Medicinal Products

ARIXTRA 2.5 mg / 0.5 mL

Generic drug of the therapeutic class: Haemostasis and blood
active ingredients: Fondaparinux
laboratory: Glaxo Group Ltd

Injectable solution
Box of 10 pre-filled syringes with 0.5 mL needles
All forms

Indication

Prevention of venous thromboembolic events in major orthopedic surgery of the lower extremity of the adult, such as hip fracture, hip prosthesis or major knee surgery.

Prevention of venous thromboembolic events in abdominal surgery in adult patients considered to be at high risk of thromboembolic complications, particularly those undergoing abdominal cancer surgery (see section 5.1 ).

Prevention of venous thromboembolic events in adults considered to be at high risk of venous thromboembolic events, bedridden for an acute medical condition such as: heart failure and / or acute respiratory disorder, and / or infectious or inflammatory disease acute.

Treatment of unstable angina or non-ST segment elevation myocardial infarction (AI / IDM ST-) in adults for whom management by an invasive strategy (percutaneous coronary intervention: PCI) in emergency (< 120 min) is not indicated (see sections Warnings and precautions for use

and 5.1).

Treatment of ST-segment-elevated myocardial infarction (ST + IDM) in adults is managed with thrombolytic therapy or initially with no other reperfusion therapy.

Treatment of symptomatic acute spontaneous superficial venous thrombosis of the lower limbs of the adult without associated deep vein thrombosis (see sections Posology and method of administration and Pharmacodynamic properties ).

Dosage ARIXTRA 2.5 mg / 0.5 mL Solution for injection Box of 10 pre-filled syringes with 0.5 mL needles

Dosage

Patients undergoing major orthopedic surgery or abdominal surgery
The recommended dosage of fondaparinux is 2.5 mg once daily, administered postoperatively by subcutaneous injection.

The initial dose should be given 6 hours after the end of the surgery, after checking for the absence of active bleeding.

Treatment will be continued until the venous thromboembolic risk is reduced, usually until the patient is ambulatory, for at least 5 to 9 days after the procedure. In patients undergoing hip fracture surgery, experience shows that venous thromboembolic risk persists beyond the 9th postoperative day. In these patients, prolonged prophylaxis with fondaparinux will be considered for up to 24 additional days (see section 5.1 ).

Medical patients at high risk of thromboembolic events according to an individual risk assessment

The recommended dosage of fondaparinux is 2.5 mg once daily, administered by subcutaneous injection. A treatment duration of 6 to 14 days has been clinically studied in patients in a medical setting (see section 5.1 ).

Treatment of unstable angina / myocardial infarction without ST segment elevation (AI / IDM ST-)

The recommended dosage of fondaparinux is 2.5 mg once daily, administered by subcutaneous injection. The treatment should be initiated as soon as possible once the diagnosis is made and will be continued up to 8 days maximum, or until discharge from the hospital if it comes before this term.

If a patient is to receive percutaneous coronary intervention (PCI), unfractionated heparin (UFH) will be administered, in accordance with standard clinical practice, during PCI, taking into account the potential risk of bleeding presented by the patient. patient, including the time elapsed since the last injection of fondaparinux (see Warnings and Precautions ). The time at which the subcutaneous injection of fondaparinux should be restarted after removal of the catheter is a judgment of the clinician. In the pivotal AI / IDM ST- study, fondaparinux treatment was not resumed until 2 hours after catheter removal.

Treatment of ST-segment elevation myocardial infarction (IDMST +)

The recommended dosage of fondaparinux is 2.5 mg once daily. The first dose of fondaparinux will be administered intravenously and subsequent doses by subcutaneous injection. Treatment should be initiated as soon as possible once the diagnosis is made and will be continued up to 8 days maximum, or until discharge from the hospital if it comes before this term.

If the patient requires a non-primary percutaneous coronary intervention (PCI), unfractionated heparin (UFH) will be administered, in accordance with standard clinical practice, during PCI, taking into account the potential risk of patient bleeding. including the time elapsed since the last dose of fondaparinux (see Warnings and Precautions ) section. The time at which the subcutaneous injection of fondaparinux should be resumed after removal of the catheter is a judgment of the clinician. In the IDM ST + pivotal clinical study, fondaparinux treatment was not resumed until 3 hours after removal from the catheter.

• Patients undergoing surgical revascularization by coronary artery bypass (PAC)

If the patient IDM ST + or AI / IDM ST- is to have a coronary artery bypass surgery (PAC) revascularization, fondaparinux, if possible, should not be given for 24 hours prior to surgery and will not be able to be re-administered only 48 hours later.

Treatment of superficial vein thrombosis

The recommended dose of fondaparinux is 2.5 mg once daily, administered by subcutaneous injection.

Patients who are likely to receive fondaparinux 2.5 mg should have acute, symptomatic, isolated, lower extremity, acute superficial venous thrombosis, at least 5 cm long, confirmed by ultrasound examination or other objective methods. Treatment should be initiated as soon as possible after diagnosis and after exclusion of concomitant Concomitant Deep Vein Thrombosis (DVT) or superficial vein thrombosis within 3 cm of the saphenofemoral junction.

Treatment should be continued for at least 30 days and not more than 45 days in patients at high risk of thromboembolic complications (see sections Warnings and Precautions and Pharmacodynamic Properties ). Patients will be able to self-administer the product if they wish and are able to do so. Doctors will provide clear instructions for self-injection.


Patients undergoing surgery or other invasive procedures

In patients with superficial venous thrombosis who require surgery or other invasive surgical procedures, fondaparinux should not be administered, as far as possible, within 24 hours of surgery. Treatment with fondaparinux can only be resumed at least 6 hours after the intervention, provided that the haemostasis is effective.

Special populations

Prevention of venous thromboembolic events occurring after surgery

In patients undergoing surgery, the time of administration of the first injection of fondaparinux should be strictly observed in patients 75 years of age and older, and / or weighing less than 50 kg and / or having renal impairment with creatinine clearance between 20 and 50 ml / min.

The first injection of fondaparinux should not be given less than 6 hours after the end of the surgery. This injection will not be performed until the absence of active bleeding has been verified (see Warnings and Precautions ).

Renal failure

• Prevention of VTE (thromboembolic events) - In patients with creatinine clearance <20 ml / min (see section 4.3 ), fondaparinux should not be used. In patients with a creatinine clearance of 20-50 ml / min, the dosage of fondaparinux should be reduced to 1.5 mg once daily (see Warnings and Precautions and Pharmacokinetic Properties sections). . No reduction in dosage is required in patients with mild renal impairment (creatinine clearance> 50 ml / min).

• Treatment of unstable angina / IDM ST- and IDMST + should not be used in patients with creatinine clearance <20 ml / min (see Contraindications section ). No dosage reduction is necessary in patients with creatinine clearance> 20 ml / min.

• Treatment of superficial vein thrombosis - Fondaparinux should not be used in patients with creatinine clearance <20 ml / min (see section 4.3 ). The dosage should be decreased to 1.5 mg once daily in patients with creatinine clearance between 20 and 50 ml / min (see sections Warnings and Precautions and Pharmacokinetic Properties ). No reduction in dosage is required in patients with mild renal impairment (creatinine clearance> 50 ml / min). The efficacy and safety of a 1.5 mg dose have not been studied (see Warnings and Precautions ).

Hepatic insufficiency

• Prevention of VTEs and treatment of unstable angina / IDMST- and IDMST + - No dose adjustment is required in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, fondaparinux should be used with caution: this group of patients has not been studied (see sections Warnings and Precautions and Pharmacokinetic Properties ).

• Treatment of superficial vein thrombosis - In patients with severe hepatic impairment, the efficacy and safety of fondaparinux has not been studied, so fondaparinux is not recommended in these patients (see section care and precautions for use ).


Pediatrics - The use of fondaparinux is not recommended for children under the age of 17, as there is insufficient evidence of safety and efficacy.

Low body weight

• Prevention of VTEs and treatment of unstable angina / IDMST- and IDMST + - Patients weighing less than 50 kg have an increased risk of bleeding. The elimination of fondaparinux decreases with weight, so fondaparinux should be used with caution in these patients (see Warnings and Precautions for Use section ).

• Treatment of superficial vein thrombosis - In patients weighing less than 50 kg, the efficacy and safety of fondaparinux has not been studied, so fondaparinux is not recommended in these patients (see section Warnings and precautions for use ).

Administration mode

• Subcutaneous administration

Fondaparinux should be injected subcutaneously deep, with the patient lying down. The injection sites should be alternated between the anterolateral and posterolateral abdominal belt, alternately on the right and left side. To avoid loss of medication when using the pre-filled syringe, do not bleed the air bubble from the syringe before performing the injection. The needle must be inserted perpendicularly throughout its length into the thickness of a skin fold made between the thumb and forefinger; this skin fold must be maintained for the duration of the injection.

• Intravenous Administration (first injection in patients with ST + IDM only)

Intravenous administration of fondaparinux should be performed via a preexisting venous route, either directly in the route or using a small pocket of 0.9% small volume saline solution (25 or 50 ml). To avoid any loss of medication when using the pre-filled fondaparinux syringe, do not bleed the air bubble from the syringe before performing the injection. It will be necessary to inject sufficient saline into the catheter to ensure that the drug has been administered in its entirety. In case of mini-bag administration, the infusion should be maintained for 1 to 2 additional minutes.

For additional instructions on use, handling and disposal, see section Instructions for use, handling and disposal .

Against indications

- hypersensitivity to the active substance or to any of the excipients

- clinically significant progressive bleeding

- acute bacterial endocarditis

- severe renal insufficiency with creatinine clearance <20 ml / min.

Arixtra side effects

The most common serious adverse reactions reported with fondaparinux are bleeding complications (in various locations including rare cases of intracranial / intracerebral or retroperitoneal bleeding) and anemia.

Fondaparinux should be used with caution in patients with an increased risk of bleeding (see Warnings and Precautions for Use section ).

The safety of fondaparinux 2.5 mg has been evaluated in:

- 3595 patients in major orthopedic surgery of the lower limb treated for a maximum of 9 days,

- 327 hip fracture surgery patients treated for 3 weeks after an initial one-week period,

- 1407 patients in abdominal surgery treated for a maximum of 9 days,

- 425 patients in medical environment, at risk of thromboembolic events, treated up to 14

days,

- 10, 057 patients treated for an AC or acute coronary syndrome without ST segment elevation (SCA ST-),

- 6, 036 patients treated for acute coronary syndrome with ST segment elevation (SCA

ST +).

Regarding the prevention of venous thromboembolic events, the undesirable effects reported by investigators as at least possibly related to fondaparinux are presented within each organ class in decreasing order of frequency of occurrence (very common: ≥ 1/10 frequent: ≥ 1/100 to <1/10, uncommon: ≥ 1 / 1, 000 to <1/100, rare: ≥ 1 / 10, 000 to <1 / 1, 000, very rare: <1 / 10, 000), and severe; these adverse effects must be interpreted in terms of the surgical and medical context.

MedDRA Organ Class

Undesirable effects in patients with major orthopedic surgery of the lower limbs or abdominal surgery

Adverse effects in patients in a medical setting

Infections and infestations

Rare: surgical scar infection

affections

hematologic and lymphatic system

Frequent: postoperative hemorrhage, anemia

Uncommon: bleeding (epitaxis, gastrointestinal bleeding, hemoptysis, hematuria, hematoma)

thrombocytopenia, purpura, thrombocythemia, platelet abnormality, bleeding disorder

Common : bleeding (hematoma, hematuria, hemoptysis, bleeding

gingival)

Uncommon: anemia

Immune system disorders

Rare: allergic reaction

Metabolism and nutrition disorders

Rare: hypokalemia

Nervous system disorders

Rare: anxiety, drowsiness, dizziness, lightheadedness, headache, confusion

Vascular disorders Rare : hypotension

Chest and mediastinal respiratory disorders

Rare: dyspnea, cough

Uncommon: dyspnoea

Gastrointestinal disorders

Uncommon: nausea,

vomiting,

Rare: abdominal pain,

dyspepsia, gastritis, constipation,

diarrhea

Hepatobiliary disorders

Uncommon: increased liver enzymes, abnormal liver function

Rare: hyperbilirubinemia

Skin and subcutaneous tissue disorders

Uncommon: rash , pruritus

Uncommon: rash, pruritus

General disorders and administration site conditions

Uncommon: edema, peripheral edema, fever, oozing of the scar,

Rare: chest pain, tiredness, leg pain, genital edema, flushing and redness, fainting

Uncommon: chest pain

Rare cases of intracranial / intracerebral or retroperitoneal bleeding have been reported in clinical development or post-marketing surveillance.

The adverse event profile reported in the SCA development program is consistent with adverse events reported in the prophylaxis of venous thromboembolic events.

Bleeding is commonly reported in patients with AI / IDM ST- and IDM ST +. In the Phase III study in patients with AI / IDM ST-, the incidence of

bleeding considered major was 2.1% (fondaparinux) vs 4.1% (enoxaparin) up to the 9th day included. In the phase III study in patients with ST + IDM, the incidence of haemorrhage judged to be severe according to modified TIMI criteria was 1.1% (fondaparinux) vs 1.4% (control [UFH / placebo] ) until the 9th day included.

In the phase III study in patients with AI / IDM ST-, the most commonly reported adverse reactions other than bleeding (reported in at least 1% of subjects receiving fondaparinux) were: headache, chest pain and atrial fibrillation.

In the phase III study in patients with ST + IDM, the most commonly reported adverse events other than bleeding (in at least 1% of fondaparinux-treated patients) were: atrial fibrillation, fever, chest pain, headache, ventricular tachycardia, vomiting and hypotension.

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