Pharmacological action – antitumor, cytostatic, antigonadotropic .
With initial or intermittent use, it stimulates the release of the anterior pituitary of LH and FSH . In this regard, in the first few days of therapy, a transient increase in the levels of estrogen and testosterone is noted. Subsequently, it blocks the release of gonadotropic hormones by the pituitary gland – LH , FSH , reduces the content of androgens and estrogens in the blood. Triptorelin is more potent than natural hormone. The maximum effect develops at 3-4 weeks (the accretion of gonadotropins – LH and FSH completely stops, estrogen production by the ovaries decreases to the level of menopause, androgen production – to the post-castration state). After the cessation of treatment, the physiological secretion of hormones is restored.
Carcinogenicity, mutagenicity, effects on fertility
There were no adverse effects on fertility or overall reproductive ability in rats given daily doses to animals exceeding the recommended therapeutic dose for humans (in terms of body surface area) of 0.2; 2 and 16 times, or 20 mcg / kg. In addition, no side effects were observed in the F 1 generation of offspring. No studies have been conducted to evaluate the effect of triptorelin on fertility in male rats.
The depot form gradually releases triptorelin 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 i / m administration – 38.8%, with s / c – 69%. T max after s / c administration – after 1 h. / In administration of 0.5 mg triptorelin apparent distribution volume in healthy male volunteers – 30-33 liters. Does not bind to plasma proteins. The metabolism of triptorelin in humans is unknown, no metabolites have been identified. Total plasma Cl (162 ml / min) consists of fast and slow components. Eliminated 3 times slower than natural gonadotropin releasing hormone (low rate of biotransformation). Afterin / in administration of 0.5 mg triptorelin men with normal renal function ( Cl Creatinine 150 ml / min) T 1/2 – 2.81 h, Cl creatinine 40 ml / min – 6.56 h, Cl creatinine 9 ml / min – 7.65 hours. In men with impaired liver function and an average Cl creatinine of 90 ml / min – 7.58 hours.
Use of the substance Triptorelin
Endometriosis (confirmed laparoscopically if there is evidence to suppress ovarian function and no surgical intervention is necessary), uterine fibroids (to reduce size before surgical removal), symptomatic treatment of progressive hormone-dependent prostate cancer (an alternative to surgical castration, to suppress testosterone secretion), early puberty , in vitro fertilization program, hypogonadotropic amenorrhea.
Hypersensitivity ( including to other GnRH analogues), in men – hormone-independent prostate cancer, condition after prostatectomy, metastases in the spine or obstruction of the urinary tract; in women – osteoporosis (increased risk of development or clinical manifestations).
Polycystic ovary (when used in the IVF program).
Pregnancy and lactation
It is contraindicated during pregnancy (adequate and strictly controlled studies have not been carried out) and during breastfeeding (it is not known whether triptorelin passes into breast milk).
Triptorelin has been shown to be toxic to the mother’s body and exhibits embryotoxic properties when administered to rats in doses exceeding 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, pregnancy should be excluded before starting therapy. Women during the treatment period must use non-hormonal methods for contraception.
Side effects of the substance Triptorelin
From the nervous system and sensory organs: headache, sleep disturbance, mood lability, irritability, depression, asthenia, fatigue, paresthesia, visual impairment.
From the digestive tract : nausea, constipation or diarrhea, anorexia, weight gain, increased activity of hepatic transaminases, hypercholesterolemia.
From the genitourinary system: symptoms associated with a decrease in the level of sex hormones in the blood, including in men – flushing of the face, decreased libido, impotence, decreased size of the testicles, gynecomastia; in women – “spotting” discharge or dryness of the vaginal mucosa, decreased libido, pain during intercourse, flushing of the face with profuse sweating.
From the musculoskeletal system: myalgia, back pain, demineralization of bone tissue.
Allergic reactions: skin rash, hyperemia, pruritus at the injection site, anaphylactic shock, anaphylactoid reactions.
Other: temporary worsening of symptoms ( including arthralgia, progression of hematuria or urination disorders), transient hypertension, anemia, swelling of the legs.
In case of an overdose, it is necessary to immediately stop the treatment with triptorelin and conduct appropriate symptomatic therapy.
Route of administration
Depot forms: v / m, s / c ,
Precautions for the substance Triptorelin
During the course, it is mandatory to control the plasma level of sex hormones (in men and women), the concentration of PSA (prostate-specific antigen) in men, using ultrasound – the size of the fibroids (a rapid decrease in the volume of the uterus compared to the size of the 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, an increase in blood testosterone levels is possible, 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 impaired urination, if necessary, symptomatic therapy.