Lovenox Special Precautions

Hemorrhage: As with all anticoagulants, bleeding may occur. If the event of bleeding, the cause must be investigated and appropriate treatment instituted.
Renal function: Before low molecular weight heparin treatment is initiated, it is essential to evaluate renal function in subjects 75 years or older by determining creatinine clearance (CrCl) using Cockcroft's formula and recent bodyweight measurement: In male patients: Clcr = (140-age) x weight / (0.814 x serum creatinine) where age is expressed in years , weight in kg and serum creatinine in mcg μmol/L.
This formula must be adjusted for female patients by multiplying the result by 0.85.
When serum creatinine is expressed in mg/mL, the value should be multiplied by a factor of 8.8.
In patients diagnosed with severe renal failure (creatinine clearance of about 30 ml/min), the use of LMWH as curative intent is contraindicated.
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.
History of HIT (>100 days): Use of enoxaparin sodium 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 Contraindications). Circulating antibodies may persist several years. Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such a case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments are considered.
Laboratory tests: Platelet monitoring: Heparin-induced thrombocytopenia (HIT): There is a risk of serious, occasionally thrombogenic heparin-induced thrombocytopenia (reported with unfractionated heparin and less often with LMWH) of immunologic origin, called type II HIT.
As a result of this risk, platelet counts must be performed regardless of the therapeutic indication and the dose administered.
Platelet counts must be performed before administration or at the latest within 24 hours of initiating treatment, then twice a week during the usual treatment duration.
Should long-term treatment prove necessary in certain specific cases (i.e. hip surgery, second and third trimesters of high-risk pregnancy, the schedule for platelet counts is twice a week during the first month of treatment (highest risk period) and then once a week until treatment discontinuation.
HIT should be suspected when the platelet count is below 100,000/mm3 and/or when there is a drop of 30 to 50% between two successive platelet counts. HIT mainly develops 5 to 21 days after heparin treatment is instituted (with a peak incidence after about 10 days).
This complication can however occur much earlier in patients with a history of heparin-induced thrombocytopenia and extremely rare cases have been reported after 21 days. This type of patient history must therefore be systematically investigated by means of an in-depth interview before starting treatment.
Furthermore, the risk of recurrence when reinstituting heparin may remain for years or even indefinitely.
In all cases, the occurrence of HIT constitutes an emergency situation and requires a specialist opinion.
Any significant drop in the platelet count (30% to 50% versus baseline) is a warning sign even before values reach a critical level. Should a decrease in platelets be observed, the following must be performed in all cases: an immediate platelet count for verification; discontinuation of heparin treatment, if the drop is confirmed or even increased based on these results and when no other obvious cause is identified. A sample must be taken using a citrate tube in order to perform in vitro platelet aggregation and immunological assays. However, under these conditions, the immediate measures to be taken are not based on in vitro platelet aggregation or immunological test results as only a few specialized laboratories perform these tests routinely and the results are available at best after several hours. These tests are, however, necessary to assist in diagnosis of the complication as the risk of thrombosis is very high if heparin treatment is continued.
Prevention or treatment of HIT-related thrombotic complications. If continued anticoagulant therapy appears to be essential, heparin must be replaced by an antithrombotic agent of a different chemical group of such as sodium danaparoid or hirudine, prescribed at curative or preventive doses on a case-by-case basis.
Replacement by oral anticoagulants can only take place after the platelet count has reverted to normal due to the risk of exacerbation of thrombosis by oral anticoagulants.
Replacement of heparin by oral anticoagulants: Clinical monitoring and laboratory tests (one stage prothrombin time expressed as the INR) must be intensified to monitor the effect of oral anticoagulants. As there is an interval before the oral anticoagulant has reached its maximum effect, heparin therapy should be maintained at an equivalent dose so that the INR remains within the desired therapeutic range for the indication in two successive tests.
Monitoring of anti-factor Xa activity: As most of the clinical studies which demonstrated the efficacy of LMWH were conducted using a dose based on bodyweight without specific laboratory monitoring, the utility of laboratory tests for assessing the efficacy of LMWH treatment has not been established. However, monitoring of anti-Xa activity may be useful in managing the risk of bleeding in certain clinical conditions often associated with a risk of overdose.
These situations mainly concern the curative indications of LMWH, due to the doses administered, in patients with: mild to moderate renal insufficiency (creatinine clearance of approximately 30 ml/min to 60 ml/min calculated using the Cockcroft formula). As LMWH is primarily eliminated by the renal route, unlike standard unfractionated heparin, any renal insufficiency can result in relative overdose. Severe renal insufficiency is a contraindication to the use of LMWH at curative treatment. Extreme bodyweight (thinness or even cachexia, obesity). Unexplained bleeding.
In contrast, laboratory monitoring is not recommended at prophylactic doses if the LMWH treatment is consistent with the therapeutic recommendations (particularly treatment duration), nor during hemodialysis.
To detect possible heparin accumulation following repeated administration, it is recommended, if necessary, to collect a blood sample at peak activity (based on available data), i.e. approximately 4 hours after the third injection when the drug is given as 2 subcutaneous injections per day.
Repeating anti-Xa activity assays to determine blood heparin levels, for example every 2 to 3 days, should be decided on a case-by-case basis, depending on the results of the preceding assay, and a possible LMWH dose adjustment should be considered.
The anti-Xa activity observed varies for each LMWH and each dosage regimen.
For information, based on available data, the mean value (± standard deviation) observed 4 hours after 7th injection of enoxaparin given at a dose of 100 anti-Xa IU/kg/injection b.i.d. was 1.20 ± 0.17 anti-Xa IU/ml.
This mean value was observed during clinical trials for anti-Xa activity assays carried out by a chromogenic method (amidolytic).
Activated partial thromboplastin time (aPTT): Some LMWHs moderately increase aPTT. As no clinical relevance has been established, there is no need to monitor treatment using this tests.
2000/4000 Anti-Xa IU: Spinal/epidural anesthesia in patients given preventive treatment with LMWH: Epidural or spinal anesthesia must never be performed in patients under curative LMWH treatment.
As with other anticoagulants, there have been rare reports of spinal hematomas following administration of LMWH during spinal/epidural anesthesia, resulting in long-term or permanent paralysis.
The risk of intra-spinal hematoma appears to be higher in epidural anesthesia with a catheter than in spinal anesthesia.
The risk of these rare events may be increased by prolonged post-operative use of indwelling epidural catheters and in patients who have undergone spinal surgery or have spinal deformities (e.g. ankylosing spondylitis).
Placement or removal of the catheter is best performed when the anticoagulant effect of enoxaparin is low. However, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known.
If pre-operative LMWH treatment is required (long term bedridden patients, trauma) and if the benefit of local/regional spinal anesthesia has been carefully weighed, patients who received a pre-operative injection of LMWH can be anesthetized provided that an interval of at least 12 hours is respected between the heparin injection and the spinal anesthesia. Since anti-Xa levels are, however, still detectable after this 12-hour interval, a neuraxial hematoma can still occur. Close neurological monitoring is recommended due to the risk of intraspinal hematoma.
In almost all patients, prophylactic treatment with LMWH can be initiated within 6 to 8 hours after the anesthesia or removal of the catheter, under neurogical monitoring.
Extra caution should be exercised during co-administration with other drugs which affect hemostasis (specifically non-steroidal anti-inflammatory drugs, aspirin).
Situations involving particular risk: Monitoring of treatment should be intensified in the following cases: hepatic insufficiency; history of gastrointestinal ulcers or any other organic lesion likely to bleed; vascular chorioretinal disease; post-operatively, following cerebral or spinal cord surgery; lumbar puncture: this should only be considered taking into account the risk of intraspinal bleeding. It should be postponed whenever possible; combined use with drug which have an effect on hemostasis.
6000 anti-Xa IU: Coronary angioplasty revascularization procedure: To minimize the risk of hemorrhage during coronary angioplasty for unstable angina, non-Q-wave myocardial infarction and acute ST segment elevation myocardial infarction, it is recommended that the advised intervals between enoxaparin injections be strictly complied with. It is important to perform hemostasis at the vascular puncture site following coronary angioplasty. If an occlusion device is used, the introducer can be removed immediately. If manual compression is performed, the introducer must be removed 6 hours after the last SC/IV injection of enoxaparin. If enoxaparin treatment is continued, the following injection must be performed at the earliest 6 to 8 hours after removal of the introducer. The puncture site must be monitored to detect any signs of bleeding or hematoma.