Frexil

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FRELSY® (FRELSY)

Composition:

Active substance: fondaparinux sodium;

1 syringe (0.5 ml) contains: fondaparinux sodium – 2.5 mg;

Excipients: sodium chloride, 1 M hydrochloric acid solution, 1 M sodium hydroxide solution, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical characteristics: clear, colorless or slightly yellowish liquid.

Pharmacotherapeutic group. Antithrombotic agents. ATC code B01A X05.

Pharmacological Properties

Pharmacodynamics

Fondaparinux is a synthetic selective inhibitor of activated factor X (Xa). The antithrombotic activity of fondaparinux results from selective inhibition of factor Xa, mediated through antithrombin III (AT III). By selectively binding to AT III, fondaparinux enhances (approximately 300-fold) the initial neutralization of factor Xa by antithrombin III. Neutralization of factor Xa interrupts the blood coagulation cascade and inhibits both thrombin generation and thrombus formation. The drug does not inactivate thrombin (activated factor II) and has no effect on platelets.

At a dose of 2.5 mg, fondaparinux does not affect results of standard coagulation tests such as activated partial thromboplastin time (aPTT), activated clotting time (ACT), or prothrombin time (PT)/international normalized ratio (INR) in plasma, nor does it alter bleeding time or fibrinolytic activity. However, isolated reports of increased aPTT have been reported.

Fondaparinux does not cross-react with serum from patients with heparin-induced thrombocytopenia.

Pharmacokinetics

Absorption.

After subcutaneous administration, the drug is rapidly and completely absorbed (absolute bioavailability – 100%). Following a single subcutaneous dose of 2.5 mg fondaparinux administered to young healthy volunteers, maximum plasma concentration (mean Cmax = 0.34 mg/L) was reached within 2 hours after dosing. A plasma concentration equal to half of the aforementioned maximum concentration was achieved within 25 minutes after administration.

In elderly healthy volunteers, the pharmacokinetics of fondaparinux are linear over the dose range of 2–8 mg subcutaneously. With once-daily subcutaneous administration, steady-state plasma concentration is achieved within 3–4 days, with a 1.3-fold increase in Cmax and AUC (area under the curve).

Mean (coefficient of variation – CV, %) pharmacokinetic parameters at steady state in patients who underwent hip surgery and received fondaparinux 2.5 mg once daily were: Cmax – 0.39 mg/L (31%), Tmax – 2.8 hours (18%), and Cmin – 0.14 mg/L (56%). In elderly patients undergoing surgery for hip fracture, steady-state concentrations were: Cmax – 0.50 mg/L (32%), Cmin – 0.19 mg/L (58%).

Distribution.

The volume of distribution is limited, ranging from 7 to 11 L. In vitro, fondaparinux binds extensively and specifically to the protein AT III, with binding degree dependent on drug concentration in plasma (from 98.6% to 97.0% over a concentration range of 0.5 to 2 mg/L). Binding to other plasma proteins, including platelet factor 4, is negligible.

Since fondaparinux does not significantly bind to plasma proteins other than antithrombin III, interactions with other medicinal products via protein-binding displacement are not expected.

Metabolism.

Although a complete assessment has not been performed, there is no evidence of fondaparinux metabolism or formation of active metabolites.

Fondaparinux does not inhibit the cytochrome CYP450 enzyme system (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4) in vitro. Therefore, interactions with other medicinal products via inhibition of CYP-mediated metabolism are not expected in vivo.

Elimination.

Fondaparinux is primarily excreted unchanged by the kidneys, accounting for 64–77% in healthy volunteers. The elimination half-life (T1/2) is approximately 17 hours in young healthy volunteers and about 21 hours in healthy elderly volunteers.

Special Patient Populations.

Renal Impairment.

Compared to patients with normal renal function (creatinine clearance > 80 mL/min), plasma clearance is 1.2–1.4 times lower in patients with mild renal impairment (creatinine clearance 50–80 mL/min) and on average 2 times lower in patients with moderate renal impairment (creatinine clearance 30–50 mL/min). In patients with severe renal impairment (creatinine clearance < 30 mL/min), plasma clearance is approximately 5 times lower than in those with normal renal function. Corresponding terminal half-lives were 29 hours in moderate and 72 hours in severe renal insufficiency. A similar relationship between fondaparinux clearance and severity of renal impairment was observed in patients treated for deep vein thrombosis.

Hepatic Impairment.

Based on pharmacokinetic data, the concentration of unbound fondaparinux is expected to remain unchanged in patients with mild to moderate hepatic impairment, and therefore dose adjustment is not required. After a single subcutaneous dose of fondaparinux in patients with moderate hepatic impairment (Child–Pugh class B), Cmax and AUC of total (bound and unbound) fondaparinux were reduced by 22% and 39%, respectively, compared to patients with normal liver function. The lower plasma concentration of fondaparinux is explained by reduced binding to AT III, as plasma concentrations of AT III are lower in patients with hepatic impairment. As a result, renal clearance of fondaparinux is increased.

Fondaparinux pharmacokinetics have not been studied in patients with severe hepatic impairment (see "Dosage and Administration" and "Special Warnings and Precautions for Use").

Pediatric Population.

The use of fondaparinux in children for prevention of venous thromboembolism or for treatment of superficial venous thrombosis or acute coronary syndrome (ACS) has not been studied in this population.

Elderly Patients.

Renal function may decline with age; therefore, elimination of fondaparinux may be impaired in patients aged 75 years and older. After orthopedic surgery, total clearance of fondaparinux was approximately 1.2–1.4 times lower in patients aged 75 years and older compared to those under 65 years. A similar relationship between drug clearance and age was observed in patients treated for deep vein thrombosis.

Gender.

No differences in pharmacokinetics between male and female patients were observed after dose adjustment for body weight.

Race.

No dedicated pharmacokinetic studies assessing racial differences have been conducted. However, studies in healthy Mongoloid volunteers showed no differences in pharmacokinetic profile compared to healthy Caucasian volunteers. No differences in plasma clearance of the drug were observed between African and Caucasian patients undergoing orthopedic surgery.

Body Weight.

Plasma clearance of fondaparinux increases with increasing body weight (by 9% per 10 kg increase in body weight).

Clinical characteristics.

Indications.

Prevention of venous thromboembolism in patients after major orthopedic surgeries on the lower limbs, including hip fracture (including extended prophylaxis), and after hip and knee replacement surgeries.

Prevention of venous thromboembolism in patients after abdominal surgeries who are at high risk of thromboembolic complications, for example, patients undergoing abdominal surgery due to oncological disease.

Prevention of venous thromboembolism in patients at high risk of such complications due to prolonged immobilization during the acute phase of illness, such as heart failure and/or acute respiratory disorders, and/or acute infectious or inflammatory diseases.

Treatment of unstable angina or myocardial infarction without ST-segment elevation in patients for whom urgent (< 120 minutes) invasive intervention (percutaneous coronary intervention – PCI) is not indicated (see "Special precautions for use").

Treatment of ST-segment elevation myocardial infarction in patients treated with thrombolytics, or in those who did not initially receive other forms of reperfusion therapy.

Contraindications.

Known hypersensitivity to the active substance or to any of the excipients of the medicinal product. Active clinically significant bleeding. Acute bacterial endocarditis. Severe renal impairment (creatinine clearance < 20 mL/min).

Interaction with other medicinal products and other forms of interaction.

Medicinal products that may increase the risk of bleeding should not be used concomitantly with Fraxiparine®, except for vitamin K antagonists used for the treatment of venous thromboembolism (see "Special precautions for use"). If such concomitant use is necessary, it should be carried out under close monitoring.

Clinical studies with fondaparinux have demonstrated that its concomitant use with oral anticoagulants (warfarin), antiplatelet agents (acetylsalicylic acid), nonsteroidal anti-inflammatory drugs (piroxicam), and cardiac glycosides (digoxin) does not significantly affect the pharmacokinetics of fondaparinux. The dose of fondaparinux (10 mg) used in interaction studies exceeded the dose recommended for use according to current indications.

Furthermore, the drug did not affect either the anticoagulant activity of warfarin (measured by international normalized ratio – INR), or bleeding time during treatment with acetylsalicylic acid or piroxicam, or the pharmacokinetics of digoxin at steady state.

Subsequent therapy with other anticoagulants. If subsequent treatment with heparin or low-molecular-weight heparin is required, the first injection should generally be administered 1 day after the last injection of fondaparinux.

If subsequent treatment with a vitamin K antagonist is required, therapy with fondaparinux should be continued until the target INR value is achieved.

Special precautions for use.

Frelsi® should not be administered intramuscularly.

Percutaneous coronary intervention and risk of catheter thrombosis.

Frelsi® is not recommended for use before and during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction. Frelsi® should not be used as the sole anticoagulant before and during non-primary PCI in patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI) who are at high risk and require urgent revascularization. These patients include those with refractory or recurrent angina associated with dynamic ST-segment changes, heart failure, life-threatening arrhythmias, or hemodynamic instability.

In patients with UA/NSTEMI or ST-segment elevation myocardial infarction (STEMI) undergoing non-primary PCI, the use of fondaparinux as the sole anticoagulant during PCI is not recommended due to an increased risk of catheter thrombosis. Therefore, during non-primary PCI, unfractionated heparin should be additionally administered according to standard clinical practice (see dosing information in section "Dosage and administration").

Bleeding.

Like other anticoagulants, Frelsi® should be used with caution in patients at increased risk of bleeding, including those with congenital or acquired bleeding disorders (e.g., thrombocytopenia < 50,000/mm³), active peptic ulcer disease, recent intracranial hemorrhage, recent neurosurgery or spinal surgery, recent ophthalmologic surgery, and patients in special populations as described below.

Prevention of venous thromboembolism.

Medicinal products that may increase the risk of bleeding should not be used concomitantly with fondaparinux. These include desirudin, fibrinolytic agents, GP IIb/IIIa receptor antagonists, heparin, heparinoids, and low-molecular-weight heparins (LMWH). Medicinal products that may increase bleeding risk should not be used concomitantly with Frelsi®, except for vitamin K antagonists used for the treatment of venous thromboembolism. If concomitant use of a vitamin K antagonist is necessary, refer to the information provided in the section "Interaction with other medicinal products and other forms of interaction". Other antiplatelet agents (acetylsalicylic acid, dipyridamole, sulfinpyrazone, ticlopidine, or clopidogrel) and nonsteroidal anti-inflammatory drugs (NSAIDs) should be used with caution. If such concomitant use is required, it should be performed under close monitoring.

Unstable angina/non-ST-segment elevation myocardial infarction and ST-segment elevation myocardial infarction.

Frelsi® should be used with caution in patients who are concomitantly receiving other medicinal products that increase bleeding risk, such as GP IIb/IIIa receptor antagonists or thrombolytics.

Epidural anesthesia/spinal puncture.

The concomitant use of Frelsi® with epidural or spinal anesthesia or lumbar puncture in patients undergoing major orthopedic surgery carries a risk of epidural or spinal hematomas, which may result in long-term or permanent paralysis. The risk of such rare events increases with the use of postoperative indwelling epidural catheters or concomitant administration of other medicinal products affecting hemostasis.

Elderly patients.

The risk of bleeding is higher in elderly patients compared to younger patients. Since renal function generally declines with age, the elimination of fondaparinux may be reduced and drug exposure increased in elderly patients (see "Pharmacological properties. Pharmacokinetics"). Therefore, Frelsi® should be used with caution in elderly patients (see "Dosage and administration").

Low body weight.

Prevention of venous thromboembolism and treatment of unstable angina/NSTEMI and STEMI.

Patients with body weight below 50 kg have an increased risk of bleeding. The clearance of fondaparinux decreases with lower body weight. Frelsi® should be used with caution in such patients (see "Dosage and administration").

Renal impairment.

Fondaparinux is predominantly eliminated via the kidneys.

Prevention of venous thromboembolism. Patients with creatinine clearance < 50 ml/min are at increased risk of bleeding and venous thromboembolism and should be treated with caution (see "Dosage and administration", "Contraindications", and "Pharmacological properties. Pharmacokinetics"). Clinical data in patients with creatinine clearance below 30 ml/min are limited.

Unstable angina/NSTEMI and STEMI.

Clinical data on the use of fondaparinux 2.5 mg once daily for the treatment of unstable angina, NSTEMI, and STEMI in patients with creatinine clearance between 20–30 ml/min are limited. Therefore, the decision to use fondaparinux should be based on an individual assessment of the benefit-risk ratio (see "Dosage and administration" and "Contraindications").

Severe hepatic impairment.

Prevention of venous thromboembolism and treatment of unstable angina/NSTEMI and STEMI. Dose adjustment of fondaparinux is not required. However, the drug should be used with caution due to an increased risk of bleeding associated with coagulation factor deficiencies in patients with severe hepatic impairment (see "Dosage and administration").

Heparin-induced thrombocytopenia.

Fondaparinux does not bind to platelet factor 4 and does not cross-react with serum from patients with heparin-induced type II thrombocytopenia. Frelsi® should be used with caution in patients with a history of heparin-induced thrombocytopenia. The efficacy and safety of Frelsi® in patients with heparin-induced type II thrombocytopenia have not been established. Isolated cases of heparin-induced thrombocytopenia have been reported in patients receiving fondaparinux. A causal relationship between Frelsi® treatment and the occurrence of heparin-induced thrombocytopenia has not been established.

This medicinal product contains less than 1 mmol sodium (less than 23 mg), i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding.

Pregnancy.

Clinical experience with the use of this medicinal product in pregnant women is currently limited. Animal studies are insufficient to determine effects on pregnancy, embryofetal development, parturition, and postnatal development due to limited exposure. Therefore, Frelsi® should not be administered during pregnancy unless the expected benefit outweighs the potential risk to the fetus.

Breastfeeding.

Fondaparinux is excreted in rat milk, but it is unknown whether the drug passes into human breast milk. Breastfeeding is not recommended during treatment with this medicinal product. However, oral absorption of the drug by the infant is unlikely.

Fertility.

There are no data on the effects of fondaparinux on human fertility. No effects on fertility were observed in animal studies.

Ability to influence the speed of reactions when driving or operating machinery.

Studies on the effect of the medicinal product on the ability to drive vehicles or operate machinery have not been conducted, but the possibility of adverse reactions affecting the nervous system should be considered.

Administration and Dosage.

Method of Administration.

Frelcsi® is intended for subcutaneous or intravenous injection. Do not administer intramuscularly.

Subcutaneous Injection.

When administering Frelcsi® as a deep subcutaneous injection, the patient should be in a lying position. Injection sites should alternate between the left and right anterolateral or left and right posterolateral abdominal wall. To avoid loss of medication, do not expel the air bubble from a prefilled syringe before injection. The needle should be inserted fully at a perpendicular angle into a skin fold pinched between the thumb and index finger; the skin fold must remain pinched throughout the injection.

Frelcsi® is intended for use only under medical supervision.

Subcutaneous injection should be administered in the same manner as with a conventional syringe.

Intravenous Injection (only the first dose in treatment of patients with ST-segment elevation myocardial infarction).

Administer intravenously through an existing intravenous line either undiluted or diluted in a small volume (25 or 50 ml) of 0.9% sodium chloride solution. To avoid loss of medication, do not expel the air bubble from a prefilled syringe before injection. After injection, flush the intravenous line or catheter thoroughly with 0.9% sodium chloride solution to ensure complete delivery of the drug. If Frelcsi® is diluted in 0.9% sodium chloride solution, administration should be completed within 1–2 minutes.

Before administration, visually inspect the injectable solution for the presence of visible particles or discoloration.

Any unused medication or materials must be disposed of according to applicable regulations.

Prevention of Venous Thromboembolism.

Major Orthopedic and Abdominal Surgery.

The recommended dose of Frelcsi® for adults is 2.5 mg once daily after surgery, administered as a subcutaneous injection.

The initial dose should be administered no earlier than 6 hours after completion of surgery, provided hemostasis has been achieved.

Treatment should continue until the risk of thromboembolism has decreased, typically until the patient is discharged to outpatient care, for no less than 5–9 days after surgery. Clinical experience shows that patients undergoing hip fracture surgery remain at risk for venous thromboembolism for more than 9 days. In such patients, additional prophylactic treatment with Frelcsi® is recommended for up to 24 days.

Patients at High Risk of Thromboembolic Complications Based on Individual Risk Assessment.

The recommended dose of Frelcsi® is 2.5 mg once daily as a subcutaneous injection. The duration of treatment in such cases is 6 to 14 days.

Unstable Angina/Non–ST-Segment Elevation Myocardial Infarction.

The recommended dose of Frelcsi® is 2.5 mg once daily as a subcutaneous injection. Treatment should be initiated as soon as possible after diagnosis and continued for up to 8 days or until hospital discharge, whichever occurs earlier.

For patients undergoing percutaneous coronary intervention during Frelcsi® treatment, unfractionated heparin should be used during the procedure, taking into account the potential risk of bleeding, including the time elapsed since the last dose of fondaparinux (see "Special Warnings and Precautions for Use"). The timing for resuming subcutaneous administration of Frelcsi® after catheter removal should be based on the patient's clinical condition. In a clinical trial on unstable angina/non–ST-segment elevation myocardial infarction, resumption of Frelcsi® treatment was initiated no sooner than 2 hours after catheter removal.

ST-Segment Elevation Myocardial Infarction.

The recommended dose of Frelcsi® is 2.5 mg once daily. The first dose of Frelcsi® should be administered intravenously, and subsequent doses via subcutaneous injection. Treatment should be initiated as soon as possible after diagnosis and continued for up to 8 days or until hospital discharge, whichever occurs earlier.

For patients undergoing non-primary percutaneous coronary intervention during Frelcsi® treatment, unfractionated heparin should be used during the procedure, taking into account the potential risk of bleeding, including the time elapsed since the last dose of fondaparinux (see "Special Warnings and Precautions for Use"). The timing for resuming subcutaneous administration of fondaparinux after catheter removal should be based on the patient's clinical condition. In a clinical trial on unstable angina/ST-segment elevation myocardial infarction, resumption of Frelcsi® treatment was initiated no sooner than 3 hours after catheter removal.

Patients Scheduled for Coronary Artery Bypass Grafting (CABG).

In patients with ST-segment elevation myocardial infarction or unstable angina/non–ST-segment elevation myocardial infarction scheduled for coronary artery bypass grafting (CABG), fondaparinux should not be administered, if possible, within 24 hours prior to surgery, and its administration may be resumed 48 hours after surgery.

Special Patient Populations.

Children.

The safety and efficacy of fondaparinux in children have not been established.

Prevention of Venous Thromboembolism After Surgery.

In surgical patients aged ≥75 years and/or with body weight <50 kg and/or with renal impairment (creatinine clearance 20–50 ml/min), strict adherence to the timing of the first fondaparinux injection is required.

The first dose of fondaparinux should be administered no earlier than 6 hours after surgical wound closure. Injection should not be performed before hemostasis is achieved (see "Special Warnings and Precautions for Use").

Elderly Patients (75 Years and Older).

Frelcsi® should be used with caution in elderly patients due to age-related decline in renal function (see "Special Warnings and Precautions for Use").

Patients with Body Weight Less Than 50 kg.

Prevention of Venous Thromboembolism and Treatment of Unstable Angina/Non–ST-Segment Elevation Myocardial Infarction and ST-Segment Elevation Myocardial Infarction.

Patients with body weight less than 50 kg have an increased risk of bleeding. Fondaparinux clearance decreases with lower body weight. Fondaparinux should be used with caution in such patients (see "Special Warnings and Precautions for Use").

Renal Impairment.

Prevention of Venous Thromboembolism. No dose adjustment is required in patients with mild renal impairment (creatinine clearance >50 ml/min).

For patients with creatinine clearance of 20–50 ml/min, a dose of 1.5 mg once daily is recommended as prescribed by a physician (see "Special Warnings and Precautions for Use" and "Pharmacological Properties. Pharmacokinetics").

Frelcsi® is not recommended for patients with creatinine clearance below 20 ml/min.

Unstable Angina/Non–ST-Segment Elevation Myocardial Infarction and ST-Segment Elevation Myocardial Infarction.

Frelcsi® is contraindicated in patients with creatinine clearance less than 20 ml/min (see "Contraindications"). Dose adjustment is not required for patients with creatinine clearance of 20 ml/min or higher.

Hepatic Impairment.

Prevention of Venous Thromboembolism and Treatment of Unstable Angina/Non–ST-Segment Elevation Myocardial Infarction and ST-Segment Elevation Myocardial Infarction. Dose adjustment is not required in patients with mild to moderate hepatic impairment. Frelcsi® should be used with caution in patients with severe hepatic impairment, as this patient group has not been studied (see "Special Warnings and Precautions for Use" and "Pharmacological Properties. Pharmacokinetics").

Children.

The safety and efficacy of Frelcsi® in children have not been established.

Overdose.

Exceeding the recommended doses of Frelcsi® may increase the risk of bleeding. There is no known antidote for fondaparinux.

In cases of overdose associated with hemorrhagic complications, treatment should be discontinued and the underlying cause of bleeding investigated. Consideration should be given to appropriate therapeutic measures such as surgical hemostasis, blood volume replacement, transfusion of fresh frozen plasma, or plasmapheresis.

Adverse reactions

The most frequently reported serious adverse reactions with fondaparinux are hemorrhagic complications (at various sites, including rare cases of intracranial/intracerebral and retroperitoneal bleeding) and anemia. Fondaparinux should be used with caution in patients with an increased risk of bleeding (see "Special precautions").

The safety of fondaparinux at a dose of 2.5 mg has been studied in patient populations:

• after major orthopedic surgery of the lower limbs, treated for up to 9 days;
• after hip fracture surgery, treated for 3 weeks following an initial 1-week prophylaxis;
• after abdominal surgery, treated for up to 9 days;
• at risk of thromboembolic complications, treated for up to 14 days;
• receiving treatment for acute coronary syndrome presenting as unstable angina or myocardial infarction without ST-segment elevation;
• receiving treatment for acute coronary syndrome presenting as myocardial infarction with ST-segment elevation.

The adverse reactions listed below are presented by organ systems and frequency of occurrence. Frequency is classified as very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), and very rare (< 1/10,000). Adverse reactions are listed in decreasing order of severity. These adverse reactions should be interpreted in the context of the surgical and medical setting.

In other studies or in the post-marketing period, rare cases of intracranial/intracerebral and retroperitoneal bleeding have been reported.

The adverse reaction profile observed in the acute coronary syndrome treatment studies is consistent with the adverse reactions identified when the drug is used for the prevention of venous thromboembolism.

Bleeding was a commonly reported event in patients with unstable angina/myocardial infarction without ST-segment elevation and in those with ST-segment elevation myocardial infarction. The incidence of confirmed major bleeding was 2.1% (fondaparinux) and 4.1% (enoxaparin) during the period up to and including day 9 in the phase III study on unstable angina/myocardial infarction without ST-segment elevation. The incidence of confirmed severe bleeding according to modified TIMI criteria was 1.1% (fondaparinux) and 1.4% (control group [unfractionated heparin/placebo]) during the period up to and including day 9 in the study on ST-segment elevation myocardial infarction.

In the study on unstable angina/myocardial infarction without ST-segment elevation, the most frequently reported non-hemorrhagic adverse reactions (reported in at least 1% of participants in the fondaparinux group) were headache, chest pain, and atrial fibrillation.

In the study involving patients with ST-segment elevation myocardial infarction, the most frequently reported non-hemorrhagic adverse reactions (reported in at least 1% of participants in the fondaparinux group) were atrial fibrillation, pyrexia, chest pain, headache, ventricular tachycardia, vomiting, and arterial hypotension.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicine. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Do not use the medicine after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Incompatibilities.

Frelsia® should not be mixed with other medicinal products, as compatibility studies have not been conducted.

Packaging. 2 pre-filled syringes of 0.5 mL each in a blister. 1 or 5 blisters with syringes per carton.

Prescription status. Prescription only.

Manufacturer.

JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.