active substance : 1 capsule for subcutaneous injection of prolonged action contains goserelin acetate equivalent to 3.6 mg goserelin-the basics;
auxiliary substances: copolymer lactide and glycolide.
Capsule for subcutaneous injection of prolonged action.
Basic physico-chemical properties: pieces of solid polymer of cylindrical shape from white to cream color.
Analogues of gonadotropin - releasing hormone.
Code ATC L02A E03.
Mechanism of action.
The Zoladex (D-Ser (But) 6 Azgly 10 LG-WG) is a synthetic analogue of the natural luteinizing hormone - releasing hormone (LH-RG). With constant use, Zoladex inhibits the release of LH by the pituitary gland, which leads to a decrease in the concentration of testosterone in serum in men and the concentration of estradiol in serum in women. This effect is reversible after discontinuation of therapy. At the primary stage, Zoladex, like other LG-RG agonists, can cause a temporary increase in the concentration of testosterone in serum in men and the concentration of estradiol in serum in women. In the early stages of treatment with Zoladex some women may experience vaginal bleeding of varying duration and intensity. These bleeding is probably a reaction to estrogen withdrawal and should stop on their own. In men, approximately by the 21st day after administration of the first capsule, the concentration of testosterone decreases to castration levels and remains reduced with constant treatment, that is, with the introduction of the drug every 28 days. This decrease in testosterone concentration in most patients leads to regression of prostate tumor and symptomatic improvement. In women, the concentration of estradiol in serum is also reduced to about 21 days after the introduction of the first capsule and with constant treatment, that is, with the introduction of the drug every 28 days, remains reduced to a level comparable to that observed in women in the postmenopausal period. This decrease leads to a positive effect in hormone-dependent forms of breast cancer, endometriosis and uterine fibroids. It also leads to a thinning of the endometrium and the occurrence of amenorrhea in the majority of patients.
It is shown that Zoladex in combination with iron preparations causes amenorrhea, which leads to an increase in the level of hemoglobin and improvement of the relevant hematological parameters in women with uterine fibroids and concomitant anemia. This combination will give an additional 10 g/l increase in the concentration of hemoglobin compared with iron therapy alone. During the treatment of Zoladex in some women may come menopause. In a small number of patients, menstruation is not restored after treatment.
Zoladex has almost complete bioavailability. The introduction of the capsule every four weeks ensures the maintenance of effective concentrations. Cumulation in the tissues does not occur. Zoladex does not bind well with protein, and its half-life from blood serum is 2-4 hours in patients with normal renal function. The half-life period increases in patients with impaired renal function. With the monthly introduction of the drug in the form of capsules, this change will not have significant consequences. Therefore, to change the dose for patients with impaired renal function is not necessary. In patients with hepatic insufficiency, significant changes in pharmacokinetics are not observed.
Treatment of prostate cancer in the following cases:
treatment of metastatic prostate cancer-the use of Zoladex beneficial effect on survival, such as the effect of surgical castration;
treatment of locally advanced prostate cancer as an alternative to surgical castration-the use of Zoladex had a beneficial effect on survival, such as the effect of antiandrogene;
as adjuvant therapy for radiation therapy in patients with localized high-risk prostate cancer or locally advanced prostate cancer - the use of Zoladex has improved survival without signs of disease and overall survival;
as Neoadjuvant therapy prior to radiation therapy in patients with localized high-risk prostate cancer or locally advanced prostate cancer, the use of Zoladex has improved survival without signs of illness;
as adjuvant therapy in radical prostatectomy in patients with locally advanced prostate cancer and a high risk of disease progression, the use of Zoladex improved survival without signs of disease.
Breast cancer. Treatment of common breast cancer sensitive to hormonal effects in women during pre-and perimenopause.
As an alternative to chemotherapy as part of the standard treatment of women in the period before/perimenopause with estrogen receptor (ER) positive early breast cancer.
Endometriosis. Alleviates symptoms including pain, reducing the size and amount of endometrial damage.
Thinning of the endometrium. For pre-thinning of endometrium before ablation or resection.
Fibroids of the uterus. In combination with therapy with iron preparations to improve the hematological status of patients with anemia and fibroids before surgery.
In in vitro fertilization. Desensitization of the pituitary gland in preparation for stimulation of superovulation.
Hypersensitivity to goserelin acetate or other analogues of LH-WP (luteinizing hormone - releasing hormone).
Pregnancy and breast-feeding.
Interaction with other medicinal products and other forms of interaction
Because androgen-deprivation therapy can lead to prolonged QT interval, should be carefully evaluated concomitant use of Zoladex with other drugs that can prolong the QT interval or drugs that can cause ventricular tachycardia type "pirouette", such as antiarrhythmic agents of class IA (quinidine, disopyramide) or class III (amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin, antipsychotics (see section "Peculiarities of use").
No data on removal or dissolution of the implant.
There is a high risk of depression (which can be severe) in patients receiving treatment with gonadotropin-releasing hormone agonists such as goserelin. Patients should be informed about this risk and, if symptoms occur, appropriate treatment should be prescribed.
Androgen-deprivation therapy can lead to prolonged QT interval.
Before the appointment of Zoladex patients with a history of prolongation of the Qt interval or risk factors for its prolongation, as well as patients who simultaneously use drugs that can cause prolongation of THE Qt interval (see section "Interaction with other drugs and other types of interactions", it is necessary to assess the ratio of benefit and risk, including the possibility of ventricular tachycardia type "pirouette".
It should be used with caution Zoladeks men who are threatened by the development of urinary tract obstruction or spinal cord compression, as well as carefully monitor such patients during the first month of therapy. In the case of the presence or occurrence of spinal cord compression or renal insufficiency due to obstruction of the urinary tract should resort to standard treatment of such complications.
Consideration should be given to the appointment of anti-androgens during the initial period of treatment with LG-R analogues (for example, ciproterone acetate 300 mg/day for 3 days before and 3 weeks after the appointment of Zoladex), as it was reported that this prevents the possible consequences of the initial rise in serum testosterone levels.
It is unlikely that patients with prostate cancer are not hormone-dependent, such treatment will be useful. This resistance to treatment can be the result of a lack of reaction to castration or hormone treatment.
The recommended dosage of testosterone prior to the introduction of treatment to assess therapeutic benefits.
The use of agonists LG-RG can lead to a decrease in bone mineral density. Preliminary data indicate that the use of bisphosphonates in men in addition to LG-R agonists can reduce the loss of bone minerals. Particular care should be taken in patients with risk factors for osteoporosis (chronic alcohol abuse, Smoking, long - term therapy with anticonvulsants or corticosteroids, the presence of osteoporosis in the family history).
There have been cases of mood changes, including depression. Patients with established depression and patients with AH requires careful supervision.
There is a high risk of pressure loss (which can be severe) in patients treated with LG-R agonists such as goserelin. Patients should be informed and treated properly if symptoms occur.
In the pharmacoepidemiological study of LG-RG agonists, which were used for the treatment of prostate cancer, there were cases of myocardial infarction and heart failure. The risk appears to be increasing, if the agonists of LH-RG used in combination with antiandrogenic agents.
A decrease in glucose tolerance was observed in men taking agonists of LH-RG. This may occur as diabetes or loss of glycemic control in people with existing diabetes mellitus. You should consider monitoring the levels of glucose in the blood.
Benign condition as the testimony
The loss of bone mineral density
Agonists LG-RG can cause a decrease in bone mineral density by an average of 1% in 6 months of treatment. The decrease in bone mineral density for every 10% increases the risk of fractures by approximately 2-3 times. According to the currently available data, for most women, after discontinuation of treatment bone mass is restored.
In patients taking Zoladex for the treatment of endometriosis, additional hormone replacement therapy weakened the decrease in bone mineral density and the severity of vasomotor symptoms.
There is no specific data on the use of the drug in patients with established osteoporosis or risk factors for its development (such as chronic alcohol abuse, Smoking, prolonged therapy with drugs that reduce bone mineral density, for example, SAPS or corticosteroids, the presence of osteoporosis in the family history, nutritional disorders, for example, nervous anorexia). Since the reduction of bone mineral density in such patients may be more dangerous, the use Of Zoladex should be considered in each case and begin therapy only if the result of a thorough evaluation determined that the benefits will prevail over the risk. Additional measures to counteract the loss of bone minerals should be resorted to.
Breast cancer as indications
A decrease in bone mineral density
The use of agonists LG-RG can lead to a decrease in bone mineral density. After 2 years of treatment for early stages of breast cancer, the average decrease in the mineral density of the femoral neck and lumbar spine in women was 6.2% and 11.5%, respectively. It was shown that these losses are partially reversible: a year after the termination of treatment, the loss of mineral density of the femoral neck and lumbar spine was respectively 3.4% and 6.4% less than the use of the drug, although data on bone mass recovery is very limited. According to the available data, in most women the bone mass is restored after the termination of treatment.
Preliminary data indicate that the use of Zoladex in combination with tamoxifen in patients with breast cancer can reduce the loss of bone minerals.
At the beginning of application of Zoladex in some patients possible vaginal bleeding of different duration and intensity. Usually, such bleeding occurs in the first month after the start of treatment, probably, is a reaction to the removal of estrogen and passes by itself. If the bleeding does not go away, you need to establish its cause.
There is no clinical data on the effect of Zoladex for the treatment of benign gynecological conditions for more than 6 months.
The use of Zoladex may lead to increased resistance of the cervix, therefore, when extension of the neck should be used with caution.
Zoladex should be used in assisted reproduction only under the supervision of a specialist with experience in this field.
As with other LG-WG agonists, cases of ovarian hyperstimulation syndrome (ohss) due to the use of Zoladex 3.6 mg in combination with gonadotropin were reported. The stimulation cycle should be carefully monitored to determine which patients may be at risk of developing ohss. If there is a risk of OHS use of human chorionic gonadotropin (HCG), if possible, should be abolished.
It is recommended to use Zoladex with caution when fertilizing patients with polycystic ovary syndrome, since it is possible to stimulate a large number of follicles.
Women of reproductive age should use nonhormonal methods of contraception during therapy with Zoladex and to restore menstruation after treatment.
Need careful supervision of patients with established depression and patients with hypertension.
The use of Zoladex can lead to a positive reaction to the anti-doping test.
How to use the envelope
Apply only if the envelope with syringe applicator is intact. Apply immediately after opening the envelope.
Application during pregnancy and lactation
The Zoladex should not be used during pregnancy and lactation, as there is a theoretical risk of abortion or the occurrence of fetal abnormalities while receiving agonists of LH-RG pregnancy. It is necessary to conduct a thorough examination of women who may become pregnant in order to exclude the possibility of pregnancy.
During treatment should use nonhormonal methods of contraception until the resumption of menstruation.
Zoladex should not be used during pregnancy, since theoretically LH-RG agonists increase the risk of abortion or fetal malformations. Women of reproductive age should be thoroughly examined before starting treatment to avoid pregnancy. To restore menstruation during treatment should use non-hormonal methods of contraception (see Also caution regarding the time to recovery of menses in the section "peculiarities of use").
Before using Zoladex for fertilization treatment pregnancy should be excluded. When using Zoladex for this indication there is no clinical data indicating the existence of a causal link between Zoladex and any subsequent abnormalities of oocyte development, pregnancy or its outcome.
The use of Zoladex during the period of breast-feeding is not recommended.
For women: are analogues of LH-WP, as the Zoladex 3.6 mg and Zoladex 10.8 mg is intended to suppress LH and FSH. As a consequence, it can affect libido (see section "Adverse reactions") and lead to the termination of ovulation and menstruation, this implies a negative but reversible effect on the fertility of women. During treatment with GnRH analogues can naturally occur in menopause. Rarely in some women, menstruation is not restored after the termination of treatment. Studies on rats show that the impact on women's fertility is reversible.
For men: such analogues of LH-WP, as the Zoladex 3.6 mg and Zoladex 10.8 mg is intended to suppress LH and FSH. As a result, it can lead to erectile dysfunction and affect libido (see section "Adverse reactions"), as well as possibly spermatogenesis. Although data on fertility men is not based on the turnover effect on the fertility of rats and turnover histopathological changes of the reproductive system in dogs after a year of treatment Zoladex can hope that this effect in men the reverse.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms
There is no evidence that Zoladex can impair the ability to drive a car and other machinery.
Method of application and doses
1 capsule (3.6 mg) of Zoladex is subcutaneously injected into the anterior abdominal wall every 28 days. The duration of the drug Zoladeks cancer corrects the doctor individually for each patient.
For patients with renal or hepatic insufficiency, as well as in elderly patients dose adjustment is not necessary.
Zoladex 3.6 mg prescribe the desensitization of the pituitary gland, which is determined by the concentration of estradiol in serum and should respond to such an early follicular phase (approximately 150 pmol/l). This usually occurs between the 7th and 21st periods of the menstrual cycle. Superovulation (controlled ovarian stimulation) with gonadotropin starts when desensitization has already been achieved. Desensitization caused by the introduction of an agonist LG-RG (Zoladeksa) is stable, which in some cases may be necessary to increase the dose of gonadotropin. At the appropriate stage of follicle development, gonadotropin administration stops and human chorionic gonadotropin is subsequently injected to induce ovulation. Monitoring of treatment, procedures for the extraction of oocytes and fertilization should be carried out in accordance with the usual practice of each medical institution.
Endometriosis can be treated no more than 6 months, since clinical data on longer periods of use are not available. Repeated courses of treatment should not be carried out because of the risk of losing part of the mineral components and reducing bone density. It was demonstrated that in patients receiving Zoladex for endometriosis, additional hormone replacement therapy (daily intake of estrogen and progestogenic drugs) reduced the loss of bone mineral density and the severity of vasomotor symptoms.
For thinning of the endometrium the drug is administered for 4-8 weeks. The larger size of the uterus or the uncertainty of the time surgical intervention may be required the introduction of the second capsule.
of uterine fibroids
Women with anemia caused by uterine fibroma, Zoladex 3.6 mg in combination with iron preparations can be administered up to 3 months before surgery.
Manual for the introduction
1. Place the patient in a comfortable position so that the upper body is slightly raised. Treat the injection site on the anterior abdominal wall. If necessary, use a local anesthetic.
2. Open the envelope on the lines of arrows and remove the syringe applicator. In good light, check for the capsule in the syringe window.
3. Carefully remove (arrow) the plastic fuse from the piston. Remove the cap from the needle. Do not try to remove air bubbles from the syringe and needle, so as not to accidentally squeeze the capsule out of the syringe.
4. Thumb and index finger to create a fold of skin on the anterior abdominal wall below the umbilical line. Keep the syringe body, at a distance of 2 cm from the needle. The needle is inserted subcutaneously, at an acute angle (30-45 °), cut up to the skin, until the moment when the syringe body touches the patient's skin.
5. Do not insert the needle intravenously or intraperitoneally. Improper seizure of the needle and an incorrect angle of insertion are shown.
6. To enter the capsule and activate a protective mechanism, push down on the plunger until the very end. At this point, you can hear a click and feel that the protective mechanism automatically extends, closing the needle. The protective mechanism will not be activated if the piston is not pressed to the end.
7. Remove the syringe as shown in the figure. 5 and allow the safety mechanism to move until, until he fully closed the needle. Disposal of a used syringe method allowed for sharp objects.
Zoladex is not indicated for use in children.
The experience of overdose in humans is small. In the case of administration of Zoladex before the scheduled time or at a higher than expected dose, clinically significant side effects were observed. The results of animal studies do not indicate any effect other than therapeutic on the concentration of sex hormones and sexual pathways in the application of high doses of Zoladex. In case of overdose should be provided symptomatic treatment.
Frequency of adverse reactions was calculated according to the clinical study reports of the drug Zoladex post-marketing and communications. The most common adverse reactions were tides, sweating and reactions at the injection site.
The frequency of side effects are as follows: very often (?1/10), often (?1/100 and <1/10), infrequently (?1/1000 and <1/100), rarely (?1/10000 < 1/1000), very rarely (<1/10000) and unknown frequency (can not be set according to available data).
Table. Adverse reactions to Zoladex 3.6 mg for the classification of authorities on MedDRA.
Class of organo-frequency systems in Ukraine
Neoplasms of benign neoplasm: malignant neoplasm of uncertain or unspecified (including cyst and polyps)Of pituitary gland
unknown chastotnye of uterine fibroids
From the immune systemnatural hypersensitivity to preparecreate hypersensitivity to the drug
redlineproductions reactionaugmentin reaction
From the endocrine systemyour of reckonability in gipofibrinogenemia in the pituitary gland
On the part of metabolism and nutritional breakdown of glucose tolerance a
mental rasstrojjstvami customizeie libido libido bСнижение b
chastisement mood, depressionen mood, depression
Very recepcionista restrictedservices disorders
From the nervous of systemcacertificates
Compression of the spinal cord
cardiologic disorders upright insufficiency f , myocardial infarction f?
Neizvestnaya QT interval (see section "peculiarities of use" and "Interaction with other medicinal products and other forms of interaction")Prolongation of the QT interval (see section "peculiarities of use" and "Interaction with other medicinal products and other forms of interaction»)
vascular rasstrojjstvami castability bприливы b
customerwhen blood pressure narushenie blood pressure
The skin and subcutaneous Khatchatrian customersites bГипергидроз b , acne and
customizepage dВысыпания d , hair loss g
Neizvestnostj vysypanija d ,
Hair loss g
From the side of musculoskeletal system and connective danceschool bones e?
The kidneys and urinary systeminstallation mochetocnikov
From the reproductive system and mammary gland, frequent erectile dysfunction
? Breast exaggeration
part of the castor
rare ovarian Kist
Sindrom ovarian hyperstimulation (when used in combination with gonadotropins)
? Blood flow cancellation
General disorders and complications in place of weenyone casereccia in place of swedenergy at the injection site
casereccia in place of swedenergy at the injection site
? Magnification of tumor in volume, painful tumor
A deviation from the norm, revealed
in laboratory issledovaniyeyami bone density, weight gain telangana bone density, increasing of body mass
a decrease in glucose tolerance was observed in men taking agonists of LH-RG. This may occur as diabetes or loss of glycemic control in people with existing diabetes mellitus.
These pharmacological effects rarely require discontinuation of therapy.
c-Hypo or hypertension, sometimes noted in patients receiving Zoladex. Changes are usually temporary and pass or continuation of therapy or after discontinuation of the drug Zoladex. Occasionally, such changes required medical intervention, including the abolition of Zoladex.
d - are Usually small, often reduced without the need to stop.
e-first, patients with prostate cancer may feel a temporary increase in bone pain, in such cases resort to symptomatic treatment.
f-Observed in pharmacological and epidemiological studies of LG-RG agonists, which was used for the treatment of prostate cancer. The risk obviously increases with the use of the antiandrogens.
g - Loss of hair on the head was observed in women, including young age, treated for benign gynecological diseases. Usually this phenomenon is not reflected, but sometimes it can be difficult.
h - Particularly loss of body hair is an expected effect of snejanna levels of androgens.
and-in most cases, acne was observed within a month after the beginning of application.
Occasionally when using Zoladex had an anomalous blood test results cases of hepatic dysfunction, pulmonary embolism and interstitial pneumonia.
In women in the treatment of endometriosis and/or fiber occasionally noted hypercalcemia. In the case of symptoms of hypercalcemia (e.g., thirst) should be examined with a view to its elimination.
In addition, the following adverse reactions were reported in women who received funds for benign gynaecological conditions:
acne, body hair change in body, dry skin, weight gain, increased serum cholesterol, ovarian hyperstimulation syndrome (when used in combination with gonadotropins), vaginitis, vaginal discharge, nervousness, sleep disorders, fatigue, peripheral edema, myalgia, spasms of the calf muscles, nausea, vomiting, diarrhea, constipation, and complaints of abdominal organs, voice changes.
At the beginning of treatment, the signs and symptoms of the disease may temporarily increase, in this case, symptomatic treatment may be prescribed.
Occasionally, during treatment with LG-RG analogues in women menopause may occur and menstruation will not resume after completion of therapy. Or it is the influence of the drug Zoladeks, or a consequence of gynecological conditions of patients is unknown.
Occasionally in patients with metastatic breast cancer at the beginning of treatment hypercalcemia developed. In the presence of symptoms indicating hypercalcemia (eg, thirst), hypercalcemia should be excluded.
Apply only if the envelope with syringe applicator is intact.
Apply immediately after opening the envelope.
Store at a temperature not exceeding 25 ° C. Keep out of reach of children.
1 capsule in a syringe applicator with a protective mechanism; 1 syringe in an envelope with an attached annotation flag with a moisture-absorbing capsule; 1 envelope in a cardboard box.
Category home away from home
AstraZeneca UK limited/AstraZeneca UK Limited.
Manufacturer's location and address of the place of business
Silk road Business Park, Macclesfield, Cheshire, SK10 2NA, UK/
Silk Road Business Park, Macclesfield, Cheshire, SK10 2NA, United Kingdom.
DEPOSITARY THE ZOLADEX 3.6 MG
The Zoladex – a drug with marked anti-tumor effect. The medication is an analogue of gonadotropin-releasing hormone. The active component of the drug in its action is aimed at reducing the concentration of testosterone and estradiol in serum in women and men.
Indications for appointment
Zoladex is used in the treatment of:
Malignant tumors in the prostate region.
If necessary, carry out in vitro fertilization.
Fibroids of the uterus, malignant and benign formations in the uterine cavity.
Severity of endometriosis, amenable to hormonal treatment, including the need to terminate the endometrium before ablation or resection.
Cancerous tumors in the mammary glands in combination with chemotherapy.
How to apply
The drug has the form of capsules with prolonged action for subcutaneous injection into the abdominal wall. The active ingredient is active for 28 days after use. The duration of therapy and the number of capsules used is set by the attending physician and is used as standard for malignant tumors for a long time. In benign formations, the remedy is used for up to 6 months.