Zoladex (gozerelin) capsules for subcutaneous use 3.6 mg. №1 in the syringe applicator

Description

Zoladex (gozerelin) capsules for subcutaneous use 3.6 mg. №1 in the syringe applicator

Composition

active substance: 1 capsule for subcutaneous prolonged action contains goserelin acetate equivalent to 3.6 mg of goserelin-based;

Excipients: copolymer of lactide and glycolide.

Dosage form

Capsule for subcutaneous prolonged action.

Main physical and chemical properties: pieces of solid polymer of cylindrical shape from white to cream color.

Pharmacotherapeutic group

Gonadotropin-releasing hormone analogues.

ATX code L02A E03.

Pharmacological properties

Zoladex 3.6 (D-Ser (But) 6 Azgly10 LH-RG) is a synthetic analogue of natural luteinizing hormone – releasing hormone (LH-RG). With constant use, Zoladex inhibits the secretion of LH by the pituitary gland, which leads to a decrease in the concentration of testosterone in the serum of men and the concentration of estradiol in the serum of women. This effect is reversible after discontinuation of therapy. In the early stages, Zoladex, like other LH-RG agonists, may cause a temporary increase in serum testosterone levels in men and serum estradiol levels in women.

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

In comparative clinical trials in the treatment of metastatic prostate cancer, Zoladex 3.6 showed survival results similar to the effect of surgical castration.

In a combined analysis of 2 randomized controlled trials comparing 150 mg bicalutamide monotherapy and castration (mostly Zoladex 3.6), there was no significant difference in overall survival between bicalutamide-treated prostate cancer patients and patients. in the form of castration (relative risk = 1.05 [confidence interval (CI) from 0.81 to 1.36]). However, the equivalence of the two treatments cannot be estimated statistically.

In comparative studies, Zoladex 3.6 improved relapse-free and overall survival during adjuvant therapy before radiation therapy in patients with high-risk localized prostate cancer (T1 – T2 and PSA) (prostate-specific antigen) at at least 10 ng / ml. or a score of 7 on the Gleason scale) or locally advanced (T3-T4) prostate cancer. The optimal duration of adjuvant therapy has not been established; A comparative study showed that adjuvant therapy with Zoladex for 3 years significantly increased survival compared to radiation therapy alone. The use of Zoladex as a neoadjuvant therapy improved the recurrence rate in patients with localized high-risk prostate cancer or locally advanced prostate cancer compared with radiation therapy.

Following prostatectomy in patients with prostate cancer, adjuvant Zoladex therapy may improve relapse-free survival, although there is no significant improvement in survival if patients did not have lymph nodes during surgery. Patients with locally advanced histopathological disease who have additional risk factors, such as a PSA level of at least 10 ng / ml or a Gleason score of 7 before the Zoladex adjuvant therapy, should be closely monitored. There is no evidence of improved clinical outcomes due to neoadjuvant Zoladex therapy after radical prostatectomy.

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

Patients may experience menopause during treatment with LH-RG analogues. In rare cases, some women do not resume menstruation after treatment.

Zoladex in combination with iron supplements has been shown to cause amenorrhea, which leads to increased hemoglobin levels and improved hematological parameters in women with uterine fibroids and concomitant anemia. This combination will give an additional 10 g / dl increase in hemoglobin concentration compared to iron-only therapy.

Indication

• Prostate cancer
  Treatment of prostate cancer in the following cases:
  treatment of metastatic prostate cancer – the use of Zoladex had a beneficial 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 Zoladex had a beneficial effect on survival, similar to the effect of antiandrogen use;
  as adjuvant therapy to radiation therapy in patients with localized high-risk prostate cancer or locally advanced prostate cancer – Zoladex improved non-disease survival and overall survival;
  as neoadjuvant therapy prior to radiation therapy in patients with high-risk localized prostate cancer or locally advanced prostate cancer, Zoladex improved no-disease survival;
  as an adjuvant therapy for radical prostatectomy in patients with locally advanced prostate cancer and a high risk of disease progression, Zoladex improved no-show survival.
• Breast cancer. Treatment of common hormone-sensitive breast cancer in pre- and perimenopausal women.
  As an alternative to chemotherapy as part of standard treatment of pre / perimenopausal women with estrogen receptor (ER) positive early breast cancer.
• Endometriosis. Relieves symptoms including pain, reduced size and amount of endometrial damage.
• Thinning of the endometrium. For pre-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 the stimulation of superovulation.

Contraindication:

• hypersensitivity to the active substance or to any of the excipients;
• pregnancy or breastfeeding;
• children’s age.

Method of application and dosage

Zoladex should be administered with caution to the anterior abdominal wall due to the proximity of the inferior epigastric artery and its branches.

Particular caution should be exercised when using Zoladex in patients with low BMI or those receiving anticoagulants.

Care should be taken to ensure that the injection is performed subcutaneously according to the procedure described in the instructions for administration. Do not inject into blood vessels, muscles or the abdomen.

If it is necessary to surgically remove the Zoladex capsule, its location can be determined by ultrasound.

Adults

One capsule of Zoladex 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
Zoladex 3.6 mg should be used for pituitary desensitization therapy, which is determined by serum estradiol levels and should correspond to that in the early follicular phase (approximately 150 pmol / l). This usually occurs between the 7th and 21st day of the menstrual cycle.

• Superovulation (controlled ovarian stimulation) with gonadotropin is started when desensitization has already been achieved. Desensitization caused by the administration of an agonist capsule is more persistent, so in some cases it may be necessary to increase the dose of gonadotropin. At the appropriate stage of follicle development, the administration of gonadotropin is stopped and further human chorionic gonadotropin (HCG) is administered to induce ovulation. Monitoring of treatment, egg collection and fertilization procedures should be performed in accordance with the usual practice of each medical institution.
• Endometriosis should be treated for only six months, as there are currently no clinical data on longer periods of use. Repeated courses of treatment should not be performed due to the risk of reduced bone mineral density. In patients receiving Zoladex for endometriosis, additional hormone replacement therapy (daily estrogen and progestogen) has been shown to reduce bone loss and severe vasomotor symptoms.
• To thin the endometrium, the drug should be prescribed for four or eight weeks of treatment. If the uterus is large or the timing of the surgery is uncertain, a second capsule may be needed.

Uterine fibroids
In women with anemia caused by uterine fibroids, Zoladex 3.6 mg in combination with iron supplements can be given three months before surgery.

Instructions for use

Use only if the syringe-applicator envelope is undamaged. Apply immediately after opening the envelope.

Dispose of the syringe with special sharps containers.

The following information is intended exclusively for healthcare professionals or healthcare professionals:

Zoladex is given by subcutaneous injection. Read the following instructions before use.

• Arrange the patient in a comfortable position so that the upper body is slightly raised. Prepare the injection site according to current recommendations.                                                                                                                                                                                                    NOTE. Caution should be exercised when administering Zoladex to 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 damage.
• Inspect the foil envelope and syringe for damage. Get the syringe out of the open foil envelope. Keep the syringe at a slight angle to the light. Make sure that the Zoladex capsule is visible at least partially.
• Pulling the plastic safety tab, separate it from the syringe and discard. Remove the protective cap from the needle. Unlike liquid injections, you do not need to remove air bubbles – you can move the Zoladex capsule if you try to do so.
• Holding the syringe by the protective case and following the rules of asepsis, pinch the patient’s skin and insert the needle at a small angle (30-45 °) to the skin. Holding the needle with the hole facing up, insert the needle into the subcutaneous tissue of the anterior abdominal wall below the navel line so that the protective case touches the patient’s skin.                                                                    NOTE. The Zoladex syringe should not be used for aspiration. If the injection needle penetrates a large vessel, the blood will be immediately visible in the chamber of the syringe. In the event of a puncture, the needle should be removed, the puncture bleeding should be stopped immediately, and the patient should be observed for signs or symptoms of abdominal bleeding. After making sure that the patient is hemodynamically stable, you can inject another Zoladex capsule with a new syringe into another part of the body. Special care should be taken when using the drug in patients with low BMI and / or those receiving treatment with full doses of anticoagulants.
• Do not insert the needle into a muscle or abdomen.
• Push the syringe plunger all the way in to insert the capsule and activate the protective mechanism. You will hear a click and feel the protective case automatically start to shift to close the needle. If the piston is not fully depressed, the protective case is not activated.  NOTE. The needle is not retracted.
• Holding the syringe, remove the needle and allow the protective case to close completely. Discard the syringe in a special container for sharp objects.                                                                                                                                                                                                                    NOTE. If it is necessary to remove the capsule surgically, but this is unlikely, its location can be determined by ultrasound scanning.

Children

Zoladex is not indicated for use in children, as safety and efficacy have not been established in this patient group.

Overdose

There are insufficient data on human overdose. No clinically relevant adverse reactions were observed when Zoladex was administered at the scheduled time or at a higher than prescribed dose. The results of animal studies do not indicate any effect, other than therapeutic, on the concentration of sex hormones and the genital tract when using higher doses of Zoladex. In case of overdose, symptomatic treatment should be provided.

Side effects:

• metabolic and nutritional disorders – impaired glucose tolerance;
• mental disorders – decreased libido, mood swings, depression;
• disorders of the nervous system – paresthesia, spinal cord compression;
• cardiac disorders – heart failure, myocardial infarction, vascular disorders, arterial pressure disorders;
• disorders of the skin and subcutaneous tissue – hyperhidrosis, acne, rashes, hair loss;
• disorders of the musculoskeletal system and connective tissue – bone pain;
• disorders of the reproductive system and breast – erectile dysfunction, vulvovaginal dryness, breast enlargement, gynecomastia.