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Fulvestrant (Solution) Instructions for Use

ATC Code

L02BA03 (Fulvestrant)

Active Substance

Fulvestrant (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiestrogenic drug with antitumor action

Pharmacotherapeutic Group

Antineoplastic hormonal agents and hormone antagonists; hormone antagonists and related compounds; antiestrogens

Pharmacological Action

Antitumor agent, antiestrogen. Fulvestrant is a competitive antagonist of estrogen receptors. Its affinity for receptors is comparable to that of estradiol.

Fulvestrant blocks the trophic effects of estrogens without exhibiting its own estrogen-like activity. The mechanism of action is associated with the suppression of activity and degradation of estrogen receptors. Fulvestrant also reliably reduces the expression of progesterone receptors.

Fulvestrant does not have a stimulatory effect on the endometrium in postmenopausal women. The effects of long-term fulvestrant therapy on the postmenopausal endometrium have not been established. There are also no data on endometrial morphology. There are no data on the effect of long-term use of fulvestrant on bone tissue.

Pharmacokinetics

After intramuscular injection, Fulvestrant is slowly absorbed, reaching Cmax in plasma approximately after 7 days. Absorption continues for more than 1 month, so with monthly injections, approximately 2-fold accumulation of the active substance occurs. Css in plasma is established approximately after 6 monthly injections, with the main part of accumulation achieved after 3-4 injections.

After intramuscular injection, exposure is approximately proportional to the administered dose (in the dose range from 50 to 250 mg). At steady state, the plasma concentration of fulvestrant fluctuates within relatively narrow limits – maximum and minimum values differ by approximately 2-3 times.

Fulvestrant is characterized by extensive and rapid distribution. The large apparent Vd (from 3 to 5 L/kg) at steady state suggests predominantly extravascular distribution. Plasma protein binding is 99%. The main binding components include VLDL, LDL, and HDL fractions. The role of sex hormone-binding globulin has not been established.

The metabolism of fulvestrant involves combinations of multiple potential biotransformation pathways, similar to the metabolism mechanisms of endogenous steroids (including 17-ketone, sulfone, 3-sulfate, 3- and 17-glucuronide metabolites). The identified metabolites are less active or equal in activity to fulvestrant. CYP3A4 is the only isoenzyme involved in the oxidation of fulvestrant. However, it appears that in vivo, biotransformation not involving P450 isoenzymes predominates.

T1/2 is 50 days. Fulvestrant is mainly excreted in the feces; less than 1% of the active substance is excreted in the urine.

Indications

Locally advanced or disseminated estrogen receptor-positive breast cancer in postmenopausal women with disease progression following or during antiestrogen therapy.

ICD codes

ICD-10 code Indication
C50 Malignant neoplasm of breast
ICD-11 code Indication
2C65 Hereditary breast and ovarian cancer syndrome
2C6Y Other specified malignant neoplasms of the breast
2C6Z Malignant neoplasms of breast, unspecified

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Administer Fulvestrant as a slow intramuscular injection into the gluteal muscle.

The recommended dose is 500 mg, administered as two separate 5 mL injections of 250 mg each, one into each buttock.

Give the injections once monthly.

Administer the initial loading dose on days 1, 15, and 29.

Thereafter, administer one 500 mg dose monthly.

Adhere strictly to the monthly dosing schedule.

Inject the solution slowly, over approximately 1-2 minutes per injection.

Do not administer Fulvestrant intravenously.

Do not mix Fulvestrant with any other medicinal products.

Use with caution in patients with bleeding diatheses, thrombocytopenia, or those taking anticoagulants.

Treatment must be supervised by a physician experienced in anticancer therapy.

Adverse Reactions

From the digestive system: often – nausea, vomiting, diarrhea, anorexia.

From the cardiovascular system: very often – hot flush; often – thromboembolism.

Dermatological reactions: often – rash.

Local reactions: often – transient pain, inflammatory reactions.

From the genitourinary system: often – urinary tract infections; rarely – vaginal bleeding, vaginal candidiasis.

Allergic reactions: rarely – edema, urticaria.

Other: often – headache, asthenia, back pain; rarely – galactorrhea.

Contraindications

Severe hepatic impairment, pregnancy, lactation (breastfeeding), hypersensitivity to fulvestrant.

Use in Pregnancy and Lactation

Fulvestrant is intended for use in postmenopausal women.

Not used during pregnancy or lactation.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment. Use with caution is recommended in patients with mild or moderate hepatic impairment.

Use in Renal Impairment

Use with caution is recommended in patients with severe renal impairment (CrCl<30 ml/min).

Special Precautions

Treatment should be carried out only under the supervision of a physician experienced in anticancer therapy.

Use with caution is recommended in patients with mild or moderate hepatic impairment, in patients with severe renal impairment (CrCl<30 ml/min), in patients with a tendency to bleeding, with thrombocytopenia, or in patients taking anticoagulants.

Thromboembolism is often observed in women with advanced breast cancer, which must be taken into account when using fulvestrant.

The effect of fulvestrant on bone tissue with long-term use has not been established. Given the mechanism of action of fulvestrant, a potential risk of osteoporosis cannot be excluded.

Fulvestrant must not be mixed with other medicinal products.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.

Medical Disclaimer

Brand (or Active Substance), Marketing Authorisation Holder, Dosage Form

Marketing Authorization Holder

AlTro, LLC (Russia)

Manufactured By

Bryntsalov-A, JSC (Russia)

Dosage Form

Bottle Rx Icon Fulvestrant Solution for intramuscular injection 250 mg

Dosage Form, Packaging, and Composition

Solution for intramuscular injection

Fulvestrant 250 mg

5 ml – vials – cardboard packs – By prescription
5 ml – vials (10 pcs.) – cardboard packs – By prescription
5 ml – vials (5 pcs.) – cardboard packs – By prescription

Marketing Authorization Holder

Jodas Expoim, LLC (Russia)

Manufactured By

Jodas Expoim, Pvt. Ltd. (India)

Dosage Form

Bottle Rx Icon Fulvestrant Solution for intramuscular injection 250 mg: 5 ml syringes 1 or 2 pcs.

Dosage Form, Packaging, and Composition

Solution for intramuscular injection clear, from colorless to yellow, viscous.

1 ml 5 ml
Fulvestrant 50 mg 250 mg

Excipients : ethanol 96%, benzyl alcohol, benzyl benzoate, castor oil.

5 ml – syringes (1) – cardboard boxes.
5 ml – syringes (2) – cardboard boxes.

Marketing Authorization Holder

Medical Leasing-Consulting, LLC (Russia)

Manufactured By

Laboratorios Farmalan, S.A. (Spain)

Dosage Form

Bottle Rx Icon Fulvestrant Solution for intramuscular injection 250 mg

Dosage Form, Packaging, and Composition

Solution for intramuscular injection

1 ml 1 syringe (5 ml)
Fulvestrant 50 mg 250 mg

5 ml – syringes – cardboard boxes /complete with sterile needles – 1 pc./ – By prescription
5 ml – syringes (2 pcs.) – cardboard boxes /complete with sterile needles – 2 pcs./ – By prescription

Marketing Authorization Holder

Oncotarget, LLC (Russia)

Dosage Form

Bottle Rx Icon Fulvestrant Solution for intramuscular injection 250 mg/5 ml: syringes 1 or 2 pcs.

Dosage Form, Packaging, and Composition

Solution for intramuscular injection in the form of a viscous, clear liquid, from colorless to yellow.

5 ml
Fulvestrant 250 mg

Excipients : ethanol 96%, benzyl alcohol, benzyl benzoate, castor oil.

5 ml – glass syringes (1 or 2) – cardboard packs.

Marketing Authorization Holder

R-Pharm JSC (Russia)

Manufactured By

R-OPRA LLC (Russia)

Dosage Form

Bottle Rx Icon Fulvestrant Solution for intramuscular injection 250 mg

Dosage Form, Packaging, and Composition

Solution for intramuscular injection

Fulvestrant 250 mg

5 ml – vials – cardboard packs – By prescription
5 ml – vials (2 pcs.) – cardboard packs – By prescription

Marketing Authorization Holder

Sunlight-Ruspharm, LLC (Russia)

Manufactured By

Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (China)

Dosage Form

Bottle Rx Icon Fulvestrant Solution for intramuscular administration 250 mg: syringes 5 ml 2 pcs.

Dosage Form, Packaging, and Composition

Solution for intramuscular injection in the form of a clear viscous liquid from colorless to yellow.

1 ml 1 syringe (5 ml)
Fulvestrant 50 mg 250 mg

Excipients : ethanol 96% (ethyl alcohol), benzyl alcohol, benzyl benzoate, castor oil.

5 ml – borosilicate glass syringes (type I) (2) – cardboard packs.

Marketing Authorization Holder

Amedart LLC (Russia)

Dosage Form

Bottle Rx Icon Fulvestrant-Amedart Solution for intramuscular injection 250 mg

Dosage Form, Packaging, and Composition

Solution for intramuscular injection

1 ml 1 syringe (5 ml)
Fulvestrant 50 mg 250 mg

5 ml – vials – cardboard packs /complete with syringe and needle – 2 pcs./ – By prescription

Marketing Authorization Holder

Pharmstandard-Ufimsky Vitaminny Zavod OJSC (Russia)

Manufactured By

Pharmstandard-UfaVITA OJSC (Russia)

Dosage Form

Bottle Rx Icon Fulvestrant-Pharmstandard Solution for intramuscular injection 250 mg/5 ml: 5 ml vials 2 pcs.

Dosage Form, Packaging, and Composition

Solution for intramuscular injection

Fulvestrant 250 mg/5 ml

5 ml – vials (2 pcs.) – cardboard packs – By prescription
5 ml – vials (2 pcs.) – cardboard packs /complete with sterile disposable syringes-2 pcs., medical needles-4 pcs., alcohol wipes-2 pcs./ – By prescription

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

Dosage Form

Bottle Rx Icon Fulvestrant-Promomed Solution for intramuscular injection 250 mg/5 ml: 5 ml vials or syringes

Dosage Form, Packaging, and Composition

Solution for intramuscular injection

Fulvestrant 250 mg/5 ml

5 ml – vials – cardboard packs /complete with needle/ – By prescription
5 ml – vials – cardboard packs /complete with syringe-1 pc., needle-1 pc./ – By prescription
5 ml – vials (10 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – vials (10 pcs.) – cardboard packs /complete with syringe-10 pcs., needle-10 pcs./ – By prescription
5 ml – vials (2 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – vials (2 pcs.) – cardboard packs /complete with syringe-2 pcs., needle-2 pcs./ – By prescription
5 ml – vials (3 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – vials (3 pcs.) – cardboard packs /complete with syringe-3 pcs., needle-3 pcs./ – By prescription
5 ml – vials (4 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – vials (4 pcs.) – cardboard packs /complete with syringe-4 pcs., needle-4 pcs./ – By prescription
5 ml – vials (5 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – vials (5 pcs.) – cardboard packs /complete with syringe-5 pcs., needle-5 pcs./ – By prescription
5 ml – syringes – cardboard packs /complete with needle/ – By prescription
5 ml – syringes (10 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – syringes (15 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – syringes (2 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – syringes (20 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – syringes (3 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – syringes (4 pcs.) – cardboard packs /complete with needle/ – By prescription
5 ml – syringes (5 pcs.) – cardboard packs /complete with needle/ – By prescription

Marketing Authorization Holder

Manas Med, LLC (Russia)

Manufactured By

Rus-Med Exports, Pvt. Ltd. (India)

Dosage Form

Bottle Rx Icon Fulvestrant-Rus Solution for intramuscular injection 250 mg

Dosage Form, Packaging, and Composition

Solution for intramuscular injection

1 ml 1 vial (5 ml)
Fulvestrant 50 mg 250 mg

5 ml – vials – cardboard packs – By prescription

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Pliva Hrvatska, d.o.o. (Croatia)

Dosage Form

Bottle Rx Icon Fulvestrant-Teba Solution for intramuscular injection 250 mg/5 ml: syringe 1 or 2 pcs. in set with sterile needles.

Dosage Form, Packaging, and Composition

Solution for intramuscular injection in the form of a transparent, colorless to yellow, viscous liquid.

1 syringe (5 ml)
Fulvestrant 250 mg

Excipients: ethanol 96%, benzyl alcohol, benzyl benzoate, castor oil.

5 ml – glass syringes (1) in a set with a sterile needle – plastic container (1) – cardboard packs.
5 ml – glass syringes (2) in a set with 2 sterile needles – plastic container (1) – cardboard packs.

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