Fazlodex ® (Faslodex)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceFulvestrantFulvestrant
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  • Fazlodex ®
    solution w / m 
    AstraZeneca AB     Sweden
    • Dosage form: & nbspsolution for intramuscular injection
    Composition:

    One filled syringe contains:

    Active substance: 250 mg fulvestrant;

    Excipients: Ethanol (96%) 500 mg, benzyl alcohol 500 mg, benzyl benzoate 750 mg, castor oil up to 5 ml.

    Description:

    Transparent, colorless to yellow, a viscous liquid.

    Pharmacotherapeutic group:Antitumor agent, antiestrogen.
    ATX: & nbsp

    L.02.B.A.03   Fulvestrant

    Pharmacodynamics:

    Fulvestrant is a competing estrogen receptor antagonist. The level of affinity for receptors is comparable with estradiol. Fulvestrant blocks the trophic action of estrogens, not showing its own estrogen-like activity. The mechanism of action is associated with inhibition of activity and degradation of estrogen receptors (ER).

    Also fulvestrant significantly reduces the expression of progesterone receptors.
    Fulvestrant does not have a stimulating effect on the endometrium in postmenopausal women. The effects of prolonged therapy with fulvestrant on endothelium, in postmenopause have not been established. There is also no data on the morphology of the endometrium.

    There are no data on the effect of long-term use of fulvestrant on bone tissue.


    Pharmacokinetics:

    After intramuscular injection fulvestrant slowly absorbed, reaching a maximum concentration of. plasma after about 7 days. When using Fazlodex at a dose of 500 mg, an equilibrium state is achieved during the first month of therapy (AUC 546 ng-day / ml, Сmах 25.1 ng / ml, Cmin 16.3 ng / ml). At equilibrium, the content of fulvestrant in plasma fluctuates within relatively narrow limits the maximum and minimum indicators differ approximately in 3 times.

    After intramuscular injection, the exposure is approximately proportional to the administered dose (in the dose range from 5 0 to 500 mg).

    Fulvestrant It is characterized by extensive and rapid distribution. A large, apparent volume of distribution (from 3 to 5 l / kg) at an equilibrium concentration assumes predominantly an extravascular distribution. The connection with plasma proteins is 99%. The main binding components include the fractions of very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). The role of sex hormone binding globulin is not established.

    The metabolism of fulvestrant includes combinations of a number of potential biotransformation pathways similar to endogenous steroids metabolism mechanisms (include metabolites 17-ketone, sulfone, 3-sulfate, 3- and 17-glucuronide).Identified metabolites are less active or equal in activity to fulvestrant, CYP ZA4 is the only isoenzyme from the P450 family, which participates in the oxidation of fulvestrant. However, it appears that in vivo biotransformation without the participation of P450 prevails.

    Fulvestrant mostly excreted with feces, with urine output less than 1% of the substance. The fulvestrant clearance is 11 ± 1.7 ml / min / kg, which implies a high level of hepatic extraction. The half-life period is 50 days.

    Special Populations:

    The pharmacokinetic profile of fulvestrant is independent of age (in the range of 33 to 89 years), body weight (40-127 kg) and race.

    Renal impairment

    Mild and moderate renal dysfunction does not have a clinically significant effect on the pharmacokinetics of fulvestrant.

    Dysfunction of the liver

    With a single administration of fulvestrant to patients with mild or moderate impairment of liver function (Child-Pugh class A and B classes), there was an increase AUC in 2,5 times in comparison with healthy volunteers. Studies of pharmacokinetics of fulvestrant in patients with severe impairment of liver function (class C according to the Child-Pugh classification) have not been conducted.

    Indications:

    Locally distributed or disseminated breast cancer with positive estrogen receptors in postmenopausal women with progression after or against the background of anti-estrogen therapy.

    Contraindications:

    • hypersensitivity to fulvestrant or any other component preparation;

    • severe violations of liver function;

    • pregnancy and the period of breastfeeding;

    • children's age till 18 years.

    Carefully:

    with violations of the kidneys and liver.

    Dosing and Administration:

    Intramuscularly, by slow injection (within 1-2 minutes). The contents of the 2 syringes are successively introduced into the right and left gluteal regions.

    Adult female patients (including the elderly):

    The recommended dose is 500 mg once a month. The first month of therapy: 500 mg 2 times a month (the second introduction - 2 weeks after the first dose of the drug).

    Children and adolescents:

    There are no data on safety and efficacy in children and adolescents.

    Patients with impaired renal function:

    In cases of mild or moderate renal impairment (creatinine clearance> 30 ml / min), dose adjustment is not required. Safety and effectiveness of the drug in patients with severe impairment of renal function (creatinine clearance <30 mL / min) are not established.

    Patients with hepatic impairment:

    The use of the drug Fazlodex® in patients with mild or moderate impairment of liver function does not require dose adjustment. However, the use of Faslodex® in this group of patients requires caution. Safety and efficacy of the drug in patients with severe impairment of liver function are not established.

    Instructions for handling and use

    Caution: do not autoclave the needle supplied with the product!

    Do not touch the needle while using it.

    1. Remove the syringe glass enclosure from the contour pack and make sure there is no damage. Tear off the outer packing of the safety needle (SafetyGlide). Break the jumper of the white plastic cap of the tip of the syringe and remove the lid with the attached rubber stopper cap (see Figure 1).

    2. Rotate the needle to fix the needle on the tip of the syringe (see Figure 2). Remove the needle case strictly in its direction, so as not to damage the tip of the needle. Visually assess the state of the solution for parenteral administration for the absence of particles and discoloration before use. Remove excess gas bubbles from the syringe.

    3. Slowly inject the solution into the gluteus muscle for 1-2 minutes.For comfort the needle "taper" plane corresponds to the location of the lever on the safety device, as shown in Figure 3.

    1. After removing the needle from the gluteus muscle, immediately activate the needle guard by pressing the lever to the front end position until the tip of the needle is fully closed (see Figure 4). When the protective mechanism is activated, minimal liquid sprays are possible, which can remain on the needle after the injection. Visually, make sure that the lever is in the end position and the tip of the needle is completely closed. If you can not activate the needle guard, immediately place the needle in the standard needle container. Caution: For maximum safety, use one hand and perform manipulations away from yourself and others.


    Side effects:

    The observed undesirable reactions are presented below.

    Determination of the frequency of adverse reactions: very often (> 10%); often (> 1 - <10%); infrequently (> 0.1 - <1%).

    On the part of the digestive system:

    Very often - nausea;

    Often - vomiting, diarrhea, anorexia.

    From the side of cardiovascular system:

    Often - the feeling of heat ("hot flashes"), thromboembolism.

    From the skin and skin appendages:

    Often - a rash.

    Local reactions:

    Very often - reactions at the site of administration drug, including mild transient pain and inflammation;

    Infrequent - bleeding, bruising in place introduction.

    From the genitourinary system:

    Often - urinary tract infections;

    Infrequently - vaginal candidiasis, leucorrhoea, vaginal bleeding.

    From the liver and bile excretory ways:

    Very often - an increase in the activity of "hepatic" enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase);

    Often - increased bilirubin concentration;

    Infrequent - hepatic insufficiency, hepatitis, increased activity of gamma-glutamyltransferase.

    Other:

    Very often - asthenia;

    Often - headache, hypersensitivity reactions (swelling, urticaria).

    Overdose:

    Cases of overdose in humans are unknown. In animal studies, when administering high doses of fulvestrant, only effects directly or indirectly associated with anti-estrogenic activity were observed.

    In cases of overdose, symptomatic therapy is recommended.

    Interaction:

    According to the results of the study of clinical interaction with midazolam fulvestrant does not suppress activity CYP AP4. Data in vitro evidence that fulvestrant does not affect activity CYP 1A2, 2C9, 2C19 and 2D6. Possible suppression of activity CYP 2A6.2C8 and 2E1 were not evaluated.

    In a study of clinical interaction with rifampicin (inducer CYP ZA4) and ketoconazole (inhibitor CYP ZA4) there were no clinically significant changes in fulvestrant clearance. Therefore, with the appointment of fulvestrant in combination with inducers or inhibitors CYP No correction of dose is required

    Special instructions:

    Treatment with Fazlodex® should only be performed under the supervision of a physician with experience in the use of antitumor drugs.

    Caution is advised when using Faslodex® in patients with mild or moderate liver dysfunction. Caution is advised when using Faslodex® in patients with severe renal impairment (creatinine clearance <30 mL / min).

    Considering the way the drug is used, it is advisable to use caution when using Faslodex ® in patients with a tendency to bleeding, thrombocytopenia or in patients taking anticoagulants.

    Thromboembolism in women with advanced breast cancer is often observed. This should be taken into account when prescribing Faslodex® to patients with a risk of thromboembolism.

    Effects of prolonged use of fulvestrant on bone tissue are not established. Given the mechanism of action fulvestranta, can not exclude the potential risk of osteoporosis.

    Fazlodex® should not be mixed with other medications.

    Effect on the ability to drive transp. cf. and fur:

    The effect of Fazlodex® on the ability to drive and other mechanisms is negligible. Patients with symptoms of asthenia should be careful when driving a car or other mechanisms.

    Form release / dosage:Solution for intramuscular injection 250 mg / 5 ml. 5 ml into a glass syringe with a safe injection system.
    Packaging:

    One syringe together with one sealed safe sterile needle (SafetyGlide ™) in a contour cellular package from polypropylene, sealed with polypropylene film. One contour pack together with instructions for use in a cardboard box.

    Or

    two syringes together with two sealed safe sterile needles (SafetyGlide ™) in a contour cellular package from polypropylene, sealed with polypropylene film. One contour cell package together with instructions for use in a cardboard box with the control of the first opening.

    Storage conditions:

    At a temperature of 2 to 8 ° C, in a place protected from light. Keep out of the reach of children.

    Shelf life:

    4 years. Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-000855
    Date of registration:06.08.2010
    The owner of the registration certificate:AstraZeneca ABAstraZeneca AB Sweden
    Manufacturer: & nbsp
    Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.
    Information update date: & nbsp10.11.2015
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