Composition, form of production and packaging
The solution for intravenous injections is transparent, from colorless to yellow, viscous.
1 ml 1 syringe (5 ml)
fulvestrant 50 mg 250 mg
Excipients: ethanol 96% - 100 mg / ml, benzyl alcohol - 100 mg / ml, benzyl benzoate - 150 mg / ml, castor oil - up to 5 ml.
5 ml - glass syringes (1) complete with sealed SafetyGlide в„ў safe sterile needle - packings of cellular outline (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
Antitumor drug, antiestrogen. Fulvestrant is a competing antagonist of estrogen receptors. The level of affinity for receptors is comparable with estradiol. Fulvestrant blocks the trophic action of estrogens, without showing its own estrogen-like activity. The mechanism of action is associated with inhibition of activity and degradation of estrogen receptors.
Also, fulvestrant significantly decreases 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.
Data on the effect of long-term use of fulvestrant on bone tissue is not available.
Suction and distribution
After a / m injection, fulvestrant is slowly absorbed, reaching C max in plasma after about 7 days. Absorption lasts more than 1 month, so with monthly injections, approximately 2-fold cumulation of the drug occurs.
C ss in plasma is established after approximately 6 monthly injections, with the bulk of the cumulation being achieved after 3-4 injections.
After a / m injection, the exposure is approximately proportional to the administered dose (in the dose range of 50 to 250 mg).
In the equilibrium state, fulvestrant content in plasma fluctuates within relatively narrow limits - maximum and minimum values вЂ‹вЂ‹differ approximately by 2-3 times.
Fulvestrant is characterized by an extensive and rapid distribution. A large apparent V d (from 3 to 5 l / kg) in the equilibrium state assumes predominantly extravascular distribution.
Binding to plasma proteins is 99%. The main binding components include fractions of VLDL, LDL and 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. CYP3A4 is the only isoenzyme that is involved in the oxidation of fulvestrant. However, it appears that in vivo biotransformation predominates without the participation of P 450isoenzymes.
T 1/2 is 50 days.
Fulvestrant is mainly excreted with feces; with urine output less than 1% of the active substance.
Pharmacokinetics in special clinical cases
The pharmacokinetic profile of fulvestrant does not depend on age (in the range 33-89 years), body weight (40-127 kg) and race.
Mild and moderate renal dysfunction does not have a clinically significant effect on the pharmacokinetics of fulvestrant.
Studies of the pharmacokinetics of fulvestrant in patients with impaired hepatic function were not performed.
- locally advanced or disseminated breast cancer with positive estrogen receptors in postmenopausal women with progression after or at the background of anti-estrogen therapy.
The drug is given in / m, by slow (within 1-2 minutes) injection. The contents of the 2 syringes are successively introduced into the right and left gluteal regions.
For adult women (including the elderly), the recommended dose is 500 mg once a month. In the first month of therapy - 500 mg 2 times a month (the second introduction - 2 weeks after the first administration of the drug).
In the case of mild or moderately severe renal dysfunction (QC-30 ml / min), dose adjustment is not required. Safety and efficacy of the drug in patients with severe renal dysfunction (CK <30 mL / min) are not established.
The use of Fazlodex В® in patients with mild or moderate impairment of liver function does not require dose adjustment, but requires caution. Safety and efficacy of the drug in patients with severe impairment of liver function are not established.
Rules of use and handling of the drug
Do not autoclave the needle that comes with the product! Do not touch the needle while using it.
1. Remove the glass syringe body 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 lid of the syringe tip and remove the lid with the rubber end cap attached.
2. Rotate the needle to fix the needle on the tip of the syringe. 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 convenience, the plane of the bevel of the tip of the needle corresponds to the location of the lever on the safety device.
4. 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. 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.
For maximum safety, you should perform all manipulations with one hand at a distance from yourself and others.
Determination of the frequency of adverse reactions: very often (> 10%); often (> 1-? 10%); rarely (> 0.1-? 1%).
From the digestive system: very often - nausea, increased activity of hepatic enzymes (ALT, AST, APF); often - vomiting, diarrhea, anorexia.
From the cardiovascular system: often - a feeling of heat (hot flashes), thromboembolism.
Dermatological reactions: often - a rash.
Local reactions: very often - reactions at the injection site.
From the genitourinary system: often - urinary tract infections.
Allergic reactions: often - swelling, hives.
Other: very often - asthenia; often - headaches.
- pronounced violations of the liver function;
- lactation period;
- children's age till 18 years;
- hypersensitivity to fulvestrant or any other component of the drug.
With caution, prescribe the drug for violations of kidney and liver.
PREGNANCY AND LACTATION
The drug is contraindicated for use in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
In the case of mild or moderately severe renal dysfunction (QC-30 ml / min), dose adjustment is not required. Safety and effectiveness of the drug in patients with severe renal dysfunction (CK <30 ml / min) are not established. Caution is advised when using Fazlodex in patients with severe renal dysfunction (KK <30 mL / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution, prescribe the drug for light and moderately severe violations of the liver. Contraindicated in severe violations of liver function.
APPLICATION FOR CHILDREN
Data on safety and efficacy in children and adolescents is not available.
Treatment with Faslodex В® should be done only under the supervision of a doctor who has experience in the use of antitumor drugs.
With caution, it is recommended to use Fazlodex В® in patients with mild or moderate impairment of liver function.
Caution is advised when using Fazlodex in patients with severe renal dysfunction (KK <30 mL / min).
Given the way the drug is used, caution should be exercised when using Faslodex В® in patients with a tendency to bleeding, with thrombocytopenia or in patients taking anticoagulants.
Thromboembolism in women with advanced breast cancer is often observed. This should be taken into account when prescribing Fazlodex В® to patients at risk of thromboembolism.
Effects of prolonged use of fulvestrant on bone tissue are not established. Given the mechanism of action fulvestranta, we can not exclude the potential risk of osteoporosis.
Fazlodex В® should not be mixed with other medicinal products.
Use in Pediatrics
There are no data on safety and efficacy in children and adolescents.
Impact on the ability to drive vehicles and manage mechanisms
The effect of the drug Fazlodex В® on the ability to drive a car and other mechanisms is negligible. Patients with symptoms of asthenia should be careful when driving a car or other mechanisms.
Cases of overdose in humans are unknown. In experimental studies on animals with fulvestrant administration at high doses, only effects directly or indirectly associated with antiestrogenic activity were observed.
In cases of overdose, symptomatic therapy is recommended.
Based on the results of the study of clinical interaction with midazolam, fulvestrant does not suppress the activity of CYP3A4. In vitro data indicate that fulvestrant does not affect the activity of CYP1A2, 2C9, 2C19 and 2D6. The possible inhibition of the activity of CYP2A6, 2C8 and 2E1 was not evaluated.
In the study of clinical interaction with rifampicin (inducer CYP3A4) and ketoconazole (inhibitor CYP3A4), clinically significant changes in fulvestrant clearance were not detected. Therefore, the appointment of fulvestrant in combination with inducers or inhibitors of CYP3A4 dose adjustment is not required.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, protected from light at a temperature of 2 В° to 8 В° C. Shelf life - 4 years.