Enixum, 8000 anti-ha me/0.8 ml 0.8 ml 10 pcs

Pharmacotherapeutic group: direct acting anticoagulant.

ATX code: B01AB05

Pharmacological properties

Characteristics
Enoxaparin sodium is a low molecular weight heparin. The average molecular weight is about 4500 daltons: less than 2000 daltons, < 20%, 2000 to 8000 daltons, > 68%, more than 8000 daltons, < 18%. Enoxaparin sodium is obtained by alkaline hydrolysis of heparin benzyl ether isolated from mucous membrane of pig small intestine. Its structure is characterized by a nonreducible fragment of 2-O-sulfo-4-enpyrazinosuronic acid and a reducible fragment of 2-N,6-O-disulfo-D-glucopyranoside. The structure of enoxaparin sodium contains about 20% (ranging from 15% to 25%) of the 1,6-anhydro derivative in the reducing fragment of the polysaccharide chain. Pharmacodynamics
In vitro sodium enoxaparin has high activity against factor Xa clotting (anti-Xa activity of approximately 100 IU/ml) and low activity against
factor IIa clotting (anti-IIa or antithrombin activity of approximately 28 IU/ml).
This anticoagulant activity is mediated by antithrombin III (AT-III). In addition to anti-Xa/IIa activity, additional anticoagulant and anti-inflammatory
properties of enoxaparin sodium have also been identified in both human and animal models, which include AT-III dependent inhibition of other clotting factors such as factor
VIIa, activation of tissue factor pathway inhibitor release, and reduced release of Willebrand factor from the vascular endothelium into the bloodstream. These factors provide anticoagulant effect of enoxaparin sodium in general.
When used in prophylactic doses enoxaparin sodium slightly changes activated partial thromboplastin time (PPT), has almost no effect on platelet aggregation and on the degree of binding of fibrinogen to platelet receptors.
Anti-IIa activity in plasma is about 10 times lower than anti-Xa activity. The average maximum anti-IIa activity is observed approximately 3-4 hours after subcutaneous
administration and reaches 0.13 IU/ml and 0.19 IU/ml after repeated administration of 1 mg/kg body weight – when administered twice and 1.5 mg/kg body weight – when administered once, respectively.
Average maximum plasma anti-Xa activity is observed 3-5 hours after subcutaneous administration of the drug and is approximately 0.2; 0.4; 1.0 and 1.3 anti-Xa IU/ml after
subcutaneous administration of 20 mg, 40 mg and 1 mg/kg and 1.5 mg/kg, respectively.

Pharmacokinetics

The pharmacokinetics of enoxaparin sodium at therapeutic doses are linear. Variability within and between patient groups is low. After a single
subcutaneous administration of Enixum® at a dose of 1 mg/kg, Cmax is 0.49±0.07 IU/ml,
Tmax is 3.19+1.08 h, AUC0-24 = 4.44+0.91 IU×ml/h. According to literature data, after repeated subcutaneous administration of enoxaparin sodium at a dose of 40 mg once daily and subcutaneous administration of enoxaparin sodium at a dose of 1.5 mg/kg once daily the equilibrium concentration is reached by the 2nd day, the area under the pharmacokinetic curve being on average 15% higher than after a single injection. After repeated subcutaneous injections of enoxaparin sodium at a daily dose of 1 mg/kg twice a day the equilibrium concentration is reached after 3-4 days, the area under the pharmacokinetic curve being on the average 65 % higher than after a single injection. The bioavailability of sodium enoxaparin when administered subcutaneously, estimated on the basis of anti-Xa activity, is close
to 100%.

The volume of distribution of anti-Xa activity of sodium enoxaparin is approximately 5 L and approaches the blood volume.
Sodium enoxaparin is a drug with low clearance. After 6 h of IV administration at a dose of 1.5 mg/kg body weight, the average plasma clearance of anti-Xa was
0.74 L/h.

Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to form low molecular weight substances with very low biological activity.

Patients with impaired renal function
The clearance of enoxaparin sodium is reduced in patients with reduced renal function.
Lower clearance of enoxaparin sodium has been noted in renal failure. After repeated subcutaneous administration of 40 mg of sodium enoxaparin once a day there is an increase of anti-Xa activity represented by the area under the pharmacokinetic curve in mild (creatinine clearance (CK) 50-80 ml/min) and moderate (CK 30-50 ml/min) renal impairment. In patients with severe renal insufficiency (CKR less than 30 ml/min) the area under pharmacokinetic curve at equilibrium is, on average, 65% higher with repeated subcutaneous administration of 40 mg of the drug once daily.

Patients with excessive body weight
In people with excessive body weight the clearance is slightly lower when the drug is given subcutaneously.
If no dose adjustments are made for body weight, after a single subcutaneous injection of 40 mg of Enoxaparin sodium anti-Xa activity will be 50% higher in women with a body mass less than 45 kg and 27% higher in men with a body mass less than 57 kg compared to patients of normal average body mass.

Indications

– prevention of venous thrombosis and embolism during surgical interventions,
especially during orthopedic and general surgery;
– prevention of venous thrombosis and embolism in bed-ridden patients due to acute therapeutic
diseases (including acute heart failure and decompensation of chronic heart failure (class III or IV NYHA), acute respiratory insufficiency; acute infectious diseases; acute stages of rheumatic diseases in combination with one of the risk factors of venous thrombosis
(see “Special indications”);
– prevention of venous thromboses
– patients on bed rest due to acute therapeutic
. “Special Indications);
– treatment of deep vein thrombosis, which is accompanied or not accompanied by pulmonary embolism;
– treatment of unstable angina and myocardial infarction without Q-wave in combination with
acetylsalicylic acid;
– Prevention of thrombosis in the extracorporeal circulation system during hemodialysis (usually, when the session lasts less than 4 hours);
– treatment of acute myocardial infarction with ST-segment elevation in patients undergoing drug treatment or subsequent percutaneous coronary
intervention.

Active ingredient

Enoxaparin sodium

Composition

Active ingredient: enoxaparin sodium 8000 anti-Ha IU (80 mg);
excipients: water for injection – up to 0.8 ml.

.

How to take, the dosage

With the exception of special cases (see “Treatment of ST-segment elevation myocardial infarction, drug or percutaneous coronary intervention” and “Prevention of thrombosis in the extracorporeal circulation system during hemodialysis” below), enoxaparin sodium is injected deep subcutaneously. Injections should preferably be performed in the “supine” position of the patient. Injections should be given alternately on the left or right anterolateral or posterolateral surface of the abdomen. The needle should be inserted vertically (not laterally) into the full length skin fold, gathered and held until the injection is completed between the thumb and forefinger. The skin fold, release only after the completion of the injection. The injection site should not be massaged
after the injection. The pre-filled disposable syringe is ready for use.

The drug must not be injected intramuscularly.

Prevention of venous thrombosis and embolism in surgical interventions, especially in orthopedic and general surgical procedures. In patients at moderate risk of thrombosis and embolism (e.g., abdominal
operations), the recommended dose is 20 mg once daily subcutaneously. The first injection should be given 2 hours before surgery.

Patients at high risk for thrombosis and embolism (e.g., orthopedic surgery, oncology surgery, patients with additional
risk factors unrelated to surgery such as congenital or acquired thrombophilia, malignancy, bed rest for more than three days,
The preparation is recommended in a dose of 40 mg once a day subcutaneously (12 hours before the operation) or in a dose of 30 mg twice a day starting 12-24 hours after the operation.
The duration of drug therapy is 7-10 days on average. If necessary the therapy can be continued until the risk of thrombosis and embolism is preserved and until the patient is outpatient.
In orthopedic surgeries it may be reasonable after the initial therapy to continue treatment by dosing the drug 40 mg once daily for
3 weeks. The peculiarities of the drug use during spinal/epidural anesthesia as well as during coronary revascularization procedures are described in section “Special indications”.
Prevention of venous thrombosis and embolism in bedridden patients due to acute therapeutic conditions.

The recommended dose of Enoxaparin Sodium is 40 mg once daily subcutaneously for at least 6 days. The therapy should be continued until the patient is fully ambulatory (maximum 14 days).
The treatment of deep vein thrombosis with or without pulmonary embolism.
Enixum® is administered subcutaneously at a rate of 1.5 mg/kg body weight once daily or at a dose of 1 mg/kg body weight twice daily. In patients with complicated thromboembolic disorders it is recommended to use the drug in a dose of 1 mg/kg twice daily.

The duration of treatment is on average 10 days. Therapy with indirect anticoagulants should be started immediately, while therapy with enoxaparin sodium should be continued until therapeutic anticoagulant effect is achieved (INR [International Normalized Ratio] values should be 2.0-3.0). If necessary, control of anticoagulant effect should be assessed by anti-Xa activity.
Treatment of unstable angina and myocardial infarction without Q-wave in combination with acetylsalicylic acid
Enixum® is administered at the rate of 1 mg/kg body weight every 12 hours, subcutaneously, with simultaneous administration of oral acetylsalicylic acid at a dose of 100-325 mg once daily.
The average duration of treatment is at least 2 days and continues until the patient’s clinical condition stabilizes. Usually the drug administration lasts from 2 to 8 days.
Treatment of myocardial infarction with ST-segment elevation, medication or by percutaneous coronary intervention.
The treatment begins with an intravenous bolus injection of sodium enoxaparin at a dose of 30 mg and immediately thereafter (within 15 minutes) administer a subcutaneous dose of 1 mg/kg body weight
(with the first two subcutaneous injections, a maximum of 100 mg of sodium enoxaparin may be administered). Thereafter, all subsequent subcutaneous doses are administered every
12 hours at a rate of 1 mg/kg of body weight (i.e., if body weight is greater than 100 kg, the dose may exceed 100 mg).
In patients 75 years and older, the initial intravenous bolus injection is not used. Enoxaparin sodium is administered subcutaneously at a dose of 0.75 mg/kg every 12 hours (with a maximum of 75 mg of enoxaparin sodium administered for the first two subcutaneous injections). Then all subsequent subcutaneous doses are administered every 12 hours at a rate of 0.75 mg/kg body weight (i.e. in case of body weight over 100 kg the dose may exceed 75 mg).
In combination with thrombolytics (fibrin-specific and fibrin-unspecific) sodium enoxaparin should be administered between 15 minutes before thrombolytic
therapy and 30 minutes after it. After detection of acute ST-segment elevation myocardial infarction, acetylsalicylic
acid should be started as soon as possible, which, if there are no contraindications, should be continued for at least 30 days in doses of 75 to 325 mg daily.
The recommended duration of treatment with the drug is 8 days or until the patient is discharged from the hospital if the hospitalization period is less than 8 days.
The intravenous bolus injection of sodium enoxaparin should be performed through a venous catheter and sodium enoxaparin should not be mixed or injected with other
drugs. In order to avoid traces of other medications in the system and their interaction with enoxaparin sodium, the venous catheter should be flushed with an adequate amount of 0.9% sodium chloride solution or 5% dextrose solution before and after intravenous bolus injection of enoxaparin sodium. Enoxaparin sodium is compatible with 0.9% sodium chloride solution and 5% dextrose solution.
To perform 30 mg bolus injection of Enoxaparin sodium in the treatment of acute ST-segment elevation myocardial infarction, the excessive amount of the drug is removed from 60 mg, 80 mg and 100 mg glass syringes so that only 30 mg (0.3 ml) remains.
The 30 mg dose may be directly administered intravenously.
Filled 60 mg, 80 mg and 100 mg hypodermic syringes may be used for intravenous bolus injection of enoxaparin sodium through a venous catheter. The 60 mg syringe is recommended because it reduces the amount of drug removed from the syringe. The 20 mg syringe is not used because it does not contain enough product for a 30 mg bolus of enoxaparin sodium. 40 mg syringes are not used because they have no divisions and therefore it is impossible to accurately measure the 30 mg.
In patients undergoing percutaneous coronary intervention, if the last subcutaneous injection of sodium enoxaparin was given less than 8 hours before
blowing the balloon catheter inserted into the coronary artery narrowing, no additional injection of sodium enoxaparin is required. If the last subcutaneous sodium enoxaparin injection was administered more than 8 hours before balloon catheter inflation, an additional intravenous bolus injection of 0.3 mg/kg of enoxaparin should be given.
In order to improve the accuracy of additional intravenous bolus injection of small volumes into the venous catheter during percutaneous coronary interventions
it is recommended to dilute the drug to a concentration of 3 mg/ml. It is recommended to dilute the solution just before injection.
To obtain a solution of Enoxaparin sodium concentration 3 mg/ml using a pre-filled syringe, it is recommended to use a container with infusion
solution, from which a part of the solution is extracted to the required volume using a standard syringe. Enoxaparin sodium (the contents of the hypodermic syringe)
is injected into the remaining infusion solution in the container.

The volume of the pre-filled
syringe

The amount of infusion solution left in the tank
./p>

0.3 ml 10 ml
0.6 ml 20 ml

The contents of the diluted enoxaparin sodium solution is gently stirred. The required volume of the diluted sodium enoxaparin solution is extracted using a syringe and calculated according to the formula: Volume of diluted solution = Patient body weight (kg) x 0.1 or using the table below.
Volumes to be administered intravenously after dilution.

Patient body weight [kg] Required dose
(0.3 mg/kg) [mg]The volume of solution diluted to 3 mg/ml required to be administered45 13.5 4.5
50 15 5
55 16.5.5
60 18 6
65 19.5 6.5
70 21 7
75 22.5 7.5
80 24 8
85 25.5 8.5
90 27 9
br>95 28.5 9.5
100 30 10

Prevention of thrombosis in the extracorporeal circulatory system during hemodialysis (usually with a session duration of 4 hours or less)
The dose of enoxaparin sodium averages 1 mg/kg body weight. For patients at high risk of bleeding, the dose should be reduced to 0.5 mg/kg body weight for dual
vascular access or 0.75 mg for single vascular access.
In hemodialysis, Enixum® should be injected into the arterial shunt site at the beginning of the hemodialysis session. One dose is usually sufficient for a four-hour
session, however, if fibrin rings are detected during a longer hemodialysis, the drug may be administered additionally at the rate of 0.5-1 mg/kg of body weight.

Interaction

Do not mix Enixum® with other drugs in the same syringe.
Concomitant use with other drugs affecting hemostasis (salicylates, including acetylacetic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, dextran with molecular weight 40. Acetylsalicylic acid, non-steroidal anti-inflammatory drugs (NSAIDs), including ketorolac, dextran with a molecular weight of 40 kDa, ticlopidine, clopidogrel, systemic glucocorticosteroids (GCS), thrombolyticsor anticoagulants, other antiplatelet drugs, including glycoprotein IIb/IIIa receptor antagonists), increases the risk of bleeding (see “Special See “Special
directions”).

Special Instructions

General

Low molecular weight heparins are not interchangeable, since they differ in manufacturing process, molecular weight, specific anti-Xa activity, dosing units and dosing regimen, with associated differences in their pharmacokinetics and biological activity (antithrombin activity and interaction with platelets). Therefore it is required to strictly follow the recommendations for the use of each
drug belonging to the class of low molecular weight heparins.

Bleeding
As with other anticoagulants, the use of Enixum® may cause bleeding of any localization (see “Adverse effects”). In
development of bleeding it is necessary to find its source and prescribe an appropriate treatment.

Bleeding in elderly patients
When using Enoxaparin sodium in preventive doses in elderly patients no increased risk of bleeding was noted.
When enoxaparin sodium is used in therapeutic doses in elderly patients (especially those aged 80 years and older) there is an increased risk of bleeding. Close monitoring of these patients is recommended (see section “Pharmacokinetics” and section “Administration and doses”, subsection “Elderly patients”).

Simultaneous use of other drugs that affect hemostasis
It is recommended that the use of drugs that affect hemostasis (salicylates, including acetylacilamide, acetylsalicylic sodium, acetylsalicylic sodium and acetylsalicylic sodium) should be performed with a high risk. acetylsalicylic acid, NSAIDs including ketorolac, dextran with molecular weight
40 kDa, ticlopidine, clopidogrel, GCS, thrombolytics, anticoagulants, antiaggregants including glycoprotein receptor antagonists IIb/IIIa) should be stopped before treatment with Enoxaparin Sodium, unless their use is necessary. If combinations of enoxaparin sodium with these drugs are indicated,
close clinical observation and monitoring of relevant laboratory parameters should be performed.

Patients with renal impairment
In patients with impaired renal function there is a risk of bleeding due to increased systemic exposure to enoxaparin sodium.
In patients with severe renal impairment (creatinine clearance less than 30 ml/min) a significant increase of sodium enoxaparin exposure is noted, therefore
Dose adjustment is recommended both during prophylactic and therapeutic use of the drug. Although no dose adjustment is required in patients with mild to moderate renal dysfunction (creatinine clearance 30-50 ml/min or 50-80 ml/min), it is recommended to closely monitor these patients (see sections “Pharmacokinetics” and “Dosage and administration”, subsection “Patients with renal impairment”).

Low body weight
Enoxaparin sodium exposure has been observed to increase when used prophylactically in women with a body weight less than 45 kg and in men with a body weight less than 57 kg, which
may lead to an increased risk of bleeding. Close monitoring of these patients is recommended.

Patients with obesity
Patients with obesity have an increased risk of thrombosis and embolism. The safety and efficacy of prophylactic doses of enoxaparin sodium in
obese patients (body mass index greater than 30 kg/m2) is not fully defined, and there is no general consensus on dose adjustment. These
patients should be closely monitored for signs and symptoms of thrombosis and embolism.

Peripheral blood platelet count monitoring
The risk of antibody-mediated heparin-induced thrombocytopenia also exists with low molecular weight heparins. If thrombocytopenia develops, it is usually detected between days 5 and 21 after the start of therapy with enoxaparin sodium. Therefore, it is recommended to monitor the peripheral blood platelet count regularly before and during treatment with Enixum®. In case of confirmed significant decrease of platelet count (by 30-50 % compared to the initial value) it is necessary to withdraw Enoxaparin sodium immediately and put the patient on another therapy.

Spinal/epidural anesthesia
Cases of neuroaxial hematomas have been described when using enoxaparin sodium concomitantly with spinal/epidural anesthesia with development of long-lasting or irreversible paralysis. The risk of these phenomena is reduced when using enoxaparin sodium at a dose of 40 mg or lower.
The risk increases when using higher doses of enoxaparin sodium as well as when using permanent catheters after surgery or when using additional drugs that affect hemostasis, such as NSAIDs (see “Interaction with other medicinal products”). The risk also increases with traumatic or repeated spinal tap or in patients with a history of spinal surgery or spinal deformity. To reduce the possible risk of bleeding associated with the use of enoxaparin sodium and epidural or spinal anesthesia/analgesia,
the pharmacokinetic profile of the drug should be considered (see “Pharmacokinetics”).
Catheter placement or removal is best performed when the anticoagulant effect of enoxaparin sodium is low, but the exact time to achieve sufficient reduction in anticoagulant effect in different patients is unknown.
Catheter placement or removal should be performed at least 12 h after lower doses of Enixum® (20 mg once daily, 30 mg once or
twice daily, 40 mg once daily) and at least 24 h after administering higher doses of Enixum® (0.75 mg/kg body weight twice daily, 1 mg/kg body weight
twice daily, 1.5 mg/kg body weight once daily). Enoxaparin sodium anti-Xa activity is still detectable at these time points, and time delays are not
a guarantee that neuroaxial hematoma development will be avoided.
Patients receiving enoxaparin sodium at doses of 0.75 mg/kg body weight twice daily or 1 mg/kg body weight twice daily on this (twice daily) dosing regimen
should not administer a second dose in order to increase the interval before inserting or replacing the catheter. Similarly, consideration should be given to delaying the administration of the next dose of enoxaparin sodium for at least 4 h, based on a benefit/risk assessment (risk of thrombosis and bleeding during
procedure, taking into account patients’ risk factors). However, it is not possible to give a clear recommendation on the timing of the next dose of sodium enoxaparin after catheter removal. Note that in patients with a creatinine clearance of less than 30 ml/min, excretion of sodium enoxaparin slows down. Therefore, in this
category of patients, consideration should be given to doubling the time from catheter removal: at least 24 h for lower doses of sodium enoxaparin (30 mg once per
day) and at least 48 h for higher doses (1 mg/kg body weight per day).
If anticoagulant therapy is prescribed by a physician during epidural/spinal anesthesia or lumbar puncture, the patient should be monitored for any neurologic symptoms such as back pain, sensory and motor disturbances (numbness or weakness in the lower
limbs), bowel and/or bladder function. The patient should be instructed to inform the physician immediately if the symptoms described above occur. If symptoms characteristic of a spinal cord hematoma are suspected, prompt diagnosis and treatment, including spinal cord decompression if necessary, are necessary.

Heparin-induced thrombocytopenia
Enixum® should be used with special caution in patients with a history of heparin-induced thrombocytopenia in combination with or without
thrombosis.
The risk of heparin-induced thrombocytopenia may persist for several years. If heparin-induced
thrombocytopenia is suspected anamnesthetically, in vitro platelet aggregation tests are of limited value in predicting the risk of its development. The decision to use Enixum® in this
case should only be made after consultation with an appropriate specialist.

The transcutaneous coronary angioplasty
To minimize the risk of bleeding associated with invasive vascular instrumental manipulation in the treatment of unstable angina and myocardial infarction
without Q-wave and acute myocardial infarction with ST-segment elevation, these procedures should be performed in intervals between Enixum® infusions. This is necessary to achieve hemostasis after percutaneous coronary intervention.
The femoral artery intromedullary device can be removed immediately if a closure device is used. When manual compression is used, the femoral artery intromedullary tube should be removed 6 hours after the last intravenous or subcutaneous injection of enoxaparin sodium. If treatment with sodium enoxaparin is continued, the next dose should not be administered before 6-8 h after removal of the femoral artery intraductor. The site of introducer insertion should be monitored to detect timely signs of bleeding and hematoma formation.
Patients with mechanical artificial heart valves

The use of sodium enoxaparin to prevent thrombus formation in patients
with mechanical artificial heart valves has not been well studied. There have been anecdotal reports of the development of heart valve thrombosis in patients with mechanical heart valves on therapy with enoxaparin sodium for thrombosis prophylaxis. The evaluation of these reports is limited because of competing factors contributing to the development of artificial heart valve thrombosis, including
the underlying disease, and because of insufficient clinical data.

Pregnant women with mechanical artificial heart valves

The use of sodium enoxaparin for thrombosis prevention in pregnant women with mechanical artificial heart valves has not been well studied.
In a clinical study of pregnant women with mechanical artificial heart valves, when enoxaparin sodium was used at a dose of 1 mg/kg body weight twice daily to reduce the risk of thrombosis and embolism, 2 of 8 women developed thrombi,
leading to heart valve blockage and maternal and fetal death.enoxaparin sodium to prevent thrombosis. Pregnant women with mechanical artificial heart valves have a high risk of thrombosis
and embolism.

Laboratory tests
In doses used for the prevention of thromboembolic complications, enoxaparin
sodium does not significantly affect bleeding time and clotting parameters, as well as platelet aggregation or their binding to fibrinogen.
Accelerated BChTB and activated clotting time may be prolonged at increasing dose.
Accelerated BChTB and activated clotting time are not in direct linear dependence on increasing anticoagulant activity of the drug, therefore there is no need for their monitoring
.

Prevention of venous thrombosis and embolism in patients with acute therapeutic conditions on bed rest
In case of acute infection, acute rheumatic conditions, prophylactic
use of enoxaparin sodium is justified only if the above conditions are combined with one of the following risk factors for venous thrombosis
– age greater than 75 years;
– malignant neoplasms;
– history of thrombosis and embolism;
– obesity;
– hormone therapy;
– heart failure;
– chronic respiratory failure.

Pediatric use
Safety and efficacy of enoxaparin sodium in children under 18 years of age have not been established.

Influence on performance of potentially hazardous activities requiring special attention and rapid reactions
No data indicating an adverse effect of enoxaparin sodium on the ability to drive vehicles and engage in other potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Synopsis

Colorless or yellowish, or brownish-yellowish transparent liquid.

Contraindications

Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins;
– active major bleeding, as well as conditions and diseases in which there is a high risk of bleeding: threatened abortion, cerebral vascular aneurysm or dissecting aortic aneurysm (unless
there is surgical intervention for this reason), recently suffered
Haemorrhagic stroke, uncontrolled haemorrhage, thrombocytopenia in combination with a positive in vitro test for antiplatelet antibodies in
the presence of enoxaparin sodium;
– children
under 18 years of age, as efficacy and safety in this
patient population has not been established (see “Special Indications”).

Cautious conditions with a potential risk of bleeding:
– hemostatic disorders (including hemophilia, thrombocytopenia, hypocoagulation,
Willebrand disease, etc.).), severe vasculitis;
– gastric or duodenal ulcer or other erosive-ulcerative lesions of the gastrointestinal tract in the anamnesis;– recent ischemic stroke;
– uncontrolled severe arterial hypertension;
– diabetic or hemorrhagic retinopathy;
– severe diabetes;
– recent or suspected neurologic or ophthalmologic
operations;
– spinal or epidural anesthesia (potential risk of hematoma), spinal tap (recent);
– recent labor;
– bacterial endocarditis (acute or subacute);
– pericarditis or pericardial effusion;
– renal and/or hepatic insufficiency;
– intrauterine contraception (IUI);
– severe trauma (especially of the central nervous system (CNS), open wounds on
large surfaces;
– simultaneous use of drugs that affect the hemostasis system;
– heparin-induced thrombocytopenia (history) in combination with thrombosis or without it.
There are no data on clinical use of enoxaparin sodium in the following
diseases: active tuberculosis, radiation therapy (recently carried out).

Side effects

The side effects were classified according to frequency as follows: very frequent
(≥1/10), frequent (≥1/100 – < 1/10), infrequent (≥1/1000 – < 1/100), rare (≥1/10000 – < 1/1000),
very rare (< 1/10000).

Bleeding
Bleeding is possible, especially in the presence of associated risk factors: organic changes with a tendency to bleeding, age, renal insufficiency, low body weight, and some combinations of drugs (see “Interactions with other drugs”). In case of bleeding it is necessary to cancel the drug administration, determine the cause of bleeding and initiate appropriate therapy.
Very common – bleeding during prophylaxis of venous thrombosis, in surgical patients and treatment of deep vein thrombosis with or without thromboembolism.
Frequent – bleeding in the prevention of venous thrombosis in patients on bed rest and in the treatment of angina, myocardial infarction without Q-wave and ST-segment elevation myocardial infarction.
Infrequent – retroperitoneal bleeding and intracranial bleeding in patients treated for deep vein thrombosis with or without thromboembolism, as well as ST-segment elevation myocardial infarction.
Rare – retroperitoneal bleeding in the prevention of venous thrombosis in surgical patients and in the treatment of angina, myocardial infarction without the Q-wave.
When using enoxaparin sodium against the background of spinal/epidural anesthesia and postoperative use of penetrating catheters there have been described rare cases
of neuroaxial hematomas resulting in neurological disorders of varying severity, including long-term persistent or irreversible paralysis (see
Precautions. “

Thrombocytopenia and thrombocytosis
Very common – thrombocytosis in prophylaxis of venous thrombosis in surgical patients and treatment of deep vein thrombosis with or without thromboembolism.
Frequent – thrombocytopenia. In the prevention of venous thrombosis in surgical patients and the treatment of deep vein thrombosis with thromboembolism or without it, as well as during ST-segment elevation myocardial infarction.
Infrequent – thrombocytopenia in the prevention of venous thrombosis in patients on bed rest and in the treatment of angina, myocardial infarction without Q wave.
Very rare are autoimmune thrombocytopenia in ST-segment elevation myocardial infarction.
In rare cases, the development of autoimmune thrombocytopenia in combination with thrombosis has been reported. In some of them thrombosis was complicated by organ infarction or limb ischemia (see section “Special Precautions”).

Others
Very common – increased activity of “hepatic” transaminases.
Frequently – allergic reactions, urticaria, itching, reddening of the skin, bruising and pain at the injection site.
Infrequent – skin (bullous rashes), inflammatory reaction at the injection site, skin necrosis at the injection site.
Rarely – anaphylactic and anaphylactoid reactions, hyperkalemia. Skin necrosis may develop at the injection site preceded by purpura or erythematous painful papules. In these cases the drug therapy should be discontinued. Solid inflammatory nodules-infiltrates may form at the injection site, which disappear after a few days and are not a reason for discontinuation of the drug.

Overdose

Symptoms: hemorrhagic complications of accidental overdose during subcutaneous injection of enoxaparin sodium. Even large doses are unlikely to be absorbed by accidental ingestion.
Treatment: neutralize the effect of enoxaparin sodium by slow intravenous (IV) administration of protamine sulfate. 1 mg of protamine sulfate will neutralize the anticoagulant effect of 1 mg of sodium enoxaparin if the drug was administered no more than 8 hours before protamine sulfate administration.
0.5 mg of protamine sulfate will neutralize the anticoagulant effect of 1 mg of sodium enoxaparin if it was administered more than 8 hours ago or if a second dose of sodium protamine sulfate is needed.
If 12 or more hours have passed since the administration of sodium enoxaparin, administration of protamine sulfate is not required. However, even when large doses of protamine sulfate are administered, the anti-Xa activity of sodium enoxaparin is not completely neutralized (maximum of
60%).

Pregnancy use

Pregnancy

There are currently insufficient clinical data to determine the possible teratogenic or fetotoxic effects of enoxaparin sodium when administered prophylactically during pregnancy. Enixum® should not be used during pregnancy unless the potential benefit to the mother outweighs the possible risk to the fetus.

With the drug treatment, spinal or epidural anesthesia should not be performed.
If epidural anesthesia is planned, preventive treatment with Enoxaparin sodium should be discontinued, if possible, at least 12 h before the anesthesia.
Enoxaparin sodium is not recommended for use in pregnant women with prosthetic heart valves.

Breastfeeding
It is not known whether unchanged enoxaparin sodium is excreted into human breast milk. Absorption of enoxaparin sodium into the gastrointestinal tract in the infant is unlikely. However, as a precautionary measure, breastfeeding women treated with enoxaparin sodium should be advised to interrupt breastfeeding.

Similarities

Clexane