Fulvestrant Mylan · 4.6 Fertility, pregnancy and lactation · 1

HOS-098497 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile 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). 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. Tabulated list of adverse reactions 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. 5 Table 1 Adverse drug reactions reported in patients treated with fulvestrant monotherapy 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 Co

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HOS-098493 · has-contraindication-information · PDF-Seite 3

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).

HOS-098492 · has-indication-information · PDF-Seite 2

Fulvestrant is indicated: • as monotherapy for the treatment of estrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women: - not previously treated with endocrine therapy, or - with disease relapse on or after adjuvant antiestrogen therapy, or disease progression on antiestrogen therapy. • in combination with palbociclib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in women who have received prior endocrine therapy (see section 5.1). In pre- or perimenopausal women, the combination treatment with palbociclib should be combined with a luteinizing hormone releasing hormone (LHRH) agonist.

HOS-098495 · has-interaction-information · PDF-Seite 4

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.

HOS-098496 · has-pregnancy-information · PDF-Seite 4

Women of childbearing potential Patients of child-bearing potential should use effective contraception during treatment with Fulvestrant Mylan and for 2 years after the last dose. 4 Pregnancy Fulvestrant is contraindicated in pregnancy (see section 4.3). Fulvestrant has been shown to cross the placenta after single intramuscular doses in rat and rabbit. Studies in animals have shown reproductive toxicity including an increased incidence of foetal abnormalities and deaths (see section 5.3). If pregnancy occurs while taking fulvestrant, the patient must be informed of the potential hazard to the foetus and potential risk for loss of pregnancy. Breast-feeding Breast-feeding must be discontinued during treatment with fulvestrant. Fulvestrant is excreted in milk in lactating rats. It is not known whether fulvestrant is excreted in human milk. Considering the potential for serious adverse reactions due to fulvestrant in breast-fed infants, use during lactation is contraindicated (see section 4.3). Fertility The effects of fulvestrant on fertility in humans has not been studied.

HOS-098494 · has-warning-information · PDF-Seite 3

Fulvestrant should be used with caution in patients with mild to moderate hepatic impairment (see sections 4.2, 4.3 and 5.2). Fulvestrant should be used with caution in patients with severe renal impairment (creatinine clearance less than 30 ml/min). Due to the intramuscular route of administration, fulvestrant should be used with caution if treating patients with bleeding diatheses, thrombocytopenia or those taking anticoagulant treatment. Thromboembolic events are commonly observed in women with advanced breast cancer and have been observed in clinical studies with fulvestrant (see section 4.8). This should be taken into consideration when prescribing fulvestrant to patients at risk. Injection site related events including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy have been reported with fulvestrant injection. Caution should be taken while administering fulvestrant 3 at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve (see sections 4.2 and 4.8). There are no long-term data on the effect of fulvestrant on bone. Due to the mechanism of action of fulvestrant, there is a potential risk of osteoporosis. The efficacy and safety of fulvestrant (either as monotherapy or in combination with palbociclib) have not been studied in patients with critical visceral disease. When fulvestrant is combined with palbociclib, please also refer to the Summary of Product Characteristics of palbociclib. Interference with estradiol antibody assays Due to the structural similarity of fulvestrant and estradiol, fulvestrant may interfere with antibody based-estradiol assays and may result in falsely increased levels of estradiol. Paediatric population Fulvestrant is not recommended for use in children and adolescents as safety and efficacy have not been established in this group of patients (see section 5.1). Fulvestrant Mylan contains 10% w/v alcohol (ethanol) This medicinal product contains 500 mg alcohol (ethanol) in each 5 ml which is equivalent to 10% w/v. The amount in one treatment dose (i.e. two syringes) of this medicinal product is equivalent to less than 25 ml beer or 10 ml wine. The small amount of alcohol in this medicinal product will not have any noticeable effects. Fulvestrant Mylan contains benzyl alcohol This medicinal product contains 500 mg benzyl alcohol in each 5 ml which is equivalent to 100 mg/ml (10% w/v). Benzyl alcohol may cause

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