Vasola

Each 0.5 mL injection contains: Fondaparinux sodium 2.5 mg.

Pharmacology: Pharmacodynamics: Mechanism of Action: Fondaparinux is a synthetic and selective inhibitor of activated Factor X (Xa). The antithrombotic activity of fondaparinux is the result of antithrombin III (ATIII) mediated selective inhibition of Factor Xa. By binding selectively to ATIII, fondaparinux potentiates (about 300 times) the innate neutralization of Factor Xa by ATIII. Neutralisation of Factor Xa interrupts the blood coagulation cascade and inhibits both thrombin formation and thrombus development. Fondaparinux does not inactive thrombin (activated Factor II) and has no known effect on platelet function.
Pharmacodynamic Effects: At the 2.5 mg dose, fondaparinux does not have a clinically relevant affect on routine coagulation test, such as activated partial thromboplastin time (aPTT), activated clotting time (ACT) or prothrombin time (PT)/lnternational Normalised Ratio (INR) tests in plasma, nor bleeding time or fibrinolytic activity. Fondaparinux does not cross-react with sera from patients with Heparin induced thrombocytopenia (HIT) type II.
Anti-Xa activity: The pharmacodynamic/pharmacokinetics of fondaparinux are derived from fondaparinux plasma concentrations quantified via anti factor Xa activity. Only fondaparinux can be used to calibrate the anti-Xa assay. The international standards of heparin or low molecular weight heparin (LMWH) are not appropriate for this use. As a result, the concentration of fondaparinux is expressed as milligrams of the fondaparinux calibrator/litre.

Prevention of Venous Thromboembolic Events (VTE) in patients undergoing major orthopaedic surgery of the lower limbs such as: Hip fracture, including extended prophylaxis; Knee replacement surgery; Hip replacement surgery.
Prevention of Venous Thromboembolic Events (VTE) in patients undergoing abdominal surgery who are at risk of thromboembolic complications.
Prevention of Venous Thromboembolic Events (VTE) in medical patients who are judged to be at high risk for VTE and thromboembolic complications who are immobilized due to acute illness.

Method of administration: Subcutaneous administration: The sites of subcutaneous injection should alternate between the left and the right anterolateral and left and right posterolateral abdominal wall. To whole length of the needle should be inserted perpendicularly into a skin fold held between the thumb and the forefinger. The skin fold should be held throughout the injection.
Fondaparinux sodium is intended for use under a physician's guidance. Patients may self-inject only if their physician determines that it is appropriate, and with medical follow-up as necessary. Proper training in subcutaneous injection technique should be provided. Instruction for self-administration is included in the monograph (See Instruction for use under Cautions for Usage).
Step by step instructions: Fondaparinux sodium is administered by subcutaneous or intravenous injection. Fondaparinux sodium should not be administered by intramuscular injection. Subcutaneous injection is administered in the same way as with a standard syringe. Intravenous administration should be through an existing intravenous line either directly or using a small volume (25 or 50 mL) 0.9% saline mini bag.
Adults: Prevention of VTE: Orthopaedic and abdominal surgery: The recommended dose of Fondaparinux sodium is 2.5 mg once daily, administered post-operatively by subcutaneous injection. The timing of the first dose should be no earlier than 6 hours following surgical closure, and only after haemostasis has been established (see PRECAUTIONS).
Treatment should be continued until the risk of venous thrombo-embolism has diminished, usually until the patients is ambulant, at least 5 to 9 days after surgery.
Experience shows that in patients undergoing hip fracture surgery, the risk of VTE continues beyond 9 days after surgery. In these patients the use of prolonged prophylaxis with Fondaparinux sodium should be considered for up to additional 24 days.
Medical patients at risk of thromboembolic complications: The recommended dose of Fondaparinux sodium is 2.5 mg once daily administered by subcutaneous injection. A treatment duration of 6 to 14 days.
Special Population: Children: The safety and efficacy of Fondaparinux sodium in patients under the age of 17 has not been established.
Elderly (from 75 years): Fondaparinux sodium should be used with caution in elderly patients as renal function decreases with age (see Renal impairment under PRECAUTIONS). In patients undergoing surgery, the timing of the first dose of Fondaparinux sodium requires strict adherence (see PRECAUTIONS).
Patients with body weight less than 50 kg: Patients with body weight below 50 kg are at increased risk of bleeding (see PRECAUTIONS). In patients undergoing surgery the timing of the first dose of Fondaparinux sodium requires strict adherence (see PRECAUTIONS).
Renal impairment: Prevention of venous thromboembolic event (VTE).
No dosage reduction is required in patients with a creatinine clearance greater than or equal to 30 mL/min. In patients with a creatinine clearance of between 20 to 30 mL/min in whom the physician determines that the benefit of thromboprophylaxis exceeds the risk, a dose of 2.5 mg on alternate days (each dose approximately 48 hours apart) is recommended (see PRECAUTIONS).
Fondaparinux sodium is not recommended for use in patients with a creatinine clearance of less than 20 mL/min (see PRECAUTIONS). In patients undergoing surgery, the timing of the first dose of Fondaparinux requires strict adherence.
Treatment of venous thromboembolic event (VTE): No dosage reduction is required in patients with a creatinine clearance greater than or equal to 30 mL/min. Fondaparinux sodium should not be used in patients with a creatinine clearance of less than 30 mL/min (see PRECAUTIONS).
Hepatic impairment: No dosing adjustment of Fondaparinux sodium is necessary in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, Fondaparinux sodium should be used with caution (see PRECAUTIONS).

Symptoms and Signs: Fondaparinux sodium doses above the recommended regimen may lead to an increased risk of bleeding.
Treatment: Overdose associated with bleeding complications should lead to treatment discontinuation search for the primary cause. Initiation of appropriate therapy which may include surgical haemostasis, blood replacements, fresh plasma transfusion, plasmapheresis should be considered.

Known hypersensitivity to Fondaparinux sodium or any of the excipients.
Active clinically significant bleeding.
Acute bacterial endocarditis.
Severe renal impairment defined by creatinine <20 mL/min.

Route of administration: Fondaparinux sodium must not be administered intramuscularly (see DOSAGE & ADMINISTRATION).
Haemorrhage: Fondaparinux sodium like other anticoagulants must be used with caution in conditions with an increased risk of haemorrhage, (such as congenital or acquired bleeding disorders, active ulcerative gastrointestinal disease, recent intracranial haemorrhage, shortly after brain, spinal or ophthalmic surgery).
Prevention and treatment VTE: Other medical products enhancing the risk of haemorrhage, with the exception of vitamin K antagonists used concomitantly for the treatment of VTE, should not be administered with Fondaparinux sodium. If co-administration is essential, close monitoring is recommended (see INTERACTIONS).
Prevention of VTE following surgery (timing of first Fondaparinux injection): The timing of the first injection requires strict adherence. The first dose should be given no earlier than 6 hours following surgical closure, and only after haemostasis has been established. Administration before 6 hours has been associated with an increased risk of major bleeding. Patients groups at particular risk are those from 75 years of age, body weight of less than 50 kg, or renal impairment with creatinine clearance less than 50 mL/min.
Spinal/epidural anaesthesia/spinal puncture: Epidural or spinal haematomas that may result in long-term or permanent paralysis can occur with the use of anticoagulant and spinal/epidural anaesthesia or spinal puncture. The risk of these rare events may be higher with post-operative use of indwelling epidural catheters or the concomitant use of other medicinal products affecting haemostasis.
Low body weight: Patients with body weight less than 50 kg are at increased risk of bleeding. Elimination of Fondaparinux sodium decreases with weight decrease. Fondaparinux sodium should be used with caution in these patients (see DOSAGE & ADMINISTRATION).
Heparin Induced Thrombocytopenia: Fondaparinux sodium does not bind to platelet factor 4 and does not cross-react with sera from patients with Heparin Induced Thrombocytopenia (HIT)-type II. It should be used with caution in patients with a history of HIT. The efficacy and safety of Fondaparinux sodium have not been formally studied in HIT-type II. Rare spontaneous reports of HIT in patients treated with Fondaparinux sodium have been received. To date a causal association between treatment with Fondaparinux sodium and the occurrence of HIT has not been established.
Effects on Ability to Drive and Use Machines: No studies on the effect on the ability to drive and to use machines have been performed.
Renal impairment: The plasma clearance of fondaparinux decreases with the severity of renal impairment, and is associated with an increased risk of haemorrhage.
Patients with renal impairment, particularly those with a creatinine clearance of less than 30 mL/min are at increased risk of both major bleeding episodes and VTE.
Prevention of VTE: There are limited clinical data available for the use of fondaparinux for prevention of VTE in patients with creatinine clearance less than 20 mL/min. Therefore, Fondaparinux sodium is not recommended for prevention of VTE in these patients (see DOSAGE & ADMINISTRATION).
Treatment of VTE: There are limited clinical data available for the use of fondaparinux for treatment of VTE in patients with creatinine clearance of less than 30 mL/min. Therefore, Fondaparinux sodium is not recommended for the treatment of VTE in these patients (see DOSAGE & ADMINISTRATION).
Severe hepatic impairment: In patients with an elevation in prothrombin time, the use of Fondaparinux sodium should be considered with caution, because of an increased risk of bleeding due to a possible deficiency of coagulation factors in patients with severe hepatic impairment (see DOSAGE & ADMINISTRATION).
Use in Elderly: The elderly population is at increased risk of bleeding. As renal function generally decreases with age, elderly patients may show reduced elimination and increased exposure of Fondaparinux sodium. Fondaparinux sodium should be used with caution in elderly patients (see DOSAGE & ADMINISTRATION).

Pregnancy: There are limited clinical data available in exposed pregnancies. Fondaparinux sodium should not be prescribed to pregnant women unless the benefit outweighs the risk.
Lactation: Fondaparinux is excreted in rat milk but it is not known whether fondaparinux is excreted in human milk. Breast-feeding is not recommended during treatment with Fondaparinux sodium.

Adverse reactions are listed as follows by system organ class and frequency and indication. Frequencies are defined as: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (≥1/10000). These adverse reactions should be interpreted within the surgical or medical context of the indications.
Infection and infestations: Rare: Post-operative wound infections.
Blood and lymphatic system disorders: Common : Anaemia, bleeding (various sites including rare cases of intracranial/intracerebral and retroperitoneal bleedings), purpura.
Uncommon: Thrombocytopenia, thrombocythaemia, abnormal platelets, coagulation disorder.
Immune system disorders: Rare: Allergic reaction (including very rare reports of angiodema, anaphylactoid/anaphylactic reaction).
Metabolism and nutrition disorders: Rare: Hypokalemia.
Nervous system disorders: Uncommon: Headache.
Rare: Anxiety, confusion, dizziness, somnolence, vertigo.
Vascular disorders: Rare: Hypotension.
Respiratory, thoracic and mediastinal disorders: Rare: Dyspnea, coughing.
Gastrointestinal disorders: Uncommon: Nausea, vomiting.
Rare: Abdominal pain, dyspepsia, gastritis, constipation, diarrhea.
Hepatobiliary disorders: Uncommon: Abnormal liver function test, hepatic enzymes increased.
Rare: Bilirubinaemia.
Skin and subcutaneous tissue disorders: Uncommon: Rash, pruritus, wound secretion.
General disorders and administration site conditions: Common: Oedema.
Uncommon: Fever.
Rare: Reaction at injection site, chest pain, leg pain, fatigue, flushing, syncope.

Fondaparinux does not markedly inhibit CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4) in vitro. Thus, Fondaparinux sodium is not expected to interact with other medicinal products in vivo by inhibition of CYP-mediated metabolism.
Since fondaparinux does not bind significantly to plasma proteins other than ATIII, no interaction with other medicinal products by protein binding displacement are expected. Fondaparinux concomitant use of warfarin (oral anticoagulant), acetylsalicylic acid (platelet inhibitor), piroxicam (non-steroidal anti-inflammatory), and digoxin (cardiac glycoside) did not significantly affect the pharmacokinetics or pharmacodynamics of fondaparinux. In addition fondaparinux neither influenced the INR activity of warfarin, nor the bleeding time under acetylsalicylic acid or piroxicam treatment, nor the pharmacokinetics or pharmacodynamics of digoxin at steady state.

Instruction for use: 1. Wash hands thoroughly with soap and water and dry them with a towel.
2. Plug 26G x ½ needle to the 1 mL syringe.
3. Remove the needle's cap then take the injection solution to the vial according to required dose.
4. Sit or lie down in a comfortable position. Choose a place in the lower abdominal (tummy) area, at least 5 cm below the belly button. Alternate the left and right side of the lower abdominal area at each injection. This will help to reduce the discomfort at the injection site. If injecting in the lower abdominal area is not possible, ask a nurse or doctor for advice.
5. Clean the injection area with an alcohol wipe.
6. Gently pinch the skin that has been cleaned to make a fold. Hold the fold between the thumb and the forefinger during the entire injection.
7. Hold the syringe firmly by the finger grip. Insert the full length of the needle at right angles into the skin fold.
8. Inject all of the contents of the syringe by pressing down as far as it goes.
9. Press a piece of gauze or a cotton ball next to the needle at the injection site.
10. Remove the needle from the skin.
Do not dispose of the used syringe in the household waste. Dispose of it as the doctor or pharmacist has instructed.

Store below 25°C. Do not freeze.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

B01AX05 - fondaparinux ; Belongs to the class of other antithrombotic agents.

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