Mechanism of action
Synthetic decapeptide, an analogue of natural GnRH. Diphereline, after a short initial period of stimulation of the gonadotropic function of the pituitary, has an inhibitory effect on the secretion of gonadotropin with subsequent suppression of the synthesis of female and male sex steroid hormones.
Experimental studies proved the mechanism of action of Diferelin: the drug has a direct effect on the gonad by reducing the sensitivity of peripheral receptors to the effects of the hormone responsible for the release of gonadotropin.
The continuous use of Diphereline in patients with prostate cancer that is sensitive to hormonal effects helps to reduce LH and FSH levels, which leads to a decrease in testosterone secretion, which concentrations can reach the levels observed after castration. At the same time, there is a temporary increase in the level of acid phosphatase in the initial stage of treatment.
In case of premature puberty, the use of the drug in patients of both sexes leads to inhibition of increased activity of the pituitary gonadotropic function due to suppression of the secretion of estradiol and testosterone, and a decrease in the peak of PH, which improves the growth / bone / age ratio.
In endometriosis, the drug, blocking the gonadotropic function of the pituitary gland, reduces the content of sex hormones in the blood to the post-cerebral level, which causes atrophy of the endometriotic sites.
In case of female infertility (in the in vitro fertilization program), the effect of the drug suppresses the intermediate peaks of LH, which contributes to folliculogenesis. Treatment is carried out to stimulate ovulation during artificial insemination and embryo transfer.
The drug helps to reduce the size of uterine fibroids. The most pronounced therapeutic effect was observed in the third month of treatment. During the first month of treatment, most patients develop amenorrhea. This contributes to the prevention of anemia due to menorrhagia or metrorrhagia.
Suction and distribution
After the i / m administration of a sustained release suspension, an initial release of the active substance takes place, followed by a regular release. With this Cmax triptorelin in plasma is 0.32 ± 0.12 ng / ml, and the average release of triptorelin is 46.6 ± 7.1 mg / day.
The bioavailability of the drug when administered once a month is 53%.
- prostate cancer, sensitive to hormonal effects;
- premature puberty;
- female infertility (in the program of in vitro fertilization);
- uterine fibroids.
At hormone sensitive prostate cancer, Diphereline is prescribed intramuscularly at 3.75 mg (1 injection) every 4 weeks. The duration of treatment is set individually.
At premature puberty the drug is prescribed in / m 1 injection at the rate of 50 mg / kg every 4 weeks. The duration of treatment is determined individually.
At endometriosis the drug is administered in / m during the first five days of the menstrual cycle. The frequency of administration of Diphereline in a dose of 3.75 mg - 1 time in 4 weeks. The duration of treatment depends on the severity of endometriosis and is evaluated by the manifestation of the clinical signs of the disease (functional and anatomical). As a rule, the duration of treatment does not exceed 6 months.
At uterine myome Treatment should begin in the first 5 days of the menstrual cycle. The drug is administered to the / m 3.75 mg (1 injection) every 4 weeks. The duration of treatment is 3 months for patients preparing for surgery and up to 6 months for patients for whom surgical treatment is not indicated.
At female infertility the drug is administered i / m in a dose of 3.75 mg (1 injection) on the 2nd day of the cycle. Communication with gonadotropins should be monitored after desensitization of the pituitary gland (plasma estrogen concentration less than 50 pg / ml is usually determined 15 days after Diferelin's injection).
Rules for the preparation and administration of suspensions
Suspension for i / m administration is prepared using the attached solvent by gently shaking the vial to obtain a homogeneous mixture, just before the injection. The drug is administered only in / m.
At the beginning of treatment: possible bone pain, progression of existing hematuria, urination disorders, feeling of weakness or paresthesia in the legs.
These phenomena are usually not permanent and disappear in 1-2 weeks after the start of treatment.
During the treatment: possible hot flashes, impotence, periodic increase in blood pressure, pain at the injection site.
With premature puberty
Maybe: small bleeding that requires additional treatment with medroxyprogesterone acetate (40 mg / day) or cyproterone acetate (100 mg / day) during the first week of treatment.
With endometriosis and uterine myoma
Maybe: hot flashes, vaginal dryness, indicating the effectiveness of pituitary-ovarian blockade.
With prolonged use: possible demineralization of bones, which is the risk of osteoporosis.
With female infertility
Seldom: hot flashes, headache, asthenia.
When combined with gonadotropins: possible development of ovarian hyperstimulation syndrome - an increase in the size of the ovaries, abdominal pain.
- polycystic ovary syndrome;
- hypersensitivity to the drug.
Pregnancy and breastfeeding
Diphereline is contraindicated for use during pregnancy and lactation. Before starting therapy, it is necessary to confirm the absence of pregnancy
In experimental studies not detected teratogenic action of Diphereline.
For prostate cancer that is sensitive to hormonal effects, careful medical observation is required during the first weeks of therapy, especially for patients with metastases in the spine, as well as patients with urinary disorders.
In female infertility, the ovarian response to the administration of Diphereline with the same dose of the drug is characterized by individual differences. Patients require regular medical examination to assess the degree of ovarian induction, including biological and clinical control: determination of the level of estrogen in the blood plasma, ultrasound examination. If ovarian hyperstimulation is suspected, it is recommended to stop gonadotropin injections.
In endometriosis and uterine myoma, long-term use of Diferilin can cause hypogonadotropic amenorrhea. After cessation of treatment, ovarian function is restored and ovulation occurs on average 58 days after the last injection of the drug.
To date, no cases of overdose of Diphereline have been reported.
Drug interaction Diphereline is not described.
The drug should be stored at a temperature of 15 ° to 25 ° C. Shelf life - 2 years.