Instruction for use: Triptorelin (Triptorelinum)

Chemical name:

D-tryptophan-6-gonadorelin acetate

Pharmacological group

Hormones of the hypothalamus, pituitary gland, gonadotropins and their antagonists

Antineoplastic hormonal agents and hormone antagonists

Nosological classification (ICD-10)

C61 Malignant neoplasm of prostate

Adenocarcinoma of the prostate, Hormone-dependent prostate cancer, Hormone-Resistant Prostate Cancer, Malignant tumor of prostate, Malignant neoplasm of prostate, Carcinoma of the prostate, Locally-distributed non-metastatic prostate cancer, Locally advanced prostate cancer, Locally spread prostate cancer, Metastatic prostatic carcinoma, Metastatic prostate cancer, Metastatic hormone-resistant prostate cancer, Non-metastatic prostate cancer, Incompatible prostate cancer, Prostate Cancer, Prostate cancer, Common prostate cancer, Testosterone-Depot Prostate Cancer

D25.9 Unspecified uterine leiomyoma

E30.1 Premature puberty

Premature puberty, Premature sexual development, Premature puberty in girls, Early puberty, Primary premature puberty

N80 Endometriosis

Endometrioid endometriosis

N91.2 Amenorrhea, unspecified

Diagnosis of amenorrhea, Lack of menstrual cycle, Congenital amenorrhea

Z31.1 Artificial insemination

Fence of egg, ICSI (Intra Cytoplasmic Sperm Injection), Controlled ovarian stimulation, Controlled superovulation, Controlled superovulation in artificial insemination, Treatment of insemination, Fertilization artificial, Premature ovulation, The IVF program, The program of in vitro fertilization, Superovulation

Code CAS

57773-63-4

Characteristics

Antitumor hormone, a synthetic analogue of the gonadotropin releasing hormone (GnRH).

Pharmacology

Pharmacological action - antitumor, cytostatic, antigonadotropic.

With initial or intermittent application stimulates the release of the anterior lobe of the pituitary gland LH and FSH. In this regard, in the first few days of therapy, there is a transient increase in the level of estrogens and testosterone. Later it blocks the release of gonadotrophic hormones by the pituitary gland - LH, FSH, reduces the content of androgens and estrogens in the blood. Triptorelin has more activity than a natural hormone. The maximum effect develops at 3-4 weeks (the increment of gonadotropins - LH and FSH completely stops, the production of estrogen by the ovaries decreases to the level of menopause, the production of androgens - before the postastratsionnogo state). After discontinuation of treatment, the physiological secretion of hormones is restored.

Carcinogenicity, mutagenicity, effects on fertility

There was no adverse effect on fertility or total reproductive capacity in rats with daily doses exceeding the recommended therapeutic dose for humans (in terms of body surface area) of 0.2; 2 and 16 times, or 20 μg / kg. In addition, there were no side effects in the F1 generation of offspring. Studies to evaluate the effect of tryptorelin on fertility in male rats have not been carried out.

The depot form gradually releases tryptorelin from the surface of the microcapsules and maintains a therapeutic concentration in the blood (200-500 ng / ml) for 30 days after a single injection. Bioavailability with the / m introduction - 38,8%, with p / k - 69%. Tmax after SC administration - 1 hour. After iv introduction of 0.5 mg of tryptorelin, the apparent volume of distribution in healthy male volunteers is 30-33 liters. Does not bind to plasma proteins. Metabolism of triptorelin in humans is unknown, there are no metabolites. The total plasma Cl (162 ml / min) consists of fast and slow components. Eliminated 3 times slower than natural gonadotropin releasing hormone (low biotransformation rate). After intravenous administration of 0.5 mg of triptorelin in men with normal renal function (Cl creatinine 150 ml / min) T1 / 2 - 2.81 h, with Cl creatinine 40 ml / min - 6.56 h, with Cl creatinine 9 Ml / min - 7.65 h. In men with a violation of liver function and a mean Cl creatinine of 90 ml / min - 7.58 h.

Indications

Endometriosis (confirmed laparoscopically in the presence of indications for ovarian suppression and no surgical intervention), uterine myoma (to reduce the size before surgical removal), symptomatic treatment of progressive hormone-dependent prostate cancer (an alternative to surgical castration, to suppress testosterone secretion), early puberty , Program of in vitro fertilization, hypogonadotropic amenorrhea.

Contraindications

Hypersensitivity (including to other analogues of GnRH), in men - hormone-independent prostate cancer, condition after prostatectomy, metastasis to the spine or obstruction of the urinary tract; Women - osteoporosis (increased risk of development or clinical manifestations).

Restrictions

Polycystic ovary (when used in the IVF program).

pregnancy and lactation

Contraindicated in pregnancy (adequate and strictly controlled studies have not been performed) and during breastfeeding (it is unknown whether triptorelin penetrates into breast milk).

Triptorelin has been shown to be toxic to the maternal organism and exhibits embryotoxic properties when administered to rats at doses in excess of those recommended for humans (in terms of body surface area) of 0.2; 0.8 and 8 times. Fetotoxic and teratogenic properties are not fixed.

In women of childbearing age, before starting therapy, pregnancy should be excluded. Women in the period of treatment should use non-hormonal methods for contraception.

Side effects

From the nervous system and sensory organs: headache, sleep disturbance, mood lability, irritability, depression, asthenia, fatigue, paresthesia, visual impairment.

On the part of the intestine: nausea, constipation or diarrhea, anorexia, weight gain, increased activity of hepatic transaminases, hypercholesterolemia.

On the part of the genitourinary system: symptoms associated with a decrease in the level of sex hormones in the blood, incl. In men - flushes to the face, decreased libido, impotence, a decrease in the size of the testicles, gynecomastia; In women - "smearing" discharge or dryness of the mucous membrane of the vagina, decreased libido, pain during intercourse, flushes of blood to the face with profuse sweating.

From the musculoskeletal system: myalgia, back pain, demineralization of bone tissue.

Allergic reactions: skin rash, hyperemia, itching at the injection site, anaphylactic shock, anaphylactoid reactions.

Other: temporary enhancement of symptoms (including arthralgia, progression of hematuria or impaired urination), transient hypertension, anemia, swelling of the legs.

Overdose

In the event of an overdose, it is necessary to immediately stop the treatment with tryptorelin and conduct appropriate symptomatic therapy.

Routes of administration

PC.

Depo-forms: in / m, ï / ê,

Precautions

During the course, it is mandatory to monitor the plasma level of sex hormones (in men and women), the concentration of PSA (prostate specific antigen) in men, using ultrasound - the size of fibroids (rapid decrease in uterine volume compared with the size of fibroids can cause bleeding and sepsis).

Menstruation usually occurs 3 months after the last injection of the depot form, but in some cases later.

In men at the beginning of treatment, it is possible to increase testosterone levels in the blood, therefore, during the first weeks of treatment, careful monitoring of the condition of patients is recommended, especially with metastases in the spine and in patients suffering from urination disorder, if necessary, symptomatic therapy.