Clexane 20mg, 40mg, 60mg, 80mg, 100mg Solution for injection

u2022 To reduce the risk of post-operative venous thrombosis and embolism in moderate and high-risk surgical patients, in particular those undergoing orthopaedic or general surgery including cancer surgery.

u2022 To reduce the risk of venous thromboembolism in patients bedridden due to debilitating medical illnesses.

u2022 Treatment of deep venous thrombosis with or without pulmonary embolism. Safety of home treatment for this indication has not been established.

u2022 To reduce the risk of ischaemic complications of unstable angina or non-Q-wave myocardial infarction, within 24 hours of onset, combined with aspirin (100 - 325 mg daily) for 8 days, or until stabilisation, revascularisation or discharge from hospital.

u2022 To reduce the risk of thrombus formation in extracorporeal circulation during haemodialysis.

u2022 Treatment of acute ST-segment Elevation Myocardial Infarction (STEMI) including patients to be managed medically or with subsequent Percutaneous Coronary Intervention (PCI).

Posology

To reduce the risk of post-operative venous thrombosis and embolism in moderate and high risk surgical patients:

Individual thromboembolic risk for patients can be estimated using validated risk stratification model.

Moderate Risk Patients: In general surgery, 20 mg (0,2 ml) once daily by subcutaneous injection. The first injection should be given 2 hours pre-operatively. Treatment is continued for as long as the risk of thromboembolism persists; in general, from 7 to 10 days after surgery or as long as there is a risk of venous thromboembolism and until the patient is ambulatory.

High Risk Patients: In orthopaedic or general surgery including cancer surgery, 40 mg (0,4 ml) once daily by subcutaneous injection. The first injection should be given 12 hours pre-operatively. If there is a need to initiate CLEXANE earlier than 12 hours pre-operatively to reduce risk (e.g. high risk patient waiting for a deferred orthopaedic surgery), the last injection should be administered no later than 12 hours prior to surgery and resumed 12 hours after surgery.

u2022 For patients who undergo major orthopaedic surgery with a high venous thromboembolism risk, an extended thromboprophylaxis up to 5 weeks is recommended.

u2022 For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is recommended. For special recommendations concerning dosing intervals for spinal/epidural anaesthesia and percutaneous coronary revascularisation procedures; see section 4.4.

To reduce the risk of venous thromboembolism in medical patients: The recommended dose of CLEXANE is 40 mg once daily by subcutaneous injection. CLEXANE treatment is prescribed for a minimum of 6 days and continued until the return to full ambulation, for a maximum of 14 days.

Treatment of deep vein thrombosis with or without pulmonary embolism: A dose of 1 mg/kg should be given subcutaneously every 12 hours. Oral anticoagulant therapy should be initiated when appropriate and CLEXANE treatment should be continued until a therapeutic anticoagulant effect has been achieved (International Normalised Ratio 2 to 3). CLEXANE treatment is usually prescribed for between 5 and 10 days.

To reduce the risk of ischaemic complications of unstable angina or non-Q-wave myocardial infarction: The recommended dose of CLEXANE is 1 mg/kg every 12 hours by subcutaneous injection, administered concurrently with aspirin (100 to 325 mg once daily). Treatment with CLEXANE in these patients should be prescribed for a minimum of 2 days and continued until clinical stabilisation. The usual duration of treatment is 2 to 8 days.

To reduce the risk of extracorporeal thrombus during haemodialysis: The recommended dose is 1 mg/kg of CLEXANE. For patients with a high risk of haemorrhage, the dose should be reduced to 0,5 mg/kg for double vascular access or 0,75 mg/kg for single vascular access. During haemodialysis, CLEXANE should be introduced into the arterial line of the circuit at the beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if fibrin rings are found, for example after a longer than normal session, a further dose of 0,5 to 1 mg/kg may be given.

Treatment of acute ST-segment Elevation Myocardial Infarction (STEMI): The recommended dose of CLEXANE is a single IV bolus of 30 mg plus a 1 mg/kg subcutaneous dose, followed by 1 mg/kg administered subcutaneously every 12 hours (maximum 100 mg for the first two doses only, followed by 1 mg/kg dosing for the remaining doses). For dosage in patients > 75 years of age, refer to the section on the Elderly.

When administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific), CLEXANE should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. All patients should receive aspirin as soon as they are identified as having STEMI and maintained on an appropriate dose once daily, unless contraindicated. The recommended duration of CLEXANE treatment is 8 days or until hospital discharge, whichever comes first.

For patients managed with Percutaneous Coronary Intervention (PCI): If the last CLEXANE subcutaneous administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last subcutaneous administration was given more than 8 hours before balloon inflation, an IV bolus of 0,3 mg/kg of CLEXANE should be administered.

Paediatric population: The safety and efficacy of enoxaparin sodium in paediatric population have not been established (see section 4.3).

Elderly: For treatment of acute ST-segment Elevation Myocardial Infarction in elderly patients > 75 years of age, do not use an initial IV bolus. Initiate dosing with 0,75 mg/kg subcutaneous every 12 hours (maximum 75 mg for the first two doses only, followed by 0,75 mg/kg dosing for the remaining doses). For other indications, no dose reduction is necessary in the elderly, unless kidney function is impaired (see section 4.4 u2013 Haemorrhage in the elderly; section 5.2 u2013 Elderly and section 4.2 u2013 Renal impairment).

The efficacy of CLEXANE injection in the elderly (> 65 years) was similar to that seen in younger patients (< 65 years). The incidence of bleeding complications was similar between elderly and younger patients when 30 mg every 12 hours or 40 mg once a day doses of CLEXANE injection were employed. The incidence of bleeding complications was higher in elderly patients as compared to younger patients when CLEXANE injection was administered at doses of 1,5 mg/kg once a day or 1 mg/kg every 12 hours. The risk of CLEXANE injection-associated bleeding increased with age. Serious adverse events increased with age for patients receiving CLEXANE injection. Other clinical experience (including post-marketing surveillance and literature reports) has not revealed additional differences in the safety of CLEXANE injection between elderly and younger patients. Careful attention to dosing intervals and concomitant medications (especially antiplatelet medications) is advised. Monitoring of geriatric patients with low body weight (< 45 kg) and those predisposed to decreased renal function should be considered (see section 5.2 and section 4.4).

Renal impairment: In the absence of safety data on dosages more than 80 mg daily and delayed elimination in patients with severe renal impairment, dosages of more than 60 mg daily should be used with caution. Special safety vigilance is warranted in patients with severe renal impairment, as there may be an increased bleeding tendency due to the renal failure.

See sections 4.4 and 5.2 u2013 Renal impairment.

Severe renal impairment: A dosage adjustment is required for patients with severe renal impairment (creatinine clearance < 30 ml/min), according to the following tables, since CLEXANE exposure is significantly increased in this patient population. The following dosage adjustments are recommended for therapeutic dosage ranges:

Standard dosing: 1 mg/kg SC twice daily

Severe renal impairment: 1 mg/kg SC once daily

1,5 mg/kg SC once daily

30 mg single IV bolus plus a 1 mg/kg SC dose followed by 1 mg/kg SC twice daily

1 mg/kg SC once daily

30 mg single IV bolus plus a 1 mg/kg SC dose followed by 1 mg/kg SC once daily

Elderly patients > 75 years of age (for acute STEMI indication only)

Standard dosing: 0,75 mg/kg SC twice daily without initial bolus

Severe renal impairment: 1 mg/kg SC once daily without initial bolus

The following dosage adjustments are recommended for prophylactic dosage ranges:

Standard dosing: 40 mg SC once daily

20 mg SC once daily

Severe renal impairment: 20 mg SC once daily

20 mg SC once daily

The recommended dosage adjustments do not apply to the haemodialysis indication.

Moderate and mild renal impairment: Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 ml/min) and mild (creatinine clearance 50-80 ml/min) renal impairment, careful clinical monitoring is advised.

Spinal/epidural anaesthesia: For patients receiving spinal/epidural anaesthesia see section 4.4, Warnings Spinal/epidural anaesthesia.

Method of administration

Subcutaneous injection: CLEXANE is administered by subcutaneous injection for the prevention of venous thromboembolic disease; treatment of deep vein thrombosis; treatment of unstable angina and non-Q-wave myocardial infarction and treatment of acute ST-segment Elevation Myocardial Infarction.

IV bolus injection: For acute ST-segment Elevation Myocardial Infarction, treatment is to be initiated with a single IV bolus injection immediately followed by a subcutaneous injection.

Arterial line injection: It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the extra-corporeal circulation during haemodialysis. CLEXANE must never be injected intramuscularly. The prefilled disposable syringe is ready for immediate use. When using CLEXANE vials, the volume to be injected should be measured precisely with a graduated syringe fitted with an appropriate needle for subcutaneous injection.

Subcutaneous injection technique: Injections should be made preferably when the patient is lying down. CLEXANE is administered by deep subcutaneous injection. Do not expel the air bubble from the syringe before injecting to avoid the loss of medicine, when using the 20 mg and 40 mg prefilled syringes. The administration should be alternated between the left and right anterolateral or posterolateral abdominal wall.

Safety device: The prefilled syringes fitted with an automatic safety device avoid accidental needle pricks after injecting. When the protective cap is removed off the needle, a drop may appear at the end of the needle. If so, remove it before injecting the medicine by lightly tapping the body of the syringe with the needle pointing down. The prefilled syringe is ready to use. Do not press on the plunger to expel any air bubbles before administering the injection. The injection must be given with the patient preferably lying down. The whole length of the needle should be introduced perpendicularly, not from the side, into a skin fold held between the thumb and index finger. This skin fold should be held throughout the injection. Do not rub the injection site after administration. The safety device is automatically activated once the plunger is fully depressed, thus completely protecting the used needle and without causing discomfort to the patient. Activation of the safety device is only possible if the plunger is fully depressed. The safety device can only be activated once the syringe is completely empty.

Intravenous (Bolus) Injection Technique (for acute STEMI indication only): For intravenous injection, the multiple-dose vial should be used. CLEXANE should be administered through an intravenous line. It should not be mixed or co-administered with other medications. To avoid the possible mixture of CLEXANE with other medicines, the intravenous access chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the intravenous bolus administration of CLEXANE to clear the port of medicine. CLEXANE may be safely administered with normal saline solution (0,9 %) or 5 % dextrose in water. No additional bolus dose is needed if the last administration of CLEXANE was less than 8 hours before balloon inflation. Do not use the multidose vial for more than 28 days after first use.

u2022 hypersensitivity to CLEXANE, heparin or its derivatives including other Low Molecular Weight Heparins

u2022 history of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies (also see section 4.4)

u2022 heparin-associated thrombocytopenia

u2022 hypersensitivity to benzyl alcohol

u2022 active major bleeding and conditions with a high risk of uncontrolled haemorrhage including recent haemorrhagic stroke; patients at risk include those with haemorrhagic blood disorders, thrombocytopenia, peptic ulcers, cerebrovascular disorders, infective endocarditis, and severe or uncontrolled hypertension

u2022 safety and efficacy in children has not been established. The multiple-dose formulation contains benzyl alcohol as a preservative and should not be used in neonates. The administration of medicines containing benzyl alcohol as a preservative to premature neonates has been associated with a fatal u201cGasping Syndromeu201d

CLEXANE should be used with care in the presence of severe liver dysfunction.

CLEXANE should be used in reduced dosages in patients with severe kidney dysfunction (creatinine clearance less than 30 ml/min). Do not administer by the intramuscular route.

Spinal/Epidural anaesthesia: There have been cases of intraspinal haematomas reported with the concurrent use of CLEXANE and spinal/epidural anaesthesia resulting in long-term or permanent paralysis. The risk is greater with higher CLEXANE dosage regimens, use of post-operative indwelling catheters or the concomitant use of additional medicines affecting haemostasis such as NSAIDs see section 4.5). The risk also appears to be increased by traumatic or repeated neuraxial puncture or in patients with a history of spinal surgery or spinal deformity.

To reduce the potential risk of bleeding, placement and removal of the catheter is best performed when the anticoagulant effect of CLEXANE is low, however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. Neuraxial techniques should be avoided in patients administered a dose of CLEXANE 2 hours pre-operatively (general surgery). Placement or removal of a catheter should be delayed for at least 12 hours after administration of lower doses (20 mg once daily or 40 mg once daily) of enoxaparin, and at least 24 hours after the administration of higher doses (0,75 mg/kg twice daily, 1 mg/kg twice daily, or 1,5 mg/kg once daily) of enoxaparin. Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial haematoma will be avoided. Patients receiving the 0,75 mg/kg twice-daily dose or the 1 mg/kg twice-daily dose should not receive the second enoxaparin dose in the twice-daily regimen to allow a longer delay before catheter placement or removal. Likewise, although a specific recommendation for timing of a subsequent enoxaparin dose after catheter removal cannot be made, consider delaying this next dose for at least four hours, based on a benefit-risk assessment considering both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors.

For patients with creatinine clearance < 30 ml/minute, additional considerations are necessary because elimination of enoxaparin is more prolonged (see section 4.2: Severe renal impairment); consider doubling the timing of placement or removal of a catheter, at least 24 hours for the lower prescribed dose of enoxaparin (20 mg once daily) and at least 48 hours for the higher dose (1 mg/kg/day).

Should the medical practitioner decide to administer anticoagulation in the context of epidural/spinal anaesthesia or lumber puncture, extreme vigilance and frequent monitoring must be exercised to detect any signs and symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), bowel and/or bladder dysfunction. Patients should be instructed to inform their medical practitioner immediately if they experience any of the above signs or symptoms. If signs or symptoms of spinal haematoma are suspected, urgent diagnosis and treatment including spinal cord decompression should be initiated.

Patients with Artificial Heart Valves: In patients with artificial heart valves, CLEXANE should only be used if regular Factor-Xa activity can be monitored.

General: Low Molecular Weight Heparins such as CLEXANE should not be used interchangeably since they differ in their manufacturing processes, molecular masses, specific anti-Xa activities, units and dosage. This results in differences in pharmacokinetics and associated biological activities {e.g. anti-thrombin (IIa) activity, and platelet interactions}. Special attention and compliance with the instructions for use specific to each proprietary medicinal product is therefore required.

Heparin-induced thrombocytopenia: Use of CLEXANE in patients with a history of immune mediated HIT within the past 100 days or in the presence of circulating antibodies is contraindicated (see section 4.3). Circulating antibodies may persist several years. CLEXANE is to be used with extreme caution in patients with a history (more than 100 days) of heparin-induced thrombocytopenia without circulating antibodies. The decision to use CLEXANE in such a case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments are considered.

Monitoring of platelet counts: The risk of antibody-mediated heparin-induced thrombocytopenia also exists with CLEXANE. Should thrombocytopenia occur, it usually appears between the 5th and 21st day following the beginning of CLEXANE treatment. Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with CLEXANE and then regularly thereafter during treatment. In practice, if confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial value), CLEXANE treatment must be immediately discontinued and the patient switched to another therapy.

Percutaneous coronary revascularisation procedures: To minimise the risk of bleeding following the vascular instrumentation during the treatment of unstable angina, non-Q-wave myocardial infarction and acute ST-segment elevation myocardial infarction, adherence to the intervals recommended between CLEXANE doses is essential. It is important to achieve haemostasis at the puncture site after PCI. In case a closure device is used, the sheath can be removed immediately. If a manual compression method is used, the sheath should be removed 6 hours after the last IV/SC CLEXANE injection. If the treatment with CLEXANE is to be continued, the next scheduled dose should be given no sooner than 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or haematoma formation.

Mechanical prosthetic heart valves: The use of CLEXANE has not been adequately studied for thromboprophylaxis in patients with mechanical prosthetic heart valves. Prosthetic heart valve thrombosis and fatalities have been reported in patients with mechanical prosthetic heart valves who have received CLEXANE for thromboprophylaxis.

Pregnant women with mechanical prosthetic heart valves: The use of CLEXANE for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves has not been adequately studied. There have been post-marketing reports of fatal valve thrombosis in pregnant women with mechanical prosthetic heart valves while receiving CLEXANE for thromboprophylaxis. Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. CLEXANE is not recommended for this use.

Haemorrhage: Bleeding may occur at any site (see section 4.8). If bleeding occurs, the origin of the haemorrhage should be investigated and appropriate treatment instituted. CLEXANE injection should be used with caution in conditions with increased potential for bleeding, such as:

u2022 history of peptic ulcer

u2022 impaired haemostasis

u2022 recent ischaemic stroke

u2022 uncontrolled severe arterial hypertension

u2022 diabetic retinopathy

u2022 recent neuro- or ophthalmologic surgery

u2022 concomitant use of medications affecting haemostasis see section 4.5).

Haemorrhage in the elderly: Elderly patients are at an increased risk for bleeding complications with both the prophylactic and therapeutic dosage ranges of CLEXANE. Careful clinical monitoring is advised (see section 4.2 u2013 Elderly and section 5.2 - Elderly).

Renal impairment: In patients with renal impairment, there is an increase in exposure of CLEXANE which increases the risk of bleeding. Since exposure of CLEXANE is significantly increased in patients with severe renal impairment (creatinine clearance < 30 ml/min), a dosage adjustment is recommended for therapeutic and prophylactic dosage ranges. Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30u201350 ml/min) and mild (creatinine clearance 50u201380 ml/min) renal impairment, careful clinical monitoring is advised (see sections 4.2 and 5.2 u2013 Renal impairment).

Low weight: An increase in exposure of CLEXANE with prophylactic dosages (non-weight adjusted) has been observed in low-weight women (< 45 kg) and low-weight men (< 57 kg), which may lead to a higher risk of bleeding. Therefore, careful clinical monitoring is advised in these patients (see section 5.2 - Weight).

Obese patients: Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in obese patients (BMI >30 kg/m2) has not been fully determined. These patients should be observed carefully for signs and symptoms of thromboembolism.

Laboratory tests: At doses used for prophylaxis of venous thromboembolism, CLEXANE does not influence bleeding time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of fibrinogen to platelets. Therefore, standard clotting tests cannot be done to monitor treatment. Inter-individual variations in bleeding and coagulation times may occur even when identical dosages are used. At higher doses than used for prophylaxis, increases in aPTT (activated partial thromboplastin time) and ACT (activated clotting time) may occur. Increases in aPTT and ACT are not linearly correlated with increasing CLEXANE antithrombotic activity and therefore are unsuitable and unreliable for monitoring CLEXANE activity.

It is recommended that medicines which affect haemostasis should be discontinued prior to CLEXANE therapy unless strictly indicated, such as:

u2022 systemic salicylates, acetylsalicylic acid and NSAIDs including ketorolac and diclofenac,

u2022 dextran 40, ticlopidine and clopidogrel,

u2022 systemic glucocorticoids,

u2022 thrombolytics and anticoagulants,

u2022 other anti-platelet agents including glycoprotein IIb/IIIa antagonists.

If the combination cannot be avoided, CLEXANE should be used with careful clinical and laboratory monitoring.

Pregnancy

Safety in pregnancy and lactation has not been established. Also see section 4.4: Mechanical prosthetic heart valves and Pregnant women with mechanical prosthetic heart valves.

As there are no adequate and well-controlled studies in pregnant women and because animal studies are not always predictive of human response, CLEXANE should be used during pregnancy only if the medical practitioner has established a clear need.

Breastfeeding

Mothers receiving CLEXANE should not breastfeed their infants.

CLEXANE has no effect on the ability to drive and operate machines.

Summary of safety profile

In clinical studies, haemorrhages, thrombocytopenia and thrombocytosis were the most commonly reported reactions (see section 4.4 and 'Description of selected adverse reactions belowu2019).

Tabulated summary list of adverse reactions

Adverse reactions observed in clinical studies and reported in post-marketing experience (* indicates reactions from post-marketing experience) are detailed below. The following frequency rating has been used:

Very common: (>1/10); Common: (>1/100, 1/1000, 1/10 000, <1/1000); Very rare: (<1/10 000), including rare isolated cases.

Blood and the lymphatic system disorders

Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis

Rare: Eosinophilia*, cases of immuno-allergic thrombocytopenia* with thrombosis (in some of them thrombosis was complicated by organ infarction or limb ischaemia (see section 4.4))

Immune system disorders

Common: allergic reaction

Rare: anaphylactic or anaphylactoid reaction including shock*

Nervous system disorders

Common: Headache*

Vascular disorders

Rare: Cases of spinal/neuraxial haematoma* have been reported with the concurrent use of CLEXANE as well as spinal/epidural anaesthesia or spinal puncture. These reactions have resulted in varying degrees of neurologic injuries including long-term or permanent paralysis.

Hepato-biliary disorders

Very common: hepatic enzymes increase (mainly transaminase levels > 3 times the upper limit of normality)

Uncommon: Hepatocellular liver injury*

Rare: Cholestatic liver injury*

Skin and subcutaneous tissue disorders

Common: urticaria, pruritus, erythema

Uncommon: bullous dermatitis

Rare: cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena are usually preceded by purpura or erythematous plaques, infiltrated and painful). Treatment with CLEXANE must be discontinued, if cutaneous vasculitis or skin necrosis occurs. Injection site nodules* (inflammatory nodules which were not cystic enclosure of enoxaparin), alopecia*

Musculoskeletal and connective tissue disorders

Rare: osteoporosis* following long-term therapy (longer than 3 months)

General disorders and administration site conditions

Common: injection site haematoma, injection site pain, other injection site reaction (such as injection side oedema, haemorrhage, hypersensitivity, inflammation, mass, pain or reaction)

Uncommon: local irritation, skin necrosis at injection site

Investigations

Rare: hyperkalaemia.

Description of selected adverse reactions

Haemorrhages

Haemorrhages were the most commonly reaction, including major and fatal haemorrhages. Haemorrhage may occur even without the presence of associated risk factors such as: organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting haemostasis.

MedDRA Prophylaxis in Prophylaxis in Treatment in Treatment in Treatment in

system organ class surgical patients medical patients patients with DVT with or without PE patients with unstable angina and non-Q-wave MI patients with acute STEMI

Vascular disorders

Very common: Haemorrhage*

Rare: Retroperitoneal haemorrhage

Common: Haemorrhage*

Very common: Haemorrhage*

Uncommon: Intracranial haemorrhage, Retroperitoneal haemorrhage

Common: Haemorrhage*

Rare: Retroperitoneal haemorrhage

Common: Haemorrhage*

Uncommon: Intracranial haemorrhage, Retroperitoneal haemorrhage

*: such as haematoma, ecchymosis other than at injection site, wound haematoma, haematuria, epistaxis and gastro-intestinal haemorrhage.

Thrombocytopenia and thrombocytosis

MedDRA system organ class Prophylaxis in surgical patients Prophylaxis in medical patients Treatment in patients with DVT with or without PE Treatment in patients with unstable angina and non-Q-wave MI Treatment in patients with acute STEMI

Blood and lymphatic system disorders

Very common: Thrombocytosis *

Common: Thrombocytopenia

Uncommon: Thrombocytopenia

Very common: Thrombocytosis *

Common: Thrombocytopenia

Uncommon: Thrombocytopenia

Common: Thrombocytosis *

Thrombocytopenia

Very rare: Immuno-allergic thrombocytopenia

*: Platelet increased > 400 G/L

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8, or to the Pharmacovigilance Unit at Sanofi at [email protected] (email) or 011 256 3700 (tel).

Signs and symptoms: Accidental overdosage with CLEXANE after intravenous, extracorporeal or subcutaneous administration may lead to haemorrhagic complications.

Management: Antidote and treatment

The anticoagulant effects may be partially neutralised by the slow intravenous injection of protamine. However, even with high doses of protamine, the anti-Xa activity of CLEXANE is never completely neutralised (maximum about 60 %). Not more than 50 mg of protamine sulphate should be injected for any one dose. Further treatment is symptomatic and supportive.