Tryptorelin - instructions for use, dose, side effects, contraindications

Synthetic analogue of the releasing factor of LH. Like the natural gonadotropin-releasing hormone produced by the hypothalamus, it stimulates the release of LH and FSH from the anterior lobe of the pituitary gland. With prolonged use leads to a complete blockade of the gonadotrophic function of the pituitary gland with suppression of the secretion of lutropin and FSH (chemical castration). In prostate cancer, and release of FSH alpha lutropina causes a transient increase in the concentration of testosterone but after the suppression of secretion of LH and FSH (within 4 weeks of starting treatment) testosterone concentration in the blood is reduced to post-castration. In women (with endometriosis, breast cancer), the initial release of FSH and LH leads to a transient increase in the concentration of estradiol,but after the suppression of their production, the size and suppression of ovarian functions decrease, the size of the uterus and mammary glands decreases, the inactivation and atrophy of the endometrium (including the ectopic), and the regress of hormone-dependent tumors. Amenorrhea usually develops within 4-8 weeks after the start of treatment. The maximum effect develops at week 3 and persists throughout the treatment period (reversible after its termination). Menstruation usually occurs no earlier than 3 months after the final injection.

Pharmacokinetics:

Bioavailability for intramuscular and subcutaneous injection - 38.8 and 69%, respectively. Microsomal liver enzymes (in particular, cytochrome P450) are not involved in metabolism; the role of other enzymes that metabolize the drug is unknown. Half-life(after intravenous administration at a dose of 0.5 mg) - 2.81 hours (in men with normal kidney function and creatinine clearance - 150 ml / min). Eliminated (after intravenous administration at a dose of 0.5 mg) with bile and kidneys (42% - in the form of unchanged substance, up to 62% - with a decrease in the clearance of creatinine and liver failure).

Indications:

Treatment of locally advanced prostate cancer in monotherapy or as an adjuvant against radiation therapy;

Treatment of metastatic prostate cancer.

Genital and extragenital endometriosis (stages I-IV).

ICD-10

II.C60-C63.C61 Malignant neoplasm of prostate

XIV.N80-N98.N80 Endometriosis

Contraindications:

Hypersensitivity to triptorelin and other analogues of releasing factors of gonadotropins.

Hormone-independent prostate cancer.

Condition after surgical castration (with prostate cancer).

Pregnancy, breast-feeding.

Clinically expressed osteoporosis or a high risk of its development in women.

Carefully:

With caution should prescribe the drug for osteoporosis, women with polycystic ovary syndrome.

Pregnancy and lactation:

Before starting treatment, pregnancy should be excluded. Studies in humans have not been conducted. In view of the potential threat to the fetus for women of childbearing age, during the first month of treatment with tryptorelin, it is recommended to use methods of non-hormonal contraception. There is no information on the penetration into breast milk.In view of the potential risk of adverse effects on the child during treatment with tryptorelin, breast-feeding is recommended to be discontinued.

Recommendations for FDA - category X.

Dosing and Administration:

In prostate cancer tryptorelin administered intramuscularly at a dose of 11.25 mg every 3 months. In combination with radiotherapy, prolonged antiandrogen therapy (3 years) is preferable to short-term antiandrogen therapy (6 months).

With endometriosis, the drug is administered intramuscularly at a dose of 11.25 mg every 3 months. Treatment should be started in the first 5 days of the menstrual cycle. The duration of treatment depends on the severity of endometriosis and the observed clinical picture (functional and anatomical changes) on the background of therapy. As a rule, treatment is carried out for 3-6 months. It is not recommended to repeat a course of treatment with tryptorelin or another analogue gonadotropin-releasing hormone.

Side effects:

In most cases, due to hypoestrogeny in women and hypothetoremonism in men.

Hematological: anemia.

From the side of cardio-vascular system: arterial hypertension.

From the side GIT: vomiting, diarrhea, nausea.

From the side urinary tract: urinary retention, urinary tract infection.

From the side nervous system: headache, dizziness, emotional lability, fatigue, insomnia, depression, irritability, paresthesia, visual impairment.

Dermatological: pain at the injection site, itching.

Hypersensitivity (patients hypersensitive to other analogues of releasing factors - Buserelin, leuprorelin, goserelin - or natural gonadotropin releasing factor, may be hypersensitive to triptorelin): angioedema, anaphylactic shock, allergic reactions.

Overdose:

Not described.

Treatment is symptomatic.

Interaction:

Triptorelin interaction studies have not been performed, but should not be used simultaneously to increase the level of prolactin, as hyperprolactinemia helps reduce the number of receptors releasing factors of gonadotropins.

Special instructions:

Triptorelin treatment of prostate cancer should be managed by specialists with experience of endocrine therapy of tumors.

The potential risk and benefit of using triptorelin in conditions accompanied by a decrease in bone mineral density (including in cases of osteoporosis, chronic alcoholism, smoking, family severe osteoporosis, long-term use of anticonvulsants, glucocorticoids that reduce bone mineral density), non-diagnostic uterine bleeding should be correlated (the use of goserelin may make diagnosis difficult); urinary tract obstruction in the anamnesis - careful monitoring is necessary during the first month of treatment); metastatic spinal cord injury (possibly development of spinal cord compression); polycystic ovary syndrome (risk of syndrome of ovarian hyperstimulation).

Monitoring of pregnancy (in the treatment of endometriosis and the beginning of therapy not on the first day of the menstrual cycle, with irregular menstrual cycles or changes in the intervals of administration), concentration prostate specific antigen and testosterone in the blood (periodically during the treatment of prostate cancer to clarify the response to treatment), osteoscintigraphy (for prostate cancer and risk of metastasis in the spine), radiation studies (intravenous urography, computed tomography, ultrasound for the diagnosis of obstructive uropathy), the size of fibroids, the growth of follicles in the luteal phase (especially when polycystic ovary syndrome to prevent their hyperstimulation).

When examining the functions of the gonadotropins of the pituitary gland and gonad it is necessary to take into account that in therapeutic doses tryptorelin suppresses the pituitary-gonadal regulatory system.

Instructions

Triptorelin (Triptorelinum)