PRESCRIBING INFORMATION

ARIXTRA (fondaparinux sodium) 1.5 mg/0.3 ml, 2.5 mg/0.5 ml solution for injection, pre-filled syringe

Please refer to Summary of Product Characteristics (SmPC) before prescribing

Indications (Common): Prevention of Venous Thromboembolic Events (VTE) in adults undergoing major orthopaedic surgery of the lower limbs such as hip fracture, major knee surgery or hip replacement surgery. Prevention of VTE in adults undergoing abdominal surgery who are judged to be at high risk of thromboembolic complications, such as patients undergoing abdominal cancer surgery. Prevention of VTE in adult medical patients who are judged to be at high risk for VTE and who are immobilised due to acute illness such as cardiac insufficiency and/or acute respiratory disorders, and/or acute infectious or inflammatory disease. Treatment of adults with acute symptomatic spontaneous superficial-vein thrombosis of the lower limbs without concomitant deep-vein thrombosis. 

Indications (2.5 mg/0.5 ml specific): Treatment of unstable angina or non-ST segment elevation myocardial infarction (UA/NSTEMI) in adults for whom urgent (< 120 mins) invasive management (PCI) is not indicated. Treatment of ST segment elevation myocardial infarction (STEMI) in adults who are managed with thrombolytics or who initially are to receive no other form of reperfusion therapy. 

Presentation: Solution for injection. The solution is a clear and colourless liquid. Arixtra 1.5mg/0.3ml: Each pre- filled syringe (0.3 ml) contains 1.5 mg of fondaparinux sodium. Arixtra 2.5mg/0.5ml: Each pre-filled syringe (0.5 ml) contains 2.5 mg of fondaparinux sodium. 

Dosage and administration (Common): Patients undergoing major orthopaedic or abdominal surgery: The recommended dose of fondaparinux is 2.5 mg once daily administered post-operatively by subcutaneous injection. The initial dose should be given 6 hours following surgical closure provided that haemostasis has been established. Treatment should be continued until the risk of venous thrombo-embolism has diminished, usually until the patient is ambulant, at least 5 to 9 days after surgery. 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 should be considered for up to an additional 24 days. Medical patients who are at high risk for thromboembolic complications based on an individual risk assessment: The recommended dose of fondaparinux is 2.5 mg once daily administered by subcutaneous injection. Treatment of superficial-vein thrombosis: The recommended dose of fondaparinux is 2.5 mg once daily, administered by subcutaneous injection. Patients eligible for fondaparinux 2.5 mg treatment should have acute, symptomatic, isolated, spontaneous superficial-vein thrombosis of the lower limbs, at least 5 cm long and documented by ultrasonographic investigation or other objective methods. Treatment should be initiated as soon as possible following diagnosis and after exclusion of concomitant DVT or superficial- vein thrombosis within 3 cm from the sapheno-femoral junction. Treatment should be continued for a minimum of 30 days and up to a maximum of 45 days in patients at high risk of thromboembolic complications. Patients who are to undergo surgery or other invasive procedures: In superficial vein thrombosis patients who are to undergo surgery or other invasive procedures, fondaparinux, where possible, should not be given during the 24 hours before surgery. Fondaparinux may be restarted at least 6 hours post-operatively provided haemostasis has been achieved. Special populations: In patients undergoing surgery, timing of the first fondaparinux injection requires strict adherence in patients ≥75 years, and/or with body weight <50 kg and/or with renal impairment with creatinine clearance ranging between 20 to 50 ml/min. The first fondaparinux administration should be given not earlier than 6 hours following surgical closure. The injection should not be given unless haemostasis has been established. Renal impairment: Fondaparinux should not be used in patients with creatinine clearance <20 ml/min. For VTE prophylaxis and treatment of superficial venous thrombosis, the dose should be reduced to 1.5 mg once daily in patients with creatinine clearance in the range of 20 to 50 ml/min. No dosage reduction is required for patients with mild renal impairment (creatinine clearance >50 ml/min). Treatment of superficial-vein thrombosis: The safety and efficacy of Arixtra 1.5 mg/0.3ml has not been studied. Hepatic impairment: No dosing adjustment is necessary in patients with either mild or moderate hepatic impairment. In patients with severe hepatic impairment, fondaparinux should be used with care and is not recommended in the treatment of superficial-vein thrombosis. Paediatric population: Fondaparinux is not recommended for use in children below 17 years of age due to a lack of data on safety and efficacy. Low body weight: Fondaparinux should be used with caution in these patients for the prevention of VTE, UA/NSTEMI and STEMI. Fondaparinux is not recommended for treatment of superficial-vein thrombosis in these patients. Method of administration: Fondaparinux is administered by deep subcutaneous injection while the patient is lying down. Sites of administration should alternate between the left and the right anterolateral and left and right posterolateral abdominal wall. 

Dosage and administration (2.5 mg/0.5 ml specific): Treatment of unstable angina/non- ST segment elevation myocardial infarction (UA/NSTEMI): The recommended dose of fondaparinux is 2.5 mg once daily, administered by subcutaneous injection. Treatment should be initiated as soon as possible following diagnosis and continued for up to a maximum of 8 days or until hospital discharge if that occurs earlier. Treatment of ST segment elevation myocardial infarction (STEMI): The recommended dose of fondaparinux is 2.5 mg once daily. The first dose of fondaparinux is administered intravenously and subsequent doses are administered by subcutaneous injection. Treatment should be initiated as soon as possible following diagnosis and continued for up to a maximum of 8 days or until hospital discharge if that occurs earlier. Renal impairment in treatment of UA/NSTEMI and STEMI: Fondaparinux should not be used in patients with creatinine clearance <20 ml/min. No dosage reduction is required for patients with creatinine clearance > 20 ml/min. Intravenous administration (first dose in patients with STEMI only): Intravenous administration should be through an existing intravenous line either directly or using a small volume (25 or 50ml) 0.9% saline minibag. 

Contraindications: Hypersensitivity to the active substance, sodium chloride, hydrochloric acid or sodium hydroxide. Active clinically significant bleeding. Acute bacterial endocarditis. Severe renal impairment defined by creatinine clearance < 20 ml/min. 

Warnings and precautions (Common): Do not administer intramuscularly. Fondaparinux should be used with caution in patients who have an increased risk of haemorrhage. Agents that may enhance the risk of haemorrhage should not be administered concomitantly with fondaparinux. If co-administration is essential, close monitoring is necessary. Presence of superficial-vein thrombosis greater than 3 cm from the sapheno-femoral junction should be confirmed and concomitant DVT should be excluded by compression ultrasound or objective methods prior to initiating treatment with fondaparinux. In patients undergoing major orthopaedic surgery, epidural or spinal haematomas that may result in long-term or permanent paralysis cannot be excluded with the concurrent use of fondaparinux and spinal/epidural anaesthesia or spinal puncture. Fondaparinux should be used with caution in elderly patients and patients with body weight <50 kg due to increased risk of bleeding. Patients with creatinine clearance <50 ml/min are at increased risk of bleeding and VTE and should be treated with caution. Fondaparinux should not be used in patients with creatinine clearance <20 ml/min. Fondaparinux is not recommended for the treatment of superficial-vein thrombosis in patients with severe hepatic impairment. Fondaparinux should be used with caution in patients with a history of HIT. The needle shield of the pre-filled syringe contains dry natural latex rubber that has the potential to cause allergic reactions in latex sensitive individuals. 

Warnings and precautions (2.5 mg/0.5 ml specific): For treatment of UA/NSTEMI and STEMI, Fondaparinux should be used with caution in patients who are being treated concomitantly with other agents that increase the risk of haemorrhage (such as GPIIb/IIIa inhibitors or thrombolytics). In STEMI patients undergoing primary PCI, the use of fondaparinux prior to and during PCI is not recommended. Similarly, in UA/NSTEMI patients with life threatening conditions that require urgent revascularisation, the use of fondaparinux prior to and during PCI is not recommended. These are patients with refractory or recurrent angina associated with dynamic ST deviation, heart failure, life-threatening arrhythmias or haemodynamic instability. In UA/NSTEMI and STEMI patients undergoing non-primary PCI, the use of fondaparinux as the sole anticoagulant during PCI is not recommended due to an increased risk of guiding catheter thrombus therefore adjunctive UHF should be used. 

Interaction with other medicinal products: Bleeding risk is increased with concomitant administration of fondaparinux and agents that may enhance the risk of haemorrhage. Oral anticoagulants (warfarin), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam) and digoxin did not interact with the pharmacokinetics of fondaparinux. Fondaparinux neither influenced the INR activity of warfarin, nor the bleeding time under acetylsalicylic acid or piroxicam treatment, nor the pharmacokinetics of digoxin at steady state. If follow-up treatment is to be initiated with heparin or LMWH, the first injection should, as a general rule, be given one day after the last fondaparinux injection. If follow up treatment with a Vitamin K antagonist is required, treatment with fondaparinux should be continued until the target INR value has been reached. 

Pregnancy and lactation: There are no adequate data from the use of fondaparinux in pregnant women. Fondaparinux should not be prescribed to pregnant women unless clearly necessary. Breast-feeding is not recommended during treatment with fondaparinux. There are no data available on the effect of fondaparinux on human fertility. 

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. 

Undesirable effects: The most commonly reported serious adverse reactions reported with fondaparinux are bleeding complications (various sites including rare cases of intracranial/ intracerebral and retroperitoneal bleedings) and anaemia. Fondaparinux should be used with caution in patients who have an increased risk of haemorrhage. Common (≥1/100 to <1/10): post-operative haemorrhage, anaemia, bleeding (haematoma, haematuria, haemoptysis, gingival bleeding). Other Adverse Effects: For uncommon, rare, very rare and unknown undesirable effects, please refer to SmPC. 

Legal Category: POM Marketing Authorisation Number: PLGB 46302/0230, PLGB 46302/0231, MAH: Mylan Products Limited NHS Price: 1.5 mg/0.3ml x 10 - £62.79, 2.5 mg/0.5 ml x 10 - £62.79, Date of Revision of Prescribing Information: June 2022. ARX-2022-0003

The SmPC for this product, including adverse reactions, precautions, contra-indications, and method of use can be found at:

http://www.mhra.gov.uk/Safetyinformation/Medicinesinformation/SPCandPILs/index.htm and from Mylan Medical Information, Building 4, Trident Place, Hatfield Business Park, Mosquito Way, Hatfield, Hertfordshire, AL10 9UL, phone no. 01707 853000, Email: info.uk@viatris.com

 

PRESCRIBING INFORMATION

ARIXTRA (fondaparinux sodium) 5mg/0.4ml, 7.5mg/0.6ml & 10mg/0.8ml solution for injection, pre-filled syringe

Please refer to Summary of Product Characteristics (SmPC) before prescribing

 

Indications: Treatment of adults with acute Deep Vein Thrombosis (DVT) and treatment of acute Pulmonary Embolism (PE), except in haemodynamically unstable patients or patients who require thrombolysis or pulmonary embolectomy.

Presentation: Solution for injection. The solution is a clear and colourless to slightly yellow liquid. Arixtra 5mg/0.4ml: Each pre-filled syringe (0.4 ml) contains 5 mg of fondaparinux sodium. Arixtra 7.5ml/0.6ml: Each pre-filled syringe (0.6 ml) contains 7.5 mg of fondaparinux sodium. Arixtra 10mg/0.8ml: Each pre-filled syringe (0.8 ml) contains 10 mg of fondaparinux sodium.

Dosage and administration: The recommended dose of fondaparinux is 7.5 mg (patients with body weight ³ 50, £ 100kg) once daily administered by subcutaneous injection. For patients with body weight < 50 kg, the recommended dose is 5 mg. For patients with body weight > 100 kg, the recommended dose is 10 mg.

Treatment should be continued for at least 5 days and until adequate oral anticoagulation is established (International Normalised Ratio 2 to 3). Concomitant oral anticoagulation treatment should be initiated as soon as possible and usually within 72 hours. The average duration of administration in clinical trials was 7 days and the clinical experience from treatment beyond 10 days is limited. Elderly patients - No dosing adjustment is necessary. In patients ³ 75 years, fondaparinux should be used with care, as renal function decreases with age Renal impairment - Fondaparinux should be used with caution in patients with moderate renal impairment There is no experience in the subgroup of patients with both high body weight (>100 kg) and moderate renal impairment (creatinine clearance 30-50 ml/min). In this subgroup, after an initial 10 mg daily dose, a reduction of the daily dose to 7.5 mg may be considered, based on pharmacokinetic modelling. Fondaparinux should not be used in patients with severe renal impairment (creatinine clearance < 30 ml/min). Hepatic impairment - No dosing adjustment is necessary in patients with either mild or moderate hepatic impairment. In patients with severe hepatic impairment, fondaparinux should be used with care as this patient group has not been studied.

Paediatric population: Fondaparinux is not recommended for use in children below 17 years of age due to a lack of data on safety and efficacy. Method of administration – Fondaparinux is administered by deep subcutaneous injection while the patient is lying down. Sites of administration should alternate between the left and the right anterolateral and left and right posterolateral abdominal wall. To avoid the loss of medicinal product when using the pre-filled syringe do not expel the air bubble from the syringe before the injection. The 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.

Contraindications: Hypersensitivity to the active substance, sodium chloride, hydrochloric acid or sodium hydroxide. Active clinically significant bleeding. Acute bacterial endocarditis. Severe renal impairment defined by creatinine clearance < 30 ml/min.

Warnings and precautions: Fondaparinux is intended for subcutaneous use only. Do not administer intramuscularly. There is limited experience from treatment with fondaparinux in haemodynamically unstable patients and no experience in patients requiring thrombolysis, embolectomy or insertion of a vena cava filter. Haemorrhage - Fondaparinux should be used with caution in patients who have an increased risk of haemorrhage, such as those with congenital or acquired bleeding disorders (e.g. platelet count <50,000/mm3), active ulcerative gastrointestinal disease and recent intracranial haemorrhage or shortly after brain, spinal or ophthalmic surgery and in special patient groups as outlined below. As for other anticoagulants, fondaparinux should be used with caution in patients who have undergone recent surgery (<3 days) and only once surgical haemostasis has been established. Agents that may enhance the risk of haemorrhage should not be administered concomitantly with fondaparinux. These agents include desirudin, fibrinolytic agents, GP IIb/IIIa receptor antagonists, heparin, heparinoids, or Low Molecular Weight Heparin (LMWH). During treatment of VTE, concomitant therapy with vitamin K antagonist should be administered in accordance with the information of interaction with other medicinal products. Other antiplatelet medicinal products (acetylsalicylic acid, dipyridamole, sulfinpyrazone, ticlopidine or clopidogrel), and NSAIDs should be used with caution. If co- administration is essential, close monitoring is necessary. Spinal / Epidural anaesthesia - In patients receiving fondaparinux for treatment of VTE rather than prophylaxis, spinal/epidural anaesthesia in case of surgical procedures should not be used. Elderly patients - 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. Above the age of 65, incidences of bleeding events in patients receiving the recommended regiment in the treatment of DVT or PE increased with age. Fondaparinux should be used with caution in elderly patients. Low body weight - Clinical experience is limited in patients with body weight <50 kg. Fondaparinux should be used with caution at a daily dose of 5 mg in this population. Renal impairment - The risk of bleeding increases with increasing renal impairment. Fondaparinux is contra-indicated in severe renal impairment (creatinine clearance <30 ml/min) and should be used with caution in patients with moderate renal impairment (creatinine clearance 30-50 ml/min). The duration of treatment should not exceed that evaluated during clinical trial (mean 7 days). Severe hepatic impairment - The use of fondaparinux should be considered with caution because of an increased risk of bleeding due to a deficiency of coagulation factors in patients with severe hepatic impairment. Patients with Heparin Induced Thrombocytopenia - Fondaparinux should be used with caution in patients with a history of HIT. The efficacy and safety of fondaparinux have not been formally studied in patients with HIT type II. Fondaparinux does not bind to platelet factor 4 and does not usually cross-react with sera from patients with Heparin Induced Thrombocytopenia (HIT) type II. However, rare spontaneous reports of HIT in patients treated with fondaparinux have been received. Latex Allergy - The needle shield of the pre-filled syringe contains dry natural latex rubber that has the potential to cause allergic reactions in latex sensitive individuals.

Interaction with other medicinal products: Bleeding risk is increased with concomitant administration of fondaparinux and agents that may enhance the risk of haemorrhage. In clinical studies performed with fondaparinux, oral anticoagulants (warfarin) did not interact with the pharmacokinetics of fondaparinux; at the 10 mg dose used in the interaction studies, fondaparinux did not influence the anticoagulation monitoring (INR) activity of warfarin. Platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam) and digoxin did not interact with the pharmacokinetics of fondaparinux. At the 10 mg dose used in the interaction studies, fondaparinux did not influence the bleeding time under acetylsalicylic acid or piroxicam treatment, nor the pharmacokinetics of digoxin at steady state.

Pregnancy and lactation: There is no adequate data from the use of fondaparinux in pregnant women. Fondaparinux should not be prescribed to pregnant women unless clearly necessary. Breast-feeding is not recommended during treatment with fondaparinux. There are no data available on the effect of fondaparinux on human fertility.

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.

Undesirable effects: The most commonly reported serious adverse reactions reported with fondaparinux are bleeding complications (various sites including rare cases of intracranial/ intracerebral and retroperitoneal bleedings). Common (≥1/100 to <1/10): bleeding (gastrointestinal, haematuria, haematoma, epistaxis, haemoptysis, utero-vaginal haemorrhage, haemarthrosis, ocular, purpura, bruise). Other Adverse Effects: For uncommon, rare, very rare and unknown undesirable effects, please refer to SmPC.

Legal Category: POM Marketing Authorisation Number: PLGB 46302/0232, PLGB 46302/0233 and PLGB 46302/0229. MAH: Mylan Products Limited NHS Price: 5 mg/0.4ml x 10 - £116.53, 7.5 mg/0.6 ml x 10 - £116.53 and 10 mg/0.8 ml x 10 - £116.53, Date of Revision of Prescribing Information: January 2023. ARX-2023-0018

The SmPC for this product, including adverse reactions, precautions, contra-indications, and method of use can be found at:

http://www.mhra.gov.uk/Safetyinformation/Medicinesinformation/SPCandPILs/index.htm and from Mylan Medical Information, Building 4, Trident Place, Hatfield Business Park, Mosquito Way, Hatfield, Hertfordshire, AL10 9UL, phone no. 01707 853000, Email: info.uk@viatris.com