Goserelin-Vista implant 3.6 mg syringe applicator No. 1

Instructions for use Goserelin-Vista implant 3.6 mg syringe applicator No. 1

Composition

active ingredient: goserelin;

1 implant contains 4.10 mg of goserelin acetate, equivalent to 3.6 mg of goserelin; excipients: Resomer® RG 502H (poly(D,L-lactide-co-glycolide) 50:50;

Dosage form

Implant in pre-filled syringes.

Main physicochemical properties: implant visible in implant holder. Dimensions: length approx. 13 mm, width approx. 1.2 mm. Functionality: after actuation of the applicator, an undamaged cylindrical rod of white to off-white color emerges from the needle.

Pharmacotherapeutic group

Gonadotropin-releasing hormone analogues. ATX code L02A E03.

Pharmacological properties

Pharmacodynamics

Mechanism of action.

Goserelin (D-Ser(But)6 Azgly10 LH-RH) is a synthetic analogue of natural luteinizing hormone-releasing hormone (LH-RH). With continuous use, goserelin inhibits the secretion of LH by the pituitary gland, which leads to a decrease in serum testosterone concentrations in men and serum estradiol concentrations in women. This effect is reversible after discontinuation of therapy. In the initial stage, goserelin, like other LH-RH agonists, may cause a temporary increase in serum testosterone concentrations in men and serum estradiol concentrations in women.

In men, testosterone levels decrease to castration levels approximately 21 days after the first implant and remain low with continued administration of the drug every 28 days. This decrease in testosterone levels results in regression of the prostate tumor and symptomatic improvement in most patients.

In the treatment of patients with metastatic prostate cancer, goserelin has been shown in clinical trials to produce results similar to those of surgical castration.

In studies comparing bicalutamide 150 mg monotherapy and castration (mostly in the form of goserelin), there was no significant difference in overall survival between patients with locally advanced prostate cancer who received bicalutamide and those who received castration (hazard ratio = 1.05 [CI 0.81 to 1.36]). However, it is not possible to statistically compare the equivalence of the two treatments.

Goserelin has been reported to improve disease-free survival and overall survival when used as adjuvant therapy to radiotherapy in patients with localized risk (T1-T2 and PSA (prostate-specific antigen) at least 10 ng/mL or Gleason score 7) or locally advanced (T3-T4) prostate cancer. The optimal duration of adjuvant therapy has not been established; studies have shown that 3 years of adjuvant therapy with goserelin provides a significant improvement in survival compared with radiotherapy alone. Neoadjuvant therapy with goserelin plus radiotherapy has been shown to improve disease-free survival in patients with localized or locally advanced prostate cancer.

After prostatectomy in patients with metastatic prostate cancer, adjuvant drug therapy may improve disease-free survival, although there is no significant improvement in survival if patients are node-negative at surgery. Patients with locally advanced disease with a defined histopathological stage who have additional risk factors such as a PSA level of at least 10 ng/mL or a Gleason score of 7 prior to adjuvant drug therapy should undergo careful evaluation. There is no evidence of improved clinical outcomes with neoadjuvant goserelin therapy after radical prostatectomy.

In women, the concentration of estradiol in the blood serum also decreases by about the 21st day after the administration of the first capsule and with continuous treatment, i.e. with the administration of the drug every 28 days, remains reduced to a level comparable to that observed in postmenopausal women. This decrease has a positive effect in hormone-dependent forms of breast cancer, uterine fibroids, endometriosis and suppression of ovarian follicle development. It also causes thinning of the endometrium and the occurrence of amenorrhea in most patients.

During treatment with LR-RG analogues, some women may experience menopause. Occasionally, menstruation does not resume after cessation of therapy.

Goserelin in combination with iron has been shown to induce amenorrhea, increase hemoglobin levels, and improve relevant hematological parameters compared with iron therapy alone. This combination resulted in a mean hemoglobin concentration 1 g/dL higher than that achieved with iron therapy alone.

Goserelin has almost complete bioavailability. The introduction of the implant every 4 weeks ensures the maintenance of effective concentrations. Cumulation in tissues does not occur. Goserelin is poorly bound to protein, and its half-life from serum is 2-4 hours in patients with normal renal function. The half-life increases in patients with impaired renal function. With monthly administration of the drug, this change will not have significant consequences, so there is no need to change the dose for patients with impaired renal function. No significant changes in pharmacokinetic parameters are observed in patients with hepatic insufficiency.

Indication

Prostate cancer.

Treatment of prostate cancer in the following cases:

– treatment of metastatic prostate cancer – the use of goserelin had a favorable effect on survival, similar to the effect of surgical castration;

– treatment of locally advanced prostate cancer as an alternative to surgical castration – the use of goserelin had a favorable effect on survival, similar to the effect of antiandrogen use;

– as adjuvant therapy to radiotherapy for patients with high-risk localized or locally advanced prostate cancer – the use of goserelin improved disease-free survival and overall survival;

– as neoadjuvant therapy preceding radiotherapy for patients with high-risk localized or locally advanced prostate cancer – the use of goserelin improved disease-free survival;

– as adjuvant therapy to radical prostatectomy for patients with locally advanced prostate cancer and high risk of disease progression – goserelin improved disease-free survival. Breast cancer. Treatment of advanced hormone-sensitive breast cancer in pre- and perimenopausal women.

As an alternative to chemotherapy as part of standard treatment for pre/perimenopausal women with estrogen receptor-positive early breast cancer. Endometriosis. Relieves symptoms, including pain, and reduces the size and number of endometrial lesions.

Endometrial thinning. For preliminary thinning of the endometrium before its ablation or resection.

Uterine fibroids. In combination with iron therapy - to improve the hematological status of patients with anemia with fibroids before surgery. In in vitro fertilization. Desensitization of the pituitary gland in preparation for superovulation stimulation.

Contraindication

Hypersensitivity to the active substance or to any of the excipients.

Pregnancy or breastfeeding.

Childhood.

Interaction with other medicinal products and other types of interactions

Since androgen deprivation therapy may prolong the QT interval, the concomitant use of goserelin with medicinal products known to prolong the QT interval or medicinal products known to induce torsades de pointes, such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmics, methadone, moxifloxacin, antipsychotic medicinal products should be carefully considered (see section 4.4).

Application features

There is a high risk of developing depression (which may be severe) in patients treated with gonadotropin-releasing hormone agonists such as goserelin. Patients should be informed of this and provided with appropriate treatment if symptoms occur.

Androgen deprivation therapy may lead to prolongation of the QT interval.

Before prescribing goserelin to patients with a history of QT prolongation or risk factors for QT prolongation, or to patients taking concomitant medications that may prolong the QT interval (see section 4.5), physicians should assess the benefit-risk ratio, including the potential for torsades de pointes.

Injection site reactions, including pain, haematoma, haemorrhage and vascular injury, have been reported with goserelin. Patients with such reactions should be monitored for signs or symptoms of abdominal bleeding. In very rare cases, administration errors have resulted in vascular injury and haemorrhagic shock requiring blood transfusion and surgery. Particular caution should be exercised when administering the medicinal product to patients with a low body mass index (BMI) and/or those receiving full anticoagulation (see section 4.2).

Goserelin should be used with caution in men at risk of developing urinary tract obstruction or spinal cord compression, and such patients should be closely monitored during the first month of therapy. If spinal cord compression or renal failure due to urinary tract obstruction is present or develops, standard treatment for these complications should be used.

Antiandrogens should be considered during the initial period of treatment with LH-GH analogues (e.g. cyproterone acetate 300 mg/day for 3 days before and for 3 weeks after goserelin administration), as this has been reported to prevent the possible consequences of the initial increase in serum testosterone levels.

Patients with non-hormonal prostate cancer are unlikely to benefit from this treatment. This resistance to treatment may be the result of a lack of response to castration or hormonal treatment.

Recommended dosage of testosterone therapy before treatment initiation to allow assessment of therapeutic benefit.

The use of LH-GH agonists may result in a decrease in bone mineral density. Preliminary data suggest that the use of bisphosphonates in addition to LH-GH agonists may reduce bone mineral loss in men. Particular caution should be exercised in patients with additional risk factors for osteoporosis (chronic alcohol abuse, smoking, long-term therapy with anticonvulsants or corticosteroids, family history of osteoporosis).

Mood changes, including depression, have been reported. Patients with established depression and patients with hypertension require close monitoring.

There is a high risk of hypotension (which may be serious) in patients treated with LH-GH agonists such as goserelin. Patients should be informed of this and treated appropriately if symptoms occur.

In a pharmacoepidemiological study of LH-GH agonists used to treat prostate cancer, cases of myocardial infarction and heart failure were observed.

The risk is increased when the drug is used in combination with antiandrogens. Decreased glucose tolerance has been observed in men using LH-RG agonists. This may manifest as diabetes mellitus or loss of glycemic control in individuals with pre-existing diabetes mellitus. Therefore, blood glucose levels should be monitored.

Women.

Breast cancer as an indication.

Decreased bone mineral density.

The use of LH-GH agonists may result in a decrease in bone mineral density. After 2 years of treatment for early breast cancer, the average decrease in bone mineral density at the femoral neck and lumbar spine in women was 6.2% and 11.5%, respectively. These losses have been shown to be partially reversible: one year after stopping treatment, the loss of bone mineral density at the femoral neck and lumbar spine was 3.4% and 6.4% less, respectively, than before the drug was used, although data on bone mass recovery are very limited. According to the available data, bone mass is recovered in most women after stopping treatment.

Preliminary data suggest that the use of goserelin in combination with tamoxifen in breast cancer patients may reduce bone mineral loss.

Benign conditions as indications.

Loss of bone mineral density.

LH-GH agonists can cause an average decrease in bone mineral density of 1% over 6 months of treatment. Each 10% decrease in bone mineral density increases the risk of fracture by approximately 2-3 times. According to available data, bone mass is restored in most women after discontinuation of treatment.

In patients taking goserelin for the treatment of endometriosis, additional hormone replacement therapy attenuated the decrease in bone mineral density and the severity of vasomotor symptoms.

There are 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, long-term therapy with drugs that reduce bone mineral density, such as anticonvulsants or corticosteroids, family history of osteoporosis, eating disorders, such as anorexia nervosa). Since the decrease in bone mineral density in such patients may be more dangerous, the appropriateness of the use of goserelin should be assessed on a case-by-case basis and therapy should be initiated only if the benefit outweighs the risk. Additional measures to counteract bone mineral loss should be taken.

Withdrawal bleeding.

At the beginning of the use of goserelin, some patients may experience vaginal bleeding of varying duration and intensity. This bleeding usually occurs within the first month after the start of treatment, which is probably a reaction to the withdrawal of estrogen, and resolves on its own. If the bleeding persists, its cause should be established.

The use of goserelin may lead to increased cervical resistance, so caution should be exercised when dilating the cervix.

Goserelin should only be used in assisted reproduction under the supervision of a specialist with experience in this field.

As with other LH-GH agonists, cases of ovarian hyperstimulation syndrome (OHSS) have been reported with the use of goserelin 3.6 mg in combination with gonadotropin. The stimulation cycle should be carefully monitored to identify patients at risk of developing OHSS. If there is a risk of OHSS, it is recommended that human chorionic gonadotropin (hCG) be discontinued.

Goserelin should be used with caution in fertility treatments for patients with polycystic ovary syndrome, as stimulation of a large number of follicles may occur.

Women of reproductive age should use non-hormonal methods of contraception during treatment with goserelin and until menstruation resumes after treatment is completed.

Close supervision is required for patients with established depression and patients with hypertension.

The use of goserelin may cause a positive reaction to an anti-doping test.

Use during pregnancy or breastfeeding

Goserelin should not be used during pregnancy because there is a theoretical risk of miscarriage or intrauterine malformations when LH-RH agonists are used during pregnancy. Women of childbearing potential should be carefully examined to exclude the possibility of pregnancy.

During treatment, non-hormonal methods of contraception should be used until menstruation resumes (see also the caveat regarding the time required for menstruation to resume in the section "Special instructions").

Pregnancy should be excluded before using goserelin. There are no clinical data to suggest a causal relationship between the use of goserelin and any subsequent abnormality of oocyte development, pregnancy or its outcome.

The use of goserelin during breast-feeding is not recommended. Menopause may occur naturally during treatment with GnRH analogues. Rarely, some women do not resume menstruation after stopping treatment.

Ability to influence reaction speed when driving vehicles or other mechanisms

The drug has no or negligible effect on the reaction rate when driving or operating other mechanisms.

Method of administration and doses

Caution should be exercised when administering Goserelin-Vista into the anterior abdominal wall due to the proximity of the inferior epigastric artery and its branches.

Particular caution should be exercised when administering the drug to patients with low BMI or those receiving anticoagulants (see section "Special warnings and precautions for use").

Care should be taken to ensure that the injection is performed subcutaneously according to the method described in the administration instructions. Do not inject the drug into blood vessels, muscle or the abdominal cavity.

If surgical removal of the goserelin implant is necessary, its location can be determined using ultrasound.

Adults.

One implant of the drug Goserelin-Vista 3.6 mg should be injected subcutaneously into the anterior abdominal wall every 28 days.

There is no need to adjust the dose for patients with renal or hepatic insufficiency, as well as for elderly patients.

In vitro fertilization.

Goserelin-Vista 3.6 mg is prescribed for pituitary desensitization therapy, which is determined by serum estradiol levels and should correspond to those in the early follicular phase (approximately 150 pmol/l). This usually occurs between the 7th and 21st days of the menstrual cycle.

Superovulation (controlled ovarian stimulation) with gonadotropin should be initiated when desensitization has been achieved. Desensitization induced by the introduction of an agonist implant is more persistent, which may require an increase in the dose of gonadotropin in some cases. At the appropriate stage of follicular development, gonadotropin administration is discontinued and human chorionic gonadotropin (hCG) should be administered to induce ovulation. Treatment monitoring, egg retrieval and fertilization procedures should be carried out according to the usual practice of each medical institution. Endometriosis should be treated for only 6 months, as there are currently no clinical data on longer periods of use. Repeated courses of treatment should not be carried out due to the risk of decreased bone mineral density. It has been demonstrated that in patients receiving goserelin for the treatment of endometriosis, additional hormone replacement therapy (daily estrogen and progestin) reduced bone mineral density loss and the severity of vasomotor symptoms.

For endometrial thinning, the drug is prescribed for 4 or 8 weeks of treatment. In case of large uterus or uncertainty about the timing of surgical intervention, a second capsule may be required.

In women with anemia caused by uterine fibroids, Goserelin-Vista 3.6 mg in combination with iron preparations can be administered 3 months before surgery. Instructions for administration.

Use as directed by the prescribing physician. Special caution should be exercised when using goserelin in patients with low BMI and/or those receiving medications for complete anticoagulation (see section "Special warnings and precautions for use").

Instructions for use.

Use only if the sachet with the syringe applicator is intact. Use immediately after opening the sachet.

Local anesthesia is permitted, but is not required in most cases. Dispose of the syringe in a sharps container. The following information is intended for healthcare professionals only.

Goserelin-Vista is administered by subcutaneous injection. Please read the instructions below before use.

1. Place the patient in a comfortable position with the upper body slightly elevated. Prepare the injection site according to current guidelines.

NOTE: Caution should be exercised when administering the drug into the anterior abdominal wall due to the proximity of the inferior epigastric artery and its branches; very thin patients are at increased risk of vascular injury.

Figure 1.

Inspect the sterile packaging and syringe applicator for damage. Remove the syringe from the sterile packaging. Hold the syringe applicator at a slight angle to the light. Make sure that the Goserelin-Vista implant is at least partially visible. Remove the protective ring.

Figure 2.

Take the syringe applicator by the body and remove the protective cap.

Unlike liquid injections, there is no need to remove air bubbles—trying to do so could dislodge the Goserelin-Vista implant.

Figure 3.

Pinch the patient's skin with two fingers, simultaneously grasping the syringe body, and insert the needle obliquely (almost parallel to the skin).

Insert the needle into the subcutaneous tissue (not into the muscle or the abdominal cavity) of the anterior abdominal wall below the navel line deep until the body of the syringe applicator touches the patient's skin.

This contact with the skin must remain throughout the entire implant insertion process!

NOTE: The Goserelin-Vista syringe applicator should not be used for aspiration. If the injection needle penetrates a major vessel, blood will be immediately visible in the syringe chamber. In the event of a vessel puncture, the needle should be removed, any bleeding resulting from the puncture should be stopped immediately, and the patient should be observed for signs or symptoms of abdominal bleeding. Once the patient is hemodynamically stable, another Goserelin-Vista implant may be administered using a new syringe at a different site. Particular caution should be exercised when administering the drug to patients with low BMI and those receiving full doses of anticoagulants.

Figure 4.

Press the plunger. When pressed, the subcutaneous implant moves from the holder to the tip of the needle.

Never pull the syringe back. When inserting the subcutaneous implant, the syringe applicator body must touch the patient's skin!

Figure 5.

When the piston reaches its final position, the automatic needle retraction system will operate and the piston will lock the implant in the subcutaneous tissue.

Figure 6.

The needle is withdrawn from the patient's tissue into the polymer body of the syringe applicator. The syringe body must remain in contact with the patient's skin. Typically, the forward movement of the piston and the withdrawal of the needle are performed in one smooth motion.

Figure 7.

The subcutaneous implant insertion process is complete. The needle is fully retracted into the syringe body.

The protective coating on the syringe applicator body prevents damage from the needle tip.

Figure 8.

Close the protective cap again.

Do not insert the needle into a muscle or the abdominal cavity.

Throw away the syringe in a sharps container.

NOTE: If the implant needs to be surgically removed, although this is unlikely, its location can be determined using an ultrasound scan.

Children.

The drug is not used in children, as the safety and effectiveness of use in this category of patients have not been established.

Overdose

Symptoms. There is little experience of overdose in humans. No clinically significant adverse effects have been observed when goserelin is administered earlier than the scheduled time or in a dose higher than the prescribed dose. Animal studies do not indicate any effect other than therapeutic on the concentration of sex hormones and the reproductive tract when higher doses of goserelin are used.

Treatment: In case of overdose, symptomatic treatment should be provided.

Adverse reactions

The frequency of adverse reactions was calculated from clinical trial reports and post-marketing reports. The most common adverse reactions were flushing, sweating and injection site reactions.

The frequency of adverse events is as follows: very common (≥ 1/10), common (≥ 1/100 to

a Impaired glucose tolerance has been reported in men treated with LH-GH agonists. This may present as diabetes mellitus or loss of glycaemic control in individuals with pre-existing diabetes mellitus.

b These pharmacological effects rarely require discontinuation of therapy. Hyperhidrosis and hot flashes may persist after discontinuation of goserelin.

c Hypotension or hypertension has occasionally been reported in patients treated with goserelin. The changes are usually transient and resolve either with continued therapy or after discontinuation of goserelin. Occasionally, these changes have required medical intervention, including discontinuation of goserelin.

d Usually minor, often resolves without the need to discontinue treatment.

e Initially, patients with prostate cancer may experience a temporary increase in bone pain - in such cases, symptomatic treatment may be prescribed.

f Observed in pharmacoepidemiological studies of LH-GH agonists used for the treatment of prostate cancer. The risk appears to be increased when used with antiandrogens.

g In particular, loss of body hair is an expected effect of reduced androgen levels.

h Hair loss on the scalp has been observed in women, including young women, treated for benign gynecological conditions. It is usually mild but can sometimes be severe.

and In most cases, acne was observed within a month of starting use.

When using goserelin, the following are possible: impaired liver function and the development of jaundice with increased levels of alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase; increased levels of lactate dehydrogenase, alkaline phosphatase, triglycerides; nosebleeds, urticaria, itching.

Also, when using the drug, the following may be observed: from the urinary system - dysuria, increased blood urea nitrogen, increased creatinine, proteinuria; from the blood system - anemia, leukopenia, thrombocytopenia.

During the use of goserelin, reactions at the injection site (bleeding, hematoma, abscess, induration, pain) and bleeding around the injection site may occur, leading to hemorrhagic shock.

Abnormal blood test results, hepatic dysfunction, pulmonary embolism and interstitial pneumonia have been reported rarely with goserelin. Hypercalcemia has been reported rarely in women treated for endometriosis and/or fibroids. If symptoms of hypercalcemia (e.g. thirst) occur, an examination should be performed to rule it out.

In addition, the following adverse reactions have been observed in women receiving the drug for benign gynecological conditions: acne, changes in body hair, 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, calf muscle spasms, nausea, vomiting, diarrhea, constipation, abdominal disorders, and voice changes.

At the beginning of treatment, the symptoms of the disease may temporarily worsen - in this case, symptomatic treatment may be prescribed.

Occasionally, during treatment with LH-RG analogues, women may experience menopause and menstruation may not resume after cessation of therapy. Whether this is due to the effects of goserelin or to the patient's underlying gynecological conditions is unknown.

Reporting of suspected adverse reactions.

Reporting adverse reactions after registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of a medicinal product to the State Expert Center of the Ministry of Health of Ukraine at the link: https://aisf.dec.gov.ua

Expiration date

4 years.

Use only if the sachet with the syringe applicator is intact.

Use immediately after opening the sachet.

Storage conditions

Store in the original packaging at a temperature not exceeding 30 ° C. Keep out of the reach of children.

Packaging

1 implant in a syringe-applicator (the syringe-applicator consists of a polymer body with an implant holder, needle and piston). 1 syringe in a sachet together with a desiccant capsule. 1 or 3 sachets in a cardboard box.

Vacation category

According to the recipe.

Producer

AMW GmbH

Location of the manufacturer and address of its place of business

Birkerfeld 11, Warngau, Bayern, 83627, Germany