Fulvestrant Mylan

Monotherapy

Fulvestrant Mylan is indicated for the treatment of hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.

Combination Therapy with Palbociclib

​Fulvestrant Mylan is indicated for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with palbociclib in women with disease progression after endocrine therapy.

Fulvestrant Mylan (Fulvestrant Mylan) is an anti-estrogen medication. It works by blocking the actions of estrogen in the body. Certain types of breast cancer use estrogen to grow and multiply in the body.

Fulvestrant Mylan is used to treat a certain type of hormone-related breast cancer in postmenopausal women, when the cancer has spread to other parts of the body after treatment with anti-estrogen medication.

Fulvestrant Mylan is also used together with a medicine called palbociclib (Ibrance), to treat certain hormone-related breast cancer that has progressed or spread after treatment with hormonal therapy.

Adult Females (including the 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.

Special Population: Children and Adolescents: Fulvestrant Mylan is not recommended for use in children or adolescents, as safety and efficacy have not been established in this age group.

Patients with Renal Impairment: No dose adjustments are recommended for patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min). Safety and efficacy have not been evaluated in patients with severe renal impairment (creatinine clearance <30 mL/min), and, therefore, caution is recommended in these patients.

Patients with Hepatic Impairment: No dose adjustments are recommended for patients with mild to moderate hepatic impairment. However, as Fulvestrant Mylan exposure may be increased, Fulvestrant Mylan should be used with caution in these patients. There are no data in patients with severe hepatic impairment.

Administration: Fulvestrant Mylan should be administered as two consecutive 5 mL injections by slow intramuscular injection (1-2 minutes/injection), one in each buttock.

For detailed instructions for administration, see Instructions for Administration and Special Precautions for Disposal and Other Handling under Cautions for Usage.

See also:
What is the most important information I should know about Fulvestrant Mylan?

Hypersensitivity to Fulvestrant Mylan or to any of the excipients of Fulvestrant Mylan. Pregnancy and lactation. Severe hepatic impairment.

Fertility, Pregnancy and Lactation: Women of Childbearing Potential: Patients of childbearing potential should be advised to use effective contraception while on treatment.

Pregnancy: Fulvestrant Mylan is contraindicated in pregnancy. Fulvestrant Mylan has been shown to cross the placenta after single IM doses in rat and rabbit. Studies in animals have shown reproductive toxicity including an increased incidence of foetal abnormalities and deaths. If pregnancy occurs while taking Fulvestrant Mylan, the patient must be informed of the potential hazard to the foetus and potential risk for loss of pregnancy.

Breastfeeding: Breastfeeding must be discontinued during treatment with Fulvestrant Mylan. Fulvestrant Mylan is excreted in milk in lactating rats. It is not known whether Fulvestrant Mylan is excreted in human milk. Considering the potential for serious adverse reactions due to Fulvestrant Mylan in breastfed infants, use during lactation is contraindicated.

Fertility: The effects of Fulvestrant Mylan on fertility in humans has not been studied.

Use Fulvestrant Mylan as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Fulvestrant Mylan. Talk to your pharmacist if you have questions about this information.
• Fulvestrant Mylan is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Fulvestrant Mylan at home, a health care provider will teach you how to use it. Be sure you understand how to use Fulvestrant Mylan. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use Fulvestrant Mylan if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Fulvestrant Mylan, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Fulvestrant Mylan.

Fulvestrant Mylan is used to treat certain types of breast cancer. Breast cancer cells need the hormone estrogen in order to grow. Fulvestrant Mylan works by blocking the effect of estrogen, slowing tumor cell growth.

How to use Fulvestrant Mylan intramuscular

Read the Patient Information Leaflet if available from your pharmacist before you start using Fulvestrant Mylan and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

This medication is injected slowly into the buttock muscle as directed by your doctor. It is usually given every 2 weeks for the first 3 doses and then monthly thereafter.

The dosage is based on your medical condition. You will be instructed on whether to give your dose as one or two injections. To minimize discomfort, the medication can be taken out of the refrigerator up to 1 hour before the scheduled dose and allowed to reach room temperature.

If you are giving this medication to yourself at home, learn all preparation and usage instructions from your health care professional. This medication is normally clear and colorless to yellow in color. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.

See also:
What other drugs will affect Fulvestrant Mylan?

There are no known drug-drug interactions. Fulvestrant Mylan does not significantly inhibit any of the major CYP isoenzymes, including CYP 1A2, 2C9, 2C19, 2D6, and 3A4 in vitro, and studies of co-administration of Fulvestrant Mylan with midazolam indicate that therapeutic doses of Fulvestrant Mylan have no inhibitory effects on CYP 3A4 or alter blood levels of drug metabolized by that enzyme. Although Fulvestrant Mylan is partly metabolized by CYP 3A4, a clinical study with rifampin, an inducer of CYP 3A4, showed no effect on the pharmacokinetics of Fulvestrant Mylan. Also results from a healthy volunteer study with ketoconazole, a potent inhibitor of CYP 3A4, indicated that ketoconazole had no effect on the pharmacokinetics of Fulvestrant Mylan and dosage adjustment is not necessary in patients co-prescribed CYP 3A4 inhibitors or inducers.

See also:
What are the possible side effects of Fulvestrant Mylan?

The following adverse reactions are discussed in more detail in other sections of the labeling:

• Risk of Bleeding
• Increased Exposure in Patients with Hepatic Impairment
• Embryo-Fetal Toxicity

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.

Monotherapy

Comparison of Fulvestrant Mylan 500 mg and Fulvestrant Mylan 250 mg

The following adverse reactions (ARs) were calculated based on the safety analysis of Study 1 comparing the administration of Fulvestrant Mylan 500 mg intramuscularly once a month with Fulvestrant Mylan 250 mg intramuscularly once a month. The most frequently reported adverse reactions in the Fulvestrant Mylan 500 mg group were injection site pain (11.6% of patients), nausea (9.7% of patients) and bone pain (9.4% of patients); the most frequently reported adverse reactions in the Fulvestrant Mylan 250 mg group were nausea (13.6% of patients), back pain (10.7% of patients) and injection site pain (9.1% of patients).

Table 1 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from Study 1.7

Table 1: Adverse Reactions in Study 1 ( ≥ 5% in Either Treatment Group)

In the pooled safety population (N=1127) from clinical trials comparing Fulvestrant Mylan 500 mg to Fulvestrant Mylan 250 mg, post-baseline increases of ≥ 1 CTC grade in either AST, ALT, or alkaline phosphatase were observed in > 15% of patients receiving Fulvestrant Mylan. Grade 3-4 increases were observed in 1-2% of patients. The incidence and severity of increased hepatic enzymes (ALT, AST, ALP) did not differ between the 250 mg and the 500 mg Fulvestrant Mylan arms.

Comparison of Fulvestrant Mylan 250 mg and Anastrozole 1 mg in Combined Trials (Studies 2 and 3)

The most commonly reported adverse reactions in the Fulvestrant Mylan and anastrozole treatment groups were gastrointestinal symptoms (including nausea, vomiting, constipation, diarrhea and abdominal pain), headache, back pain, vasodilatation (hot flashes), and pharyngitis.

Injection site reactions with mild transient pain and inflammation were seen with Fulvestrant Mylan and occurred in 7% of patients (1% of treatments) given the single 5 mL injection (predominantly European Trial Study 3) and in 27% of patients (4.6% of treatments) given the 2 x 2.5 mL injections (North American Trial Study 2).

Table 2 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from the two controlled clinical trials comparing the administration of Fulvestrant Mylan 250 mg intramuscularly once a month with anastrozole 1 mg orally once a day.

Table 2: Adverse Reactions in Studies 2 and 3 ( ≥ 5% from Combined Data)

Table 4: Laboratory Abnormalities in Study 4

Postmarketing Experience

For Fulvestrant Mylan 250 mg, other adverse reactions reported as drug-related and seen infrequently ( < 1%) include thromboembolic phenomena, myalgia, vertigo, leukopenia, and hypersensitivity reactions including angioedema and urticaria.

Vaginal bleeding has been reported infrequently ( < 1%), mainly in patients during the first 6 weeks after changing from existing hormonal therapy to treatment with Fulvestrant Mylan. If bleeding persists, further evaluation should be considered.

Elevation of bilirubin, elevation of gamma GT, hepatitis, and liver failure have been reported infrequently ( < 1%).

Fulvestrant Mylan is a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor.