Differelin for IVF: a drug for the desired pregnancy. Lowering Sex Hormone Levels with Dipherelin Triptorelin Dipherelin Benefits
A drug Diphereline 11.25- antineoplastic agent, gonadotropin - hormone-releasing analogue.
Triptorelin is a synthetic decapeptide analogous to the natural gonadotropin-releasing hormone (GnRH).
After a short initial period of stimulation of the gonadotropic function of the pituitary gland, triptorelin has an inhibitory effect on the secretion of gonadotropins, followed by suppression of the function of the testicles and ovaries.
In the initial period of application, Dipherelin 11.25 mg temporarily increases the concentration of luteinizing hormone (LH) and follicle-stimulating hormone (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 levels (to levels corresponding to the state after testiculectomy) and a decrease in estradiol indicators (to levels corresponding to the state of postovariectomy) - by about 20 days after the first injection and then remains unchanged throughout period of drug administration.
Long-term treatment with triptorelin suppresses the secretion of estradiol in women and, thus, prevents the development of endometrioid ectopias.
Pharmacokinetics:
With the intramuscular injection of Dipherelin at a dose of 11.25 mg, the maximum concentration of triptorelin in the blood plasma (in men and women) is determined approximately 3 hours after injection. After a phase of decrease in concentration, lasting during the first month, until day 90, the concentration of circulating triptorelin remains constant (about 0.04 to 0.05 ng / ml in the treatment of endometriosis and about 0.1 ng / ml in the treatment of prostate cancer).
Indications for use
A drug Diphereline 11.25 It is used to treat metastatic prostate cancer, genital and extragenital endometriosis (stages I - IV).Mode of application
Prostate cancer: Diphereline 11.25 injected intramuscularly at a dose of 11.25 mg every 3 months.Endometriosis: Diphereline is injected intramuscularly at a dose of 11.25 mg every 3 months.
Treatment should 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) during therapy.
As a rule, treatment is carried out for 3 to 6 months. Repeated treatment with triptorelin or GnRH is not recommended.
Suspension preparation rules:
The dissolution of the lyophilisate in the supplied solvent should be carried out immediately prior to administration. Stir the contents of the vial with caution until a homogeneous suspension is obtained.
Cases of incomplete injection, leading to the loss of more suspension than usually remains in the injection syringe, must be reported to the attending physician.
The introduction should be carried out in strict accordance with the instructions. The patient should be in the supine position. Disinfect the skin of your buttocks.
1. Break the neck of the ampoule (dot on the front side at the top).
2. Draw all of the solvent into the syringe and needle.
3. Remove the protective plastic cap from the top of the bottle.
4. Transfer the solvent to the lyophilisate vial
5. Pull the needle so that it remains in the vial, but does not touch the suspension.
6. Without turning the bottle, gently shake the contents until a homogeneous suspension is obtained.
7. Check the absence of agglomerates before drawing the suspension into the syringe (if there are agglomerates, shake until completely homogeneous).
8. Without turning the bottle over, draw the entire suspension into the syringe.
9. Remove the suspension needle and firmly attach the other needle to the tip of the syringe. Only hold on to the colored tip.
10. Remove air from the syringe.
11. Immediately inject into the gluteus muscle.
12. Dispose of needles in sharps containers.
Side effects
In men at the beginning of treatment - Dysuric disorders (difficulty urinating, incomplete emptying of the bladder, soreness), bone pain associated with metastases and compression by metastases of the spinal cord, which can be aggravated by a temporary increase in testosterone levels in the blood plasma at the beginning of treatment. These symptoms disappear in 1 to 2 weeks. Also during this period, there may be a temporary increase in the activity of liver enzymes in the blood plasma.During treatment: hot flashes, decreased libido, gynecomastia, impotence, which is associated with a decrease in testosterone levels in the blood plasma.
In women, at the beginning of treatment. Symptoms associated with endometriosis (pelvic pain, dysmenorrhea), which may increase due to an initial transient increase in plasma estradiol concentration and disappear after 1 to 2 weeks.
Metrorrhagia may occur a month after the first injection.
During treatment.
Vaginal dryness, hot flashes, decreased libido, enlarged mammary glands, dyspareunia, which is associated with pituitary-ovarian blockade.
Rarely - headache, arthralgia, myalgia.
In men and women. Allergic reactions such as hives, rash, itching, and very rarely - Quincke's edema; mood disturbances, irritability, depression, fatigue, sleep disturbances, nausea, vomiting, weight gain, profuse sweat, hypertension, paresthesias, blurred vision, pain at the injection site and fever.
Long-term use of GnRH analogues can lead to bone demineralization and is a possible risk factor for osteoporosis.
Contraindications
:Hypersensitivity to Diphereline, its components or other analogs of gonadotropin-releasing hormone.
In men, hormone-independent prostate cancer, a condition after a previous surgical testiculectomy.
In women - pregnancy, lactation and breastfeeding.
Use with caution in patients with osteoporosis, in women with polycystic ovary syndrome.
Pregnancy
:It is contraindicated to use the drug Diphereline 11.25.
According to the available data, no teratogenic effects were found in animal studies. In isolated cases of the use of GnRH analogues (by negligence), no defects in fetal development and fetotoxicity were found.
Since there is no data on the penetration of the drug into breast milk and its possible effects on a breastfed baby, treatment should not be carried out during breastfeeding.
Interaction with other medicinal products
Not described.Overdose
:Drug overdose cases Diphereline 11.25 are not known.
Storage conditions
At a temperature not exceeding 25 ° C, out of the reach of children.Release form
Diphereline 11.25 - lyophilisate for the preparation of a suspension for intramuscular administration of prolonged action of 11.25 mg.11.25 mg of triptorelin in a slightly darkened glass vial, sealed with a rubber stopper under an aluminum rim with a hole for a needle in the center and closed with a protective plastic cover for the first opening control.
2 ml of solvent in an ampoule.
One empty sterile disposable polypropylene syringe with a capacity of 3 ml, two hypodermic disposable needles measuring 0.90 x 40 mm with yellow tips in a PVC and laminated paper blister pack.
One bottle with the drug, one ampoule with a solvent, one blister pack with a syringe and two needles is placed in a cardboard box along with instructions for use.
Composition
:Diphereline 11.25(1 bottle) contains: active ingredient: triptorelin pamoate, in terms of triptorelin 11.25 * mg.
Auxiliary components: copolymer of DL-lactic and glycolic acids 250.0 mg, mannitol 85.0 mg, sodium carmellose (sodium carboxymethyl cellulose) 30.0 mg, polysorbate-80 2.0 mg, solvent (1 ampoule), mannitol 16.0 mg, water for injection up to 2000.0 mg.
* Taking into account the characteristics of the dosage form, the preparation contains an excess of the active component to ensure the administration of an effective dose.
Additionally
:When treating endometriosis:
Pregnancy must be ruled out before starting treatment.
During the first month of therapy, non-hormonal contraceptives should be used. Intramuscular injection of the drug leads to persistent hypogonadotropic amenorrhea. Treatment should not be recommended for a period longer than 6 months. It is not recommended to repeat the course of therapy with triptorelin or another GnRH analog.
The occurrence of metrorrhagia during treatment, apart from the first month, is not the norm, and therefore it is necessary to determine the concentration of plasma estradiol. With a decrease in the concentration of estradiol less than 50 pg / ml, the presence of other organic lesions is possible.
Ovarian function is restored after completion of therapy. The first period occurs on average 134 days after the last injection. For this reason, contraceptive use should be started 15 days after discontinuation of treatment, that is, 3.5 months after the last injection.
When treating prostate cancer:
The most pronounced beneficial effect is observed in patients in the absence of other previous hormone therapy.
At the beginning of treatment, there may be the appearance and intensification of clinical symptoms (in particular, bone pain, dysuric disorders), which are transient.
This implies careful observation of these patients during the first few weeks of therapy (the level of testosterone in the blood plasma should not exceed 1 ng / ml).
Treatment with Dipherelin must be carried out in strict accordance with the instructions for use. Any change in the volume of the suspension administered intramuscularly should be recorded.
main parameters
| Name: | DIFERELIN 11.25 |
| ATX code: | L02AE04 - |
Diphereline is an antineoplastic hormonal drug analogous to the gonadotropin-releasing hormone. This drug contributes to the provision of antigonadotropic effects.
Diphereline is available in the form of a lyophilisate for the preparation of a suspension intended for intramuscular administration.
Triptorelin acetate acts as an active ingredient. The lyophilisate is supplied with a solvent containing water for injection and sodium chloride.
The drug is administered in strict accordance with the manufacturer's instructions. In this case, the patient should be in the supine position.
- It is necessary to break the neck of the ampoule and take the solvent into the syringe.
- Remove the protective cap from the bottle and pour in the solvent.
- Pull the needle - it should remain in the vial and not touch the suspension.
- Stir the contents of the vial until a homogeneous liquid is obtained. In this case, you cannot turn the bottle over.
- Draw up the contents of the vial into the syringe.
- Remove the needle that was used during the preparation of the suspension and attach a clean needle.
- Remove the remaining air from the syringe and immediately inject the drug into the gluteal muscle (the skin must be pre-disinfected).
- Dispose of needles and syringe.
Adverse Reactions
General information for all dosages. Diphereline can contribute to the development of the following undesirable side reactions:
- Quincke's edema, urticaria, itching, rash.
- In the treatment of infertility, which is carried out in combination with gonadtropins, manifestations of ovarian hyperstimulation can be observed: the development of pain in the abdomen, an increase in the size of the ovaries.
- During treatment, there may be the development of hot flashes, vaginal dryness, decreased libido. Long-term use of the drug increases the risk of developing osteoporosis.
- Rarely: the development of nausea, vomiting, visual impairment, increased blood pressure, weight gain, impaired psychoemotional state, pain at the injection site.
- Isolated cases: the development of joint and muscle pain, headache.
During treatment, men may experience a lack or decrease in potency. At the beginning of therapy, patients with malignant neoplasms of the prostate gland may experience bone pain. In this case, symptomatic treatment is required.
In the event that the drug is used during the treatment of premature puberty in girls, short-term spotting from the vagina may occur.
Prolonged use of the drug Diphereline can provoke the development of hypogonadotropic amenorrhea.
After cessation of therapy with the drug Dipherelin in the dosage [information on the dose of the drug has been deleted], the restoration of ovulation and normal ovarian function occurs approximately 58 days after the last injection. The first menstrual period may occur about 70 days after the last injection. This should be taken into account when planning contraception.
The interaction of the drug Dipherelin with other groups of drugs has not been described. If it is necessary to combine this remedy with other drugs, you must first consult with your doctor.
At the beginning of therapy, it is possible to increase all the symptoms of the disease, therefore, Dipherelin is used with extreme caution during the treatment of malignant neoplasms of the prostate gland. Due to the risk of ureteral obstruction and spinal cord compression, patients should be systematically monitored by a physician in the first 30 days of therapy.
Before starting treatment with the use of the drug, it is necessary to exclude the possible pregnancy of the patient.
Analogues, cost
The cost of the drug Dipherelin for the period of autumn 2016 was formed as follows:
- Lyophilisate for preparation of a solution of 0.1 mg, 7 pcs. - 2500-3000 rubles.
- Powder for injection i.m. 3.75 mg, 1 bottle - 7400-8700 rubles.
- Lyophilisate for preparing a solution of 11.25 mg - 18,000 - 20,000 rubles.
The following drugs can act as analogues of the drug Dipherelin: Decapeptil, Triptorelin.
Bofur Ipsen Industry Ipsen Pharma Biotech Ipsen Pharma Biotech / Raduga Production ZAOCountry of origin
France France / RussiaProduct group
Hormonal drugsAnalogue of gonadotropin-releasing hormone - depot form, anticancer drug
Forms of issue
- Bottles (7) complete with solvent (amp. - 7) - contoured cell packs (1) - cardboard packs. Vials of slightly darkened glass (1) complete with a solvent (amp. 2 ml 1), a disposable polypropylene syringe, needles for and (2) - cardboard packs. Vials of slightly darkened glass (1) complete with a solvent (amp.), A disposable polypropylene syringe, needles for and (2) - cardboard packs.
Description of the dosage form
- Lyophilizate for preparing a solution for subcutaneous administration of an almost white color, dispersing in the supplied solvent to form a transparent solution, practically free of particles. Lyophilisate for preparation of a suspension for intramuscular administration of prolonged action of white or white with a creamy shade, dispersing in the supplied solvent to form a suspension of white or white with a creamy shade. Lyophilisate for preparing a suspension for intramuscular administration of prolonged action of white or slightly yellowish color, dispersing in the supplied solvent to form a suspension of white or slightly yellowish color; the solvent is a clear, colorless solution.
pharmachologic effect
Antineoplastic agent, synthetic analogue of GRF. It has an antigonadotropic effect. The mechanism of action is based on a direct effect on the gonads by decreasing the sensitivity of peripheral receptors to the effects of GRF. After a short initial period of stimulation of the gonadotropic function of the pituitary gland (a short-term increase in the concentration of gonadotropins), triptorelin suppresses the secretion of LH, FSH and, accordingly, the function of the testicles and ovaries. As a result, the secretion of estrogen by the ovaries is inhibited until menopause, as well as a decrease in the secretion of testosterone, the concentration of which can reach the levels that are observed after surgical castration. The maximum effect develops at 3 weeks (the incretion of gonadotropins, LH and FSH completely stops, the production of estrogen by the ovaries decreases to the level of menopause or post-castration). Menstruation usually occurs no earlier than 3 months after the final injection. The depot form gradually releases triptorelin from the surface of the microcapsules and maintains the therapeutic concentration in the blood (200-500 ng / ml).Pharmacokinetics
Absorption and distribution With the intramuscular injection of Dipherelin at a dose of 11.25 mg Cmax of triptorelin in blood plasma (in men and women) is determined approximately 3 hours after injection. After a phase of decrease in concentration, lasting during the first month, until day 90, the concentration of circulating triptorelin remains constant (about 0.04 to 0.05 ng / ml in the treatment of endometriosis and about 0.1 ng / ml in the treatment of prostate cancer).Special conditions
In the treatment of endometriosis Before starting treatment, it is necessary to exclude pregnancy. During the first month of therapy, non-hormonal contraceptives should be used. IM injection of the drug leads to persistent hypogonadotropic amenorrhea. Treatment should not be recommended for more than 6 months. It is not recommended to repeat the course of therapy with triptorelin or another GnRH analog. The occurrence of metrorrhagia during treatment, apart from 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 the concentration of estradiol less than 50 pg / ml, the presence of other organic lesions is possible. Ovarian function is restored after completion of therapy. The first period occurs on average 134 days after the last injection. Therefore, contraceptive measures should be started 15 days after stopping treatment, that is, 3.5 months after the last injection. In the treatment of prostate cancer The most pronounced beneficial effect is observed in patients in the absence of other previous hormonal therapy. At the beginning of treatment, the appearance and intensification of clinical symptoms (in particular, bone pain, dysuric phenomena), which are transient, may be observed. This implies careful observation of these patients during the first few weeks of therapy (the level of testosterone in the blood plasma should not exceed 1 ng / ml). Treatment with Dipherelin® must be carried out in strict accordance with the instructions for use. Any change in the volume of the injected i / m suspension should be recorded. Influence on the ability to drive vehicles and use mechanisms No data available.Composition
- triptorelin (in the form of acetate) 100 mcg Excipients: mannitol 10 mg. Solvent: sodium chloride solution 0.9% - 1 ml. triptorelin (in the form of acetate) 3.75 mg * * - taking into account the characteristics of the dosage form, the preparation contains an excess of the active substance to ensure the administration of an effective dose. Excipients: copolymer of D, L-lactic and glycolic acids, mannitol, sodium carmellose, polysorbate 80. Solvent: mannitol, d / i water (2 ml). Triptorelin 11.25MG; Auxiliary substances: sodium carmellose, mannitol, polysorbate-80, DL-milk and glycolic copolymer
Diphereline indications for use
- - prostate cancer; - premature puberty; - genital and extragenital endometriosis; - fibroids of the uterus (before surgery); - female infertility (in the in vitro fertilization program)
Diphereline contraindications
- - hypersensitivity to triptorelin, other components of the drug or other analogs of GnR. In men: - hormone-independent prostate cancer, a condition after a previous surgical testiculectomy. In women, pregnancy; - lactation period (breastfeeding). With caution, the drug should be prescribed for osteoporosis, women with polycystic ovary syndrome.
Diphereline dosage
- 0.1 mg 3.75 mg
Diphereline side effects
- Allergic reactions: urticaria, rash, itching; in isolated cases - Quincke's edema. On the part of the musculoskeletal system: with prolonged use - demineralization of bones, which is a risk of osteoporosis. At the beginning of treatment for prostate cancer, patients may experience a temporary increase in pain in the bones affected by metastases. There have been isolated cases of ureteral obstruction and the onset of symptoms associated with compression by metastases of the spinal cord (disappear in 1-2 weeks). Also, during this period, there may be a temporary increase in the activity of acid phosphatase in the blood plasma. On the part of the reproductive system: in men - decreased potency; in women, headache, depression, sweating and changes in libido, dryness of the vaginal mucosa, dyspareunia, and changes in the size of the mammary glands. When used in combination with gonadotropins, cases of ovarian hyperstimulation syndrome have been reported. When treating premature puberty, girls may experience bleeding from the vagina. Long-term use of the drug can cause hypogonadotropic amenorrhea. From the digestive system: in isolated cases - nausea, vomiting. From the side of the cardiovascular system: in isolated cases - arterial hypertension, sensation of hot flashes. From the side of the central nervous system: in isolated cases - increased emotional lability, visual impairment. Others: in isolated cases - an increase in body weight, an increase in body temperature.
Drug interactions
The drug interaction of the drug Dipherelin® is not described.Storage conditions
- keep away from children
Online pharmacy price website: from 3 054
Statistics and facts
The drug Dipherelin is an innovative agent with an anti-tumor effect of proven effectiveness. Produced by the French company Ipsen Pharma, which also has a representative office in Russia. The main disease in which this drug is prescribed - prostate cancer - is a urological malignant neoplasm that develops from the secretory epithelium of the prostate.
The incidence is 400 thousand new cases every year. The number of newly diagnosed patients is growing every year. Experts believe that this is due to the progression of diagnostic methods of research and conditions for the detection of the disease. Prostate cancer is the second leading cause of cancer death in men. The percentage of patients who survive after five years from the detection of the first and second stages of cancer is almost 100%, the third is 50%. Stage 4, as a rule, is accompanied by distant metastases, usually affecting the liver, lungs, bones. If cancer is detected only at this stage, the prognosis is very unfavorable, therefore, timely diagnosis and medical examination of the population is important. There are proven risk factors that increase the likelihood of cancer of this male exocrine gland: - age: the older the man, the higher the risk of developing; - genetic predisposition: 9-10% of cases; - race: African Americans have the highest incidence; - dietary features: eating a large amount of fatty, fried foods, smoked meats, milk increases the risk, the presence of vitamin E and selenium in the diet reduces;
Metastasis occurs in two ways: with the flow of blood (hematogenous) and lymph (lymphogenous). Distant metastases spreading beyond the affected organ indicate the neglect of the process. At the time of diagnosis, this pattern is observed in 22% of patients. Both huge tumors and modest ones can metastasize. First of all, foci of such a lesion are sought in the bones: the pelvis, spine, ribs, and skull. Less commonly, metastasis occurs in the lungs, liver, and brain.
Pharmacological group
Diphereline is a hormonal drug with an antitumor effect that has a biological similarity to gonadoliberin. It is used in urology and gynecology.
Release form and component composition
The drug Dipherelin is available in a form convenient for obtaining a faster and better result - in the form of a lyophilisate mixed with a solvent to obtain a solution or suspension. The medicine box contains an instruction with all the necessary recommendations. There are 3 varieties of Dipherelin, which differ in the spectrum of indications for use, the dose of the active substance, the duration of action and the type of injection.
The yellow marked box contains seven sets of solvent vials. Active pharmaceutical ingredient triptorelin acetate - 0.1 mg. The component required to give the dosage form, mannitol - 10 mg. The solvent is isotonic 0.9% NaCl, Aqua destillata. The prepared solution is injected subcutaneously. It is used in women for the treatment of infertility, during the in vitro fertilization procedure.
The blue box contains vials of dry active ingredient, solvent, syringe, and two needles. The active pharmacological substance of triptorelin acetate is 3.75 mg. Excipients required to give the dosage form and enhance the effect of the main component: mannitol, copolymer of DL-lactate and hydroxyacetic acid, cellulose gum, polysorbate-80. The solvent is Aqua destillata water and mannitol. Has increased duration of action due to modified release. The prepared suspension is injected intramuscularly.
The drug with a dark green mark has the same set of contents: vials, water for injection, a syringe, two needles. The active ingredient of triptorelin pamoate is 11.25 mg. The excipients are the same. Mannitol is added to the solvent, in addition to Aqua destillata. The action is long-lasting due to the modification of the release. The method of administration of the prepared suspension is intramuscularly.
Pharmacological action and pharmacokinetic parameters of the drug
The main substance triptorelin has a biological similarity to gonadoliberin secreted by the hypothalamus. Acting on the pituitary gland, it realizes an antigonadotropic effect: first, it stimulates the release of gonadotropins by the pituitary gland, then inhibits, which causes suppression of the function of the testicles in men, the ovaries in women. The constant use of the drug Dipherelin causes the onset of menopause or chemical castration, depending on the sex of the patient, which leads to an improvement in the condition in diseases for which Dipherelin is used. After the introduction of 0.1 mg. Dipherelin, used for subcutaneous injection, is rapidly absorbed and distributed. The time required for the loss of half of the pharmacological properties is 6-8 hours. When using the drug with a dose of 3.75 mg triptorelin. the effect increased in duration of action is realized. At first, the active substance is released quickly, and then it goes through a continuous release phase. After taking 11, 25 mg. the maximum concentration of the active ingredient is noted after 3 hours. In the initial month, there is a decrease in the degree of saturation, then for 60 days the concentration remains constant.
Spectrum of indications, ICD-10
According to the international classification of diseases of the tenth revision, prostate cancer belongs to the class of neoplasms, has the code C61. In addition, the drug is effective against diseases of the female reproductive system - endometriosis. Endometriosis belongs to the class of diseases of the genitourinary system, to the block of non-inflammatory diseases of the female genital organs. Code - N80. Includes endometriosis of various localization: uterus (adenomyosis), ovaries, fallopian tubes, pelvic peritoneum, vagina, intestines, etc. Lyophilisate for subcutaneous administration in a minimum dose is used for in vitro fertilization in women with certain types of infertility. The drug Dipherelin in large doses is effective, in addition to prostate cancer and endometriosis, in women with estrogen-dependent malignant breast cancer, endometrioid ovarian cysts. Diphereline with the maximum concentration of the main component has a special indication - glandular prostate cancer with metastases.
Range of contraindications
Increased individual sensitivity to triptorelin and excipients necessary to give the dosage form and enhance the action of the main component. - Chronic disease or syndrome, accompanied by a decrease in bone density, strength, increased fragility, fragility. - Castration refractory prostate cancer.
Side effects of Dipherelin
Allergic reactions in the form of redness of the skin, a rash accompanied by itching, Quincke's edema; - a decrease in the content of calcium in the bone; - obstruction of the ureters; - symptoms of spinal cord compression; - a decrease in the body's ability to have sexual intercourse; - hyperhidrosis; - vaginal dryness, pain in women during intercourse; - testicular hypotrophy; - absence of menstruation in women; - long, more than 7 days, menstruation; - ovarian hypertrophy; - from the digestive system: nausea, vomiting; - a feeling of heat spreading through the body; - weakness, impotence, decreased performance;
Increased pressure; - instability of mood; - visual impairment; - red blood cells in the urine; - a condition accompanied by fever and chills, fever; - violation of appetite up to anorexia; - increased heart rate; - a feeling of crawling, numbness, tingling in different parts of the body; shortness of breath; - redness and swelling at the injection site.
Method and features of application, dose
The drug Dipherelin 0.1 mg. in women, it can be prescribed as a short or long course. In the first case, simultaneously with stimulation of the ovaries, on the second day of the menstrual cycle, 100 micrograms are injected subcutaneously and the injections are continued daily. The injections are finished the day before the administration of hCG. In the case of a long course, the dosage is the same; the day of the first injection corresponds to the second day of the cycle. The duration of the course is prescribed by a specialist, it ends the day before the introduction of hCG. Aqua destillata, isotonic sodium chloride, is injected into the vial with the active substance, mix by shaking without inverting until a homogeneous solution is obtained. How to inject: - Press down on the plunger of the syringe to remove visible air droplets. - Prepare the skin for the injection of the needle: treat with an antiseptic solution. The injection site can be selected on the upper third of the outer surface of the shoulder, the lateral part of the abdominal wall, the anterolateral upper part of the thigh. - Take the skin of the injection site with the fingers of the left hand (for right-handed people), forming a fold. - Insert the needle into this fold to a depth of 1.5 cm at an angle of 45 degrees to the skin surface.
Inject the solution slowly. - After removing the needle, wipe the injection site with an antiseptic solution again. Diphereline 3.75 mg. in men with prostate cancer - 1 intramuscular injection per month. A long course is prescribed individually by the treating urologist. In women with endometriosis of various localization, Dipherelin injections are given on one of the first five days of the cycle, once a month. The course of therapy is six months. In case of infertility, 1 intramuscular injection is performed on the second day of the menstrual cycle. Water for injection, mannitol is injected into the vial with the active ingredient, gently, with twisting movements, stirred until a suspension is obtained. Brief instructions for performing intramuscular injection: 1) Wipe the injection site (the skin of the upper outer quadrant of the buttock) with an antiseptic solution. Insert the syringe deeply, directing it vertically into the skin. 2) Inject the solution slowly. 3) Gently removing the needle, wipe the injection site with an antiseptic solution. Diphereline Long 11, 25 mg. in men with prostate cancer - 1 injection every three months intramuscularly. They apply both a short course for 6 months and a long one - 3 years. The duration of therapy is prescribed by a specialist, taking into account the severity of the disease and the use of additional methods of treatment. With endometriosis in women, 1 ampoule is also administered once every 3 months for 3-6 months, depending on the clinical picture. The preparation of the suspension and the technique for performing intramuscular injection are similar to those of Dipherelin 3.75 mg.
special instructions
In the first month of therapy, use hormone-free drugs to prevent unwanted pregnancy. Therapy with high doses leads to the absence of menstruation. This condition is reversible, menstruation resumes after drug withdrawal. Monitor the appearance of gynecological uterine bleeding and the level of estradiol in the blood. In men, at the initial stages of the course of therapy, symptoms may increase, such as: bone pain, impaired urination and urine composition. It is necessary to regularly take a urine test and be monitored by a treating specialist, take the drug, observing the dosage prescribed in the instructions for use or prescribed by a doctor. Since visual impairment is sometimes observed among the side effects, it is necessary to be careful when driving and performing activities that require increased concentration of attention. For children under 18 years of age, the appointment of the drug Dipherelin is possible and indicated only in case of premature puberty. In case of liver diseases with decompensation, use is contraindicated. Elderly patients and with impaired renal function, take according to the standard regimen.
During pregnancy and before breastfeeding stops
Diphereline is prohibited.
Overdose
There is no information about the cases of taking the drug in doses greater than the recommended ones. It is necessary to take the doses strictly prescribed in the instructions for use or prescribed by the attending physician. There may be manifestations similar to the symptoms from the point about side effects. Treatment is symptomatic.
Concomitant use with other medications and compatibility with alcoholic beverages
Storage conditions
Diphereline requires optimal storage conditions, including items such as: adherence to a dry temperature regime up to 25 degrees, use before the expiration date - 2 years, inaccessibility for children.
Dispensing from pharmacies
Officially, the purchase of this drug is possible in the pharmacy network with the provision of a prescription to the pharmacist.
Analog medicines
Antineoplastic agents with a similar composition, purpose or pharmacological action: Buserelin, Vizanne, Danazol, Danol, Indinol, Duphaston, Norkolut, Prostap, Epigallat.
in vials (complete with solvent); 7 sets in a contour cell package; in a pack of cardboard 1 packing.
in vials (complete with solvent in ampoules, syringe and two needles) in a cardboard box 1 set.
Description of the dosage form
Diphereline® 0.1 mg: an almost white lyophilisate dispersed in the supplied solvent to form a clear solution practically free of particles.
Dipherelin ® 3.75 mg: white or off-white lyophilisate, dispersible in the supplied solvent to form a white or off-white suspension.
Diphereline® 11.25 mg: white or slightly yellowish lyophilisate, dispersed in the supplied solvent to form a white or slightly yellowish suspension.
Solvent supplied- a clear, colorless solution.
pharmachologic effect
pharmachologic effect- antigonadotropic.Pharmacodynamics
Triptorelin is a synthetic decapeptide analogous to the natural gonadotropin-releasing hormone that releases gonadotropin.
Diphereline® 0.1 mg
Animal studies and clinical studies have shown that after the initial period of stimulation, prolonged use of Dipherelin ® 0.1 mg suppresses the secretion of gonadotropins, followed by suppression of ovarian function.
Constant use of Dipherelin ® 0.1 mg suppresses the secretion of gonadotropins (FSH and LH). Suppression of intermediate endogenous peaks of LH allows to improve the quality of folliculogenesis, increasing the number of maturing follicles, and, as a consequence, to increase the likelihood of pregnancy per cycle.
Dipherelin ® 3.75 mg
After a short initial period of stimulation of the gonadotropic function of the pituitary gland, triptorelin suppresses the secretion of gonadotropins and, accordingly, the function of the testicles and ovaries. Continuous use of the drug inhibits the secretion of estrogen by the ovaries until menopause, and also reduces the secretion of testosterone, the concentration of which can reach the levels that are observed after surgical castration.
Diphereline® 11.25 mg
In the initial period of application, Dipherelin® 11.25 mg 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 (to levels corresponding to the state after testiculectomy) and estradiol (to levels corresponding to the state of postovariectomy) by about the 20th day after the first injection and then remain unchanged throughout the entire period drug administration.
Long-term treatment with triptorelin suppresses the secretion of estradiol in women and, thus, prevents the development of endometrioid ectopias.
Pharmacokinetics
Diphereline® 0.1 mg
After subcutaneous injection into healthy adult volunteers at a dose of 0.1 mg, triptorelin is rapidly absorbed (time to reach C max - (0.63 ± 0.26) h with a peak plasma concentration of (1.85 ± 0.23) ng / ml).
T 1/2 is (7.6 ± 1.6) hours, after 3-4 hours the distribution phase ends.
The total plasma clearance is (161 ± 28) ml / min.
The volume of distribution is (1562 ± 158) ml / kg.
Dipherelin ® 3.75 mg
After intramuscular administration of a prolonged form of the drug, the initial stage of rapid release of the drug occurs, followed by a phase of constant release of triptorelin. C max is (0.32 ± 0.12) ng / ml.
The average amount of continuously released triptorelin is (46.6 ± 7.1) μg / day.
The bioavailability of the drug is about 53% in 1 month.
Diphereline® 11.25 mg
With intramuscular injection of Dipherelin® at a dose of 11.25 mg, C max of triptorelin in blood plasma (in men and women) is determined approximately 3 hours after injection. After a phase of decrease in concentration, lasting during the first month, until the 90th day, the concentration of circulating triptorelin remains constant (about 0.04-0.05 ng / ml - in the treatment of endometriosis and about 0.1 ng / ml - in the treatment of prostate cancer ).
Indications of the drug Dipherelin ®
Diphereline® 0.1 mg
Female infertility. Conducting ovarian stimulation together with gonadotropins (human menopausal, human chorionic), FSH in in vitro fertilization and embryo transfer programs, as well as other assisted reproductive technologies.
Dipherelin ® 3.75 mg
prostate cancer;
premature puberty;
genital and extragenital endometriosis;
fibroids of the uterus (before surgery);
female infertility (in the in vitro fertilization program).
Diphereline® 11.25 mg
metastatic prostate cancer;
genital and extragenital endometriosis (stages I-IV).
Contraindications
Common to all dosages:
hypersensitivity;
pregnancy;
lactation.
hormone-independent prostate cancer;
condition after previous surgical testiculectomy.
Dipherelin® 3.75; 11.25 mg (optional):
Carefully- with osteoporosis.
Diphereline® 11.25 mg (optional):
Carefully- in women with polycystic ovary syndrome.
Application during pregnancy and lactation
Currently, analogs of gonadotropin-releasing hormone are used in combination with gonadotropins to stimulate ovulation and pregnancy.
Pregnancy is a contraindication for the use of the drug. However, practice has shown that after ovulation stimulated in the previous cycle, some women became pregnant without stimulation and continued a further course of ovulation stimulation.
Summary 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 with the use of this drug. 2 qualitatively performed animal studies 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-releasing hormone showed the absence of fetal malformations or fetotoxicity.
However, further research is needed on the effects of the drug on pregnancy.
Since there is no data on the penetration of the drug into breast milk and its possible effects on a breastfed baby, treatment should not be carried out during breastfeeding.
Side effects
Common to 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. The most common side effects are sudden flushes, vaginal dryness, decreased libido, and dyspareunia associated with pituitary-ovarian blockade.
Long-term use of analogs of gonadotropin-releasing hormone can lead to demineralization of bones, the risk of osteoporosis (the above-described side effect was not observed with short-term use of Dipherelin® 0.1 mg).
Allergic reactions: urticaria, rash, itching, rarely - Quincke's edema.
On rare occasions- nausea, vomiting, weight gain, increased blood pressure, emotional lability, visual impairment, pain at the injection site.
Rarely- headache, joint and muscle pain.
Dipherelin ® 3.75 mg additionally
In men- decreased potency. At the beginning of treatment, patients with prostate cancer may experience a temporary increase in pain in the bones affected by metastases (symptomatic treatment). In some cases, obstruction of the ureters and symptoms associated with compression by metastases of the spinal cord (disappear after 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.
When treating premature puberty, girls may experience bleeding from the vagina.
Long-term use of the drug can cause hypogonadotropic amenorrhea.
After stopping treatment, ovarian function is restored and ovulation occurs on average on the 58th day after the last injection of the drug. The first menstruation occurs on the 70th day after the last injection of Dipherelin ®. This must be taken into account when planning contraception.
Diphereline 11.25 mg additionally
In men
At the beginning of treatment. Dysuric disorders (difficulty urinating, incomplete emptying of the bladder, soreness), bone pain associated with metastases and compression by metastases of the spinal cord, which can be aggravated by a temporary increase in testosterone levels in the blood plasma at the beginning of treatment. These symptoms disappear in 1-2 weeks. Also during this period, there may be a temporary increase in the activity of liver enzymes in the blood plasma.
During treatment: flushing of the face, decreased libido, gynecomastia, impotence, which is associated with a decrease in the content of testosterone in the blood plasma.
Among women
At the beginning of treatment. Symptoms associated with endometriosis (pelvic pain, dysmenorrhea), which may increase due to the initial transient increase in the concentration of estradiol in the blood plasma and disappear after 1-2 weeks.
Metrorrhagia may occur a month after the first injection.
In men and women:
Mood disorders, irritability, depression, fatigue, sleep disturbance, weight gain, profuse sweat, paresthesia, blurred vision, fever.
Interaction
Not described.
Method of administration and dosage
Dipherelin® 0.1 mg. PC.
Short protocol. Starting from the 2nd day of the cycle (simultaneously starting stimulation of the ovaries), and ending the treatment 1 day before the scheduled administration of human chorionic gonadotropin. The course of treatment is 10-12 days.
Long protocol. Daily subcutaneous injections of Dipherelin ® 0.1 mg begin on the 2nd day of the cycle. With 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.
Solution preparation rules. Immediately before injection, transfer the solvent to the vial with the lyophilisate. Shake until completely dissolved. Used needles should be placed in a designated sharps container.
Dipherelin ® 3.75 mg. V / m.
Prostate cancer. Differelin ® is administered at a dose of 3.75 mg every 4 weeks for a long time.
Premature puberty. Children weighing more than 20 kg - 3.75 mg every 28 days; children weighing less than 20 kg - 1.875 mg every 28 days.
Endometriosis The drug should be administered in the first 5 days of the menstrual cycle - at a dose of 3.75 mg every 4 weeks. The duration of therapy is no more than 6 months.
Female infertility. Dipherelin ® should be administered on the second day of the cycle at a dose of 3.75 mg. The connection with gonadotropins should be monitored after desensitization of the pituitary gland (the concentration of estrogen in the blood plasma is less than 50 pg / ml is usually determined 15 days after the injection of Dipherelin®).
Fibroids of the uterus. The drug must be administered in the first 5 days of the menstrual cycle. The introduction of Dipherelin ® 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 surgery).
1. Treat the injection site with a napkin containing alcohol. Remove the cap from the pink tip needle and attach it to the syringe. Draw all the solvent from the ampoule into the syringe.
4. Gently shake the contents until a homogeneous suspension is obtained, without inverting the bottle.
5. Without turning the bottle over, draw the entire suspension into the syringe.
6. Remove the pink needle from the syringe. Attach a green needle to the syringe (screw tight), taking only the colored tip.
7. Remove air from the syringe.
8. Inject immediately. The injection should be administered intramuscularly only.
Push the guard towards the tip of the needle. Close the needle and snap the device;
Turn the syringe over. Using a flat surface, press down on the device and close the needle.
11. Use the colored attachment to detach the needle. Dispose of needles in sharps containers.
Diphereline® 11.25 mg. V / m
Prostate cancer. Differelin ® is administered at a dose of 11.25 mg every 3 months.
Endometriosis Differelin ® is administered at a dose of 11.25 mg every 3 months. Treatment should 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) during therapy. As a rule, treatment is carried out for 3-6 months. Repeated treatment with triptorelin or gonadotropin-releasing hormone is not recommended.
Suspension preparation rules
The dissolution of the lyophilisate in the supplied solvent should be carried out immediately prior to administration. Stir the contents of the vial with caution until a homogeneous suspension is obtained.
Cases of incomplete injection, leading to the loss of more suspension than usually remains in the injection syringe, must be reported to the attending physician.
The introduction should be carried out in strict accordance with the instructions.
1. Treat the injection site with a napkin containing alcohol. Remove the cap from the pink tipped needle and attach it to the syringe. Draw up all the solvent from the ampoule into the syringe.
2. Remove the plastic cap from the lyophilisate vial. Insert the needle through the chlorobutyl rubber stopper and transfer the solvent into the vial.
3. Pull the needle so that it remains in the vial, but does not touch the suspension.
4. Without turning the bottle over, gently shake the contents until a homogeneous suspension is obtained.
5. Without turning the bottle over, draw the entire suspension into the syringe.
6. Remove the pink tipped needle from the syringe. Attach a green-tipped needle (or a green-tipped needle with a safety device) to the syringe, screw tightly, taking only the colored tip.
7. Remove air from the syringe.
8. Inject immediately.
If using a green tipped needle with a safety device:
9. Immediately after injection, close the needle with a safety device in one of the following ways:
9.1. Push the guard towards the tip of the needle. Close the needle and snap the device into place.
9.2. Invert the syringe using a flat surface, push down on the device and close the needle.
10. The needle is closed when the needle tip is covered by the device. Check if the device is securely closed.
11. Use a colored tip to detach the needle.
12. Dispose of needles in sharps containers.
Overdose
Cases of drug overdose are unknown.
special instructions
Diphereline® 0.1 mg
A warning. The response of the ovaries to the introduction of Dipherelin ® 0.1 mg in combination with gonadotropins can significantly increase in patients predisposed to this, and, in particular, in cases of polycystic ovarian diseases.
The response of the ovaries to the administration of the drug in combination with gonadotropins can differ in patients, and it can also be different in the same patients in different cycles.
Preventive action. Stimulation of ovulation should be carried out under the supervision of a physician and with regular biological and clinical analysis methods: increasing the content of estrogen in plasma and conducting ultrasound echocardiography. If the ovarian response is excessive, it is recommended to interrupt the stimulation cycle and stop gonadotropin injections.
Dipherelin ® 3.75 mg
At the beginning of treatment, an increase in clinical symptoms may be observed, and therefore, Dipherelin® should be prescribed with caution to patients with prostate cancer who are at risk of developing ureteral obstruction or spinal cord compression. Careful observation of these patients is necessary during the first month of therapy.
Before starting therapy with Dipherelin ®, it is necessary to confirm the absence of pregnancy.
Use with caution in patients with polycystic ovary syndrome when performing ovulation stimulation schemes. This is due to the fact that in a small number of patients, the number of induced follicles may increase.
It is necessary to carefully monitor the level of cycle stimulation during in vitro fertilization in order to identify patients at risk of developing ovarian hyperstimulation syndrome, since the severity and frequency of manifestations of the syndrome may depend on the gonadotropin dosage regimen. If necessary, the introduction of human chorionic gonadotropin should be discontinued.
Diphereline® 11.25 mg
Endometriosis treatment. Pregnancy must be ruled out before starting treatment.
During the first month of therapy, non-hormonal contraceptives should be used.
Intramuscular injection of the drug leads to persistent hypogonadotropic amenorrhea.
The occurrence of metrorrhagia during treatment, apart from the first month, is not the norm, and therefore it is necessary to determine the concentration of plasma estradiol. With a decrease in the concentration of estradiol to less than 50 pg / ml, the presence of other organic lesions is possible.
Ovarian function is restored after completion of therapy. The first period occurs on average 134 days after the last injection. For this reason, the use of contraception should be started 15 days after discontinuation of treatment, i.e. 3.5 months after the last injection.
In the treatment of prostate cancer. The most pronounced beneficial effect is observed in patients in the absence of other previous hormone therapy.
At the beginning of treatment, there may be the appearance and intensification of clinical symptoms (in particular, bone pain, dysuric disorders), which are of a transient nature.
This implies careful observation of these patients during the first few weeks of therapy (the level of testosterone in the blood plasma should not exceed 1 ng / ml).
Treatment with Dipherelin® must be carried out in strict accordance with the instructions for use. Any change in the volume of the injected i / m suspension should be recorded.
Storage conditions of the drug Dipherelin ®
At a temperature not exceeding 25 ° C.Keep out of the reach of children.
Shelf life of the drug Dipherelin ®
lyophilisate for the preparation of a suspension for intramuscular administration of prolonged action 3.75 mg - 2 years.
lyophilisate for the preparation of a suspension for intramuscular administration of prolonged action 11.25 mg - 3 years. 5 years - solvent.
lyophilisate for preparation of a solution for subcutaneous administration of 0.1 mg - 2 years.
Do not use after the expiration date printed on the package.
Synonyms for nosological groups
| ICD-10 heading | Synonyms of diseases according to ICD-10 |
|---|---|
| C61 Malignant neoplasm of the prostate gland | Adenocarcinoma of the prostate |
| Hormone-dependent prostate cancer | |
| Hormone-resistant prostate cancer | |
| Malignant tumor of the prostate | |
| Malignant neoplasm of the prostate | |
| Carcinoma of the prostate | |
| Locally advanced non-metastatic prostate cancer | |
| Locally advanced prostate cancer | |
| Locally advanced prostate cancer | |
| Metastatic prostate carcinoma | |
| Metastatic prostate cancer | |
| Metastatic hormone-resistant prostate cancer | |
| Non-metastatic prostate cancer | |
| Inoperable prostate cancer | |
| Prostate cancer | |
| Prostate cancer | |
| Advanced prostate cancer | |
| Testosterone-dependent prostate cancer | |
| D26 Other benign neoplasms of the uterus | Meigs syndrome |
| Myoma | |
| Myoma of the uterus | |
| Uterine fibroids | |
| Tumors of the uterus | |
| Fibriomas | |
| Fibroids | |
| Fibroids of the uterus | |
| E30.1 Premature puberty | Primary precocious puberty |
| Puberty premature | |
| Premature sexual development | |
| Premature puberty in girls | |
| Early puberty | |
| N80 Endometriosis | Endometrioid heterotropy |
| N97 Female infertility | Anovulatory infertility |
| Female infertility | |
| Infertility on the background of hyperprolactinemia | |
| Ovarian infertility | |
| Infertility due to hypothalamic-pituitary dysfunction | |
| Barren marriage | |
| Hyperprolactinemic infertility | |
| Hyperprolactinemia with infertility | |
| Female infertility with anovulation | |
| Stimulation of the growth of one follicle | |
| Functional infertility | |
| Endocrine infertility |
