Faslodex 250mg / 5ml Injection

FASLODEX is indicated for the treatment of oestrogen 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 anti-oestrogen therapy, or disease progression with an anti-oestrogen.

In the absence of incompatibility studies, this medicinal product must not be mixed with other medicinal products.

Adult females (including the elderly): The recommended dose is 500 mg to be administered intramuscularly as two 5 ml injections, one in each buttock (gluteal area), at intervals of 1 month with an additional 500 mg dose 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.

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

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 u201cWarnings and Special Precautionsu201d).

Patients with hepatic insufficiency: No dose adjustments are recommended for patients with mild to moderate hepatic impairment. However, as fulvestrant exposure may be increased two fold, FASLODEX should be used with caution in these patients. Safety and efficacy have not been evaluated in patients with severe hepatic impairment (See u201cContraindicationsu201d).

Elderly: No dose adjustment is required for elderly patients.

Interactions requiring dose adjustments: There are no known drug-drug interactions requiring dose adjustment.

FASLODEX is contraindicated in:

• patients with a known hypersensitivity to any of its ingredients
• patients with severe hepatic impairment
• pregnancy and women breastfeeding their infants

FASLODEX should be used with caution in patients with mild to moderate hepatic impairment (See u201cPharmacokineticsu201d and u201cDosage and Directions for Useu201d).

Caution should be used before treating patients with creatinine clearance less than 30 ml/min (See u201cDosage and Directions for Use). 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 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 u201cDosage and Directions for Use and u201cSide Effectsu201d).

Special Precautions

Hypersensitivity Reactions: Hypersensitivity reactions such as angioedema and urticaria have been commonly reported (incidence of 1-10 %) and may be serious (see u201cSide Effectsu201d).

Fulvestrant does not significantly inhibit any of the major cytochrome P450 (CYP) isoenzymes in vitro, and results from a clinical pharmacokinetic study involving co-administration 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, and indirectly suggests that fulvestrant clearance would not be affected by CYP3A4 inhibitors. Results from a clinical study with ketoconazole, a potent inhibitor of CYP3A4, also indicated that there is no clinically relevant change in fulvestrant clearance. Dosage adjustment is not necessary in patients co-prescribed CYP3A4 inhibitors or inducers.

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.

Studies in animals have shown reproductive toxicity. Fulvestrant is found in ratsu2019 milk at levels significantly higher than those in rat plasma. The potential risk for humans is unknown. Therefore use of FASLODEX should be avoided in pregnant or women breastfeeding their infants.

FASLODEX is unlikely to impair the ability of patients to drive or operate machinery. However, 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.

Table 1: Summary of adverse reactions seen in clinical studies for FASLODEX 500 mg.

Frequency descriptor System organ class Adverse reaction

Very common (u226510 %)

• General disorders and administration site conditions: Injection site reactions, asthenia
• Hepatobiliary disorders: Elevated liver enzymes (ALT, AST, ALP)
• Gastrointestinal disorders: Nausea
• Immune system disorders: Hypersensitivity reactions: angioedema and urticaria
• Musculoskeletal and connective tissue disorders: Joint and musculoskeletal pain
• Skin and subcutaneous tissue disorders: Rash
• Vascular disorders: Hot flushes

Common (u2265 1 - < 10 %)

• Nervous system disorders: Headache
• Hepatobiliary disorders: Elevated bilirubin
• Blood and lymphatic system: Reduced platelet count
• Gastrointestinal disorders: Vomiting, diarrhoea
• Metabolism and nutrition disorders: Anorexia
• Infections and infestations: Urinary tract infections

Uncommon (< 1 %)

• Hepatobiliary disorders: Elevated gamma-GT

a Including more severe injection site related sciatica, neuralgia, neuropathic pain, and peripheral neuropathy.

b Based on any CT grade change from baseline.

c Includes: arthralgia, and less frequently musculoskeletal pain, back pain, myalgia and pain in extremity.

d Frequency category differs between pooled safety dataset and FALCON.

Post-marketing side effects: Hepatobiliary disorders: Hepatic failure and hepatitis.

There is no human experience of overdosage. Animal studies suggest that no effects other than those related directly or indirectly to anti-oestrogenic activity were evident with higher doses of fulvestrant. If overdose occurs, this should be managed symptomatically.