英文药名:Clexane(Enoxaparin Sodium Injection) 中文药名:依诺肝素钠注射液 生产厂家:安万特
Treatment of unstable angina and non-Q-wave myocardial infarction The recommended dose is 1 mg/kg Clexane every 12 hours by subcutaneous injection, administered concurrently with oral 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.
The recommended dose of enoxaparin sodium is a single IV bolus of 30mg plus a 1mg/kg SC dose followed by 1mg/kg administered SC every 12 hours (max 100mg for the first two doses only, followed by 1mg/kg dosing for the remaining doses). For dosage in patients ≥75 years of age, see section 4.2 Posology and method of administration: Elderly.
(1) Not to be given for the first two doses - (maximum 100mg for the first two doses only, followed by 1mg/kg dosing for the remaining doses) When administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific) enoxaparin sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. All patients should receive acetylsalicylic acid (ASA) as soon as they are identified as having STEMI and maintained under (75 to 325mg once daily) unless contraindicated. The recommended duration of enoxaparin sodium treatment is 8 days or until hospital discharge, whichever comes first. For patients managed with Percutaneous Coronary Intervention (PCI): If the last enoxaparin sodium SC administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last SC administration was given more than 8 hours before balloon inflation, an IV bolus of 0.3mg/kg of enoxaparin sodium should be administered. Prevention of extracorporeal thrombus formation during haemodialysis: A dose equivalent to 1 mg/kg (100 IU/kg) introduced into the arterial line at the beginning of a dialysis session is usually sufficient for a 4 hour session. If fibrin rings are found, such as after a longer than normal session, a further dose of 0.5 to 1 mg/kg (50 to 100 IU/kg) may be given. For patients at a high risk of haemorrhage the dose should be reduced to 0.5 mg/kg (50 IU/kg) for double vascular access or 0.75 mg/kg (75 IU/kg) for single vascular access. 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 0.75mg/kg SC every 12 hours (maximum 75mg for the first two doses only, followed by 0.75mg/kg dosing for the remaining doses). For other indications, no dosage adjustments are necessary in the elderly, unless kidney function is impaired (see also section 4.2 Posology and method of administration: Renal impairment; section 4.4 Special warnings and precautions for use: Haemorrhage in the elderly; Renal impairment and Monitoring; section 5.2 Pharmacokinetic properties).
(2) not to be given for the first two doses - (maximum 75mg for the first two doses only, followed by 0.75mg/kg dosing for the remaining doses) Children: Not recommended, as dosage not established. Renal impairment: (See also section 4.4 Special warnings and precautions for use: Renal impairment and Monitoring; section 5.2 Pharmacokinetic properties). 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 enoxaparin sodium exposure is significantly increased in this patient population: Dosage adjustments for therapeutic dosage ranges
Dosage adjustments for prophylactic dosage ranges
The recommended dosage adjustments do not apply to the haemodialysis indication. Moderate and mild renal impairment: Although no dosage adjustments are recommended in patients with moderate renal impairment (creatinine clearance 30-50 ml/min) or mild renal impairment (creatinine clearance 50-80 ml/min), careful clinical monitoring is advised. Hepatic impairment: In the absence of clinical studies, caution should be exercised. Body weight: No dosage adjustments are recommended in obesity or low body weight (see also section 4.4 Special warnings and precautions for use: Low body weight and Monitoring; section 5.2 Pharmacokinetic properties). Clexane is administered by subcutaneous injection for the prevention of venous thromboembolic disease, the treatment of deep vein thrombosis or for the treatment of unstable angina, non-Q-wave myocardial infarction and acute ST elevation myocardial infarction (STEMI); through the arterial line of a dialysis circuit for the prevention of thrombus formation in the extra-corporeal circulation during haemodialysis; and via intravenous (bolus) injection through an intravenous line only for the initial dose of acute STEMI indication and before PCI when needed. It must not be administered by the intramuscular route. Subcutaneous Injection Technique When using vials of enoxaparin sodium, the volume to be injected should be measured precisely with a graduated syringe fitted with an appropriate needle for subcutaneous injection. Clexane should be administered when the patient is lying down by deep subcutaneous injection. The administration should be alternated between the left and right anterolateral or posterolateral abdominal wall. The whole length of the needle should be introduced vertically into a skin fold held between the thumb and index finger. The skin fold should not be released until the injection is complete. Do not rub the injection site after administration. Intravenous (Bolus) Injection Technique (for acute STEMI indication only): For intravenous injection, either the Multidose Vial or 60mg, 80mg or 100mg prefilled syringes can be used. Enoxaparin sodium should be administered through an intravenous line. It should not be mixed or co-administered with other medications. To avoid the possible mixture of enoxaparin sodium with all other drugs, 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 enoxaparin sodium to clear the port of the drug. Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water. 4.3 Contraindications Contraindicated in patients with acute bacterial endocarditis, active major bleeding and conditions with a high risk of uncontrolled haemorrhage, including recent haemorrhagic stroke; thrombocytopenia in patients with a positive in-vitro aggregation test in the presence of enoxaparin; active gastric or duodenal ulceration; hypersensitivity to either enoxaparin sodium, heparin or its derivatives including other Low Molecular Weight Heparins, hypersensitivity to benzyl alcohol; in patients receiving heparin for treatment rather than prophylaxis, locoregional anaesthesia in elective surgical procedures is contra-indicated. Because of the content of benzyl alcohol, Clexane Multidose Vial must not be given to newborns or premature neonates. 4.4 Special warnings and precautions for use Low Molecular Weight Heparins should not be used interchangeably since they differ in their manufacturing process, molecular weights, specific anti Xa activities, units and dosage. This results in differences in pharmacokinetics and associated biological activities (e.g. anti-IIa activity, and platelet interactions). Special attention and compliance with the instructions for use specific to each proprietary medicinal product are therefore required. Enoxaparin is to be used with extreme caution in patients with a history of heparin-induced thrombocytopenia with or without thrombosis. As there is a risk of antibody-mediated heparin-induced thrombocytopenia also occurring with low molecular weight heparins, regular platelet count monitoring should be considered prior to and during therapy with these agents. Thrombocytopenia, should it occur, usually appears between the 5th and the 21st day following the beginning of therapy. Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with enoxaparin sodium and then regularly thereafter during the treatment. In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial value), enoxaparin sodium treatment must be immediately discontinued and the patient switched to another therapy. Enoxaparin injection, as with any other anticoagulant therapy, should be used with caution in conditions with increased potential for bleeding, such as: impaired haemostasis, history of peptic ulcer, recent ischaemic stroke, uncontrolled severe arterial hypertension, diabetic retinopathy, recent neuro- or ophthalmic surgery. As with other anticoagulants, bleeding may occur at any site (see section 4.8 Undesirable effects). If bleeding occurs, and sometimes anaemia, the origin of the haemorrhage should be investigated and appropriate treatment instituted. Heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, a raised plasma potassium or taking potassium sparing drugs. The risk of hyperkalaemia appears to increase with duration of therapy but is usually reversible. Plasma potassium should be measured in patients at risk before starting heparin therapy and monitored regularly thereafter particularly if treatment is prolonged beyond about 7 days. As with other anticoagulants, there have been cases of intra-spinal haematomas reported with the concurrent use of enoxaparin sodium and spinal/epidural anaesthesia or spinal puncture resulting in long term or permanent paralysis. These events are rare with enoxaparin sodium dosage regimens 40 mg od or lower. The risk is greater with higher enoxaparin sodium dosage regimens, use of post-operative indwelling catheters or the concomitant use of additional drugs affecting haemostasis such as NSAIDs (see section 4.5 Interaction with other medicinal products and other forms of interaction). 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 associated with the concurrent use of enoxaparin sodium and epidural anaesthesia/analgesia, the pharmacokinetic profile of the drug should be considered (see section 5.2 Pharmacokinetic properties). Placement and removal of the catheter is best performed when the anticoagulation effect of enoxaparin is low. Placement or removal of a catheter should be delayed for 10 to 12 hours after administration of DVT prophylactic doses of enoxaparin sodium, whereas patients receiving higher doses of enoxaparin sodium (1.5 mg/kg once daily) will require longer delays (24 hours). The subsequent enoxaparin sodium dose should be given no sooner than 4 hours after catheter removal. Should the physician decide to administer anticoagulation in the context of epidural/spinal anaesthesia, 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 nurse or physician 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. The Multidose vial contains benzyl alcohol as a preservative and should not be given to premature babies or neonates. The administration of medicines containing benzyl alcohol as a preservative may cause toxic reactions and anaphylactoid reactions in children up to 3 years old. The administration of medications containing benzyl alcohol to newborns or premature neonates has been associated with a fatal “Gasping Syndrome” (symptoms include a striking onset of gasping syndrome, hypotension, bradycardia, and cardio-vascular collapse). As benzyl alcohol may cross the placenta, solution for injection should be used with caution in pregnancy. Percutaneous coronary revascularisation procedures: To minimise the risk of bleeding following vascular instrumentation during the treatment of unstable angina, non-Q-wave myocardial infarction and acute ST-elevation myocardial infarction, adhere precisely to the intervals recommended between enoxaparin sodium doses. It is important to achieve homeostasis at the puncture site after PCI. If a closure device is used, the sheath can be removed immediately. If a manual compression method is used, sheath should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If the treatment is continued, the next scheduled dose should be given no sooner than 6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or haematoma formation. For some patients with pulmonary embolism (e.g. those with severe haemodynamic instability) alternative treatment such as thrombolysis or surgery may be indicated. Prosthetic Heart Valves: There have been no adequate studies to assess the safe and effective use of enoxaparin sodium in preventing valve thrombosis in patients with prosthetic heart valves. Prophylactic doses of enoxaparin are not sufficient to prevent valve thrombosis in patients with prosthetic heart valves. Confounding factors, including underlying disease and insufficient clinical data, limit the evaluation of these cases. Therapeutic failures have been reported in pregnant women with prosthetic heart valves on full anti-coagulant doses (see section 4.6 Pregnancy and lactation). The use of enoxaparin sodium cannot be recommended for this purpose. Haemorrhage in the elderly: No increased bleeding tendency is observed in the elderly within the prophylactic dosage ranges. Elderly patients (especially patients aged eighty years and above) may be at an increased risk for bleeding complications within the therapeutic dosage ranges. In the treatment of acute ST-segment Elevation Myocardial Infarction (STEMI), an increase in bleeding events was observed in patients aged 65-75 years suggesting these patients might be at particular risk of bleeding. Careful clinical monitoring is advised (see also section 4.2 Posology and method of administration: Elderly; section 5.2 Pharmacokinetic properties). Renal impairment: In patients with renal impairment, there is an increase in enoxaparin exposure which increases the risk of bleeding. Since enoxaparin exposure is significantly increased in patients with severe renal impairment (creatinine clearance < 30 ml/min) dosage adjustments are recommended in therapeutic and prophylactic dosage ranges. Although no dosage adjustments are 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 (see also section 4.2 Posology and method of administration: Renal impairment; section 5.2 Pharmacokinetic properties). In the treatment of acute ST-segment Elevation Myocardial Infarction (STEMI), the data are limited in patients with creatinine levels above 220 and 175 µmol/L for males and females respectively. Low body weight: In low-weight women (< 45 kg) and low-weight men (< 57 kg), an increase in enoxaparin exposure has been observed within the prophylactic dosage ranges (non-weight adjusted), which may lead to a higher risk of bleeding. Therefore, careful clinical monitoring is advised in these patients (see also section 5.2 Pharmacokinetic properties). 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 and there is no consensus for dose adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism. Monitoring: Risk assessment and clinical monitoring are the best predictors of the risk of potential bleeding. Routine anti-Xa activity monitoring is usually not required. However, anti-Xa activity monitoring might be considered in those patients treated with LMWH who also have either an increased risk of bleeding (such as those with renal impairment, elderly and extremes of weight) or are actively bleeding. Laboratory tests: At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of fibrinogen to platelets. At higher doses, 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 enoxaparin sodium antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium activity. 4.5 Interaction with other medicinal products and other forms of interaction It is recommended that agents which affect haemostasis should be discontinued prior to enoxaparin therapy unless their use is essential, such as: systemic salicylates, acetylsalicylic acid, NSAIDs including ketorolac, dextran, and clopidogrel, systemic glucocorticoids, thrombolytics and anticoagulants. If the combination cannot be avoided, enoxaparin should be used with careful clinical and laboratory monitoring. 4.6 Pregnancy and lactation Pregnancy: Animal studies have not shown any evidence of foetotoxicity or teratogenicity. In the pregnant rat, the transfer of 35S-enoxaparin across the maternal placenta to the foetus is minimal. In humans, there is no evidence that enoxaparin crosses the placental barrier during the second trimester of pregnancy. There is no information available concerning the first and the third trimesters. As there are no adequately powered and well-controlled studies in pregnant women and because animal studies are not always predictive of human response, this drug should be used during pregnancy only if the physician has established a clear need. . Pregnant women with mechanical prosthetic heart valves The use of enoxaparin for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic heart valves given enoxaparin (1 mg/kg bid) to reduce the risk of thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal and foetal death. There have been isolated postmarketing reports of valve thrombosis in pregnant women with mechanical prosthetic heart valves while receiving enoxaparin for thromboprophylaxis. Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism. Enoxaparin sodium is not recommended for use in pregnant women with prosthetic heart valves (see section 4.4 Special warnings and precautions for use: Prosthetic heart valves). Lactation: In lactating rats, the concentration of 35S-enoxaparin or its labelled metabolites in milk is very low. It is not known whether unchanged enoxaparin is excreted in human breast milk. The oral absorption of enoxaparin is unlikely. However, as a precaution, lactating mothers receiving enoxaparin should be advised to avoid breast-feeding 4.7 Effects on ability to drive and use machines Enoxaparin has no effect on the ability to drive and operate machines. 4.8 Undesirable effects The adverse reactions observed in clinical studies and reported in post-marketing experience are detailed below. Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); and very rare (< 1/10,000) or not known (cannot be estimated from available data). Post-marketing adverse reactions are designated with a frequency “not known”. Haemorrhages In clinical studies, haemorrhages were the most commonly reported reaction. These included major haemorrhages, reported at most in 4.2 % of the patients (surgical patients1). Some of these cases have been fatal. As with other anticoagulants, haemorrhage may occur during enoxaparin therapy in the presence of associated risk factors such as: organic lesions liable to bleed, invasive procedures or the concomitant use of medications affecting haemostasis (see section 4.5). The origin of the bleeding should be investigated and appropriate treatment instituted.
1 In surgical patients, haemorrhage complications were considered major: (1) if the haemorrhage caused a significant clinical event, or (2) if accompanied by an haemoglobin decrease ≥ 2 g/dL or transfusion of 2 or more units of blood products. Retroperitoneal and intracranial haemorrhages were always considered major. Thrombocytopenia and thrombocytosis
Other clinically relevant adverse reactions These reactions are presented below, whatever the indications, by system organ class, frequency grouping and decreasing order of seriousness.
**: transaminases levels > 3 times the upper limit of normality
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依诺肝素钠注射液|Clexane(Enoxaparin Sodium Injection)简介:
英文药名:Clexane(Enoxaparin Sodium Injection)
中文药名:依诺肝素钠注射液
生产厂家:安万特药品介绍【别名】克赛,依诺肝素【外文名】Enoxaparin,LMW-H,Clexane克赛 预装针剂 Clexane制造商 ... 责任编辑:admin
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