FULVESTRANT EVER PHARMA

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 EVER Pharma 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 EVER Pharma plus palbociclib, and throughout its duration, pre/perimenopausal women should be treated with LHRH agonists according to local clinical practice. Special populations 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 EVER Pharma 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 EVER Pharma 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 EVER Pharma at the dorsogluteal site due to the proximity of the underlying sciatic nerve. 6.

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.

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 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 Very common NauseaGastrointestinal disorders Common Vomiting, diarrhoea Very common Elevated hepatic enzymes (ALT, AST, ALP)a Common Elevated bilirubina Hepatobiliary disorders Uncommon Hepatic failurec, f, hepatitisf, elevated gamma-GTf Skin and subcutaneous tissue disorders Very common Rashe Musculoskeletal and connective tissue disorders Very common Joint and musculoskeletal paind Common Back paina Reproductive system and breast disorders Common Vaginal haemorrhagee Uncommon Vaginal moniliasisf, leukorrheaf, Very common Astheniaa, injection site reactionsb Common Neuropathy peripherale, sciaticae General disorders and administration site conditions Uncommon Injection site haemorrhagef, injection site haematomaf, neuralgiacf a Includes adverse drug reactions for which the exact contribution of fulvestrant cannot be assessed due to the underlying disease.

2). Fulvestrant EVER Pharma 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 EVER Pharma 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 EVER Pharma to patients at risk. Injection site related events including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy have been reported with fulvestrant injection.

8). The amount of alcohol in each syringe of this medicine is equivalent to less than 10 ml beer or 4 ml wine. The small amount of alcohol in this medicine will not have any noticeable effects. To be taken into account in pregnant or breast-feeding women, and high-risk groups such as patients with liver disease, or epilepsy.

Fulvestrant EVER Pharma contains 500 mg benzyl alcohol in each syringe which is equivalent to 100 mg/ml. Benzyl alcohol may cause allergic reactions. High volumes should be used with caution and only if necessary, especially in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).

This medicine contains 750 mg benzyl benzoate in each syringe which is equivalent to 150 mg/ml. 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 EVER Pharma 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. 1). Fulvestrant EVER Pharma contains benzyl alcohol.

1. 6). 2).