Goserelin-Vista implant 10.8 mg syringe applicator No. 1

Instructions for use Goserelin-Vista implant 10.8 mg syringe applicator No. 1

Composition

active ingredient: goserelin;

1 implant contains 12.50 mg of goserelin acetate, equivalent to 10.8 mg of goserelin; excipients: Resomer® R202H poly(D,L-lactide), Resomer® RG752H (poly(D,L-lactide-co-glycolide) 75:25.

Dosage form

Implant in pre-filled syringes.

Main physicochemical properties: implant visible in implant holder. Dimensions: length approx. 20 mm, width approx. 1.5 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

Goserelin (D-Ser (But)6 Azgly10LH-RH) is a synthetic analogue of natural luteinizing hormone-releasing hormone (LH-RH). With continuous use, goserelin 10.8 mg inhibits the secretion of luteinizing hormone by the pituitary gland, which leads to a decrease in serum testosterone concentrations in men and estradiol in women. At the initial stage, goserelin 10.8 mg, like other LH-RH agonists, may cause a temporary increase in serum testosterone concentrations in men and estradiol in women.

By approximately 21 days after the first injection, testosterone levels in men have fallen to castrate levels and remain low with continued administration every 12 weeks. Evidence suggests that, unless re-administration of goserelin occurs in exceptional circumstances after 3 months, testosterone levels remain at castrate levels in most patients for up to 16 weeks. In studies of metastatic prostate cancer, goserelin has shown survival results similar to those of surgical castration.

In studies comparing bicalutamide 150 mg monotherapy with castration (mainly in the form of goserelin), there was no significant difference in overall survival between patients with prostate cancer who received bicalutamide and those who received castration (relative risk = 1.05 [CI 0.81 to 1.36]). However, the equivalence of the two treatments could not be assessed statistically. In comparative trials, goserelin improved relapse-free survival and overall survival in the adjuvant setting before radiotherapy in patients with high-risk localized (T1-T2 and PSA (prostate-specific antigen) at least 10 ng/mL or 7 Gleason score) or locally advanced (T3-T4) prostate cancer. The optimal duration of adjuvant therapy has not been established: a comparative trial has shown that three years of adjuvant therapy with goserelin shows a significant improvement in survival compared with radiotherapy alone. Neoadjuvant therapy before radiotherapy has shown an improvement in relapse-free survival in patients with high-risk localized or locally advanced prostate cancer.

After prostatectomy in patients with metastatic prostate cancer, adjuvant goserelin therapy may improve disease-free survival, although there is no significant improvement in survival if patients have no lymph nodes at the time of surgery. Patients with locally advanced disease at the pathological stage have additional risk factors, such as a PSA level of at least 10 ng/mL or

Gleason score 7 should be carefully evaluated before adjuvant goserelin therapy. There is no evidence of improved clinical outcomes with neoadjuvant goserelin therapy after radical prostatectomy.

In women, serum estradiol concentrations decrease within 4 weeks after the first implant and remain decreased until the end of the treatment period. In patients whose estradiol levels are already decreased by LH-RG analogues, concentrations remain decreased when switched to goserelin 10.8 mg. Estradiol suppression is accompanied by a response in patients with endometriosis or uterine fibroids and results in amenorrhea in the majority of patients.

At the beginning of the use of goserelin, some women may experience vaginal bleeding of varying duration and intensity. Such bleeding is likely to be a reaction to the withdrawal of estrogen and usually resolves on its own.

During treatment with LH-RG analogues, patients may experience natural menopause; in rare cases, menstruation does not resume after treatment is completed.

Pharmacokinetics

Administration of 10.8 mg of goserelin every 12 weeks provides stable exposure without clinically significant accumulation. Goserelin is poorly bound to blood proteins and has a serum half-life of 2 to 4 hours in patients with normal renal function. In patients with renal impairment, the half-life is increased. When the drug is administered as an implant at 10.8 mg every 12 weeks, this change does not lead to accumulation and no dose adjustment is required for such patients. No significant changes in pharmacokinetics have been observed in patients with hepatic impairment.

Indication

Prostate cancer. Use for the treatment of prostate cancer, in which hormonal effects are possible.

Endometriosis: Used for the treatment of endometriosis, including relief of symptoms such as pain and reduction of the size and number of endometrial lesions.

Uterine fibroids. Use for the treatment of fibroids, including reducing damage, improving hematological status, and alleviating symptoms such as pain. As an adjunct to surgery to facilitate surgical technique and reduce blood loss during surgery.

Breast cancer in premenopausal women.

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

Injection site lesions, including pain, haematoma, haemorrhage and vascular injury, have been reported with goserelin. Patients with such lesions 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 goserelin to patients with a low body mass index (BMI) and/or those receiving full anticoagulation (see section 4.2).

There are no data on implant removal or dissolution.

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

Cases of bleeding around the injection site leading to hemorrhagic shock have been reported.

Therefore, injections should be made in an area with a lower probability of vascular damage. The use of goserelin in patients with a tendency to bleeding (for example, those taking anticoagulants) should also be carefully considered. 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 Interactions with other medicinal products and other forms of interaction), the benefit-risk balance should be assessed, including the possibility of torsades de pointes.

Men.

Goserelin 10.8 mg 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 secondary to urinary tract obstruction is present or develops, standard treatment for such complications should be used. Antiandrogens should be considered during the initial period of treatment with LH-RG 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 rise in serum testosterone levels. Patients with non-hormone-dependent 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 therapy.

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

Use of LH-GH agonists may result in decreased bone mineral density. Preliminary evidence suggests 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 treatment with anticonvulsants or corticosteroids, family history of osteoporosis). Patients with established depression and patients with hypertension require close monitoring.

In a pharmacoepidemiological study of LH-GH agonists used for the treatment of prostate cancer, cases of myocardial infarction and heart failure were observed. The risk is increased when goserelin is used in combination with antiandrogens.

Impaired glucose tolerance has been reported in men treated with LH-GH agonists. This may manifest as diabetes or loss of glycemic control in individuals with pre-existing diabetes. Monitoring of blood glucose levels should be considered.

Women.

In the case of breast cancer in premenopausal women, the hormone receptor status of the tumor should be determined before initiating the use of Goserelin-Vista 10.8 mg. If the disease is found to be receptor-negative, Goserelin-Vista 10.8 mg implant should not be used.

After starting therapy with LH-RG agonists, a temporary increase in blood estradiol levels is observed in women.

Decreased bone mineral density.

The use of LH-GH agonists can lead to a decrease in bone mineral density of approximately 1% per month during the 6-month treatment period. Each 10% decrease in bone mineral density increases the risk of fracture 2-3-fold.

Existing evidence suggests that in most women, bone density recovers after discontinuation of goserelin.

In patients taking goserelin for the treatment of endometriosis, additional hormone replacement therapy (HRT) attenuated the decrease in bone mineral density and the severity of vasomotor symptoms. There is no experience with the use of HRT in women taking goserelin 10.8 mg.

There are no specific data on the use of goserelin in patients with established osteoporosis or risk factors for its development (such as chronic alcohol abuse, smoking, long-term treatment with medicinal products that reduce bone mineral density, e.g. anticonvulsants or corticosteroids, family history of osteoporosis, eating disorders, e.g. anorexia nervosa). Since the reduction in bone mineral density may be more dangerous in such patients, the use of goserelin should be considered on a case-by-case basis and treatment should only be initiated if, after careful assessment, the benefits outweigh the risks. Additional measures to counteract bone mineral loss should be taken.

Decreased bone mineral density during treatment of breast cancer in women.

The use of GnRH (gonadotropin-releasing hormone) agonists may cause a decrease in bone mineral density. After 2 years of treatment for early breast cancer, the mean bone mineral density loss was 6.2% and 11.5% at the hip and lumbar spine, respectively. This loss was found to be partially reversible, with a recovery of 3.4% and 6.4% from baseline at the hip and lumbar spine, respectively, during a one-year follow-up without treatment, although this recovery is based on very limited data. For most women, the data available to date suggest that recovery of bone loss occurs after cessation of treatment.

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

Withdrawal bleeding.

At the beginning of the use of goserelin, some patients may experience vaginal bleeding of varying duration and intensity. Usually, such bleeding occurs in the first month after the start of treatment, which is probably a reaction to estrogen withdrawal, and usually resolves on its own. If the bleeding does not resolve, its cause should be established. The time to the resumption of menstruation after discontinuation of drug therapy may be prolonged in some cases (the average duration of secondary amenorrhea after discontinuation of goserelin 10.8 mg is 7-8 months). If rapid resumption of menstruation is required, goserelin 3.6 mg is recommended.

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

There are no clinical data on the effect of using goserelin for the treatment of benign gynecological conditions for more than 6 months.

Women of childbearing potential should use non-hormonal methods of contraception during treatment with goserelin and until menstruation resumes after treatment is completed. Patients with established depression and hypertension should be closely monitored.

The use of goserelin may result in a positive reaction in an anti-doping test. There is a high risk of excessive 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.

Use during pregnancy or breastfeeding

Goserelin should not be used during pregnancy or breastfeeding, as there is a theoretical risk of miscarriage or foetal abnormalities if 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.

Fertility.

For women, LH-RG analogues such as Goserelin-Vista 3.6 mg and Goserelin-Vista 10.8 mg are intended to suppress LH and FSH. As a result, this may affect libido (see section 4.8) and cause cessation of ovulation and menstruation, with a negative but reversible effect on female fertility. During treatment with GnRH analogues, menopause may occur naturally. Rarely, some women do not resume menstruation after discontinuation of treatment. Studies in rats show that the effect on female fertility is reversible.

For men: LH-RG analogues such as Goserelin-Vista 3.6 mg and Goserelin-Vista are designed to suppress LH and FSH. As a result, this may cause erectile dysfunction and affect libido (see section 4.8) and possibly spermatogenesis. Although there are no data on the effects on male fertility, based on the reversibility of the effects on fertility in rats and the reversibility of histopathological changes in the reproductive system in dogs after one year of treatment with goserelin, it is expected that such effects in men are reversible.

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").

Local anesthesia is permitted, but is not required in most cases. Adult males (including elderly patients).

1 implant (10.8 mg) of the drug Goserelin-Vista should be injected subcutaneously into the anterior abdominal wall every 12 weeks.

Adult women (including elderly patients).

1 implant (10.8 mg) of the drug Goserelin-Vista should be injected subcutaneously into the anterior abdominal wall every 12 weeks.

Endometriosis and uterine fibroids: treatment should only last 6 months, as clinical data on longer periods of use are lacking.

Repeated courses of treatment should not be carried out due to the risk of loss of some mineral components and a decrease in bone density.

In patients taking goserelin for the treatment of endometriosis, additional hormone replacement therapy (daily estrogen and progestin medications) reduced bone mineral density loss and the severity of vasomotor symptoms.

There is no experience with the use of hormone replacement therapy in women receiving goserelin at a dosage of 10.8 mg.

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

Instructions for introduction.

Use according to the recommendations of the doctor who prescribed the medicine.

Care should be taken to ensure that the injection is given subcutaneously, following the procedure described in the instructions for administration. Do not inject into blood vessels, muscle or the abdominal cavity.

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 using a sharps container. The following information is intended for medical or 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 Goserelin-Vista into the anterior abdominal wall due to the proximity of the inferior epigastric artery and its branches; very thin patients may be 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. Ensure 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 – attempting to do so may dislodge the Goserelin-Vista implant.

Figure 3

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 goserelin to patients with low BMI and/or 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 barrel.

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, which is unlikely, its location can be determined using an ultrasound scan.

Children.

The drug should not be used in children, as the safety and effectiveness of use in this age group 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 effects 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.

Post-marketing experience.

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