Fulvestrant

Introduction: Fulvestrant is an estrogen blocker. It is used in the treatment of breast cancer in women who have gone through menopause. It works by adjusting the level of estrogen and slowing down the growth of cancer cells.

How it works: Fulvestrant competitively binds to estrogen receptors, forming a nuclear complex, leading to down-regulation of estrogen receptor protein levels and inhibition of tumour growth.

Important Information: It is given as an injection into the muscles under the supervision of a doctor. The dose and how often you take it depends on what you are taking it for. You should take this medicine for as long as it is prescribed for you.

• HR-positive, HER2-negative advanced breast cancer: in postmenopausal women not previously treated with endocrine therapy.
• HR-positive advanced breast cancer: in postmenopausal women with disease progression following endocrine therapy.
• HR-positive, HER2-negative advanced or metastatic breast cancer: in combination with ribociclib in postmenopausal women.
• HR-positive, HER2-negative advanced or metastatic breast cancer: in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy.

Cytotoxic Chemotherapy

Estrogen Receptor Antagonist

Many breast cancers have estrogen receptors (ER) and the growth of these tumors can be stimulated by estrogen. Fulvestrant is an estrogen receptor antagonist that binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol and downregulates the ER protein in human breast cancer cells.

Fulvestrant binds to estrogen receptors and blocks estrogen action, thereby inhibiting the growth of estrogen-dependent breast cancer cells.

Adult Dose (Intramuscular):

• 500 mg (250 mg into each buttock) on Days 1, 15, 29, then once monthly thereafter.
• Moderate hepatic impairment (Child-Pugh Class B): 250 mg (into 1 buttock) on Days 1, 15, 29, then once monthly thereafter.
• Severe hepatic impairment: Contraindicated.

Renal Impairment: Negligible amounts eliminated in urine - no dose adjustment needed (eCrCl ≥30 mL/min).

Children: Safety and effectiveness not established.

* Use as directed by the registered physician

Intramuscular injection (into the buttocks). Your doctor or nurse will give you this medicine. Do not self-administer. Administer slowly (1-2 minutes per injection).

If you miss a dose, please consult your doctor.

Common Side Effects (≥5%):

• Injection site pain
• Nausea
• Bone pain
• Arthralgia
• Headache
• Back pain
• Fatigue
• Hot flash
• Vomiting
• Anorexia
• Asthenia
• Cough
• Dyspnea
• Constipation

Increased hepatic enzymes: ALT, AST, ALP in >15% of patients.

Precautions:

• Risk of Bleeding: Use with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use.
• Increased Exposure in Hepatic Impairment: Use 250 mg dose for moderate hepatic impairment.
• Injection Site Reaction: Caution at dorsogluteal injection site due to proximity of sciatic nerve.
• Embryo-Fetal Toxicity: Can cause fetal harm - use effective contraception in females of reproductive potential.

Contraindications:

• Pregnancy and lactation

Drug Interactions:

• Increased risk of bleeding when taken concomitantly with anticoagulants.
• No dose adjustment needed with CYP3A4 inhibitors or inducers (although metabolized by CYP3A4 in vitro, ketoconazole or rifampin do not alter pharmacokinetics).

Food Interactions:

• Caution is advised when consuming alcohol. Please consult your doctor.

Use in Pregnancy: Unsafe during pregnancy. There is definite evidence of risk to the developing baby.

Use in Lactation: Unsafe during breastfeeding. Data suggests the drug may cause toxicity to the baby.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: No specific dosage adjustment is necessary for elderly patients.

Renal Impairment: Use with caution in severe kidney disease. No dose adjustment recommended in mild to moderate kidney disease.

Hepatic Impairment: Use with caution in liver disease. Moderate (Child-Pugh Class B): 250 mg. Severe: Contraindicated.

Overdose: Human experience of overdose is limited. No specific treatment. Give general supportive measures and symptomatic treatment.

Storage: Refrigerate 2°-8°C. Store in the original carton to protect from light until the time of use.

Fulvestrant Injection