2010/06/16

Faslodex

Composition, structure and packing

Solution for i / m injections transparent, ranging from colorless to yellow, viscous.

1 ml.fulvestrant 50 mg.

1 syringe (5 ml) fulvestrant 250 mg.

Excipients: ethanol 96% (100 mg / ml), benzyl alcohol (100 mg / ml), benzyl benzoate (150 mg / ml), castor oil (5 ml).

Clinico-pharmacological group: antiestrogens drug with antitumor activity.

Pharmacological action

The antitumor drug, antiestrogen. Fulvestrant is a competitive antagonist of estrogen receptors. The level of affinity to the receptors is comparable with estradiolom.Fulvestrant blocks trophic effect of estrogens, without showing their own estrogenopodobnoy activity. The mechanism of action is associated with suppression of the activity and degradation of estrogen receptors.

Also fulvestrant significantly decreased expression of progesterone receptors.

Fulvestrant does not have a stimulating effect on the endometrium in postmenopausal women. Effects of prolonged therapy on endothelium fulvestrant in postmenopausal women is not installed. Also, there are no data on the morphology of the endometrium.

Data on the impact of prolonged use of fulvestrant on bone tissue is not available.

Pharmacokinetics

Absorption and distribution

After i / m injection of fulvestrant is slowly absorbed, reaching a Cmax in the plasma after about 7 days. Absorption takes longer than 1 month, so if monthly injections are about 2-fold accumulation of the drug. Css in plasma determined approximately after 6 monthly injections, while the bulk of accumulation is reached after 3-4 injections.

After i / m injection exposure is approximately proportional to the dose introduced (in the range of doses from 50 to 250 mg).

In the equilibrium state the content of fulvestrant in the plasma varies in a relatively narrow range - maximum and minimum rates differ by about 2-3 times.

Fulvestrant is characterized by extensive and rapid distribution. Large apparent Vd (from 3 to 5 l / kg) in the equilibrium state involves mainly ekstravaskulyarnoe distribution.

Plasma protein binding is 99%. The main components include binding fractions VLDL, LDL and HDL. The role of sex hormone binding of globulin is not installed.

Metabolism

Metabolism of fulvestrant includes a combination of multiple potential pathways of biotransformation, similar mechanisms of metabolism of endogenous steroids (including metabolites of 17-ketone, sulfone, 3-sulfate, 3 - and 17-glucuronide).

Identified metabolites are less active or equal to the activity of fulvestrant. CYP3A4 isoenzyme is the only one who participates in the oxidation of fulvestrant. However, it appears that predominates in vivo biotransformation without the involvement of P450 isozymes.

Withdrawal

T1 / 2 is 50 days.

Fulvestrant is mainly excreted in the feces, urine output less than 1% of the active substance.

Pharmacokinetics in special clinical situations

The pharmacokinetic profile of fulvestrant does not depend on age (range 33-89 years), weight (40-127 kg), and race.

Light and mild renal dysfunction do not have a clinically significant effect on the pharmacokinetics of fulvestrant.

Fulvestrant pharmacokinetics studies in patients with impaired liver function was carried out.

Statement
locally advanced or disseminated breast cancer with positive estrogen receptors in postmenopausal women with progression after or during therapy with antiestrogens.

Dosage regimen

The drug is introduced into / m, by slow injection.

For adult women (including elderly) the recommended dose is 250 mg 1 time per month.

In the case of light to moderate renal dysfunction (CC ≥ 30 ml / min) dose adjustment is required. Safety and efficacy in patients with severe impaired renal function (CC <30 ml / min) is not installed.

Precautions recommended Fazlodeks patients with mild or moderate hepatic impairment. Safety and efficacy in patients with impaired liver function is not installed.

Terms of use and handling of drug

Remove glass syringe body contour of the blister and make sure no damage.

Breaking the outer package of safe needles (SafetyGlide). Remove the needle case strictly according to its direction, so as not to damage the needle tip. Touch the needle during its use impossible.

Break jumper white plastic cover the tip of a syringe and remove the cover from the attached rubber plug tip. Rotational motion to consolidate the needle at the tip of the syringe. Remove the cover from the needle.

Visually estimate the state of solution for parenteral administration for the lack of particles and discoloration prior to use.

Remove excess gas bubbles from the syringe (small bubbles may remain). Slowly introduce the solution into the gluteal muscle.

After removing the needle from the gluteal muscles to immediately activate the needle safety device by pushing the lever to transfer to a forward position for as long as the needle tip is fully closed. For the convenience of the plane bevel needle tip location meets the lever on the device security. When you activate the protective mechanism may be minimal splashing liquids, which may remain on the needle after injection. Visually verify that the lever moved to the extreme position and the needle tip is fully closed. If you can not activate the protective device needle, immediately put the needle in a standard container for needles.

For maximum security, you should perform all manipulations with one hand away from yourself and others.

Side effect

Determining the frequency of adverse reactions: very common (> 10%), frequent (> 1 - ≤ 10%), rarely (> 0.1-≤ 1%).

On the part of the digestive system: frequent - nausea, vomiting, diarrhea, anorexia.

Since the cardiovascular system: very frequently - feel the heat ("hot flushes"); often - thromboembolism. Local reactions: often - transient pain and inflammatory reactions.

On the part of the urogenital system: often - urinary tract infections, rarely - vaginal bleeding, vaginal candidiasis.

Dermatological reactions: often - a rash. Allergic reactions: seldom - edema, urticaria.

Other: often - headaches, asthenia, back pain, rarely - galactorrhea.

Contraindications
marked disturbances of liver function;
Pregnancy
lactation;
Hypersensitivity to the drug's components.

Precautions appoint a drug in violation of the kidneys and liver.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Application for violations of liver function

Precautions appoint a drug in mild and moderately expressed violations of liver function.

Contraindications disturbancies liver function.

Application for violations of renal function

In the case of light to moderate renal dysfunction (CC ≥ 30 ml / min) dose adjustment is required. Safety and efficacy in patients with severe impaired renal function (CC <30 ml / min) is not installed.

We recommend caution when using Fazlodeksa in patients with severe impaired renal function (CC <30 ml / min).

Cautions

Treatment Fazlodeksom should only be undertaken under the supervision of a physician who has experience of anticancer drugs.

Precautions recommended Fazlodeks patients with mild or moderate hepatic impairment.

We recommend caution when using Fazlodeksa in patients with severe impaired renal function (CC <30 ml / min).

Given the way the drug is recommended to use caution when applying Fazlodeksa patients with a bleeding tendency with thrombocytopenia or patients taking anticoagulants. Thromboembolism in women with advanced breast cancer occur frequently. This should be taken into account when appointing Fazlodeksa patients with risk of thromboembolism.

Effect Fazlodeksa on bone for prolonged use has not been established.

Given the mechanism of action of fulvestrant, we can not exclude the potential risk of developing osteoporosis.

Fazlodeks not be mixed with other drugs.

Use in Pediatrics

Data on the safety and efficacy in children and adolescents are not available.

Effects on ability to drive vehicles and management mechanisms

Effect Fazlodeksa driving ability and other mechanisms is negligible. Patients with symptoms of asthenia be careful when driving or other mechanisms.

Overdose

Cases of overdose in humans is unknown.

Symptoms: In experimental animal studies, the introduction of fulvestrant high-dose effects were observed only, directly or indirectly associated with Antiestrogenic activity. Treatment: In cases of overdose recommended symptomatic therapy.

Drug Interactions

According to the study of the clinical interaction with midazolam fulvestrant does not inhibit the activity of CYP3A4. Data in vitro suggest that fulvestrant does not affect the activity of CYP1A2, 2C9, 2S19, and 2D6. Possible suppression of CYP2A6, 2S8 and 2E1 were not assessed.

In a study of the clinical interaction with rifampicin (inducer CYP3A4) and ketoconazole (an inhibitor of CYP3A4) have been found clinically significant changes in clearance of fulvestrant. Therefore, the appointment fulvestrant in combination with inducers, or inhibitors of CYP3A4 dose adjustment is required.

Terms and Conditions of storage

The drug should be stored out of reach of children protected from light at 2 ° to 8 ° C.

Shelf life - 4 years.