Fulveject (Solution) Instructions for Use

Marketing Authorization Holder

S.C. Rompharm Company S.R.L. (Romania)

ATC Code

L02BA03 (Fulvestrant)

Active Substance

Fulvestrant (Rec.INN registered by WHO)

Dosage Form

Fulveject

Solution for intramuscular administration 250 mg/5 ml: syringe 1 or 2 pcs.

Dosage Form, Packaging, and Composition

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

Excipients: ethanol 96% – 500 mg, benzyl alcohol – 500 mg, benzyl benzoate – 750 mg, castor oil – up to 5 ml.

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

Clinical-Pharmacological Group

Antiestrogenic drug with antitumor action

Pharmacotherapeutic Group

Antineoplastic agent, antiestrogen

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 action 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 C_max 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.

C_ss 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 V_d (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 (includes 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.

T_1/2 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

Dosage Regimen

Administer Fulveject 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 in each buttock.

Administer the initial dose as a single 500 mg administration.

For all subsequent doses, administer 500 mg once per month.

Adhere strictly to the once-monthly dosing schedule.

Do not administer the solution intravenously.

Ensure the oily solution is at room temperature before administration.

Inject slowly over 1-2 minutes to reduce site discomfort.

Rotate injection sites between left and right gluteal muscles for consecutive administrations.

Adverse Reactions

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

From the cardiovascular system: very frequently – hot flushes; frequently – thromboembolism.

Dermatological reactions: frequently – rash.

Local reactions: frequently – transient pain, inflammatory reactions.

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

Allergic reactions: rarely – edema, urticaria.

Other: frequently – 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 8°C (46°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.