Decapeptyl

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DECAPEPTYL (DECAPEPTYL)

Composition:

Active substance: triptorelin acetate;

1 syringe with 1 ml of solution contains 100 mcg of triptorelin acetate, equivalent to 95.6 mcg of free triptorelin;

Excipients: sodium chloride, glacial acetic acid, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group. Gonadotropin-releasing hormone analogs.

ATC code L02A E04.

Pharmacological properties.

Pharmacodynamics.

Triptorelin is a synthetic decapeptide and analogue of the natural hypothalamic gonadotropin-releasing hormone (GnRH). Triptorelin has a longer duration of action than natural GnRH and exhibits a biphasic effect at the pituitary level. Following an initial strong surge in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations (the "flare-up" effect), serum levels of LH and FSH decrease due to desensitization of pituitary GnRH receptors, resulting in significant suppression of gonadal function. The exact duration of action of Decapeptyl has not been fully established, but pituitary suppression persists for at least 6 days after the last administration. After discontinuation of Decapeptyl, a further decline in serum LH levels is expected, with LH levels returning to baseline values approximately 2 weeks later.

Pituitary suppression with Decapeptyl can prevent the LH surge and thereby avoid premature ovulation and/or luteinization of follicles. Treatment with a GnRH agonist helps reduce the frequency of cycle cancellations and increases the pregnancy rate in assisted reproductive technology (ART) cycles.

Pharmacokinetics.

Pharmacokinetic data indicate that after subcutaneous administration of Decapeptyl, the systemic bioavailability of triptorelin is approximately 100%. The elimination half-life of triptorelin is about 3–5 hours, indicating that triptorelin will be cleared from the body within 24 hours and will therefore be absent from the circulation at the time of embryo transfer. Metabolism, resulting in simpler peptides and amino acids, occurs mainly in the liver and kidneys. Triptorelin is primarily excreted in urine.

Clinical studies indicate that the risk of triptorelin accumulation in patients with severe hepatic or renal impairment is negligible (the elimination half-life in such patients is approximately 8 hours).

Clinical characteristics.

Indications.

• Prevention of premature increase in luteinizing hormone (LH) levels in women undergoing controlled ovarian hyperstimulation within assisted reproductive technologies (ART).

Contraindications.

Decapeptyl is contraindicated in the following cases:

• Hypersensitivity to the active substance or to any of the excipients;
• Hypersensitivity to gonadotropin-releasing hormone (GnRH) or to any other GnRH analogue;
• Pregnancy or breastfeeding period.

Interaction with other medicinal products and other forms of interaction.

Triptorelin should be used with great caution together with agents affecting pituitary gonadotropin secretion; in such cases, monitoring of the patient's hormonal status is recommended.

The possibility of interactions with commonly used medicinal products, including histamine-releasing agents, cannot be excluded.

Special precautions for use.

Decreased bone mineral density

Administration of GnRH agonists may lead to a decrease in bone mineral density by an average of 1% per month during the first 6 months of treatment. Each 10% reduction in bone mineral density is associated with a 2–3-fold increased risk of fracture. The drug should be used with particular caution in patients with additional risk factors for osteoporosis (e.g., chronic alcohol abuse, smoking, long-term therapy with drugs that reduce bone mineral density such as anticonvulsants or corticosteroids, family history of osteoporosis, nutritional disorders, anorexia nervosa).

Available data indicate that in most women, bone mass recovers after discontinuation of treatment.

Since decreased bone mineral density may be more hazardous in patients with additional risk factors for osteoporosis, the decision to treat with triptorelin should be carefully considered on an individual basis, and therapy should only be initiated if, after thorough evaluation, the benefits are judged to outweigh the risks. Additional measures to counteract bone mineral loss should be implemented.

Before initiating triptorelin, pregnancy must be excluded in female patients.

In rare cases, therapy with GnRH agonists may reveal a previously undiagnosed gonadotroph adenoma of the pituitary gland. In such patients, pituitary apoplexy may develop, characterized by sudden headache, vomiting, visual disturbances, and ophthalmoplegia.

Patients receiving therapy with GnRH agonists such as triptorelin have an increased risk of developing depressive disorders (which may be severe). Patients should be informed about this risk, and appropriate treatment should be initiated if such symptoms occur.

Cases of mood changes, including depression, have been reported. Patients with a history of depression should be closely monitored during treatment.

Ovarian stimulation must be performed under strict medical supervision.

In patients with impaired renal or hepatic function, the terminal half-life of triptorelin is 7–8 hours, compared to 3–5 hours in healthy individuals. Despite this prolonged action, triptorelin is expected to be cleared from the circulation by the time of embryo transfer.

The drug should be used with particular caution in women with signs and symptoms of active allergic conditions or a known predisposition to allergic reactions in their medical history. Decapeptyl is not recommended for use in women with a history of severe allergic conditions. Women of reproductive age should be carefully examined before initiating treatment to exclude the possibility of pregnancy.

Hormonal therapy is associated with an increased risk of multiple pregnancies, fetal loss during pregnancy, ectopic pregnancy, and congenital malformations. These risks persist when Decapeptyl is used as an adjunctive therapy during controlled ovarian hyperstimulation. Administration of Decapeptyl during controlled ovarian hyperstim游戏副本

Method of Administration and Dosage

Treatment with Decapeptyl should be initiated under the supervision of a physician experienced in the management of female infertility. Decapeptyl is intended for subcutaneous injection once daily into the lower abdominal wall. After the first injection, patients should be observed for 30 minutes to detect symptoms of possible allergic/pseudoallergic reactions to the injection. Appropriate facilities and emergency treatment measures should be available in case such reactions occur. Subsequent injections may be self-administered by patients, provided they have received proper instructions from their physician regarding signs and symptoms indicating hypersensitivity reactions, the consequences of such reactions, and the need for immediate medical intervention. To prevent lipoatrophy, the injection site should be rotated regularly.

Treatment may be initiated either at the beginning of the follicular phase (day 2 or 3 of the menstrual cycle) or in the mid-luteal phase (day 21–23 of the menstrual cycle, or 5–7 days before the expected onset of menstruation). Controlled ovarian hyperstimulation with gonadotropins should be started approximately 2–4 weeks after initiation of Decapeptyl therapy. Ovarian response should be monitored using methods including either ultrasound examination of the ovaries alone, or preferably in combination with estradiol concentration measurements, and gonadotropin dosage should be adjusted as necessary. Once a sufficient number of follicles have reached adequate size, Decapeptyl and gonadotropin treatment should be discontinued, and a single injection of human chorionic gonadotropin (hCG) should be administered to induce final follicular maturation. If there is no evidence of treatment efficacy after 4 weeks—defined either by ultrasound confirmation of endometrial shedding, or preferably by ultrasound combined with estradiol concentration measurements—the continuation of Decapeptyl therapy should be reconsidered. The total duration of treatment is usually between 4 and 7 weeks. When using Decapeptyl, luteal phase support should be provided according to approved treatment protocols.

Patients with renal or hepatic impairment do not require dose adjustment.

Children. Not to be used in children.

Overdose.

Overdose may result in a prolonged duration of drug action. In case of overdose, Decapeptyl treatment should be (temporarily) discontinued.

No adverse reactions due to overdose have been reported.

Adverse Reactions

The adverse reactions listed below were frequently reported (≥ 2%) during clinical trials in patients treated with Decapeptyl, both prior to and concomitantly with gonadotropins. The most commonly reported adverse reactions are headache (27%), vaginal bleeding/spotting (24%), abdominal pain (15%), injection site inflammation (12%), and nausea (10%).

Flushing of varying intensity, from mild to severe, and hyperhidrosis may occur, which usually do not require discontinuation of treatment.

At the beginning of Decapeptyl treatment, administration of the drug in combination with gonadotropins may lead to the development of ovarian hyperstimulation syndrome. In such cases, ovarian enlargement, dyspnea, and pelvic and/or abdominal pain may be observed. Genital bleeding, including menorrhagia and metrorrhagia, may also occur at the beginning of Decapeptyl treatment.

Ovarian cysts have been reported in isolated cases (1%) during the initial phase of Decapeptyl treatment.

During treatment with triptorelin, certain adverse reactions reflect the general picture of hypoestrogenic conditions associated with pituitary-ovarian blockade, such as sleep disturbances, headache, mood changes, vulvovaginal dryness, dyspareunia, and decreased libido.

During Decapeptyl treatment, breast pain, muscle spasms, arthralgia, weight gain, nausea, abdominal pain, abdominal discomfort, asthenia, blurred vision, and visual disturbances may occur.

Localized or generalized allergic reactions have been reported after Decapeptyl injection.

Adverse reactions are categorized by frequency as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), frequency not known.

Infections and infestations: common – upper respiratory tract infection, pharyngitis.

Immune system disorders: frequency not known – hypersensitivity reactions.

Psychiatric disorders: uncommon – mood alterations, depression; frequency not known – sleep disturbances, decreased libido.

Nervous system disorders: very common – headache; common – dizziness.

Eye disorders: frequency not known – visual disturbances, blurred vision.

Vascular disorders: common – flushing.

Respiratory, thoracic and mediastinal disorders: frequency not known – dyspnea.

Gastrointestinal disorders: very common – abdominal pain, nausea; common – bloating, vomiting; frequency not known – abdominal discomfort.

Skin and subcutaneous tissue disorders: frequency not known – hyperhidrosis, pruritus, rash, angioneurotic edema, urticaria.

Musculoskeletal and connective tissue disorders: common – back pain; frequency not known – muscle spasms, arthralgia.

Pregnancy, puerperium and perinatal conditions: common – miscarriage.

Reproductive system and breast disorders: very common – vaginal bleeding; common – pelvic pain, ovarian hyperstimulation syndrome, dysmenorrhea, ovarian cyst; frequency not known – ovarian enlargement, menorrhagia, metrorrhagia, vulvovaginal dryness, dyspareunia, breast pain.

General disorders and administration site conditions: very common – injection site inflammation; common – injection site pain, injection site reaction, fatigue, influenza-like illness; frequency not known – asthenia, injection site erythema.

Investigations: frequency not known – weight gain.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging, protected from light and out of reach of children, at a temperature of +2 to +8 °C. Do not freeze.

Incompatibilities.

Due to lack of compatibility studies, the drug should not be mixed with other medicinal products.

Packaging.

1 ml of solution in a pre-filled syringe; 7 syringes in a blister pack; 1 blister pack in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

Ferring GmbH, Germany.

Manufacturer's name and address of the place of business.

Wittland 11, 24109 Kiel, Germany.