, elevated gamma-GT f Skin and subcutaneous tissue disorders Very common Rashe Musculoskeletal and connective tissue Very common Joint and musculoskeletal paind disorders Common Back paina Reproductive system and breast disorders Common Vaginal haemorrhagee Uncommon Vaginal moniliasis f, leukorrhea f General disorders and administration site Very common Astheniaa, injection site reactionsb conditions Common Neuropathy peripherale, sciaticae Uncommon Injection site haemorrhage f, injection site haematoma f, neuralgiac,f a Includes adverse drug reactions for which the exact contribution of fulvestrant cannot be assessed due to the underlying disease. b The term injection site reactions does not include the terms injection site haemorrhage, injection site haematoma, sciatica, neuralgia and neuropathy peripheral. c The event was not observed in major clinical studies (CONFIRM, FINDER 1, FINDER 2, NEWEST). The frequency has been calculated using the upper limit of the 95% confidence interval for the point estimate. This is calculated as 3/560 (where 560 is the number of patients in the major clinical studies), which equates to a frequency category of ‘uncommon’. d Includes: arthralgia, and less frequently musculoskeletal pain, myalgia and pain in extremity. e Frequency category differs between pooled safety dataset and FALCON. f ADR was not observed in FALCON.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 6

HOS-140283 · Präparat HOS-098490

Description of selected adverse reactions

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 6

HOS-140284 · Präparat HOS-098490

The descriptions included below are based on the safety analysis set of 228 patients who received at least one (1) dose of fulvestrant and 232 patients who received at least one (1) dose of anastrozole, respectively in the Phase 3 FALCON study.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 6–7

HOS-140285 · Präparat HOS-098490

6 Joint and musculoskeletal pain In the FALCON study, the number of patients who reported an adverse reaction of joint and musculoskeletal pain was 65 (31.2%) and 48 (24.1%) for fulvestrant and anastrozole arms, respectively. Of the 65 patients in the fulvestrant arm, 40% (26/65) of patients reported joint and musculoskeletal pain within the first month of treatment, and 66.2% (43/65) of patients within the first 3 months of treatment. No patients reported events that were CTCAE Grade ≥3 or that required a dose reduction, dose interruption, or discontinued treatment due to these adverse reactions.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 7

HOS-140286 · Präparat HOS-098490

Combination therapy with palbociclib The overall safety profile of fulvestrant when used in combination with palbociclib is based on data from 517 patients with HR-positive, HER2-negative advanced or metastatic breast cancer in the randomised PALOMA3 study (see section 5.1). The most common (≥20%) adverse reactions of any grade reported in patients receiving fulvestrant in combination with palbociclib were neutropenia, leukopenia, infections, fatigue, nausea, anaemia, stomatitis, diarrhoea, thrombocytopenia and vomiting. The most common (≥2%) Grade ≥3 adverse reactions were neutropenia, leukopenia, infections, anaemia, AST increased, thrombocytopenia, and fatigue.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 7

HOS-140287 · Präparat HOS-098490

Table 2 reports the adverse reactions from PALOMA3. Median duration of exposure to fulvestrant was 11.2 months in the fulvestrant + palbociclib arm and 4.8 months in the fulvestrant + placebo arm. Median duration of exposure to palbociclib in the fulvestrant + palbociclib arm was 10.8 months.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 7

HOS-140288 · Präparat HOS-098490

Table 2 Adverse reactions based on PALOMA3 Study (N=517)

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 7

HOS-140289 · Präparat HOS-098490

Fulvestrant + Palbociclib Fulvestrant + placebo System Organ Class (N=345) (N=172) Frequency Preferred Terma All Grades Grade ≥ 3 All Grades Grade ≥ 3 n (%) n (%) n (%) n (%) Infections and infestations Very common Infectionsb 188 (54.5) 19 (5.5) 60 (34.9) 6 (3.5) Blood and lymphatic system disorders Very common Neutropeniac 290 (84.1) 240 (69.6) 6 (3.5) 0 Leukopeniad 207 (60.0) 132 (38.3) 9 (5.2) 1 (0.6) Anaemiae 109 (31.6) 15 (4.3) 24 (14.0) 4 (2.3) Thrombocytopeniaf 88 (25.5) 10 (2.9) 0 0 Uncommon Febrile neutropenia 3 (0.9) 3 (0.9) 0 0 Metabolism and nutrition disorders Very common Decreased appetite 60 (17.4) 4 (1.2) 18 (10.5) 1 (0.6) Nervous system disorders Common Dysgeusia 27 (7.8) 0 6 (3.5) 0 Eye disorders Common Lacrimation increased 25 (7.2) 0 2 (1.2) 0 Vision blurred 24 (7.0) 0 3 (1.7) 0

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 7–8

HOS-140290 · Präparat HOS-098490

7  Dry eye 15 (4.3) 0 3 (1.7) 0 Respiratory, thoracic and mediastinal disorders Common Epistaxis 25 (7.2) 0 4 (2.3) 0 Gastrointestinal disorders Very common Nausea 124 (35.9) 2 (0.6) 53 (30.8) 1 (0.6) g Stomatitis 104 (30.1) 3 (0.9) 24 (14.0) 0 Diarrhoea 94 (27.2) 0 35 (20.3) 2 (1.2) Vomiting 75 (21.7) 2 (0.6) 28 (16.3) 1 (0.6) Skin and subcutaneous tissue disorders Very common Alopecia 67 (19.4) NA 11 (6.4) NA h Rash 63 (18.3) 3 (0.9) 10 (5.8) 0 Common Dry skin 28 (8.1) 0 3 (1.7) 0 General disorders and administration site conditions Very common Fatigue 152 (44.1) 9 (2.6) 54 (31.4) 2 (1.2) Pyrexia 47 (13.6) 1 (0.3) 10 (5.8) 0 Common Asthenia 27 (7.8) 1 (0.3) 13 (7.6) 2 (1.2) Investigations Very common AST increased 40 (11.6) 11 (3.2) 13 (7.6) 4 (2.3) Common ALT increased 30 (8.7) 7 (2.0) 10 (5.8) 1 (0.6) ALT=alanine aminotransferase; AST=aspartate aminotransferase; N/n=number of patients; NA=Not applicable a Preferred Terms (PTs) are listed according to MedDRA 17.1. b Infections includes all PTs that are part of the System Organ Class Infections and infestations. c Neutropenia includes the following PTs: Neutropenia, Neutrophil count decreased. d Leukopenia includes the following PTs: Leukopenia, White blood cell count decreased. e Anaemia includes the following PTs: Anaemia, Haemoglobin decreased, Haematocrit decreased. f Thrombocytopenia includes the following PTs: Thrombocytopenia, Platelet count decreased. g Stomatitis includes the following PTs: Aphthous stomatitis, Cheilitis, Glossitis, Glossodynia, Mouth ulceration, Mucosal inflammation, Oral pain, Oropharyngeal discomfort, Oropharyngeal pain, Stomatitis. h Rash includes the following PTs: Rash, Rash maculo-papular, Rash pruritic, Rash erythematous, Rash papular, Dermatitis, Dermatitis acneiform, Toxic skin eruption.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 8

HOS-140291 · Präparat HOS-098490

Neutropenia In patients receiving fulvestrant in combination with palbociclib in the PALOMA3 study, neutropenia of any grade was reported in 290 (84.1%) patients, with Grade 3 neutropenia being reported in 200 (58.0%) patients, and Grade 4 neutropenia being reported in 40 (11.6%) patients. In the fulvestrant + placebo arm (n=172), neutropenia of any grade was reported in 6 (3.5%) patients. There were no reports of Grade 3 and 4 neutropenia in the fulvestrant + placebo arm.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 8–9

HOS-140292 · Präparat HOS-098490

8 In patients receiving fulvestrant in combination with palbociclib, the median time to first episode of any grade neutropenia was 15 days (range: 13-512 days) and the median duration of Grade ≥3 neutropenia was 16 days. Febrile neutropenia has been reported in 3 (0.9%) patients receiving fulvestrant in combination with palbociclib.

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Nebenwirkungen · Fulvestrant Mylan

Fulvestrant Mylan 250 mg solution for injection in prefilled syringe · Abschnitt 4.8 · PDF-Seite 9

HOS-140293 · Präparat HOS-098490

Reporting of suspected adverse reactions

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