Fragmin - instructions for use, dose, side effects, contraindications

Active substanceDalteparin sodiumDalteparin sodium

Similar drugsTo uncover

Fragmin®

solution in / in PC

Pfizer IFG Belgium N.V. Belgium

Dosage form: & nbspsolution for intravenous and subcutaneous administration

Composition:

Ampoules (composition per ml):

Active substance: 10000 IU (anti-Xa)

Excipients: sodium chloride q.s., sodium hydroxide q.s. (pH adjustment) or hydrochloric acid q.s. (adjustment of pH), water for injection up to 1 ml.

Syringes (composition per 1 syringe):

Dosages 2500 IU (anti-Xa) / 0.2ml and 5000 IU (anti-Xa) / 0.2ml

Active substance: dalteparin sodium 2500 IU (anti-Xa) and 5000 IU (anti-Xa)

Excipients: sodium chloride q.s. (0-0.3 mg) (for dosage 2500 IU (anti-Xa) / 0.2 ml), hydrochloric acid or sodium hydroxide q.s. (adjustment of pH), water for injection up to 0.2 ml.

Dosages 7500 IU (anti-Xa) / 0.3 mL, 10,000 IU (anti-Xa) / 0.4 mL, 12,500 IU (anti-Xa) / 0.5 mL, 15,000 IU (anti-Xa) / 0.6 mL and 18,000 IU (anti-Xa) / 0.72ml

Active substance: 7500 IU (anti-Xa), 10,000 IU (anti-Xa), 12,500 IU (anti-Xa), 15,000 IU (anti-Xa) and 18,000 IU (anti-Xa), respectively.

Excipients: water for injection up to 0.3 ml, up to 0.4 ml, up to 0.5 ml, up to 0.6 ml, up to 0.72 ml, respectively.

Description:Transparent, colorless or with a yellowish tinge solution.

Pharmacotherapeutic group:Anticoagulant means of direct action

ATX: & nbsp

B.01.A.B.04 Dalteparin

B.01.A.B Heparin and its derivatives

Pharmacodynamics:

Characteristic. Dalteparin sodium is a low molecular weight heparin isolated during controlled depolymerization (with nitrous acid) of sodium heparin from the mucous membrane of the small intestine of the pig and subjected to additional purification by ion exchange chromatography. The preparation consists of sulfated polysaccharide chains having an average molecular weight of 6,000 daltons; with 90% having a molecular weight of from 2,000 to 9,000 daltons; the degree of sulphation is from 2 to 2.5 per disaccharide.

Pharmacodynamics

Dalteparin sodium through plasma antithrombin inhibits the activity of coagulation factor Xa and thrombin. The anti-coagulant effect of sodium dalteparin is due primarily to the inhibition of coagulation factor Xa; for the time of blood clotting the drug affects slightly. Compared with heparin dalteparin sodium has a weak effect on the adhesion of platelets and, thus, has a lesser effect on primary hemostasis.

Use in children

Safety and effectiveness of dalteparin sodium in children is not established. When dalteparin is used in patients in this category, anti-Xa activity.

The predictability of the anticoagulant effect in dose selection in children corrected for body weight appears to be lower than in adults, presumably due to a change in the binding of the drug to plasma proteins.

Pharmacokinetics:

The half-life after intravenous (iv) administration of the drug is 2 hours, after subcutaneous (PC) introduction - 3-5 hours. Bioavailability after PC of the administration is about 90%; pharmacokinetic parameters do not depend on the dose.

In patients with uremia, the half-life of the drug is increased. Dalteparin sodium is mainly excreted through the kidneys, but the biological activity of the fragments excreted by the kidneys has not been sufficiently studied. In urine, less than 5% of anti-Xa activity is detected. The clearance of anti-Xa activity of dalteparin from plasma after a single intravenous bolus injection at a dose of 30 and 120 IU (anti-Xa) / kg averaged 24.6 ± 5.4 and 15.6 ± 2.4 ml / h / kg, respectively, and the period the elimination half-lives are 1.47 ± 0.3 and 2.5 ± 0.3 hours.

Special Groups

In patients with chronic renal insufficiency in need of hemodialysis, the half-life of anti-Xa activity after a single intravenous injection of dalteparin in a dose of 5000 IU was 5.7 ± 2.0 h and was significantly higher than in healthy volunteers.Accordingly, in such patients, one can expect a more pronounced cumulation of the drug.

Use in children

Breast children aged up to 2-3 months or with a body weight below 5 kg require large doses of low molecular weight heparin per kilogram of body weight, probably because of the larger volume of distribution in them. Other explanations for the need for higher doses of low molecular weight heparin per kilogram of body weight in young children may be the differing pharmacokinetics of heparin and / or a lower manifestation of anticoagulant action of heparin in children due to a reduced concentration of antithrombin in the blood plasma.

Indications:

· treatment of acute deep vein thrombosis and pulmonary embolism;

· prevention of blood coagulation in the extracorporeal circulation system during hemodialysis or hemofiltration in patients with acute or chronic renal failure;

· prevention of thrombosis during surgical interventions;

· prevention of thromboembolic complications in patients with a therapeutic disease in the acute phase and limited mobility (including in conditions requiring bed rest);

· unstable angina or myocardial infarction without segment elevation ST on the ECG;

· long-term treatment (up to 6 months) in order to prevent recurrence of venous thromboembolic complications in patients with malignant neoplasms.

Contraindications:

- hypersensitivity to sodium dalteparin or other low molecular weight heparins and / or heparin;

- established heparin-induced immune thrombocytopenia (type II) in the history or suspicion of its presence;

- bleeding (clinically significant, for example, from the organs of the gastrointestinal tract against a stomach ulcer and / or duodenal ulcer, intracranial hemorrhages);

- severe disorders of the blood coagulation system;

acute or subacute infective endocarditis;

- recent injuries or surgical interventions on the organs of the central nervous system, vision and / or hearing;

- in patients receiving therapy with Fragmin^®in therapeutic doses (for example, for the treatment of acute deep vein thrombosis, pulmonary embolism, unstable angina, or myocardial infarction without segment elevation ST on ECG), local and / or regional anesthesia should not be used for routine surgical interventions.

Carefully:

High doses of the drug Fragmin^Ò (eg, for the treatment of acute deep vein thrombosis, pulmonary embolism, unstable angina, or myocardial infarction without segment elevation ST on ECG) should be used with extreme caution in patients in the early postoperative period.

Care should be taken when using the drug Fragmin® in patients with an increased risk of bleeding; this group includes patients with thrombocytopenia, impaired platelet function, severe hepatic or renal insufficiency, uncontrolled hypertension, hypertensive or diabetic retinopathy.

Safety and effectiveness of dalteparin sodium in children is not established. When applying Fragmin® children need to monitor the level of anti-Xa (see section "Method of administration and dose").

Pregnancy and lactation:

The results of the studies showed a satisfactory level of safety of dalteparin sodium in pregnant women (low frequency of clinically significant bleeding, baboutmost of which were observed in the postpartum period; no cases of heparin-induced thrombocytopenia; Only one case of osteoporosis was diagnosed; the rate of spontaneous abortions and premature births corresponded to the general population; the level of congenital anomalies did not exceed the average value in the general population).

In the experiment, Fragmin^® does not have a teratogenic or fetotoxic effect. When used in pregnant women, there was no adverse effect on the course of pregnancy, as well as on the health of the fetus and the newborn. When applying Fragmin^® during pregnancy, the risk of adverse effects on the fetus is assessed as low.

However, since the possibility of adverse influence can not be completely ruled out, Fragmin^® during pregnancy can be used only if there are clear indications when the expected benefit for the mother exceeds the possible risk to the fetus.

It is recommended to use the drug with care to treat patients with an increased risk of bleeding, for example, women in the postpartum period (see section "Special instructions").

Ineffective treatment in pregnant women with artificial valves of the heart, receiving as anticoagulant therapy low molecular weight heparin in a full dose. Sufficiently complete studies of the use of dalteparin in pregnant women with artificial heart valves have not been conducted.

It was found that after taking preventive doses of dalteparin in breast milk, a small activity of anti-Xa, equivalent to the milk / plasma ratio <0.025-0.224. Since the likelihood of absorption of low molecular weight heparin when ingested with mother's milk is very small, the clinical effect of small anticoagulant activity on the newborn is unknown. Caution should be exercised when using dalteparin sodium in nursing mothers.

Influence on reproductive function

Currently available clinical data do not indicate negative effects of dalteparin sodium on reproductive function. In animal studies, there was no adverse effect of dalteparin sodium on fertility, copulation and peri- and postnatal development.

Dosing and Administration:

Fragmin^® can not be administered intramuscularly!

Treatment of acute deep vein thrombosis and pulmonary embolism

Fragmin^® is introduced PC 1-2 times a day. In this case, you can immediately begin therapy with indirect anticoagulants (antagonists of vitamin K). Combination therapy should be continued until the prothrombin index reaches therapeutic value (usually not earlier than 5 days later). Treatment of patients in outpatient settings can be carried out at the same doses that are recommended for inpatient treatment.

· When administered once a day - 200 IU / kg body weight PC. Single daily dose should not exceed 18000 IU. Monitoring anticoagulant activity of the drug is not necessary.

· With the introduction of 2 times a day - 100 IU / kg body weight PC 2 times a day. Monitoring of anticoagulant activity can be avoided, but it should be borne in mind that it may be required for the treatment of special groups of patients (see section "Special instructions"). The recommended maximum concentration of the drug in blood plasma should be 0.5-1 IU anti-Xa / ml.

Prevention of blood coagulation in the extracorporeal circulation system during hemodialysis or hemofiltration

Fragmin^® should be entered in / in, choosing the dosing regimen from the following.

· Patients with chronic renal failure or patients without risk of bleeding

Such patients usually require a minor dose adjustment, and therefore most patients do not need to monitor anti-Xa levels frequently. When the recommended doses are administered during hemodialysis, a blood plasma level of 0.5-1 IU anti-Xa / ml is usually achieved.

· With a duration of hemodialysis or hemofiltration no more than 4 hours - in / in struyno 30-40 IU / kg body weight, followed by iv drip introduction of 10-15 IU / kg / hour, or once in / in struino in a dose of 5000 IU.

· With a duration of hemodialysis or hemofiltration more than 4 hours - in / in struyno 30-40 IU / kg body weight, followed by iv dropwise administration of 10-15 IU / kg / hour.

· Patients with acute renal failure, or patients with a high risk of bleeding

Intravenous injection of 5-10 IU / kg of body weight followed by iv dropwise administration of 4-5 IU / kg / hour. In patients who undergo hemodialysis for acute renal failure, the drug has a narrower therapeutic index than patients in chronic hemodialysis (therefore, they need adequate monitoring of anti-Xa levels).The recommended maximum plasma level should be 0.2-0.4 IU anti-Xa / ml.

Prevention of thrombosis during surgical interventions

Fragmin^® should be entered PC. Monitoring of anticoagulant activity, as a rule, is not required. When the drug is used in recommended doses, the maximum plasma concentrations are from 0.1 to 0.4 IU anti-Xa / ml.

· When conducting operations in general surgical practice

- Patients with a risk of developing thromboembolic complications - PC 2500 IU for 2 hours before the operation, then after the operation - PC for 2500 IU / day (every morning) for the entire period, while the patient is on bed rest (usually 5 to 7 days).

- Patients with additional risk factors for thromboembolic complications (eg, patients with malignant tumors) - Fragmin^® should be used during the entire period, while the patient is on bed rest (usually 5 - 7 days or more).

a. at the beginning of prophylaxis the day before the operation: 5000 IU PC the evening before the operation, then 5000 IU PC every evening after surgery.

b. at the beginning of prophylaxis on the day of the operation: 2500 IU PC 2 hours prior to surgery and 2500 IU PC in 8-12 hours, but not earlier than 4 hours after the end of the operation. Then, from the next day, every day, 5000 IU PC.

· When performing orthopedic operations (for example, in operations on hip replacement)

Fragmin^® should be administered for up to 5 weeks after surgery by selecting one of the dosing regimens listed below.

a. at the beginning of prophylaxis the day before the operation: 5000 IU in the evening on the eve of the operation, then 5000 IU per / every evening after the operation.

b. at the beginning of prophylaxis on the day of the operation: 2500 IU SC for 2 hours before the operation and 2500 IU SC after 8-12 hours, but not earlier than 4 hours after the end of the operation. Then the next day every morning - 5000 IU each PC.

at. at the beginning of prophylaxis after operation: 2500 IU SC after 4 - 8 hours after the operation, but not earlier than 4 hours after the end of the operation. Then the next day to 5000 IU per day.

Prevention of thromboembolic complications in patients with a therapeutic disease in the acute phase and limited mobility (including under conditions requiring bed rest)

Fragmin^® should enter the by 5000 IU once a day, usually for 12 to 14 days or longer (in patients with continued mobility restriction). Monitoring of anticoagulant activity, as a rule, is not required.

Unstable angina or myocardial infarction without segment elevation ST on the ECG

Monitoring of anticoagulant activity, as a rule, is not required, but it should be borne in mind that it may be required in the treatment of special groups of patients (see section "Special instructions"). The recommended maximum plasma concentration in the plasma should be 0.5-1 IU anti-Xa / ml. Fragmin^® injected sc, 120 IU / kg body weight every 12 hours. The maximum dose should not exceed 10,000 IU every 12 hours. Simultaneously, in the absence of contraindications, it is advisable to conduct therapy with acetylsalicylic acid in a dose of 75 to 325 mg / day. Therapy should continue until the patient's clinical condition becomes stable (usually at least 6 days), or longer (at the doctor's discretion). Then it is recommended to go to a long-term therapy with Fragmin^® in a constant dose up to revascularization (percutaneous interventions or aortocoronary bypass surgery).The total duration of therapy should not exceed 45 days.

Dose of Fragmin^® is selected taking into account the sex and body weight of the patient:

- women with a body weight of less than 80 kg and men weighing less than 70 kg should be administered 5000 IU SC every 12 hours;

- for women with a body weight of 80 kg and more, and for men weighing 70 kg or more, 7500 IU should be injected every 12 hours.

Long-term treatment to prevent recurrence of venous thromboembolism in patients with malignant neoplasms

1 month

200 IU / kg body weight once a day. Single daily dose should not exceed 18000 IU.

2 - 6 months

about 150 IU / kg body weight once a day, using syringes with a fixed dose (Table 1).

Table 1. Determination of the dose of Fragmin^® depending on the body weight for the treatment period of 2-6 months.

Body weight, kg	Dose of Fragmin^®, IU
£ 56	7 500
57 - 68	10 000
69 - 82	12 500
83 - 98	15 000
³ 99	18 000

Thrombocytopenia - in the case of thrombocytopenia, which developed against the background of chemotherapy with the number of platelets < 50 000 / mkl, application of Fragmin^® should be suspended until the platelet count is increased to more than 50,000 / μL. For the concentration of platelets from 50 000 / μLup to 100 000 / mkl dose of the drug should be reduced by 17% - 33% relative to the initial dose, depending on the patient's body weight (Table 2).When the platelet count is restored to the level of ³ 100 000 / mkl, the drug should be used in a full dose.

Table 2. Decrease in the dose of Fragmin^® with thrombocytopenia 50 000 / μL - 100 000 / μL.

Body weight, kg	Planned dose of Fragmin^®, IU	Reduced dose of Fragmin^®	Dose reduction,%
£ 56	7 500	5 000	33
57 - 68	10 000	7 500	25
69 - 82	12 500	10 000	20
83 - 98	15 000	12 500	17
³ 99	18 000	15 000	17

Renal insufficiency - in the case of renal insufficiency with a serum creatinine concentration exceeding 3 times the upper limit of the norm, the dose of Fragmin^® should be adjusted so as to maintain the therapeutic level of anti-Xa 1 IU / mL (range 0.5 to 1.5 IU / mL) measured within 4-6 hours after the administration of dalteparin. If the level of anti-Xa, below or above the therapeutic range, the dose of Fragmin^® should be increased or decreased, respectively, and the measurement of anti-Xa should be repeated after the administration of 3 to 4 new doses. The dose adjustment should be performed before the therapeutic level of anti-Xa is reached.

Use in children

Safety and effectiveness of dalteparin sodium in children is not established. At present, it is not possible to give recommendations on the dosage regimen in children.

Monitoring of anti-Xa-factor activity in children

For some groups of patients receiving dalteparin sodium, for example for children, it is necessary to consider the expediency of determining the maximum level of anti-Xa activity in about 4 hours after the administration of the drug. When the drug is administered once a day, the maximum level of anti-Xa activity in general cases should be maintained within 0.5-1.0 IU / ml when measured at 4 hours after administration. In the case of impaired renal function or its physiological changes, for example in infants, careful monitoring of anti-Xa activity. In the prevention regime, the level of anti-Xa activity in general cases should be maintained within 0,2-0,4 IU / ml.

Side effects:

About 3% of patients who received the drug Fragmin^® in preventive doses, reported the development of side effects.

The undesirable reactions reported and that may have been associated with the administration of sodium dalteparin are listed in the following table with the classification according to the Sistema-Organ-Class categories and the frequency of occurrence as follows: very frequent (≥ 1/10), frequent (≥ 1/100 and < 1/10), infrequent (≥ 1/1 000 and < 1/100), sparse (≥ 1/10 000 and < 1/1 000), very rare (< 1/10 000).

System-Organ-Class	Frequency	Undesirable reactions
Violations of the blood and lymphatic system	Often Unknown *	Thrombocytopenia of mild degree (I type), usually reversible during treatment Immune thrombocytopenia, caused by the introduction of heparin (type II, with or without thrombotic complications)
Immune system disorders	Infrequently Unknown *	Hypersensitivity reactions Anaphylactic reactions
Disturbances from the nervous system	Unknown *	There have been reports of intracranial hemorrhages, some of which have resulted in death
Vascular disorders	Often	Bleeding
Disorders from the gastrointestinal tract	Unknown *	There were reports of hemorrhages in the retroperitoneal space, some of which resulted in death
Disturbances from the liver and bile ducts	Often	Temporary increase in the level of transaminases
Disturbances from the skin and subcutaneous tissues	Rarely Unknown *	Necrosis of the skin, temporary alopecia Rash
General disorders and disorders at the site of administration	Often	Subcutaneous hematoma at the injection site, pain at the injection site
Trauma, intoxication and complications of manipulation	Unknown *	Spinal or epidural hematoma (see section "Contraindications" and section "Special instructions")

* can not be determined from available data

Use in children

Children are expected to have the same frequency, types and severity of adverse reactions as adults. The safety of prolonged use of dalteparin sodium in children is not established.

Overdose:

Excessive dose of Fragmin^® can lead to hemorrhagic complications. It should be borne in mind that a decrease in blood pressure and a decrease in hematocrit may indicate latent bleeding. In the event of bleeding, dalteparin sodium should be suspended to assess the severity of bleeding and the risk of developing blood clots.

Anticoagulant Fragmin effect^®can be eliminated by the administration of protamine sulfate. However, protamine has an inhibitory effect on primary hemostasis, so it can only be used in emergency cases. 1 mg protamine sulphate partially neutralizes the effect of 100 IU (anti-Xa) dalteparin sodium (despite the fact,that complete neutralization of the induced increase in clotting time is noted, from 25 to 50% of the anti-Xa activity of sodium dalteparin is still preserved).

Interaction:

When used simultaneously with drugs that affect hemostasis, such as thrombolytic agents (alteplase, streptokinase, urokinase), indirect anticoagulants, vitamin K antagonists, non-steroidal anti-inflammatory drugs (NSAIDs) (acetylsalicylic acid, indomethacin etc.), inhibitors of platelet function or dextran, anticoagulant action of Fragmin^® may increase (increases the risk of bleeding) (see section "Method of administration and dose").

Since NSAIDs in therapeutic doses reduce the production of vasodilating prostaglandins and, thus, reduce renal blood flow and renal excretion, use Phragmin^® At the same time with this group of drugs it is necessary with extreme caution in patients with renal insufficiency.

Compatibility with solutions for in / in introduction. Fragmin^® is compatible with 0.9% sodium chloride solution (9 mg / ml) and dextrose solution (50 mg / ml).

Special instructions:

Fragmin^®can not be administered intramuscularly!

When performing neuroaxial anesthesia (epidural / spinal anesthesia) or performing spinal puncture in patients who are receiving anticoagulant therapy or who are planning to perform anticoagulant therapy using low molecular weight heparins or heparinoids to prevent thromboembolic complications, there is an increased risk of developing epidural or spinal hematoma, which in turn can lead to prolonged or persistent paralysis. The risk of such complications increases with the use of permanent epidural catheters for the administration of analgesics or with the simultaneous use of drugs that affect hemostasis, such as NSAIDs, platelet function inhibitors and other anticoagulants. The risk also increases with injuries and with repeated epidural or lumbar punctures. In such cases, patients should be under constant supervision for the timely detection of pathological neurological symptoms. When detecting neurologic pathology, urgent intervention is shown (decompression spinal cord).

The installation or extraction of the epidural or spinal catheter should be done 10-12 hours after the last dalteparin sodium in the prevention of venous thromboembolic complications; in individuals receiving higher therapeutic doses of dalteparin sodium (100-120 IU / kg every 12 hours or 200 IU / kg once a day), this interval should be at least 24 hours. It is necessary to provide extremely careful periodic monitoring of the patient's condition in order to detect any symptoms and signs of neurologic disorders (for example, numbness or weakness in the legs, bowel or bladder dysfunction).

There are no clinical data on the use of Fragmin^® in patients with pulmonary embolism, who also had circulatory disorders, arterial hypotension or shock.

It is recommended that the number of platelets in the patients be monitored before treatment with Fragmin^®, and then regularly throughout the treatment period. Particular attention is required by patients who, when treated with Fragmin^® there is a rapid development of thrombocytopenia, or thrombocytopenia with a platelet count of less than 100,000 / μL.In such cases it is recommended to conduct a test in vitro on antiplatelet antibodies in the presence of heparin or low molecular weight heparins. If the result of this test in vitro is positive or questionable, or testing has not been carried out at all, then treatment with Fragmin^® should be discontinued (see section "Contraindications").

Fragmin^®causes only temporary lengthening of activated partial thromboplastin time (APTT) and thrombin time. Accordingly, increasing the dose of the drug to extend the APTT can lead to an overdose and the development of bleeding. Extension of APTT should be considered only as a sign of an overdose of the preparation Fragmin^®.

To assess the anticoagulant activity of the preparation Fragmin^®method of choice is the definition of anti-Xaactivity by the chromogenic method. In this case, do not use tests to determine APTT and thrombin time, because these tests are relatively insensitive to sodium dalteparin activity. Increase in the dose of Fragmin^® to increase the APTT can lead to bleeding (see section "Overdose").

In monitoring the anti-coagulant activity of Fragmin^® is generally not necessary, but it may be necessary in the treatment of specific groups of patients: children, patients with kidney failure, low-weight or obese patients, pregnant women, and patients at increased risk for bleeding or recurrence of thromboembolism.

As with all anticoagulants, there is a risk of systemic bleeding when sodium dalteparin is taken. Caution should be exercised when treating high doses of dalteparin sodium patients after surgery. After the start of treatment, it is necessary to constantly monitor the possible development of bleeding in the patient by regular physical examination of the patient, a careful study of wound detachable and periodic determination of hemoglobin levels and anti-Xa activity.

Blood sampling for analysis of Fragmin's activity^® should be performed in the period when the maximum concentration of the drug in the blood plasma is reached (3 to 4 hours after injection).

Fragmin^®, like other low molecular weight heparins, can suppress adrenal secretion of aldosterone, leading to hyperkalemia, especially in patients with diabetes mellitus II type, chronic renal insufficiency, metabolic acidosis, increased potassium concentration in the blood or using potassium-sparing drugs. It is necessary to control potassium in the blood of patients belonging to risk groups.

Units of action Fragmina^®, unfractionated heparin, other low molecular weight heparins and synthetic polysaccharides are not equivalent, so if you need to replace one drug with another, you need to make a dose adjustment.

It is known that prolonged therapy with heparin is associated with a risk of osteoporosis. Although no similar effect was observed with the use of Phragmin^®, the risk of developing osteoporosis can not be ruled out.

In patients with severe acute or chronic renal insufficiency (creatinine clearance less than 30 ml / min) dalteparin sodium administration at a preventive dose of 5,000 IU once a day does not lead to excessive anticoagulation due to lack of bioaccumulation and, therefore, does not increase the risk of bleeding.

Assess the effectiveness and safety of the use of the drug Fragmin^® for the prevention of thrombosis of artificial heart valves is impossible, so apply Fragmin^® for this purpose is not recommended.

In patients with severe impairment of liver function, a dose reduction of the Fragmin preparation^®, as well as regular monitoring of anti-Xaactivity.

Have patients who are on hemodialysis, usually requires a slight adjustment of the dose of the drug Fragmin^®, and monitoring of anti-Xaactivity.

No need to cancel the Phragmin^® in patients with myocardial infarction with segment elevation ST and in the presence of indications for thrombolytic therapy.

In elderly patients (especially in patients older than 80 years) there is an increased risk of bleeding with the use of the drug Fragmin^® in therapeutic doses. Therefore, careful monitoring is recommended.

Effect on the ability to drive transp. cf. and fur:

The effect of the preparation Fragmin® on the ability to drive a car or complex mechanisms was not systematically evaluated.

Form release / dosage:Solution for intravenous and subcutaneous administration 10,000 IU (anti-Xa) / ml.

Packaging:

Ampoules: solution for intravenous and subcutaneous administration of 10,000 IU (anti-Xa) / ml. By 1 ml of preparation in an ampoule of colorless glass of type I. 2 contourcell packings according to 5 ampoules are placed in a cardboard box together with instructions for use.

Syringes: solution for intravenous and subcutaneous administration of 2,500 IU (anti-Xa) / 0.2 ml, 5,000 IU (anti-Xa) / 0.2 ml, 7 500 IU (anti-Xa) / 0.3 ml, 10 000 IU (anti-Xa) / 0.4 ml, 12 500 IU (anti-Xa) / 0.5 ml, 15 000 IU (anti-Xa) / 0.6 ml or 18 000 IU (anti-Xa) / 0.72 ml are placed in a Type I syringe .Farm.) With a stainless steel needle and a protective bezel-free cap. 5 syringes per blister; 2 blisters for volumes of 0.2 ml (for both dosages) or 0.3 ml, or 1 blister for volumes of 0.4; 0.5; 0.6 or 0.72 ml is placed in a cardboard box with instructions for use.

Storage conditions:

Ampoules: at a temperature of no higher than 25 ° C.

Syringes: at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012506 / 01

Date of registration:04.10.2011

Expiration Date:Unlimited

The owner of the registration certificate:Pfizer IFG Belgium N.V.Pfizer IFG Belgium N.V. Belgium

Manufacturer: & nbsp

PFIZER MFG. BELGIUM, N.V. Belgium

Representation: & nbspPfizer LtdPfizer LtdUSA

Information update date: & nbsp31.10.2016

Illustrated instructions

Instructions

Fragmin® (Fragmin® )