Sign Out
Enantone 1-Month DPS 3.75 mg: Careful Administration: ENANTONE should be administered with care in the following patients.
Endometriosis, Uterine Myoma, Premenopausal Breast Cancer: Patients with submucous myoma: Bleeding symptom may be aggravated. (See Important Precautions as follows.)
Prostate Cancer: Patients who have already had renal dysfunction due to spinal cord compression or ureteral obstruction or those who may be at a risk of developing such manifestations: There is a possibility that the symptoms of underlying disease are aggravated with the elevation of serum testosterone level in the early period after the first administration.
Important Precautions: Endometriosis: In administration of ENANTONE, care should be taken to differentiate a similar disease (malignant tumor, etc.) from endometriosis. If, during administration of ENANTONE, any growing phyma is found or no improvement is seen in the clinical symptom, the administration should be discontinued.
In the early period after the first administration of ENANTONE, a transient elevation of the serum level of estrogen may occur owing to the stimulating effect of ENANTONE, as a highly active LH-RH derivative, on the pituitary-gonad system, resulting in a transient aggravation of clinical condition. However, such an aggravation usually disappears in the course of continued administration.
Since a depressed state like climacteric disturbance may occur, the patient's condition should be closely observed. (See Clinically significant adverse reactions under Adverse Reactions.)
Uterine Myoma: In administration of ENANTONE, care should be taken to differentiate a similar disease (malignant tumor, etc.) from uterine myoma. If, during administration of ENANTONE, any growing phyma is found or no improvement is seen in the clinical symptom, the administration should be discontinued.
In administration of ENANTONE to patients with submucous myoma, bleeding symptom may worsen. Therefore, close observation should be made, and if any abnormality is observed, appropriate measures should be taken. In addition, the patients should be instructed to contact the attending physician in case of any aggravation of the bleeding symptom.
In the early period after the first administration of ENANTONE, a transient elevation of the serum level of estrogen may occur owing to the stimulating effect of ENANTONE, as a highly active LH-RH derivative, on the pituitary-gonad system, resulting in a transient aggravation of clinical condition. However, such an aggravation usually disappears in the course of continued administration.
Since a depressed state like climacteric disturbance may occur, the patient's condition should be closely observed. (See Clinically significant adverse reactions under Adverse Reactions.)
Premenopausal Breast Cancer: Since ENANTONE is an agent for endocrine therapy, use of this drug for premenopausal breast cancer should be limited to patients for whom treatment with ENANTONE is considered appropriate under the supervision of a physician who has adequate knowledge and experience in medication for cancer.
In the early period after the first administration of ENANTONE, a transient elevation of the serum level of estrogen may occur owing to the stimulating effect of ENANTONE, as a highly active LH-RH derivative, on the pituitary-gonad system, resulting in a transient aggravation of bone pain, etc. In such a case, symptomatic treatment should be given.
If antitumor effect is not obtained with ENANTONE and any progression of the tumor is observed, the administration should be discontinued.
Since a depressed state like climacteric disturbance may occur, the patient's condition should be closely observed. (See Clinically significant adverse reactions under Adverse Reactions.)
Prostate Cancer: Since ENANTONE is an agent for endocrine therapy, use of this drug for prostate cancer should be limited to patients for whom treatment with ENANTONE is considered appropriate under the supervision of a physician who has adequate knowledge and experience in medication for cancer.
In the early period after the first administration of ENANTONE, a transient elevation of the serum level of testosterone may occur owing to the stimulating effect of ENANTONE, as a highly active LH-RH derivative, on the pituitary-gonad system, resulting in a transient aggravation of bone pain, etc. In such a case, symptomatic treatment should be given. Since ureteral obstruction or spinal cord compression may occur, this drug should be carefully administered and close observation should be made during the first month after initiation of administration, and if any of such symptoms occurs, appropriate measures should be taken.
Central Precocious Puberty: In the early period after the first administration of ENANTONE, a transient elevation of the serum level of gonadotropic hormone may occur owing to the stimulating effect of ENANTONE, as a highly active LH-RH derivative, on the pituitary-gonad system, resulting in a transient aggravation of clinical condition. However, such an aggravation usually disappears in the course of continued administration.
During the treatment with ENANTONE, LH-RH test should be performed at regular intervals. When suppression of the action of LH and FSH in blood is not achieved, the administration of this drug should be discontinued.
Other Precautions: It has been reported that the benign pituitary adenoma was observed in rats in a study in which this drug was administered subcutaneously in doses of 0.8, 3.6 and 16 mg (as leuprorelin acetate)/kg at 4-week intervals for 1 year and another study in which an aqueous injectable solution of Leuprorelin Acetate was similarly administered in doses of 0.6, 1.5 and 4 mg/kg/day for 2 years.
Use in Children: Central Precocious Puberty: The safety of ENANTONE in prematures, newborns and nursing infants has not been established.
Enantone 3-Month DPS 11.25 mg: Epidemiological data have shown that inhibiting the production of an endogenous sex hormone that occurs during androgen or estrogen deprivation therapy (for example, in menopausal women) is associated with metabolic changes (for example, reduction of glucose tolerance or worsening of pre-existing diabetes) as well as an increased risk of cardiovascular diseases. However the prospective data did not confirm the link between GnRH analogues treatment and increased cardiovascular mortality. Patients at high risk of metabolic changes or syndromes or cardiovascular diseases must be adequately monitored. ENANTONE 3 MONTH DPS, may be associated with increased risk of diabetes and certain cardiovascular diseases (including heart attack, sudden cardiac death or stroke) in men receiving these medications for the treatment of prostate cancer.
Androgen deprivation therapy may lead to QT interval prolongation. In patients with a history of QT interval prolongation or with risk factors for QT interval prolongation, and in patients receiving concomitant drugs that may prolong the QT interval (see Interactions), before beginning the treatment with Enantone the physicians must evaluate the risk-benefit ratio of each medicinal product, including the possibility of Torsades de pointes.
Seizures have been reported in post-marketing report in patients receiving leuprorelin acetate and these events have been reported in both children and adults, with or without history of epilepsy, seizure disorders, or risk factors for seizures.
There is an increased risk of incident depression (which can be severe) in patients receiving GnRH agonists, such as leuprolide. Patients should be informed accordingly and treated appropriately if symptoms occur.
Idiopathic intracranial hypertension: Cases of idiopathic intracranial hypertension (pseudotumor cerebri) have been reported in patients taking leuprorelin. Patients should be warned of the signs and symptoms of idiopathic intracranial hypertension, including severe or recurrent headache, visual disturbances and tinnitus. In case of idiopathic intracranial hypertension, consideration should be given to discontinuing the administration of leuprorelin.
In Males: In the early stage of prostate cancer treatment initial phase with GnRH analogues, some cases of transitory worsening of the clinical symptomatology may occur, such as urinary tract obstruction and haematuria (as urinary symptoms) following a temporary increase in testosterone levels. In patients with compression of the spinal cord due to spinal cord metastasis, bone pain, weakness of the lower extremities and transitory paresthesia (as neurological symptoms) may occur (see Adverse Reactions). This warrants particularly careful medical supervision during the first few weeks of treatment for the patient with urinary tract obstruction and for those with vertebral metastasis. For the same reason, subjects who have warning signs of bone marrow compression should be carefully monitored at the beginning of treatment.
In the initial period of treatment, a transitory increase in acid phosphatase may be observed.
These manifestations are usually transitory and disappear in one or two weeks from the beginning of treatment.
It may be useful to periodically check for testosteronaemia, that should not exceed 1 ng/ml, PSA and acid phosphatase, which may transiently increase in the first weeks of treatment. The therapeutic response can be evaluated in the bone by means of scintigraphy and/or tomographic examination; prostate response will be assessed by ultrasound and/or tomography (as well as clinical tests and rectal examination).
In the event of prolonged androgenic deprivation, bilateral orchiectomy or administration of GnRH analogues, it may be worthwhile periodically verifying the bone densitometry values as it can produce a state of hypoandrogenism, which induces a reduction of the bone mineral density. In patients who present additional risk factors, this may lead to osteoporosis and an increased risk of bone fractures.
Cardiovascular illnesses: There have been reports of an increased risk of onset of myocardial infarct, sudden cardiac death and stroke associated with the use of GnRH agonists in men. On the basis of the probabilities reported, the risk seems low and must be assessed carefully on the basis of the cardiovascular risk factors at the time of the set-up of the treatment for patients with prostate cancer. The patients treated with GnRH agonists must be checked for symptoms and signs which suggest development of a cardiovascular illness and must be managed in accordance with current clinical practice.
In Females: In females with endometriosis and uterine fibroids, the occurrence of severe metrorrhagia during the treatment is considered abnormal and involves checking plasma oestradiol levels which, if less than 50 pg/ml, requires further investigation for the identification of any associated organic lesions. Prior to administering Lupron (leuprolide acetate), severe undiagnosed vaginal bleeding (see Contraindications) should be investigated, diagnosis must be confirmed and appropriate treatment given. In the event of severe vaginal bleeding during treatment, the patient should be closely monitored and appropriately treated if necessary.
Prior to treatment, women of childbearing potential should be carefully monitored to rule out pregnancy (see Contraindications). Non-hormonal contraception must be used during treatment. These methods should be maintained until the menstrual cycle is resumed.
In case of prolonged estrogen deprivation, bilateral ovariectomy, ovarian ablation or administration of GnRH, it may be useful to verify periodically the values of bone densitometry as it can produce a state of hypoestrogenism, that can also occur in patients who have undergone a bilateral ovariectomy or ovarian ablation, which causes a reduction of the bone mineral content. In patients who present additional risk factors, it may lead to osteoporosis and an increased risk of bone fractures.
Treatment duration should be limited to 6 months in the treatment of endometriosis and uterine fibroids because its use is associated with an increased risk of bone mineral loss. If retreatment is necessary, changes in bone parameters should be closely monitored. Initially, after the first administration of the drug, temporary worsening of clinical picture may occur. However, these symptoms disappear as the treatment continues.
Effects on Driving and Using Machines: Enantone may affect the ability to drive or operate machinery because it can cause visual disturbances and dizziness.
Use in Children: In Girls: In girls with precocious puberty, the gonadic stimulation may be responsible for small amounts of genital bleeding after the first injection which requires the addition of appropriate treatment only if these occur beyond the first month of treatment. Before starting treatment, girls of childbearing age must be tested to rule out pregnancy (see Contraindications).
In Infancy: The inhibition of pituitary gonadotropic activity manifests in both sexes as suppression of oestradiol secretion or testosterone secretion, with the lowering of LH peak and improvement in the growth age/bone age ratio.
Since the child is growing, it is recommended to regularly check that the oestradiol/testosterone levels remain low, especially if their weight is approaching 20 kg.
Before starting therapy, a precise diagnosis of idiopathic and/or neurogenic central precocious puberty is necessary. Therapy consists of long-term individually regulated treatment. Enantone should be carefully administered at regular quarterly intervals. Exceptional delay of the injection date of a few days (90 ± 2 days) does not affect the results of therapy.
In the case of sterile abscess of the injection site (mainly reported after injection of a higher than recommended dosage), the absorption of leuprorelin acetate from the depot may be decreased. In this case hormonal parameters (testosterone, oestradiol) should be checked at 2-week intervals (see Dosage & Administration).
In patients with progressive brain tumours, caution should be exercised if the risk from a clinical point of view is substantially greater than the benefits.
Bleeding and vaginal discharge after the first injection may indicate suspending hormone therapy in girls. Vaginal bleeding lasting beyond the first/second month of treatment must be investigated.
Bone mineral density (BMD) may decrease during central precocious puberty therapy with GnRH agonists. However, after treatment discontinuation, subsequent maturation of bone mass is preserved and the peak growth of bone mass in late adolescence does not appear to be affected by treatment.
Slippage of the femoral epiphysis may occur after stopping GnRH treatment. The suggested theory is that low oestrogen concentrations during treatment with GnRH agonists weaken the epiphyseal plate. Increasing the rate of growth after stopping treatment results in a reduction in the cutting force required for the dislocation of the epiphysis.
This medicinal product contains less than 1 mmol (23 mg) sodium per dose, so it is essentially "sodium free".
Enantone 6-Month DPS 30 mg: Patients with hypertension should be monitored closely.
There is an increased risk of incident depression (which may be severe) in patients undergoing treatment with GnRH agonists, such as leuprorelin. Patients should be informed accordingly and treated as appropriate if symptoms occur.
After surgical castration, treatment with ENANTONE 6 MONTH DPS does not lead to further reduction of testosterone levels.
Administration of ENANTONE 6 MONTH DPS leads to an initial short-term increase in the serum level of testosterone, potentially resulting in a transient exacerbation of certain disease symptoms. Patients with potential neurological complications, spinal metastases, or urinary tract obstruction should be monitored closely during the first few weeks of treatment.
In the initial phase of therapy the adjuvant administration of a suitable anti-androgen is to be considered to alleviate the symptoms potentially associated with the initial increase in testosterone levels and to attenuate the exacerbated clinical symptoms.
The success of the treatment should be monitored regularly (particularly in the presence of signs of progression despite adequate treatment) by means of clinical examinations (rectal palpation of the prostate gland, ultrasound, bone scan, computed tomography) and investigations of phosphates and the prostate-specific antigen (PSA) as well as serum testosterone.
A long-term androgen deprivation therapy with GnRH analogues or orchiectomy is associated with an increased risk of bone demineralisation. In patients with high risk it may lead to osteoporosis and increased risk for bone fracture.
Metabolic modification and cardiovascular risk: Epidemiological data have shown that the inhibition of endogenic sexual hormone production such as a gonadotropin deprivation (e.g., during menopause) during therapy with GnRH analogues results in a metabolic change (reduction in glucose tolerance or aggravation of pre-existing diabetes mellitus) and that there can be an increased risk for cardiovascular diseases (see Adverse Reactions). However, prospective data does not confirm a correlation between the treatment with GnRH analogous and an increased cardiovascular mortality. An appropriate monitoring of diabetic patients and patients with increased risk of metabolic or cardiovascular disorders treated with ENANTONE 6 MONTH DPS is recommended.
Androgen deprivation therapy may prolong the QT interval. In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval (see Interactions) physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating ENANTONE 6 MONTH DPS.
After the launch of leuprorelin acetate seizures were monitored and reported in children and adults with or without a history of epilepsy, seizures or risk factors for seizures.
The use of ENANTONE 6 MONTH DPS can lead to positive results in doping tests.
ENANTONE 6 MONTH DPS contains less than 1 mmol sodium (23 mg) per one dual chamber prefilled syringe.
Idiopathic intracranial hypertension: Idiopathic, intracranial hypertension (pseudotumor cerebri) was reported in patients receiving leuprorelin. The patients should be informed of signs and symptoms of idiopathic intracranial hypertension, including severe or recurrent headache, visual disturbance, and tinnitus. Discontinuation of leuprorelin should be considered if idiopathic intracranial hypertension occurs.
Abuse and dependence: The risk of dependence to leuprorelin acetate is very low, as only medical professions perform the application. Leuprorelin acetate abuse would only suppress endogenic production.
Effects on ability to drive and use machines: In view of the tiredness that may occur in a few patients especially at the start of treatment, which can also be caused by the underlying tumour, this medicinal product, even when used as directed, may alter reactivity to such an extent that the ability to drive or to operate machines is impaired. This applies even more in combination with alcohol.
