Treatment with Diperelin® should be carried out in strict accordance with the instructions for use. Any change in the volume of the intramuscular injection to be administered should be recorded. Diferelin® 11.25 mg contains less than 1 mM sodium (23 mg) per dose, which is clinically insignificant.
Caution should be observed in patients taking anticoagulants, since it is possible to develop a hematoma at the injection site.
Endometriosis
Before starting treatment, pregnancy should be excluded.
Throughout the treatment period, including within 3 months of the last injection, non-hormonal contraceptives should be used.
Intramuscular injection of the drug leads to persistent hypogonadotropic amenorrhea.
Treatment should not be recommended for more than 6 months. It is not recommended to repeat a course of therapy with tryptorelin or another analogue of GnRH.
The emergence of metrorrhagia during treatment, not counting the first month, is not the norm, therefore, it is necessary to determine the concentration of estradiol in plasma. When the concentration of estradiol is lower than 50 pg / ml, other organic lesions are possible.
The function of the ovaries is restored after the completion of therapy. The first menstruation occurs on average 5 months after the last injection. Given that menstruation must stop for the duration of therapy with tryptorenone, the patient should be properly instructed about what she should tell her doctor if regular menstruation persists.
Prostate Cancer
The most pronounced beneficial effect of therapy with tryptorelin is observed in patients in the absence of other previously conducted hormone therapy.
At an early stage tryptorelin, like other GnRH agonists, causes a temporary increase in testosterone concentration in the blood serum.As a result, during the first weeks of therapy, the appearance and intensification of clinical symptoms (in particular, bone pains, dysuric disorders) that are transitory in nature and in which symptomatic therapy should be given may occur. As with the use of other GnRH agonists, individual cases of compression of the spinal cord or obstruction of the urinary tract can be identified. With compression spinal cord or obstruction of the urinary tract, standard treatment of these complications should be prescribed and, in case of emergency, an orchiectomy (surgical castration) is to be performed. Patients should be carefully monitored during the first few weeks of therapy (testosterone concentration in the blood plasma should not exceed 1 ng / ml), especially patients with metastatic spinal cord injuries, patients with risk of spinal cord compression or obstruction of the urinary tract. For the same reason, special attention should be given at the beginning of treatment to patients with signs of compression of the spinal cord, identified in the preliminary examination.During the initial phase of therapy, the use of an additional prescription of anti-androgenic drugs should be considered to prevent an initial increase in plasma testosterone concentration and worsening of clinical symptoms.
After surgical castration tryptorelin does not cause a further decrease in the concentration of testosterone in the plasma.
Epidemiological data have shown that metabolic disorders (such as impaired glucose tolerance) can develop in patients during androgen deprivation therapy. increase the risk of cardiovascular disease. However, prospective data did not confirm the relationship between the treatment of GnRH agonists and the increase in mortality from cardiovascular diseases. Patients with a high risk of metabolic or cardiovascular disease should be carefully examined prior to the appointment of treatment and carefully observed during androgen deprivation therapy.
At the beginning of therapy, there may be a temporary increase in acid phosphatase activity.
It may be advisable to periodically check the testosterone concentration in the blood plasma by the appropriate method, since it should not exceed 1 ng / ml.
Function of the sex glands and pituitary gland
The use of tryptorelin in therapeutic doses leads to suppression of the "sex glands-pituitary" system. The normal functioning of the gonads and pituitary gland is usually restored after the cessation of therapy. The results of a diagnostic test of the gonadotropic function of the pituitary gland, performed during and after discontinuation of therapy, can, therefore, be incorrect.
Osteoporosis
The use of GnRH agonists can cause a decrease in bone mineral density (BMD).
In men prolonged androgen deprivation with bilateral orchiectomy or with the use of GnRH analogs may be associated with an increased risk of bone loss and can lead to osteoporosis and an increased risk of fracture of the bones.
Preliminary data suggest that the use of bisphosphonates in combination with GnRH can reduce the loss of BMD. Particular attention should be given to patients with risk factors for developing osteoporosis (for example: chronic alcohol dependence, smoking, long-term therapy with drugs that lower the MIC, such as anticonvulsants or glucocorticosteroids, history of hereditary osteoporosis, insufficiency or malnutrition).
Among women the use of GnRH agonists may be the cause of a decrease in BMD by an average of 1% per month for six months of treatment. Every 10% reduction in BMD leads to an increase in the risk of fracture of the bones by approximately 2-3 times.
In most women, as current data suggest, IPC is restored after discontinuation of therapy.
There is no available data on the use of tiriporelin in patients with established osteoporosis or with risk factors for osteoporosis (eg: chronic alcohol dependence, smoking, prolonged therapy with anti-MBH drugs, such as anticonvulsants or glucocorticosteroids; the presence of an anamnesis of hereditary osteoporosis; insufficiency or malnutrition, for example, anorexia nervosa). Given that a decrease in the BMD is more possible in such patients, treatment with tryptorelin should be administered on an individual basis and can only be initiated if the benefits obtained from the treatment exceed the risk. An additional survey should be considered to avoid loss of BMD.
Pituitary Tumor
Rarely, the use of GnRH agonists may reveal the presence of previously unidentified gonadotropic pituitary adenoma.Hemorrhage in the pituitary gland is characterized by sudden headache, visual disturbances and ophthalmoplegia.
Depression
In patients receiving therapy with GnRH agonists, such as tryptorelin, there is an increased risk of developing depression (which can be severe). Patients should be informed about the possible development of depression, and in the case of development of depression should receive appropriate therapy. Patients with already known depression should be carefully monitored during therapy.
Interval lengthening QT
Long-term androgen deprivation can prolong the interval QT. It is necessary to assess the risk / benefit ratio prior to the appointment of triptorelin to patients with congenital elongated interval syndrome QT, with electrolyte disorders or chronic heart failure, or patients taking antiarrhythmic drugs of class IA (eg, quinidine, procainamide) or class III (for example, amiodarone, sotalol).
Premature puberty of central genesis
The use of tryptorelin in children with premature puberty should be conducted under the supervision of a pediatric endocrinologistor pediatrician or endocrinologist with experience in the therapy of premature puberty.
Treatment of children with a progressive pituitary tumor should be performed after an individual assessment of the risk / benefit ratio.
In girls, initial stimulation of the ovaries, leading to the cessation of estrogen production, may cause vaginal bleeding of mild or moderate intensity, requiring medroxyprogesterone or cyproterone acetate therapy, in the first month.
After the end of treatment, puberty traits develop. Information on the effect of GnRH analogue therapy on the future fertility of patients is still limited. In most girls, regular menstruation began an average of one year after the end of therapy. Premature puberty due to tumor or hyperplasia of the gonads or adrenal glands, or gonadotropin-independent premature puberty (testicular damage due to intoxication, hereditary Leydig cell hyperplasia) should be ruled out before therapy begins.
The MIC can be reduced during the treatment of premature puberty by GnRH agonists.However, after discontinuation of treatment, further bone mass build-up is restored, and the therapy does not affect the peak of bone mass at the end of the pubertal period.
After the end of GnRH agonist therapy, epiphysis of the head of the femur is possible. low estrogen concentrations during treatment with GnRH agonists weaken the epiphyseal growth plate. The increase in the rate of growth after the end of therapy leads to a displacement of the proximal epiphysis of the thigh.