DIFERELIN 0 2 before puncture for what. Application of diffelin at eco

The date: 23.06.2020

A drug DIFERELIN 0.1.- Gonadotropin - hormone rilizing analogue, antitumor agent.
Triptorelin is a synthetic decapidide, analogue of natural gonadotropin - hormone rillation (release of gonadotropin).
Studies on animals and clinical studies have shown that after the initial period of stimulation, the long-term use of diffelin 0.1 mg suppresses gonadotropin secretion, followed by the suppression of the ovarian function.
The constant use of diffelin 0.1 mg suppresses the secretion of the gonadotropin (follicularity immuling hormone and luteinizing hormone). The suppression of intermediate endogenous peaks of the luteinizing hormone makes it possible to improve the quality of follicleogenesis, increasing the number of ripening follicles, and as a result, increase the likelihood of pregnancy per cycle.

Pharmacokinetics

:
In healthy adult volunteers.
After subcutaneous injection in a dose of 0.1 mg, Triptorelin is quickly absorbed (the time to achieve a maximum concentration of 0.63 ± 0.26 hours) with a plasma peak of 1.85 ± 0.23 ng / ml. The half-life is 7.6 ± 1.6 hours, after 3- 4 hours, the distribution phase ends.
General plasma clearance: 161 ± 28 ml / min.
Distribution volume: 1562 ± 158 ml / kg.

Indications for use

Indications for the use of the drug DIFERELIN 0.1.these are: female infertility, carrying out ovarian stimulation together with gonadotropins (FMG, CHG, FSH) in the vitro in the vitro fertilization and the transfer of the embryo, as well as other auxiliary reproductive technologies.

Mode of application

Short protocol: Dieferin 0.1 mgthey are introduced subcutaneously, starting from the 2nd day of the cycle (at the same time, starting the ovarian stimulation), and finish treatment 1 day before the planned introduction of human chorionic gonadotropin. The course of treatment is 10 - 12 days.
Long Protocol: Daily subcutaneous injections DIFERELIN 0.1 mg starts from the 2nd day of the cycle. During pituitary desensitization (E2< 50 пг/мл, то есть примерно на 15 день после начала лечения) начинают стимуляцию гонадотропинами и продолжают инъекции Диферелина в дозе 0,1 мг, заканчивая их за день до запланированного введения человеческого хорионического гонадотропина.
The duration of treatment is determined by the doctor individually.
Rules for preparing a solution.
Immediately before injection to transfer the solvent into the bottle with a lyophilisate. Shake until completely dissolved. The needles used must be placed in a container dedicated for acute items.

Side effects

At the beginning of treatment:
In the treatment of infertility, the combination with gonadotropins can lead to ovarian hyperstimulation. In this case, there is an increase in the size of the ovaries, pain in the abdomen. In the treatment of tripnelin in the dosage of 3.75 mg and 11.25 mg at the beginning of treatment, very often bleeding and bleeding from the vagina.
During treatment:
Most often there are such side phenomena as: sudden "tides", dryness of the vagina, a decrease in libido and disparatensions associated with the pituitary-ovarian blockade.
There are such side effects as: nausea, vomiting, increasing body weight, an increase in blood pressure, emotional lability, vision, pain in the injection site, headache, articular and muscle pain, increasing the activity of "liver" enzymes.
Allergic reactions: urticaria, rash, itching, rarely - quinque swelling.
Prolonged use of gonadotropin - rillation of hormone analogs can lead to bone demineralization, risk of development of osteoporosis.
The above-described side effect was not observed in short-term use. Diffelin 0.1 mg.
In the treatment of tripnelin in the dosage of 3.75 mg and 11.25 mg besides the most commonly described: headache, sleep disorders; Often - pain in lactic glands, muscle spasms, discomfort at the bottom of the abdomen, asthenia, peripheral edema, parastzia.

Contraindications

:
Contraindications for the use of the drug DIFERELIN 0.1.are: pregnancy, hypersensitivity.

Pregnancy

:
Currently, gonadotropin - hormone rillation analogues are used in combination with gonadotropins for stimulation of ovulation and pregnancy.
Pregnancy is a contraindication for the use of the drug. However, the practice has shown that after ovulation stimulated in the previous cycle, some women were pregnant without stimulation and continued to further stimulate ovulation.
Total data: Animal experiments have shown that the drug does not have a teratogenic effect.
Thus, the development of congenital anomalies in humans is not expected when using this drug, since 2 qualitatively performed animal studies did not reveal its teratogenic effect.
The results of the clinical studies with the participation of a small number of pregnant women using gonadotropin - the rillation of the hormone analogue showed the lack of malfunctions of fetal or fetotoxicity.
Nevertheless, it is necessary to further study the effects of the effect of the drug for pregnancy.

Interaction with other medicines

Not described.

Overdose

:
Cases of overdose by the drug DIFERELIN 0.1.not known.

Storage conditions

A drug DIFERELIN 0.1.it should be stored at a temperature not higher than 25 ° C.
Keep out of the reach of children.

Form release

DIFERELIN 0.1 - lyophilisate for the preparation of a solution for subcutaneous administration 0.1 mg(Complete with solvent - 0.9% solution of chloride sodium).
0.1 mg Triptorelin into a bottle of colorless hydrolytic glass type I (euro. F.), baked with a cork from a chlorobutyl rubber under an aluminum runner with a hole for the needle in the center and a closed protective plastic cover of the first autopsy control.
1 ml of solvent in an ampoule from colorless hydrolytic glass type I (ebfarm).
7 vials with triptery and 7 ampoules with solvent are laid into the contour cellular packing from PVC and together with the instructions for use are placed in a pack of cardboard.

Composition

:
DIFERELIN 0.1.(1 bottle) Contains: Active Component: Triptoreline acetate, in terms of triptoraline 0.1 mg.
Auxiliary component: mannitol 10.0 mg, solvent (1 ampoule), sodium chloride, water for injection.

Additionally

:
Before starting therapy, it is necessary to eliminate pregnancy.
The response of the ovaries to the administration of diffelin 0.1 mg in combination with gonadotropins may noticeably increase in patients predisposed to this and in particular in cases of polycystic diseases of the ovaries.
The response of the ovaries to the administration of the drug in combination with gonadotropins may differ in patients, also the reaction may be different in the same patients at different cycles.
Preventive action
Ovulation stimulation should be carried out under the supervision of the doctor and with regular biological and clinical analysis methods: an increase in the content of estrogen in plasma and carrying out ultrasound echography. If the response of the ovarian is redundant, it is recommended to interrupt the stimulation cycle and stop the gonadotropin injections.
Since the drug in rare cases may cause impairment, then, in this case, during treatment with DIFenelin, it is not recommended to manage vehicles and engage in other potentially hazardous activities that require increased concentrations of attention and speed of psychomotor reactions.

Main settings

Name:	DIFERELIN 0.1.
ATH code:	L02ae04. -

in bottles (complete with solvent); in the packing of the contour cell 7 sets; In a pack of cardboard 1 package.

in the vials (complete with a solvent in ampoules, syringe and two needles) in a pack of cardboard 1 set.

Description of the dosage form

DIFERELIN ® 0.1 mg: The lyophilisate is almost white, dispersing in the attached solvent with the formation of a transparent solution, practically free of particles.

DIFERELIN ® 3.75 mg: White or white lyophilisate with a creamy color shade, dispersible in the attached solvent with the formation of a white or white suspension with a creamy color shade.

DIFERELIN ® 11.25 mg: White or slightly yellowish lyophilisate, dispersible in the attached solvent with the formation of a white suspension or a slightly yellowish color.

The attached solvent - Transparent colorless solution.

pharmachologic effect

pharmachologic effect - Antigonadotropic.

Pharmacodynamics

Triptorelin is a synthetic decaptide, an analogue of the natural gonadotropin-rillation of a hormone released by gonadotropin.

DIFERELIN ® 0.1 mg

Studies on animals and clinical studies have shown that after the initial period of stimulation, the long-term use of difereline ® 0.1 mg suppresses the secretion of gonadotropins, followed by the suppression of the ovarian function.

The constant use of diffelin ® 0.1 mg suppresses the secretion of gonadotropins (FSH and LH). The suppression of intermediate endogenous peaks of LH makes it possible to improve the quality of follicleogenesis, increasing the number of ripening follicles, and, as a result, increase the likelihood of pregnancy per cycle.

DIFERELIN ® 3.75 mg

After a short initial period of stimulation of the gonadotropic functions of the Triptorelin pituitary, suppresses the secretion of gonadotropins and, accordingly, the function of the testicles and ovaries. The constant use of the drug inhibits the secretion of estrogen by the ovaries to the state of menopause, and also reduces the secretion of testosterone, the concentration of which can achieve indicators that are observed after surgical castration.

DIFERELIN ® 11.25 mg

In the initial period of application, DIFereline ® 11.25 mg temporarily increases the concentration of LH and FSH in the blood, respectively increases the concentration of testosterone in men and estradiol in women. Long-term treatment reduces the concentration of LH and FSH, which leads to a decrease in testosterone indicators (to levels corresponding to the state after testingctomy) and estradiol (to the levels corresponding to the state of the post-leadingctomy) about the 20th day after the first injection and then remain unchanged throughout the entire period administration of the drug.

Prolonged TRPTorelin treatment suppresses the secretion of estradiol in women and, thus, prevents the development of endometrioid ectopy.

Pharmacokinetics

DIFERELIN ® 0.1 mg

After p / k injecting with healthy adult volunteers in a dose of 0.1 mg, Triptorelin is quickly absorbed (the achievement time C max - (0.63 ± 0.26) h with a peak of a plasma concentration, components (1.85 ± 0.23) ng / ml).

T 1/2 is (7.6 ± 1.6) h, after 3-4 hours, the distribution phase ends.

General plasma clearance - (161 ± 28) ml / min.

Distribution volume - (1562 ± 158) ml / kg.

DIFERELIN ® 3.75 mg

After intramuscular administration of the prolonged form of the drug, the initial stage of the rapid release of the drug substance comes with the subsequent phase of permanent release of Triptorelin. C Max is (0.32 ± 0.12) ng / ml.

The average number of constantly released triporline is (46.6 ± 7.1) μg / day.

The bioavailability of the drug is about 53% per 1 month.

DIFERELIN ® 11.25 mg

With intramuscular administration of DIFerelin ® in a dose of 11.25 mg C Max Triptorelin in the blood plasma (in men and women) is determined by about 3 hours after injection. After the phase of a decrease in the concentration ongoing during the first month, until the 90th day, the concentration of circulating tripluetin remains constant (approximately 0.04-0.05 ng / ml - in the treatment of endometriosis and about 0.1 ng / ml - in the treatment of prostate cancer ).

DIFERELINE DIFERENE DIPERTY ®

DIFERELIN ® 0.1 mg

Female infertility. Conducting the ovarian stimulation together with gonadotropins (human menopausal, human chorionic), FSH in the vitro in extracorporeal fertilization programs and the transfer of the embryo, as well as other auxiliary reproductive technologies.

DIFERELIN ® 3.75 mg

prostate cancer;

premature puberty;

genital and extragnenital endometriosis;

fibromyoma of the uterus (before surgery);

female infertility (in an extracorporeal fertilization program).

DIFERELIN ® 11.25 mg

prostate cancer with metastases;

genital and extragenital endometriosis (I-IV stages).

Contraindications

Total for all dosages:

hypersensitivity;

pregnancy;

lactation.

hormone-dependent prostate cancer;

condition after preceding surgical testing netomy.

DIFERELIN ® 3.75; 11.25 mg (optional):

Carefully - with osteoporosis.

DIFERELIN ® 11.25 mg (optional):

Carefully - In women with polycystic ovarian syndrome.

Application in pregnancy and breastfeeding

Currently, the analogues of gonadotropin-rillation hormone are used in combination with gonadotropins for stimulation of ovulation and pregnancy.

Pregnancy is a contraindication for the use of the drug. However, the practice has shown that after ovulation, stimulated in the previous cycle, some women were pregnant without stimulation and continued to further stimulate ovulation.

Total data: Animal experiments have shown that the drug does not have a teratogenic effect.

Thus, the development of congenital anomalies in humans is not expected when using this drug, because 2 qualitatively performed studies on animals did not reveal its teratogenic effect.

The results of clinical studies with the participation of a small number of pregnant women using an analogue of gonadotropin-rillation hormone showed the lack of malformations of fetal or fetotoxicity.

Nevertheless, it is necessary to further study the effects of the effect of the drug for pregnancy.

Since there are no data on the penetration of the drug into breast milk and its possible effects on the breastfeeding of the child, treatment should be treated during breastfeeding.

Side effects

Total for all dosages

At the beginning of treatment. In the treatment of infertility, the combination with gonadotropins can lead to ovarian hyperstimulation. In this case, there is an increase in the size of the ovaries, pain in the abdomen.

During treatment. Most often there are such side effects as: sudden tides, dryness of the vagina, a decrease in libido and disparatensions associated with the pituitary-ovarian blockade.

Prolonged use of hormone gonadotropin-rillation analogs can lead to bone demineralization, risk of osteoporosis development (the side effect described above has not been observed with the short-term use of diffelin ® 0.1 mg).

Allergic reactions: Urthmitsa, rash, itching, rarely - Svet Quincke.

In rare cases - nausea, vomiting, increase in body weight, increase blood pressure, emotional lability, violation, pain in the injection site.

Rarely - Headache, articular and muscle pain.

DIFERELIN ® 3.75 mg additionally

In men - Reduced potency. At the beginning of treatment, patients with prostate cancer may experience a temporary increase in pain in bones affected by metastases (symptomatic treatment). In some cases, obstruction of the ureters and symptoms associated with the compression of the spinal cord metastasis (pass through 1-2 weeks) are noted. Also during this period there may be a temporary increase in the activity of acid phosphatase in the blood plasma.

In the treatment of premature puberty, there may be bleeding from the vagina.

Long-term use of the drug may cause hypogonadotropic amenorrhea.

After discontinuation of treatment, the ovarian function is restored and ovulation occurs on average for the 58th day after the last injection of the drug. The first menstruation occurs on the 70th day after the last injection of Diferelin ®. This must be taken into account in the planning of contraception.

DIFERELINE 11.25 mg additionally

In men

At the beginning of treatment. Dysuric disorders (difficulty urination, incomplete emptying of the bladder, pain), bone pain associated with metastases and compression of spinal cord metastases, which can be exacerbated due to a temporary increase in testosterone content in blood plasma at the beginning of treatment. These symptoms take place after 1-2 weeks. Also during this period there may be a temporary increase in the activity of hepatic enzymes in the blood plasma.

During treatment: Blood tides to face, decreased libido, gynecomastia, impotence, which is associated with a decrease in testosterone content in blood plasma.

Among women

At the beginning of treatment. Symptoms associated with endometriosis (pelvic pain, dysmenorrhea), which can enhance due to the initial transient increase in the concentration of estradiol in the plasma of blood and disappear after 1-2 weeks.

A month after the first injection, metroralia may occur.

In men and women:

Violation of mood, irritability, depression, feeling of fatigue, sleep impairment, increase in body weight, profuse sweat, paresthesia, impairment of vision, feverish state.

Interaction

Not described.

Method of application and dose

DIFERELIN ® 0.1 mg. PC.

Short protocol. Starting from the 2nd day of the cycle (at the same time starting the ovarian stimulation), and the treatment is completed 1 day before the planned introduction of human chorionic gonadotropin. The course of treatment is 10-12 days.

Long protocol. Daily subcutaneous injections of diffelin ® 0.1 mg start from the 2nd day cycle. During the desensitization of the pituitary gland (E2<50 пг/мл, т.е. примерно на 15-й день после начала лечения) начинают стимуляцию гонадотропинами и продолжают инъекции Диферелина ® в дозе 0,1 мг, заканчивая их за день до запланированного введения человеческого хорионического гонадотропина. Продолжительность лечения определяется врачом индивидуально.

Rules for preparing a solution. Immediately before injection to transfer the solvent into the bottle with a lyophilisate. Shake until completely dissolved. The needles used must be placed in a container dedicated for acute items.

DIFERELIN ® 3.75 mg. In / m.

Prostate cancer. DIFERELIN ® is introduced at a dose of 3.75 mg every 4 weeks, long.

Premature puberty. Children with a body weight of more than 20 kg - 3.75 mg every 28 days; Children with body weight less than 20 kg - 1.875 mg every 28 days.

Endometriosis. The drug should be introduced in the first 5 days of the menstrual cycle - at a dose of 3.75 mg every 4 weeks. The duration of therapy is not more than 6 months.

Female infertility. DIFERELIN ® must be introduced on the second day of the cycle at a dose of 3.75 mg. Communication with gonadotropins should be monitored after the dessensitization of the pituitary gland (the concentration of estrogen in the blood plasma is less than 50 pkg / ml is usually determined 15 days after the injection of DIFherlin ®).

Fibromomomomomoma of the uterus. The drug must be introduced in the first 5 days of the menstrual cycle. The introduction of diffelin ® should be carried out every 4 weeks at a dose of 3.75 mg. The duration of the course of treatment is 3 months (for patients preparing for operation).

1. Process the place of injection with a napkin with alcohol. Remove the cap with a needle with a pink nozzle and attach it to the syringe. Dial the entire solvent from the ampoule in the syringe.

4. Gently shake the contents until a homogeneous suspension is obtained, without turning the bottle.

5. Not turning the bottle, to gain the entire suspension into the syringe.

6. Remove the pink needle from the syringe. Attach the green needle to the syringe (tightly fasten), taking over the color tip only.

7. Remove air from the syringe.

8. Immediately make an injection. Injection to enter only intramuscularly.

Press the protective device towards the tip of the needle. Close the needle and snap the device;

Turn the syringe. Using a smooth surface, pressed on the device and close the needle.

11. To disconnect the needle, use the color nozzle. Dispose of needles in containers intended for acute items.

DIFERELIN ® 11.25 mg. V / M.

Prostate cancer. DIFERELIN ® is introduced at a dose of 11.25 mg every 3 months.

Endometriosis. DIFERELIN ® is introduced at a dose of 11.25 mg every 3 months. Treatment must be started in the first five days of the menstrual cycle. The duration of treatment depends on the severity of endometriosis and the observed clinical picture (functional and anatomical changes) on the background of therapy. As a rule, treatment is carried out for 3-6 months. It is not recommended to conduct a repeated course of treatment with tripterlin or gonadotropin-rilizing hormone.

Rules of preparation of suspension

The dissolution of the lyophilisate in the attached solvent should be carried out immediately before administration. Stir the contents of the bottle should be caution until a homogeneous suspension is obtained.

On cases of incomplete injection, leading to the loss of more suspension than usually remains in the injection syringe, you must inform the doctor.

Introduction should be carried out in strict accordance with the instructions.

1. Process the place of injection with a napkin with alcohol. Remove the cap with a needle with a pink tip and attach it to the syringe. Dial the entire solvent from the ampoule in the syringe.

2. Remove the plastic cover from the bottle with lyophilisate. Enter the needle through the cork from the chlorobutylikuka and transfer the solvent into the bottle.

3. Pull the needle so that it remains in the bottle, but did not touch the suspension.

4. Do not turn the bottle, carefully shake the contents until a homogeneous suspension is obtained.

5. Do not turn over the bottle, recruit the entire suspension in the syringe.

6. Remove the needle with a pink tip from the syringe. Attach the needle with a green tip (or a needle with a green tip and a protective device to the syringe with a green tip and a protective device), tightly taping only for the color tip.

7. Remove air from the syringe.

8. Immediately make an injection.

If a needle is used with a green tip and a protective device, then:

9. Immediately after injection, close the needle using a protective device in one of the following ways:

9.1. Press the protective device towards the tip of the needle. Close the needle and snap the device.

9.2. Turn over the syringe using a smooth surface, press on the device and close the needle.

10. The needle is closed if the needle tip is covered with a device. Check if the device is reliably closed.

11. To disconnect the needle, use the color tip.

12. Recycle needles in containers intended for acute items.

Overdose

Cases of overdose by the drug are unknown.

special instructions

DIFERELIN ® 0.1 mg

Warning. The response of the ovaries on the administration of diffelin ® 0.1 mg in combination with gonadotropins may noticeably increase in patients predisposed to this and, in particular, in cases of polycystic diseases of the ovaries.

The response of the ovaries on the administration of the drug in combination with gonadotropins may differ in patients, it can also be different in the same patients at different cycles.

Preventive action.Ovulation stimulation should be carried out under the supervision of a doctor and with regular biological and clinical analysis methods: increasing the content of estrogen in plasma and carrying out ultrasonic echocardiography. If the response of the ovarian is redundant, it is recommended to interrupt the stimulation cycle and stop the gonadotropin injections.

DIFERELIN ® 3.75 mg

At the beginning of treatment, an increase in clinical symptoms may be observed, and therefore, with caution to prescribe DIFherlin ® with patients with prostate cancer, exposed to risk of ureteral obstruction or spinal cord compression. It is necessary to carefully observe patient data during the first month of therapy.

Before the start of therapy, diffelin ® must confirm the absence of pregnancy.

With caution to apply in patients with polycystic ovary syndrome when conducting ovulation stimulation schemes. This is due to the fact that a small number of patients may increase the number of induced follicles.

It is necessary to carefully monitor the level of stimulation of the cycle with an extracorporeal fertilization to identify patients with the risk of developing the ovaries hyperstimulation syndrome, since the severity and frequency of manifestations of the syndrome may depend on the dosing mode of gonadotropin. If necessary, the introduction of human chorionic gonadotropin should be discontinued.

DIFERELIN ® 11.25 mg

Treatment of endometriosis. Before starting treatment, it is necessary to exclude pregnancy.

During the first month of therapy, non-flame contraceptives should be used.

The intramuscular injection of the drug leads to a resistant hypogonadotropic amenorhea.

The emergence of metrragia during treatment, not counting the first month, is not the norm, and therefore it is necessary to determine the concentration of estradiol plasma. With a decrease in estradiol concentration to level of less than 50 pg / ml, it is possible to have other organic lesions.

The ovarian function is restored after the end of therapy. The first menstruation occurs on average 134 days after the last injection. For this reason, the use of contraception should be started 15 days after the cancellation of treatment, i.e. After 3.5 months after the last injection.

In the treatment of prostate cancer. The most pronounced effect is noted in patients in the absence of another previously conducted hormone therapy.

At the beginning of treatment, the emergence and strengthening of clinical symptoms (in particular pain in bones, dysuric disorders), which are transient character.

This implies a thorough observation of patient data during the first few weeks of therapy (the level of testosterone in the blood plasma should not exceed 1 ng / ml).

Diffelin ® treatment must be carried out in strict accordance with the instructions for use. Any change in the volume of the suspension introduced in / m must be configured.

Conditions for the storage of drug DIFERELIN ®

At a temperature not higher than 25 ° C.

Keep out of the reach of children.

The shelf life of DIFERELIN ®

the lyophilisate for the preparation of a suspension for intramuscular administration of a prolonged action is 3.75 mg - 2 years.

the lyophilisate for the preparation of a suspension for intramuscular administration of a prolonged action is 11.25 mg - 3 years. 5 years - solvent.

lyophilisate for the preparation of a solution for subcutaneous administration 0.1 mg - 2 years.

Do not apply after the expiration date indicated on the package.

Synonyms of nosological groups

Rubric ICB-10	Synonyms for diseases of the ICD-10
C61 Malignant Prostate Breast Town	Prostate adenocarcinoma
	Hormone-dependent prostate cancer
	Hormonistant prostate cancer
	Malignant prostate tumor
	Malignant prostate neoplasm
	Karcinoma prostate gland
	Locally common non-metastatic prostate cancer
	Locally common prostate cancer
	Local prostate cancer
	Metastasizing prostate carcinoma
	Metastasive prostate cancer
	Metastatic hormone escaternity prostate cancer
	Nonmetatic prostate cancer
	Non-Orobeile Prostate Cancer
	Prostate cancer
	Prostate cancer
	Common prostate cancer
	Testosterone-dependent prostate cancer
D26 Other benign uterine neoplasms	Maigs Syndrome
	Myoma
	Myoma uterus
	Moma uterus
	Tumors of uterus
	Fibrisians
	Fibromomoma
	Fibromyoma uterus
E30.1 Premature puberty	Primary premature puberty
	Policy ripening premature
	Premature sexual development
	Premature puberty among girls
	Early puberty
N80 endometriosis	Endometrioid heterotropy
N97 female infertility	Insuulator infertility
	Infertility female
	Infertility against the background of hyperprolactinemia
	Infertility of the ovarian genesis
	Infertility due to hypothalamic-pituitary dysfunction
	Marriage forever
	Hyperprolactinemic infertility
	Hyperprolactinemia with infertility
	Female infertility when angular
	Stimulation of the growth of one follicle
	Functional infertility
	Endocrine infertility

Analogue Gonadotropin Rilizing Hormone - Depot Form

Active substance

Triptorelin (in the form of Pamooca) (TripTorelin)

Release form, composition and packaging

Lyophilisate for the preparation of suspension for the introduction of prolonged action White or slightly yellowish color, dispersible in the attached solvent with the formation of a suspension of white or slightly yellowish color; Solvent - transparent colorless solution.

* - Taking into account the peculiarities of the dosage form in the drug, an excess of the active substance is laid to ensure the introduction of an effective dose.

Auxiliary substances: copolymer D, L-dairy and glycolic acids - 250 mg, - 85 mg, sodium carmellosis (sodium carboxymethylcellulose) - 30 mg, polysorbate 80 - 2 mg.

Solvent: Mannitol - 16 mg, water d / and - up to 2000 mg.

Flakes slightly darkened glass (1) complete with solvent (AMP 2 ml 1 PC.), Disposable polypropylene syringe, needles d / and (2 pcs.) - Cardboard packs.

pharmachologic effect

Synthetic decapeptide, analogue of natural GNRG.

After the short initial period of stimulation of the gonadotropic functions of the Triptorelin pituitary gland, it has an inhibitory effect on the secretion of gonadotropins, followed by the suppression of the function of testicles and ovaries.

In the initial period of application, DIFenelin temporarily increases the concentration of LH and FSH in the blood, respectively, the concentration of testosterone in men and estradiol in women increases. Long-term treatment reduces the concentration of LH and FSH, which leads to a decrease in testosterone indicators (to levels corresponding to the state after testingctomy) and a decrease in estradiol indicators (to levels corresponding to the state of the post-leadingctomy) - approximately 20 days after the first injection and then remains unchanged throughout The period of administration of the drug.

Prolonged TRPTorelin treatment suppresses the secretion of estradiol in women and, thus, prevents the development of endometrioid ectopy.

Pharmacokinetics

Suction and distribution

At the introduction of diffelin in a dose of 11.25 mg C Max Triptorelin in the blood (in men and women) is determined by about 3 hours after injection. After the phase of a decrease in the concentration ongoing during the first month, up to 90 days the concentration of circulating tripathelin remains constant (from about 0.04 to 0.05 ng / ml in the treatment of endometriosis and about 0.1 ng / ml during treatment).

Indications

Prostate cancer:

treatment of the forensic prostate cancer in monotherapy or as adjuvant means on the background of radiation therapy;
treatment of metastatic prostate cancer.

Genital and extragenital endometriosis (stage I-IV).

Contraindications

increased sensitivity to tripathereline, other components of the drug or other analogs of GNR.

In men:

hormone-dependent prostate cancer, condition after preceding surgical testsomectomy.

Among women:

pregnancy;
lactation period (breastfeeding).

FROM caution It should be prescribed a drug during osteoporosis, women with ovarian polycystic syndrome.

Dosage

For prostate cancer Difelinine is introduced in a dose of 11.25 mg every 3 months. In combination with long-term antandrogenic therapy (3 years), it is preferable to short-term antandrogenic therapy (6 months).

For endometriosis The drug is introduced in a dose of 11.25 mg every 3 months. Treatment must be started in the first 5 days of the menstrual cycle. The duration of treatment depends on the severity of endometriosis and the observed clinical picture (functional and anatomical changes) on the background of therapy. As a rule, treatment is carried out for 3-6 months. It is not recommended to conduct a repeated course of treatment with tripothelin or another analogue of GNVG.

Rules of preparation of suspension

On cases of incomplete injection, leading to the loss of more suspension than usually remains in the injection syringe, you must inform the doctor.

Introduction should be carried out in strict accordance with the instructions.

The patient must be in the lying position. Disinfection the skin of the buttock.

1. Felt the neck of the ampoule (point on the front side from above).

2. Type the solvent in the syringe with the needle.

3. Remove the green protective plastic cover from the top of the vial.

4. Transfer the solvent to the bottle with lyophilisate.

5. Pull the needle so that it remains in the bottle, but did not touch the suspension.

6. Not turning the bottle, carefully shake the contents until a homogeneous suspension is obtained.

7. Check out the absence of agglomerates before reconnecting the suspension into the syringe (in the absence of agglomerates, shake up to full homogeneity).

8. Not turning the bottle, type the entire suspension into the syringe.

9. Remove the needle used to prepare the suspension, and attach a touch of another needle on the tip of the syringe. Hold on only for the color tip.

10. Remove the air from the syringe.

11. Immediately make an injection into the buttock muscle.

12. Dispose needles in containers intended for acute items.

Side effects

In men

At the beginning of treatment: Dizuriy (difficulty urination, incomplete emptying of the bladder, soreness), bone pain associated with metastases and compression of spinal cord metastases, which can be exacerbated due to a temporary increase in testosterone content in blood plasma at the beginning of treatment. These symptoms take place after 1-2 weeks. Also during this period there may be a temporary increase in the activity of hepatic enzymes in the blood plasma.

During treatment:flips, decrease in libido, gynecomastia, impotence, which is associated with a decrease in testosterone content in blood plasma.

Among women

At the beginning of treatment:symptoms associated with endometriosis (pelvic pain, dysmenorrhea), which can enhance due to the initial transient increase in the concentration of estradiol in the blood plasma and disappear after 1-2 weeks. After 1 month after the first injection, genital bleeding may occur, including both menorragia and metrragia.

During treatment:dryness of the vagina, tides, the decrease in the libido, an increase in the mammary glands, dispensing, which is associated with the pituitary-ovarian blockade; Rarely -, Arthralgia, Malgy.

In men and women

Allergic reactions, such as urticaria, rash, itching and very rarely - swelling quinque; Violation of mood, irritability, depression, feeling of fatigue, sleep disorders, nausea, vomiting, increase body weight, profuse sweat, arterial hypertension, paresthesia, impairment, pain at the injection site and feverish state.

Prolonged use of analogs of GNVGs can lead to bone demineralization and is a possible risk risk factor for the occurrence of osteoporosis.

According to the data collected during the use of analogs of GNVG, the following adverse reactions may occur in patients: erectile dysfunction, ears, dizziness, diabetes (hyperglycemia), constipation, diarrhea, bloating, dry oral mucosa, disgusting, disgusting, meteorism, asthenia; drowsiness, influenza-like syndrome, anaphylactic reactions; increasing the activity of Alt, AST, SFF; HypercreatyNiamia, urea increase, anorexia, gout, increased appetite, musculoskeletal pain, pain in limbs, muscle cramps, muscle weakness, dizziness, memory deterioration, insomnia, confusion of consciousness, anxiety, egg atrophy, shortness of breath, orthopneus, nasal bleeding , acne, alopecia, decreased blood pressure; At the injection site - Erythema, inflammation, pain.

Overdose

To date, cases of overdose of the drug DIFherlin are unknown.

Medicinal interaction

The drug interaction of the drug diherlin is not described.

special instructions

In the treatment of endometriosis

Before starting treatment, it is necessary to exclude pregnancy.

During the first month of therapy, non-flame contraceptives should be used.

Injecting the drug leads to a resistant hypogonadotropic amenorhea.

The emergence of metrragia during treatment, not counting the first month, is not the norm, and therefore it is necessary to determine the concentration of estradiol in the blood plasma. With a decrease in estradiol concentration of less than 50 pg / ml, the presence of other organic lesions is possible.

The ovarian function is restored after the end of therapy. The first menstruation occurs on average 134 days after the last injection. Therefore, contraception measures should begin to apply 15 days after the cessation of treatment, that is, after 3.5 months after the last injection.

In the treatment of prostate cancer

The most pronounced effect is noted in patients in the absence of another previously conducted hormone therapy.

At the beginning of treatment, the appearance and strengthening of clinical symptoms (in particular, pain in bones, dysuric phenomena), which are transient character.

This implies a thorough observation of patient data during the first few weeks of therapy (the level of testosterone in the blood plasma should not exceed 1 ng / ml).

For the same reason, careful observation at the beginning of treatment must be carried out for patients with diagnosed spinal cord compression.

In addition, at the beginning of treatment, a temporary increase in acid phosphatases may be observed.

In patients receiving GNVG agonists, the risk of developing hyperglycemia and diabetes is registered. In addition, the risk of developing cardiovascular diseases and, with long-term use, osteoporosis is possible.

Impact on the ability to driving vehicles and control mechanisms

No information.

Pregnancy and lactation

Differelin is contraindicated for use during pregnancy and during lactation (breastfeeding).

Since there are no data on the removal of tripatherelin in with breast milk and its possible effects on the breastfeeding of the child, do not conduct treatment with DIFERELIN drug during breastfeeding period.

According to available data, no teratogenic effects were detected at experimental studies on animals. In isolated cases, the use of analogs of GNRG (by negligence) of any defects for the development of fetus and fetotoxicity is not detected.

Conditions of vacation from pharmacies

The drug is released by the prescription.

Terms and Storage Terms

The drug should be stored in an inaccessible place at temperatures not higher than 25 ° C. The shelf life of the lyophilisate is 3 years, the solvent is 5 years.

DIFERELIN®

International non-proprietary title

Triptohelin

Dosage form

Lyophilisate for the preparation of a solution for subcutaneous administration of 0.1 mg in a set with solvent (0.9% sodium chloride solution)

Composition

One bottle contains

active substance:triptoreline acetate in terms of triptonelin 0.1 mg

ancillary:mannitol

solvent:sodium chloride, water for injection

Description

The lyophilisate is almost white ones. Solvent - transparent colorless liquid. Reduced solution - colorless transparent solution, practically free of particles

Pharmacotherapeutic group

Antitumor hormonal drugs. Hormones and their derivatives. Gonadotropin-rillation hormone analogues. Triptohelin

ATH code L02ae04.

Pharmacological properties

Pharmacokinetics

After subcutaneous administration of diffelin® 0.1 mg, the drug is quickly absorbed (the time to achieve the maximum concentration T max \u003d 0.630.26 h) with the peak of the plasma concentration (maximum concentration - with max \u003d 1,850.23 ng / ml ). The preparation half-life is 7.61.6 hours after 3-4 hours of the distribution phase. Plasma clearance: 16128 ml / min. Distribution volume: 1562158 ml / kg

Pharmacodynamics

Triptorelin is a synthetic decapidide, an analogue of the natural GNRG (hormone released gonadotropin). DIFERELIN®, after the initial period of stimulation of the gonadotropic function of the pituitary gland, with long-term administration at a dose of 0.1 mg, it has an inhibitory effect on the secretion of gonadotropin, followed by suppressing the synthesis of genital steroid hormones.

Indications for use

Female infertility: comprehensive treatment, in combination with gonadotropins (xg - chorionic gonadotropin, FSH - follicle-stimulating hormone), for artificially creating conditions for ovulation, in order to conceive iN. vitro. and subsequent embryo transplant

Method of application and dose

"Short" Protocol:0.1 mg of DIFerelin® is administered subcutaneously, starting from 2 days of the menstrual cycle (at the same time starting the ovarian stimulation), and finish treatment a day before the planned introduction of human chorionic gonadotropin. The course of treatment of diffelin® is 10-12 days.

"Long" Protocol: Daily subcutaneous injections of DIFerelin® 0.1 mg begin with 2 days of the menstrual cycle. During the desensitization of the pituitary< 50 пг/мл, то есть примерно на 15 день после начала лечения) начинают стимуляцию гонадотропинами и продолжают инъекции Диферелина® в дозе 0,1 мг, заканчивая их за день до запланированного введения человеческого гонадотропина. Продолжительность лечения определяется врачом индивидуально.

Rules of preparation of suspension

Immediately before injection to transfer the solvent into the bottle with a lyophilisate. Shake up to completely dissolve lyophilisate. Injection should be made immediately after dissolving the lyophilisate.

Side effects

At the beginning of treatment

In the treatment of infertility, the combination with gonadotropins can lead to ovarian hyperstimulation (increase in the size of the ovaries, pain in the abdomen).

During treatment

- "stuffs", dryness in the vagina, reduced libido and dispresia (associated with a pituitary-ovarian blockade)

Seldom

Headache, Arthralgia and Malgia

Allergic reactions (urticaria, rash, itching)

Mood change, sleep disorder, irritability, depression, feeling fatigue

Nausea, vomiting, increase body weight, increase blood pressure, impairment, pain at the injection site, feverish state.

Rarely

Sweet Qincke

Contraindications

Increased sensitivity to tripranhelin or other analogs of GNVGs, to other components of the drug

Pregnancy and lactation period

Polycystic ovarian

Osteoporosis

Medicinal interactions

Do not know

special instructions

Before starting therapy, it is necessary to eliminate the pregnancy. The reaction of the ovaries on the introduction of diffelin® with the same dose of the drug may vary in patients.

Precautions when applied: The ovarian induction should be monitored by a thorough medical examination, including biological and clinical control: control of estrogen in blood plasma and ultrasound examination. In the case of suspicion of hyperstimulation, it is recommended to stop gonadotropin injections.

Long-term use of hormone gonadotropin-rillation analogs can lead to bone demineralization and is a possible risk factor for osteoporosis.

Pregnancy and lactation

Pregnancy and lactation are contraindications for the use of the drug.

Features of the influence of the medicinal product on the ability to control the vehicle or potentially hazardous mechanisms

Since the drug in rare cases can cause impairment of vision, then, in this case, during treatment with DIFherine®, it is not recommended to control vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

DIFERELIN® Overdose Cases are not described

Release form and packaging

The lyophilisate is placed in vials from a colorless type 1 glass, clapped by corks made of halobutyl, compressed aluminum caps with polypropylene covers of yellow color.

Female infertility. Conducting ovarian stimulation together with gonadotropins [FMG (human menopausal gonadotropin), CHG (human chorionic gonadotropin), FSH (follicle-sustamulating hormone)] in the vitro in extracorporeal fertilization programs and the transfer of the embryo, as well as other auxiliary reproductive technologies.

Contraindications DIFERELINE FIFILITY FOR INJECTIONS 0.1MG

Pregnancy and breastfeeding period: It is necessary to exclude pregnancy before the treatment with therapy. Hypersensitivity to GNRG, preparation of diferlin, its components or other analogs of GNVG. With caution, the drug should be used in polycystic ovaries syndrome, depression.

Method of application and dosage DIFERELINE Lyophilisate for injection 0.1 mg

Short protocol. DIFERINE 0.1 mg preparation is administered subcutaneously, starting from the 2nd day of the cycle (at the same time starting the ovarian stimulation), and the treatment is completed 1 day before the planned introduction of human chorionic gonadotropin. The course of treatment is 10-12 days. Long protocol. Daily subcutaneous injections of the drug DIFERELIN 0.1 mg start from the 2nd day of the cycle. During the desensitization of the pituitary gland (E2