Pharmacological properties of the drug Diferelin
Triptorelin is a synthetic decapeptide, an analogue of the natural gonadotropic RG. After a short initial period of stimulation of the gonadotropic function of the pituitary gland, triptorelin causes inhibition of gonadotropin secretion and, accordingly, the hormone-producing function of the testes or ovaries. With continuous use, the drug inhibits the secretion of estrogen by the ovaries until menopause, and also suppresses the secretion of testosterone, the concentration of which decreases to a level corresponding to the state after surgical castration. Diferelin 0.1 mg After subcutaneous administration of 0.1 mg Diferelin is rapidly absorbed; time to reach the maximum concentration of the drug in the blood plasma - 0.63±0.26 hours; the maximum concentration of the drug in blood plasma is 1.85±0.23 ng/ml. The biological half-life is 7.6±1.6 hours after a 3-4 hour distribution phase. Total plasma clearance - 161±28 ml/min. Conditional volume of distribution is 1562±158 ml/kg. Diferelin 3.75 mg It is a prolonged release drug due to the microspherical structure of triptorelin deposition, which provides a clinically effective concentration for 28 days. After intramuscular administration of a prolonged form of the drug, an initial stage of triptorelin release is observed with further normal release (maximum drug concentration in blood plasma - 0.32 ± 0.12 ng/ml) with an average triptorelin release rate of 46.6 ± 7.1 mg /day Bioavailability: after 1 month - 53%. Diferelin 11.25 mg After intramuscular administration of a dose of Diferelin 11.25 mg, the maximum concentration of triptorelin in the blood plasma is observed after approximately 3 hours. After the phase of decreasing concentration, which occurs during the first month, until the 90th day the level of circulating triptorelin remains constant (approximately 0.03 to 0.06 ng/ml).
Analogs
Analogues of the drug:
- Decapeptyl;
- Decapeptyl depot;
- Buserelin;
- Buserelin depot;
- Buserelin long FS;
- Visanne;
- Danazol;
- Danoval;
- Danodiol;
- Danol;
- Derinat;
- Duphaston;
- Zoladex;
- Indinol;
- Lucrine depot;
- Nemestran;
- Norkolut;
- Omnadren 250;
- Orgametril;
- They will grind down Nor;
- Prostap;
- Epigallate.
Without the approval of the attending physician, any independent replacement of the main product is strictly prohibited. Uncontrolled use of pharmacological substances can cause serious negative reactions in response to the drug used.
Indications for use of the drug Diferelin
Diferelin 3.75 mg - prostate cancer, genital and extragenital endometriosis (stages I–IV), endometrioid cysts, endometrial hyperplastic processes, female infertility (complex treatment in combination with gonadotropins, to artificially create conditions for ovulation, for the purpose of in vitro fertilization and subsequent embryo transfer ) , premature puberty in children, breast cancer, uterine fibroids. Dipherelin 11.25 mg - adenocarcinoma of the prostate with metastases, when inhibition of testosterone secretion is indicated, premature puberty in children (onset of the disease before 8 years in girls and in boys under 9 years), genital and extragenital endometriosis, breast cancer, when indicated hormonal therapy. Diferelin 0.1 mg - female infertility, ovulation stimulation in combination with gonadotropins for the purpose of in vitro and embryo transplantation (IVFET), as well as in other assisted reproductive technologies.
Infertility caused by endometrial insufficiency
A common cause of infertility is the thinning of the endometrium, the inner layer of uterine tissue. This reduces the chances of successful embryo implantation. The main task in this case is to achieve a reduction in the area of thin areas, and this can be achieved using a long protocol.
Before IVF, Diferelin can be used to build up the endometrium for up to six months.
The depot method is used - administering the drug once per cycle. As a result, ovarian function is suppressed and the endometrium begins to grow. A kind of “deception” occurs, conditions similar to the onset of pregnancy are created. And during pregnancy, the endometrium grows significantly, because this is necessary not only for fixation of the embryo, but also for its nutrition until the placenta is formed and begins to function.
When the desired thickness of the endometrium is reached, ovulation stimulation begins according to the scheme chosen by the doctor.
Use of the drug Diferelin
Diferelin 3.75 mg The drug is used only intramuscularly. For prostate cancer, Diferelin 3.75 mg of prolonged action is administered intramuscularly every 4 weeks. For endometriosis, endometrioid cysts, endometrial hyperplastic processes, treatment should begin in the first 5 days of the cycle; one IM injection every 4 weeks. The duration of treatment depends on the severity of the disease and the dynamics of clinical manifestations during the treatment period. For the treatment of female infertility, it is prescribed according to the usual therapeutic regimen - one intramuscular injection on the 2nd day of the cycle. Parallel use of gonadotropins begins after achieving pituitary desensitization (the content of estrogens in the blood plasma does not exceed 50 pg/ml), usually on the 15th day after Diferelin injection. It is very important that the injection of the prolonged form is carried out exactly according to the rules specified in the instructions. For premature puberty - one intramuscular injection at a rate of 50 mcg/kg every 4 weeks. For breast cancer - intramuscular injection of Diferelin 3.75 mg of prolonged action every 4 weeks. For uterine fibroids, treatment begins in the first 5 days of the menstrual cycle; Diferelin is administered every 4 weeks. The duration of treatment is 3 months for patients who are being prepared for surgical treatment, and up to 6 months for patients who are not indicated for surgical treatment. Diferelin 11.25 mg For prostate adenocarcinoma - intramuscular injection of Diferelin 11.25 mg prolonged action every 3 months. For endometriosis, treatment begins in the first 5 days of the cycle, one intramuscular injection every 3 months. The duration of treatment depends on the initial severity of endometriosis and the dynamics of clinical manifestations during the period of therapy. The course of treatment is no more than 6 months. For breast cancer - one intramuscular injection every 3 months. For premature puberty - one intramuscular injection every 3 months. Diferelin 0.1 mg 1 ampoule of solvent (1 ml of sodium chloride solution 0.9%) is introduced into a bottle with powder for injection, shake the bottle thoroughly and carefully and immediately make a subcutaneous injection. Short protocol: Diferelin is administered 0.1 mg subcutaneously, starting from the 2nd day of the cycle (simultaneously starting ovarian stimulation) and ending treatment the day before the planned administration of human chorionic gonadotropin. The course of treatment is 10–12 days. Long protocol: injections are carried out subcutaneously daily, starting from the 2nd day of the cycle. After desensitization of the pituitary gland (E2 50 pg/mg, that is, approximately on the 15th day from the start of treatment), ovarian stimulation begins and Diferelin injections are continued at a dose of 0.1 mg/day, ending them the day before the planned administration of human chorionic gonadotropin.
How to give an injection yourself?
Sometimes your doctor may prescribe self-injections. This is justified if the clinic is located far from the patient’s place of residence or a holiday weekend is expected, and injections cannot be interrupted. Naturally, the expectant mother has a logical question about how to give this injection correctly and not cause harm. If the injection is given incorrectly, a hematoma may form, which will hurt for a long time and then the next injection will be even more painful.
In this useful video, the girl tells and shows how to inject herself with Diferelin in the stomach:
It's easy to give an injection:
- Following the instructions, prepare the solution. Dissolve the lyophilisate in the liquid supplied with it.
- Next, you should treat the area of skin where the injection is made with alcohol.
- Then you need to remove the cap from the bottle of Diferelin and take the solution with a syringe using a needle with a pink cap.
- Next, remove the pink needle and put the needle with the green cap on the syringe.
- Remove air from the syringe.
- Carefully inject subcutaneously into the treated area of skin.
Everything necessary for administering the drug is included in the package; there is no need to purchase additional syringes. The bottle and needle are disposed of without being reused.
Side effects of the drug Diferelin
Manifestations of allergic reactions are possible, such as urticaria, rash, itching, and very rarely - Quincke's edema. Isolated cases of nausea, vomiting, weight gain, increased blood pressure, emotional lability, visual disturbances, pain at the injection site, increased body temperature, and hot flashes have been described. Long-term use of gonadotropin RG analogues can cause bone demineralization and is a possible risk factor for the development of osteoporosis. In men - decreased potency, swelling and tenderness of the mammary glands (noted very rarely). Patients with prostate adenocarcinoma at the beginning of treatment may experience a temporary increase in pain in the bones affected by metastases (treatment is symptomatic). In some cases, ureteral obstruction, as well as symptoms associated with compression of the spinal cord (pass after 1–2 weeks). During this period, a temporary increase in alkaline phosphatase activity in the blood plasma is also possible. In women - sweating and changes in libido, headache, depression, dryness of the vaginal mucosa, changes in the size of the mammary glands. When Diferelin is used in combination with gonadotropins, cases of the development of ovarian hyperstimulation syndrome have been reported. When treating precocious puberty, girls may experience bloody vaginal discharge. Long-term use of the drug may cause hypogonadotropic amenorrhea. After cessation of treatment, ovarian function is restored and ovulation occurs on average on the 58th day after the last injection of the drug.
Impact
Diferelin is a GnRH analogue produced by the hypothalamus. The hormone affects the pituitary gland, which produces sex hormones. They are responsible for stable functioning and its regulation in the male and female genital organs.
With a decrease in the production of tropic hormones, a decrease in the activity of the ovaries and testes is observed in the process of synthesis of sex hormonal substances. The positive effects of the drug consist in the treatment of pathologies that arise under the influence of estrogen in women and testosterone in men.
The stimulating effect of the drug affects the process of ovulation and the subsequent transfer of a fertilized egg. After drug therapy, the IVF procedure is permitted.
Special instructions for the use of the drug Diferelin
At the beginning of treatment, clinical symptoms may intensify, and therefore it is necessary to prescribe Diferelin carefully to patients with prostate cancer who have an increased risk of developing ureteral obstruction or spinal cord compression. Such patients should be closely monitored during the first month of treatment. It is necessary to carefully monitor the level of cycle stimulation during in vitro fertilization to identify patients with an increased risk of developing ovarian hyperstimulation syndrome, since the degree and frequency of the syndrome may depend on the gonadotropin dosage regimen. If it is necessary to administer human chorionic gonadotropin, the use of Diferelin should be discontinued. Before starting treatment with Diferelin, the absence of pregnancy should be confirmed.
Contraindications
Diferelin is not recommended for certain pathologies:
- with a malignant neoplasm in the body of the prostate gland, non-hormonal etiology;
- after surgical removal of the testicles in males;
- during the period of bearing and feeding a baby;
- with the development of spontaneous allergic reactions to the ingredients included in the medication.
It is recommended to prescribe Diferelin with caution when:
- osteoporosis – a chronic, constantly progressive decrease in bone density;
- polycystic ovary syndrome - characterized by multiple formations in the female gonads.
After treatment
The first menstrual cycle (from the moment it ceases under the influence of the drug) is characterized by scanty discharge, absence of pain or its minimal manifestations. The normal limits include the first menstruation, which came within six months - after the end of the last injection.
Taking into account the doctors’ ban on conception during the first half of the year – from the moment of undergoing therapy, patients are recommended to use contraceptives.
Diferelin is a highly effective drug for suppressing the symptomatic manifestations of serious diseases. Treatment of female and male infertility is a labor-intensive process and not always effective. Carefully following the recommendations of your treating specialist will help you achieve the long-awaited event - pregnancy and the subsequent birth of a healthy child.
Low AMH protocols
There are 2 types of IVF protocols designed for women with low ovarian reserve - a modified cycle protocol (Shanghai) and a French protocol.
Protocol in a modified cycle
This type of IVF protocol is intended for women in whom high doses of stimulating drugs cause the growth of only one follicle. There is no point in prescribing stimulation when the ovarian response is manifested by the maturation of one oocyte.
For women with a poor ovarian reserve, this is the optimal IVF protocol
:
- financial costs are reduced;
- the risk of stimulation cancellation is reduced;
- the chances of pregnancy increase.
Stimulation is initiated when the follicle reaches a diameter of 10–12 mm. Use minimal doses of gonadotropins. Follicles grow up to 14 mm. After that, antagonists and an ovulation trigger are included in the regimen (with a follicle diameter of 18 mm). In this scheme, the likelihood of premature spontaneous ovulation is increased.
For the French IVF protocol
characteristically similar to a long protocol. The difference is that regulatory drugs are prescribed from days 19–21 of the cycle in minimal doses, due to which the pituitary gland is partially blocked. This allows you to use lower dosages of hormones to induce ovulation.
The advantages of the French protocol are the same as those of the long one:
- uniform growth of follicles;
- higher percentage of complete oocytes.
The disadvantage is the possibility of premature ovulation.
Composition and release form
The release form of Diferelin is lyophilisate (powdery mass for dilution). A suspension for injection is prepared from it. The powder is white or slightly yellowish. The finished suspension is yellow or white. The lyophilisate is supplied with a transparent solvent. Also included is a disposable syringe and 2 needles.
The medicine is placed in dark glass bottles. The solvent is in ampoules. The composition of the medicine includes:
- triptorelin pamoate (active ingredient);
- copolymer of glycolic and lactic acids;
- mannitol;
- polysorbate 80;
- carmellose sodium.
To ensure the effectiveness of the medicine, the active substance is in excess in the powder. The liquid for preparing a solution for subcutaneous and intramuscular administration includes mannitol 16 mg and water.
Features of a long IVF protocol
The long protocol is not suitable for everyone. The program is indicated for women with an average ovarian reserve, with cystic changes in the ovaries,. The choice in favor of a long stimulation scheme is made when the quality of eggs obtained earlier in a short protocol is low.
USEFUL INFORMATION: Spermogram with Kruger morphology
Advantages of the long IVF protocol scheme:
- Synchronous development of follicles. They come out the same size.
- Less percentage of immature eggs.
In contrast to the short protocol, the long stimulation regimen is characterized by an increased risk for women with a very rich ovarian reserve.
Scheme of a long IVF protocol
prescribed from the second phase of the cycle on days 21–22. First, the drugs Diferelin and Decapeptyl are administered and wait for menstruation. Against the background of these drugs, from the 2-3rd day of menstruation, stimulant drugs are prescribed - Puregon, Menopur, Gonal F or analogues for 10-12 days (sometimes longer). Ultrasound control is repeated 3–4 times.
Onset of menstruation
In most cases, therapy using Diferelin is difficult. This is because the patient will experience all the symptoms of menopause. This:
- Bad mood;
- increased sweating;
- tides;
- dryness in the vaginal area.
Feedback from patients receiving Diferelin therapy boils down to the fact that the average period from injection to first menstrual blood is within 2.5-6 months. The ovaries need such a long time to recover after artificial suppression of their functioning.
In the first menstrual cycle after therapy, bleeding is scanty, and there are no manifestations of premenstrual syndrome. This situation does not surprise doctors at all, since the restoration of the entire reproductive system occurs gradually.
In some cases, menstruation may be heavy, but this is not a pathology. The second menstrual cycle is already becoming more similar to the periods that the woman had before starting therapy.
The volume of menstrual blood after treatment with Diferelin should be subject to additional monitoring. It can let the doctor know how effective the therapy was, but even with a normal recovery process, an ultrasound examination of the ovaries is necessary.
