FULVESTRANT ZENTIVA

Posology Adult females (including elderly) The recommended dose is 500 mg at intervals of one month, with an additional 500 mg dose given two weeks after the initial dose. When fulvestrant is used in combination with palbociclib, please also refer to the Summary of Product Characteristics of palbociclib.

Prior to the start of treatment with the combination of fulvestrant plus palbociclib, and throughout its duration, pre/perimenopausal women should be treated with LHRH agonists according to local clinical practice. Special population Renal impairment No dose adjustments are recommended for patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml/min).

4). Hepatic impairment No dose adjustments are recommended for patients with mild to moderate hepatic impairment. However, as fulvestrant exposure may be increased, fulvestrant should be used with caution in these patients. 2). Paediatric population The safety and efficacy of fulvestrant in children from birth to 18 years of age have not been established.

2, but no recommendation on a posology can be made. Method of administration Fulvestrant should be administered as two consecutive 5 ml injections by slow intramuscular injection (1-2 minutes/injection), one in each buttock (gluteal area) Caution should be taken if injecting fulvestrant at the dorsogluteal site due to the proximity of the underlying sciatic nerve.

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Summary of safety profile Monotherapy This section provides information based on all adverse reactions from clinical trials, post-marketing studies or spontaneous reports. In the pooled dataset of fulvestrant monotherapy, the most frequently reported adverse reactions are 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 the following table were based on all reported adverse drug reactions, regardless of the investigator assessment of causality.

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. 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 Very common Hypersensitivity reactionse Immune system disorders Uncommon Anaphylactic reactions Metabolism and nutrition disorders Common Anorexiaa Nervous system disorders Common Headache Very common Hot flushese Vascular disorders Common Venous thromboembolisma Very common NauseaGastrointestinal disorders Common Vomiting, Diarrhoea Very common Elevated hepatic enzymes (ALT, AST, ALP)a Common Elevated bilirubina Hepatobiliary disorders Uncommon Hepatic failurecf, Hepatitisf, Elevated gamma-GTf Skin and subcutaneous tissue disorders Very common Rashe Very common Joint and musculoskeletal paind Musculoskeletal and connective tissue disorders Common Back paina Common Vaginal haemorrhagee Reproductive system and breast disorders Uncommon Vaginal moniliasisf, Leukorrheaf Very common Asthenia, Injection site reactionsb Common Neuropathy peripherale, Sciaticae General disorders and administration site conditions Uncommon Injection site haemorrhagef, Injection site haematomaf, 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 and 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. Description of selected adverse reactions 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.

1%) for fulvestrant and anastrozole arms, respectively. 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.

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, anaemia, infections, AST increased, thrombocytopenia, and fatigue. 8 months in the fulvestrant + placebo arm. 8 months. 6) 6 […]

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.

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.

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.

Ethanol This medicinal product contains 500 mg of alcohol (ethanol) in each injection which is equivalent to 100 mg/ ml (10% w/v). The amount in each injection of this medicine is equivalent to 13 ml beer or 5 ml wine. 4 mg /100 ml (see Appendix I of report EMA/CHMP/43486/2018).

For comparison, for an adult drinking a glass of wine or 500 ml of beer, the BAC is likely to be about 50 mg/ 100 ml. g. propylene glycol or ethanol may lead to accumulation of ethanol and induce adverse effects. Benzyl alcohol This medicinal product contains benzyl alcohol as an excipient which may cause allergic reactions.

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