Consumer medicine information

Faslodex

Fulvestrant

BRAND INFORMATION

Brand name

Faslodex

Active ingredient

Fulvestrant

Schedule

What is in this leaflet

This leaflet answers some of the common questions people ask about FASLODEX. It does not contain all the information that is known about FASLODEX.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor will have weighed the risks of you taking FASLODEX against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What FASLODEX is for

FASLODEX is used to treat women who have been through menopause with:

hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative, locally advanced or metastatic breast cancer who have not been previously treated with endocrine therapy.
HR positive, locally advanced or metastatic breast cancer who have progressive disease following prior endocrine (anti-oestrogen or aromatase inhibitor) therapy.

FASLODEX stops some of the actions of oestrogen within the body.

Oestrogen is a female sex hormone that may help cancer cells grow in women with breast cancer.

FASLODEX should only be given to women.

FASLODEX is not recommended for use in men or children.

FASLODEX does not kill cancer cells, however it stops or slows their growth.

Your doctor will have explained why you are being treated with FASLODEX and will determine what dose to give you.

Follow all directions given to you by your doctor. They may differ from the information contained in this leaflet.

Your doctor may prescribe this medicine for another use. Ask your doctor if you want more information.

FASLODEX is not addictive.

Before you are given FASLODEX

When you must not use it

Do not use FASLODEX if you have any allergies to the active ingredient fulvestrant, or any of the other ingredients used in FASLODEX.

Do not use FASLODEX if you have not reached menopause. We do not have information on its use in women before menopause.

Do not use FASLODEX if you are pregnant or breastfeeding. It is not known if it is safe for you to be given it while you are pregnant. It may affect your baby if you are given it at any time during pregnancy. If you can become pregnant, you should use effective contraception while you are being treated with FASLODEX and for 2 years after the last dose.

Do not use FASLODEX if you are breastfeeding.

FASLODEX should not be given to children. There is no information on its use in children.

FASLODEX should not be given to men. There is no information on its use in men.

FASLODEX injection should only be used if the solution is clear, the package is undamaged and the use by (expiry) date marked on the pack has not been passed.

Before you are given it

You must tell your doctor if:

you have any allergies to

any medicines
any other substances, such as foods, preservatives or dyes

If you have an allergic reaction, you may get a skin rash, swelling of the extremities, hayfever, difficulty breathing or feel faint.

you have any of these medical conditions

liver problems
kidney problems
bleeding disorders
a low blood platelet count

It may not be safe for you to be given FASLODEX if you have any of these conditions.

Taking other medicines

Tell your doctor if you are taking any other medicines, including:

tamoxifen or any medicine which contains oestrogen (female sex hormone). These medicines may reduce the effect of FASLODEX
other medicines used to treat cancer
medicines that you buy at the chemist, supermarket or health food shop.

These medicines may affect the way FASLODEX works.

Your doctor or pharmacist can tell you what to do if you are taking any of these medicines.

If you have not told your doctor about any of these things, tell them before you are given FASLODEX.

How FASLODEX is given

The usual dose is 500 mg fulvestrant (two (2) x 250 mg/5 ml injections) given once a month with an additional 500 mg dose given 2 weeks after the initial dose.

Your doctor or nurse will give you FASLODEX as a slow intramuscular injection, one into each of your buttocks

Overdose

The doctor or nurse giving you FASLODEX will be experienced in its use, so it is unlikely that you will be given too much. If you are concerned that you have been given too much Faslodex, tell your doctor or nurse immediately. Otherwise telephone the Poisons Information Centre (telephone 13 11 26) for advice.

While you are using it

Things you must do

Be sure to keep all your appointments with your doctor so your progress can be checked.

Tell any other doctors, dentists and pharmacists who are treating you that you have been given FASLODEX.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you have been given FASLODEX.

If you go into hospital, please let the medical staff know that you are being treated with FASLODEX.

Things to be careful of

Be careful driving or operating machinery until you know how FASLODEX affects you. Some patients may occasionally feel weak, tired or sleepy.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking FASLODEX.

FASLODEX helps most people with breast cancer, but it may have unwanted side-effects in some people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

pain or inflammation at the injection site
hot flushes
headache
weakness, tiredness, sleepiness
nausea or vomiting
diarrhoea
loss of appetite
skin rash
urinary tract infections
hypersensitivity, including swelling of the face, lips, tongue and/or throat and hives/welts
joint or muscle pain.

These are all possible side effects of FASLODEX.

FASLODEX may be associated with changes in your blood, urine or liver. Your doctor may want to perform tests from time to time to check on your progress and detect any unwanted side effects.

Tell your doctor if you notice anything else that is making you feel unwell. Some people may get other side effects while being treated with FASLODEX.

After using it

Storage

FASLODEX should be stored in a fridge (2°C - 8°C) until ready for use. Your doctor or pharmacist will usually store the medicine for you.

Disposal

Your doctor or pharmacist will dispose of any needles, syringes and FASLODEX that may be left over.

Product description

What FASLODEX looks like

FASLODEX is a clear, colourless to yellow viscous liquid for injection. Each pack contains two (2) x 5mL pre-filled syringes.

Ingredients

Each FASLODEX syringe contains 250mg/5mL of the active ingredient fulvestrant

plus

ethanol

benzyl alcohol

benzyl benzoate

castor oil

Supplier

FASLODEX is sponsored and supplied in Australia by:

AstraZeneca Pty Ltd
ABN 54 009 805 342
66 Talavera Road
MACQUARIE PARK NSW 2113
Phone 1800 805342

This leaflet was prepared on 15 March 2021

Australian Registration Number
AUST R 106955

Doc ID-003508991 v 5.0

Published by MIMS April 2021

BRAND INFORMATION

Brand name

Faslodex

Active ingredient

Fulvestrant

Schedule

1 Name of Medicine

The active ingredient in Faslodex is fulvestrant.

2 Qualitative and Quantitative Composition

Faslodex contains 250 mg/5 mL fulvestrant drug substance.
Fulvestrant is a white powder with low aqueous solubility. Only 1 morphological form is known to exist. Fulvestrant is highly lipophilic and does not ionise at physiological pH.

Excipients with known effects.

Benzoates and alcohol. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Faslodex 250 mg/5 mL solution for injection is a clear, colourless to yellow, viscous liquid.

4 Clinical Particulars

4.1 Therapeutic Indications

Faslodex is indicated for the treatment of postmenopausal women with:
hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative, locally advanced or metastatic breast cancer who have not been previously treated with endocrine therapy;
HR positive, locally advanced or metastatic breast cancer who have progressive disease following prior endocrine (anti-oestrogen or aromatase inhibitor) therapy.

4.2 Dose and Method of Administration

In the absence of incompatibility studies, Faslodex must not be mixed with other drugs. Faslodex is not recommended for use in men.

Adult females (including the elderly).

The recommended dose (500 mg) is to be administered intramuscularly as two 5 mL injections, one in each buttock (gluteal area), at intervals of 1 month.
An additional 500 mg dose is to be given 2 weeks after the initial dose.
It is recommended that the injection be administered slowly (1-2 minutes/injection).
Caution should be taken if injecting Faslodex at the dorsogluteal site due to the proximity of the underlying sciatic nerve.

Special patient populations.

Patients with hepatic insufficiency.

No dose adjustments are recommended for patients with mild hepatic impairment. Safety and efficacy have not been further evaluated in patients with moderate to severe hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use).

Patients with renal insufficiency.

No dose adjustments are recommended for patients with a creatinine clearance greater than 30 mL/min. Safety and efficacy have not been further evaluated in patients with creatinine clearance less than 30 mL/min (see Section 4.4 Special Warnings and Precautions for Use).

Use in the elderly.

No dose adjustment is required for elderly patients.

Paediatric use.

Not recommended for use in children or adolescents as safety and effectiveness have not been established in this age group.

4.3 Contraindications

Faslodex is contraindicated in patients with a known hypersensitivity to the drug substance or to any of the excipients.
Faslodex is contraindicated in pregnancy.

4.4 Special Warnings and Precautions for Use

Use in hepatic impairment.

Fulvestrant is metabolised primarily in the liver. In clinical trials in patients with advanced breast cancer, in which Faslodex has been administered to patients with mild hepatic impairment (alanine aminotransferase concentration greater than the upper limit of the normal reference range [ULN] but less than twice the ULN). There was no clear relationship between fulvestrant clearance and hepatic impairment. The safety profile in patients with mild hepatic impairment was similar to that seen in patients with no hepatic impairment. Caution should be used with Faslodex in patients with moderate to severe hepatic impairment, as clearance may be reduced.

Use in renal impairment.

Caution should be used before treating patients with creatinine clearance less than 30 mL/min. See Section 5.2 Pharmacokinetic Properties.

Coagulation disorders.

Caution should be used before treating patients with bleeding diatheses or thrombocytopenia or patients on anticoagulants due to the route of administration.

Injection site related events.

Injection site related events including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy have been reported with Faslodex injection. Caution should be taken while administering Faslodex at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve (see Section 4.2 Dose and Method of Administration; Section 4.8 Adverse Effects (Undesirable Effects)).

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

Interference with oestradiol assay.

Due to the structural similarity of fulvestrant and oestradiol, fulvestrant may interfere with antibody based oestradiol assays and may result in falsely increased levels of oestradiol.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Fulvestrant does not significantly inhibit any of the major cytochrome P450 (CYP) isoenzymes in vitro and results from a clinical pharmacokinetic trial involving coadministration of fulvestrant with midazolam also suggest that therapeutic doses of fulvestrant will have no inhibitory effects on CYP3A4. In addition, although fulvestrant can be metabolised by CYP3A4 in vitro, a clinical study with rifampicin showed no change in fulvestrant clearance as a result of the induction of CYP3A4. Dosage adjustment is not necessary in patients coprescribed CYP3A4 inhibitors or inducers.
There are no known drug-drug interactions requiring dose adjustment.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fulvestrant affected oestrus cycling in rats causing a reduction in female fertility at doses as low as 0.01 mg/kg/day, considerably lower than the clinical dose on a body surface area basis. Embryonic survival was also reduced. These effects are consistent with the antioestrogenic activity of fulvestrant. These effects were largely reversible in rats after a 1 month withdrawal period from the drug. Faslodex is not proposed for use in males, but loss of spermatozoa from the seminiferous tubules, seminiferous tubular atrophy and degenerative changes in the epididymides were observed in a 6 month study in rats given fulvestrant by the intramuscular route.
(Category D)
Faslodex is proposed for use in postmenopausal women only. Faslodex may cause foetal harm when administered to a pregnant woman. If Faslodex is used during pregnancy or if the patient becomes pregnant while receiving this drug, the patient should be informed of the potential hazard to the foetus or potential risk for loss of the pregnancy. If Faslodex is used in patients of childbearing potential, patients should use effective contraception during treatment with Faslodex and for 2 years after the last dose. In rats, fulvestrant caused a reversible reduction in embryonic survival at intramuscular doses as low as 0.01 mg/kg/day, considerably lower than the clinical dose calculated on a body surface area basis. Fulvestrant also caused dystocia and an increased occurrence of foetal abnormalities in rats, including tarsal flexure, at an intramuscular dose of 2 mg/kg/day, corresponding to approximately twice the clinical dose calculated on a body surface area basis. Rabbits given intramuscular fulvestrant at ≥ 1 mg/kg/day (corresponding to approximately twice the clinical dose calculated on a body surface area) failed to maintain pregnancy, while at doses of 0.25 mg/kg/day, there were small increases in postimplantation loss, placental weight and incidences of two foetal variations.
Studies in rats have shown that fulvestrant levels in rat milk are significantly higher than those in rat plasma. The potential risk for nursing infants is unknown. Therefore, breastfeeding should be avoided in women receiving Faslodex.

4.7 Effects on Ability to Drive and Use Machines

During treatment with Faslodex, asthenia has been reported and caution should be observed by those patients who experience this symptom when driving or operating machinery.

4.8 Adverse Effects (Undesirable Effects)

The following frequency categories for adverse drug reactions (ADRs) were calculated based on the Faslodex 500 mg treatment group in pooled safety analyses of studies that compared Faslodex 500 mg with Faslodex 250 mg [CONFIRM (Study D6997C00002), FINDER 1 (Study D6997C00004), FINDER 2 (Study D6997C00006), and NEWEST (Study D6997C00003) studies], or from FALCON (Study D699BC00001) that compared Faslodex 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 events, regardless of the investigator assessment of causality.
In the combined studies (CONFIRM, NEWEST, FIRST, FINDER1 and FINDER2) the adverse effect profile of the 500 mg dose was comparable to that seen with the 250 mg dose but more cases of osteoporosis (4 vs 0), vaginitis (3 vs 1) and pruritus (23 vs 8) were reported with the higher dose.
Table 2 lists adverse experiences reported with an incidence of 5% or greater, regardless of assessed causality, from the two controlled clinical trials comparing the administration of Faslodex 250 mg intramuscularly once a month with anastrozole 1 mg orally once a day.
Faslodex has been commonly associated with elevation of liver enzymes, the vast majority < 2 x ULN (frequency > 1 - < 10%).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There are isolated reports of overdose with Faslodex in humans. If overdose occurs, this should be managed symptomatically. The acute toxicity of fulvestrant in laboratory animal species is low. Animal studies suggested that no effects, other than those related directly or indirectly to antioestrogenic activity, were evident with higher doses of fulvestrant. In dog studies following oral and intravenous administration, effects on the cardiovascular system (slight elevations of the ST segment of the ECG [oral] and sinus arrest in one dog [intravenous]) were seen, but these occurred in animals exposed to far higher levels of fulvestrant than those recorded in patients (C_max > 15 times).
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Fulvestrant is an antioestrogen that binds to oestrogen receptors in a competitive manner, with a high affinity comparable to that of oestradiol and downregulates the oestrogen receptor. Fulvestrant completely inhibited the uterotrophic action of exogenous oestradiol, but showed no agonistic effects in uterotrophic assays in immature or ovariectomised mice, rats and monkeys. Thus, it appears to have antioestrogen activity without having any partial agonist (oestrogen-like) activity.
Fulvestrant inhibited the growth of the oestrogen sensitive human breast cancer cell line MCF-7 in vitro and of xenografts of MCF-7 cells in nude mice. Fulvestrant inhibited the growth of tamoxifen resistant breast cancer cells in vitro and of tamoxifen resistant breast tumours in nude mice.

Effects on breast cancer tissue in vivo.

Clinical trials in postmenopausal women with primary breast cancer have shown that fulvestrant significantly downregulates oestrogen receptor expression in oestrogen receptor positive tumours compared with placebo and tamoxifen. There was also a significant decrease in progesterone receptor expression consistent with the preclinical data demonstrating that fulvestrant lacks intrinsic oestrogen agonist activity. These changes in oestrogen receptor and progesterone receptor expression were accompanied by reductions in expression of Ki67, a marker of tumour cell proliferation, which were also related to dose with fulvestrant 500 mg having a significantly greater effect than the 250 mg dose.

Effects on the postmenopausal endometrium.

The preclinical data for fulvestrant suggest that it will not have a stimulatory effect on the postmenopausal endometrium. A trial in healthy postmenopausal volunteers showed that compared to placebo, pretreatment with 250 mg fulvestrant resulted in significantly reduced stimulation of the postmenopausal endometrium in volunteers treated with 20 micrograms per day ethinyloestradiol. This demonstrates a potent antioestrogenic effect on the postmenopausal endometrium.

Clinical trials.

Effects on advanced breast cancer.

A phase 3 clinical trial (CONFIRM) was completed in 736 postmenopausal women with advanced breast cancer who had disease recurrence on or after adjuvant endocrine therapy or progression following endocrine therapy for advanced disease. This trial compared the efficacy and safety of Faslodex 500 mg (n = 362) with Faslodex 250 mg (n = 374). Progression free survival (PFS) was the primary endpoint; key secondary efficacy endpoints included objective response rate (ORR); clinical benefit rate (CBR) and overall survival (OS). PFS for Faslodex 500 mg was significantly longer than for Faslodex 250 mg. Efficacy results are summarized in Table 3 and Figure 1. In the initial OS analysis after a minimum follow-up duration of 18 months, there was no statistically significant difference in OS between the two treatment groups. After a minimum follow-up duration of 50 months, an updated OS analysis was performed. Final OS analysis at 75% maturity showed that Faslodex 500 mg was associated with a 4.1 month increase in median OS and a 19% reduction in the risk of death compared with Faslodex 250 mg [HR = 0.81; 95% CI 0.69-0.96; p = 0.016 (nominal p-value as no adjustment was made for multiplicity)].

Irrespective of the last endocrine therapy (antioestrogen or aromatase inhibitor), the treatment effect (PFS) for Faslodex 500 mg vs Faslodex 250 mg was consistent. There was no significant difference in CBR for patients receiving Faslodex 500 mg vs 250 mg (45.6% vs 39.6%; odds ratio 1.28 [95% CI 0.95, 1.71]; p = 0.1) or in duration of clinical benefit (median 16.6 vs 13.9 months for Faslodex 500 mg and Faslodex 250 mg, respectively).
Two phase 3 clinical trials (study 9238IL/0020 and 9238IL/0021) were completed in a total of 851 postmenopausal women with advanced breast cancer who had disease recurrence on or after adjuvant endocrine therapy or progression following endocrine therapy for advanced disease. These trials compared the safety and efficacy of Faslodex with a third generation aromatase inhibitor, anastrozole. Both trials used a dose of 250 mg every 28 days. The primary endpoint was progression free survival.
Overall, Faslodex 250 mg was at least as effective as anastrozole in terms of progression free survival (PFS), objective response, clinical benefit, time to treatment failure and quality of life.
In study 21, median PFS was 165 days with fulvestrant and 103 days with anastrozole (HR 0.92; 95% CI: 0.74-1.14). In study 20, median PFS was 166 days with fulvestrant and 156 days with anastrozole (HR 0.98; 95% CI: 0.80-1.21).
Faslodex 250 mg had an ORR of 20.7% in study 20 (vs 15.7% with anastrozole) and 17.5% in study 21 (vs 17.5% with anastrozole).
Faslodex 250 mg showed durable responses in both trials. In study 20, the median duration of response (DoR) was 19.3 months for Faslodex 250 mg and 10.5 months for anastrozole. In study 21, the median DoR was 14.3 months and 14.0 months for Faslodex 250 mg and anastrozole 1 mg respectively.
The majority of patients in these trials had ER+ and/or PgR+ tumors (about 80%). Patients who had ER-/ PgR- or unknown disease must have shown prior response to endocrine therapy.
There are no efficacy data to support use of Faslodex in premenopausal patients with advanced breast cancer.
FALCON (Study D699BC00001) was a Phase 3, randomised, double-blind, double-dummy, multicentre study of Faslodex versus anastrozole conducted in post-menopausal women with hormone receptor positive (oestrogen receptor positive and/or progesterone receptor positive) locally advanced or metastatic breast cancer who had not previously been treated with any endocrine therapy. A total of 462 patients were randomised 1:1 to receive Faslodex 500 mg intramuscularly on Days 1, 15, 29, and monthly thereafter, or anastrozole 1 mg orally daily. Randomisation was stratified by disease setting (locally advanced or metastatic), use of prior chemotherapy for advanced disease (yes or no), and presence or absence of measurable disease.
The primary efficacy endpoint of the study was investigator-assessed progression-free survival (PFS) evaluated according to RECIST 1.1 (Response Evaluation Criteria in Solid Tumors). Key secondary efficacy endpoints included overall survival (OS) and objective response rate (ORR).
Patients enrolled in this study had a median age of 63 years (range 36-90). The majority of patients (87%) had metastatic disease at baseline. Fifty-five percent (55%) of patients had visceral metastasis at baseline. A total of 17% of patients received a prior chemotherapy regimen for advanced disease; 84% of patients had measurable disease. Sites of metastases were as follows: musculoskeletal 59%, lymph nodes 50%, respiratory 40%, liver (including gall bladder) 18%. For 10% of patients, musculoskeletal sites were the only sites of metastasis.
The results of the FALCON study are summarised in Table 4 and Figure 2. OS was not mature at the time of primary analysis. Consistent results for PFS were observed across the majority of pre-specified patient subgroups. However, for the subgroup of patients with visceral metastasis (n=254), the hazard ratio (HR) for PFS was 0.993 (95% CI: 0.740, 1.331) for the Faslodex arm compared to the anastrozole arm. For the subgroup of patients with disease limited to non-visceral metastasis (n=208), the HR was 0.592 (95% CI: 0.419, 0.837) for the Faslodex arm compared to the anastrozole arm.

5.2 Pharmacokinetic Properties

Absorption.

After administration of Faslodex long acting intramuscular injection, fulvestrant is slowly absorbed and maximum plasma concentrations are reached after about 7 days. Absorption continues for over one month and monthly administration results in an approximate 2-fold accumulation. Steady-state levels are reached after about 6 doses during monthly injections with the major part of the accumulation achieved after 3-4 doses. The terminal half-life is governed by the absorption rate and was estimated to be 50 days. At steady state, fulvestrant plasma concentrations are maintained within a relatively narrow range with approximately 2 to 3-fold difference between maximum and trough concentrations.
Results from single dose studies of fulvestrant are predictive of multiple dose pharmacokinetics.
Administration of Faslodex 500 mg at day 0 and 14 achieves exposure levels at or close to steady state within the first month of dosing (mean [CV]): AUC 475 (33.4%) nanogram.days/mL, C_max 25.1 (35.3%) nanogram/mL, C_min 16.3 (25.9%) nanogram/mL, respectively).

Distribution.

Fulvestrant is subject to extensive and rapid distribution. The apparent volume of distribution at steady state is large (approximately 3 to 5 L/kg), which suggests that the compound distribution is largely extravascular. Fulvestrant is highly (99%) bound to plasma proteins. Very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) fractions are the major binding components. Therefore, no drug interaction studies were conducted on competitive protein binding. The role of sex hormone binding globulin has not been determined.

Metabolism.

The metabolism of fulvestrant has not been fully evaluated, but involves combinations of a number of possible biotransformation pathways analogous to those of endogenous steroids (includes 17-ketone, sulphone, 3-sulphate, 3 and 17-glucuronide metabolites). Identified metabolites are either less active or exhibit similar activity to fulvestrant in antioestrogen models. Studies using human liver preparations and recombinant human enzymes indicate that CYP3A4 is the only P450 isoenzyme involved in the oxidation of fulvestrant, however non-P450 routes appear to be more predominant in vivo.

Excretion.

Fulvestrant is eliminated mainly by metabolism. The major route of excretion is via the faeces with less than 1% being excreted in the urine. Fulvestrant has a high clearance, 11 ± 1.7 mL/min/kg, suggesting a high hepatic extraction ratio.

Special populations.

Hepatic impairment.

Fulvestrant is metabolized primarily in the liver. In clinical trials in patients with locally advanced or metastatic breast cancer, pharmacokinetic data were obtained following administration of a 250 mg dose of Faslodex to 261 patients classified as having normal liver function and to 24 patients with mild impairment. Mild impairment was defined as an alanine aminotransferase concentration (at any visit) greater than the upper limit of the normal (ULN) reference range, but less than 2 times the ULN; or if any 2 of the following 3 parameters were between 1 and 2 times the ULN: aspartate aminotransferase, alkaline phosphatase or total bilirubin.
There was no clear relationship between fulvestrant clearance and hepatic impairment and the safety profile in patients with mild hepatic impairment was similar to that seen in patients with no hepatic impairment. Safety and efficacy have not been evaluated in patients with moderate to severe hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).

Renal impairment.

Negligible amounts of fulvestrant are eliminated in urine; therefore, a study in patients with renal impairment was not conducted. In the advanced breast cancer trials, fulvestrant concentrations in women with estimated creatinine clearance as low as 30 mL/min were similar to women with normal creatinine (see Section 4.4 Special Warnings and Precautions for Use).

Other populations.

No difference in fulvestrant pharmacokinetic profile was detected with regard to age (range 33 to 89 years).
No difference in fulvestrant pharmacokinetic profile was detected with regard to ethnic groups.

5.3 Preclinical Safety Data

Genotoxicity.

Faslodex showed no genotoxic potential in bacterial reverse mutation assays, in vitro mouse lymphoma assays, an in vitro chromosome aberration assay in human lymphocytes and an in vivo micronucleus assay in rats.

Carcinogenicity.

A two year rat oncogenicity study (intramuscular administration with the Faslodex formulation) showed increased incidence of benign ovarian granulosa cell tumours in females at the high dose, 10 mg/rat/15 days (approx. 5 times the human dose based on plasma AUC values). Induction of such tumours is consistent with the pharmacology related endocrine feedback alteration in gonadotropin levels caused by antioestrogen in cycling animals. Therefore, this finding is not considered to be clinically relevant to the use of fulvestrant in postmenopausal women with advanced breast cancer.

6 Pharmaceutical Particulars

6.1 List of Excipients

Faslodex contains ethanol 96%, benzyl alcohol, benzyl benzoate and castor oil.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store between 2°C-8°C (in a refrigerator).
Store in original pack.

6.5 Nature and Contents of Container

Faslodex 250 mg/5 mL solution in pre-filled syringes (two (2) syringes per pack).
Each pre-filled syringe consists of:
One 5 mL clear neutral glass (Type 1) barrel containing a nominal 5 mL of Faslodex solution for injection and fitted with a tamper evident closure. The syringes are presented in a tray with polystyrene plunger rod and a safety needle (SafetyGlide) for connection to the barrel.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

The chemical name is 7α-[9-(4,4,5,5,5-pentafluoro pentylsulphinyl)nonyl] estra-1,3,5(10)- triene-3,17β-diol.

Chemical structure.

CAS number.

129453-61-8.

Molecular formula.

C₃₂H₄₇F₅O₃S.

MW.

606.8.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (Schedule 4).

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