Heparin J - instructions for use, dose, side effects, contraindications

Composition:Each ml contains:
Active substance:
heparin sodium 5000 ME
Auxiliary components:
benzyl alcohol 9.0 mg
sodium chloride 3.4 mg
hydrochloric acid Q.S.
sodium hydroxide Q.S.
water for injection up to 1.0 ml

Description:Transparent, from a colorless to light yellow solution.

Pharmacotherapeutic group:anticoagulant

ATX: & nbsp

B.01.A.B.01 Heparin

Pharmacodynamics:Anticoagulant direct action, refers to the group of medium-molecular heparins, slows the formation of fibrin. Anticoagulant effect is detected in vitro and in vivo, occurs immediately after intravenous application.
The mechanism of action of heparin is based primarily on binding to antithrombin III, serving as a physiological inhibitor of activated blood coagulation factors IXa, Xa, XIa, XIIa and thrombin.Particularly important is the ability to inhibit the activated factor X involved in the internal and external coagulation system (this action is manifested against a background of much smaller doses of heparin than is required to suppress thrombin activity promoting the formation of fibrin from fibrinogen, which serves as a rationale for the possibility of subcutaneous administration of small doses of heparin for prevention of venous thrombosis and large doses - for treatment). Heparin also has the ability to suppress platelet aggregation (prolongs bleeding time). Heparin is not able to dissolve the thrombus (not fibrinolytic), but it can reduce the size of the thrombus, stopping its growth, and in this case part of the thrombus dissolves under the action of natural fibrinolytic enzymes. The drug inhibits the activity of hyaluronidase, has a hypolipidemic effect. Anticoagulant action with a single intravenous (IV) introduction develops in a few minutes and lasts up to 4-5 hours. With subcutaneous (sc) injection, the action begins in 20-30 minutes and lasts up to 8 hours or more, depending on the dose.For unfractionated standard heparin, the ratio of antiaggregant activity (antifactor Xa) and anticoagulant activity (APTT-activated partial thromboplastin time) is 1: 1.

Pharmacokinetics:The maximum concentration (Cmах) after IV introduction is achieved almost immediately, after SC administration in 2-4 hours. The connection with plasma proteins is up to 95%, the distribution volume is very small - 0.06 l / kg (does not leave the vascular bed because of strong binding to plasma proteins). It does not penetrate the placenta and into breast milk. Intensively captured by endothelial cells and cells of the mononuclear-macrophage system (cells of the reticulo-endothelial system), it is concentrated in the liver and spleen. It is metabolized in the liver with the participation of N-desulfamidase and platelet heparinase, which is included in the metabolism of heparin at later stages. Participation in the metabolism of platelet factor IV (anti-heparin factor), as well as the binding of heparin to the macrophage system, explains the rapid biological inactivation and short-term action. Desulfated molecules under the influence of kidney endoglycosidase are converted into low-molecular fragments.The half-life period (T1 / 2) is 1-6 hours (on average - 1.5 hours); increases with obesity, hepatic and / or renal insufficiency; decreases with thromboembolism of the pulmonary artery, infections, malignant tumors. It is excreted by the kidneys, mainly in the form of inactive metabolites, and only with the introduction of high doses is it possible to excrete (up to 50%) unchanged.

Indications:Prevention and treatment of venous thrombosis (including thrombosis of the superficial and deep veins of the lower limbs, thrombosis of the renal veins) and pulmonary embolism; prevention and treatment of thromboembolic complications associated with atrial fibrillation; prevention and treatment of peripheral arterial embolism (including those associated with myrtle heart defects); treatment of acute and chronic coagulopathy of consumption (including the first stage of DIC syndrome); acute coronary syndrome without stable rise of the ST segment on the ECG (unstable angina, myocardial infarction without ST segment elevation on the ECG); myocardial infarction with ST segment elevation: with thrombolytic therapy, with primary percutaneous coronary revascularization (balloon angioplasty with or without stenting)and with a high risk of arterial or venous thrombosis and thromboembolism; prevention and treatment of microthrombogenesis and microcirculatory disorders, incl. with hemolytic-uremic syndrome; glomerulonephritis (including lupus nephritis) and with forced diuresis; prevention of blood clotting in blood transfusion, extracorporeal circulation systems (extracorporeal circulation in heart surgery, hemosorption, cytaresis) and hemodialysis; treatment of peripheral venous catheters.

Contraindications:Increased sensitivity to heparin and other components of the drug, heparin-induced thrombocytopenia (with or without thrombosis) in the anamnesis or currently, bleeding (except when the use of sodium heparin exceeds the potential risk), heparin sodium in a therapeutic dose should not be administered if there is no possibility to provide regular monitoring of blood coagulability, premature and newborns (due to the presence of benzyl alcohol).

Carefully:Polyvalent allergy (including bronchial asthma), with pathological conditions,associated with an increased risk of bleeding (diseases of the cardiovascular system: acute and subacute infective endocarditis, severe uncontrolled arterial hypertension, exfoliation of the aorta, aneurysm of the cerebral vessels); erosive and ulcerative lesions of the digestive tract, varicose veins of the esophagus with cirrhosis of the liver and other diseases, long-term use of gastric and intestinal drainage, ulcerative colitis, hemorrhoids; diseases of the blood, blood and lymphatic system: leukemia, hemophilia, thrombocytopenia, hemorrhagic diathesis; diseases of the central nervous system (hemorrhagic stroke, craniocerebral injury); malignant neoplasms; congenital deficiency of antithrombin III and substitution therapy with antithrombin III preparations (lower doses of heparin should be used to reduce the risk of bleeding); other physiological and pathological conditions (menstrual period, threat of miscarriage, early postpartum period, severe liver disease with impaired protein-synthetical function, chronic renal failure, recently undergone surgical intervention on the eyes,head or spinal cord, recent spinal (lumbar) puncture or epidural anesthesia, proliferative diabetic retinopathy, vasculitis, advanced age, (over 60 years, especially women).

Pregnancy and lactation:Sodium Heparin does not penetrate the placental barrier. To date, there are no data indicating the possibility of malformations of the fetus due to the use of heparin sodium during pregnancy; there are also no results of experiments on animals that would indicate the embryo or fetotoxic effect of sodium heparin. However, there is evidence of an increased risk of preterm labor and spontaneous abortion associated with bleeding. It is necessary to take into account the likelihood of complications when using heparin sodium in pregnant women with concomitant diseases, as well as in pregnant women receiving additional treatment. Daily use of high doses of heparin sodium for more than 3 months may increase the risk of osteoporosis in pregnant women. Therefore, the continuous use of high doses of sodium heparin should not exceed 3 months.Epidural anesthesia should not be used in pregnant women who undergo anticoagulant therapy. Anticoagulant therapy is contraindicated if there is a threat of bleeding, for example, with a threatening abortion. Sodium Heparin Do not excrete with breast milk. Daily use of high doses of heparin sodium for more than 3 months may increase the risk of osteoporosis in lactating women. In case of need of application in the specified periods it is necessary to correlate the benefit / risk.

Dosing and Administration:Heparin is given in the form of continuous IV infusion or in the form of subcutaneous or IV injections. The initial dose of heparin administered for therapeutic purposes is 5000 IU and is administered iv, after which treatment is continued using subcutaneous injections or intravenous infusions. Supporting doses are determined depending on the method of application:
With continuous IV infusion, administer at a dose of 1000-2000 IU / h (24000-48000 IU / day), diluting heparin in a 0.9% solution of sodium chloride;
With regular IV injections, 5000-10000 IU of heparin is administered every 4 to 6 hours; with n / to the introduction of every 12 hours to 15000-20000 ME or every 8 hours to 8000-10000 ME.
Laboratory monitoring of efficacy and safety of heparin sodium therapy.
The dose of sodium heparin must be adjusted on the basis of laboratory indicators of blood coagulability. When sodium heparin is used, it is necessary to monitor activated partial thromboplastin time (APTT) or coagulation time (VSC). The administered dose of sodium heparin is considered adequate if the APTT is 1.5-2.0 times higher than normal values or if the patient's VSK is 2.5-3.0 times higher than the reference values.
With continuous intravenous infusion, it is recommended to determine the initial APTT, then determine the APTT every 4 hours, then increase or decrease the infusion rate until the target APTT level is reached (1.5-2 times higher than the norm), further define the APTT every 6 hours.
With the bolus in / in the introduction, it is recommended to determine the initial APTT, then determine the APTT before each bolus injection, followed by an increase or decrease in the administered dose.
In case of n / n introduction, it is recommended to control the APTT 4-6 hours after the injection, followed by an increase or decrease in the administered dose of sodium heparin.
When used in low doses for the prevention of thromboembolic complications, it is not necessary to monitor the APTT.
In the prevention of thrombosis in the postoperative period, the first injection should be performed 1-2 hours before the operation; In the postoperative period, administer within 7-10 days, and if necessary - for a longer time.
The use of heparin sodium in special clinical situations:
Primary percutaneous coronary angioplasty in acute coronary syndrome without ST segment elevation and myocardial infarction with ST segment elevation: heparin sodium is administered iv bolus in a dose of 70-100 IU / kg (unless the use of inhibitors of glycoprotein Pb / Sh receptors is planned).
Thrombolytic therapy for myocardial infarction with ST segment elevation: heparin sodium is administered intravenously at a dose of 60 IU / kg (maximum dose of 4000 IU), followed by intravenous infusion at a dose of 12 IU / kg (not more than 1000 IU / h) for 24-48 hours. The target level of the APTT 50- 70 seconds or 1.5-2.0 times higher than normal; Control of APTT at 3, 6, 12 and 24 hours after initiation of therapy.
Prevention of thromboembolic complications after surgical interventions using low doses of heparin sodium: sc, deep into the fold of the abdominal skin.
The initial dose is 5000 IU for 2 hours before the operation. In the postoperative period - 5000 ME every 8-12 hours for 7 days or until the patient's mobility is completely restored (whichever comes first).When sodium heparin is used in low doses for the prevention of thromboembolic complications, it is not necessary to control the APTT.
Application in cardiovascular surgery during operations using the extracorporeal blood circulation system: an initial dose - at least 150 IU / kg. Further heparin sodium is introduced by continuous intravenous infusion at a rate of 15-25 drops / min at 30,000 IU per 1 liter of the infusion solution. The total dosage is typically 300 IU / kg (if the estimated duration of surgery less than 60 minutes) or 400 IU / kg (if the estimated duration of the operation 60 or more minutes).
Use in hemodialysis: initial dose - 25-30 IU / kg (or 10000 ME) / in bolus, followed by continuous infusion of sodium heparin 20000 IU / 100 mg sodium chloride solution at a rate of 1500-2000 IU / h (unless otherwise indicated in manual for the use of systems for hemodialysis).
The dose of heparin should be selected taking into account the parameters of blood coagulation (the target level of APTT is 60-85 sec).
Use in pediatrics: adequate controlled trials of the use of heparin sodium in children have not been conducted. These recommendations are based on clinical experience.Initial dose: 75-100 IU / kg IV bolus for 10 minutes. The maintenance dose: children aged 1-3 months - 25-30 IU / kg / h (800 IU / kg / day), children aged 4-12 months - 25-30 IU / kg / h (700 IU / kg / day), children older than 1 year - 18-20 IU / kg / h (500 IU / kg / day) in / in the drip. The dose of heparin sodium should be selected taking into account the parameters of blood coagulation (the target level of APTT is 60-85 sec).

Side effects:Allergic reactions: skin hyperemia, drug fever, urticaria, rhinitis, pruritus and sensation of heat in the soles, bronchospasm, collapse, anaphylactic shock. Other potential side effects include dizziness, headache, tinnitus, decreased appetite, vomiting, diarrhea, joint pain, increased blood pressure, and eosinophilia.
At the beginning of treatment with heparin, transient thrombocytopenia can sometimes be noted with a platelet count in the range of 80 x 109 / l to 150 x 109 / l. Usually this situation does not lead to the development of complications and the treatment with heparin can be continued. In rare cases, severe thrombocytopenia (white clot syndrome) can occur, sometimes fatal. This complication should be assumed in the event of a decrease in the number of platelets below 80 x 109 / L or more than 50% of the baseline, the administration of heparin in such cases is urgently discontinued.Patients with severe thrombocytopenia may develop coagulopathy of consumption (depletion of fibrinogen stores).
Against the background of heparin-induced thrombocytopenia: skin necrosis, arterial thrombosis, accompanied by the development of gangrene, myocardial infarction, stroke.
With prolonged use: osteoporosis, spontaneous bone fractures, calcification of soft tissues, hypoaldosteronism, transient alopecia, priapism.
On the background of heparin therapy, changes in biochemical blood parameters can be observed (an increase in the activity of "hepatic" transaminases, free fatty acids and thyroxine in blood plasma, hyperkalaemia, recurrent hyperlipidemia with a reversal of heparin sodium, a false increase in blood glucose and an error in the results of bromsulfalein test).
Local reactions: irritation, pain, hyperemia, hematoma and ulceration at the injection site, bleeding.
Bleeding: typical - from the gastrointestinal tract and urinary tract, at the site of injection, in areas undergoing pressure, from operating wounds; hemorrhages in various organs (including adrenal glands, yellow body, retroperitoneal space).

Overdose:Symptoms: signs of bleeding.
Treatment: with small bleeding caused by an overdose of heparin, it is enough to stop using it. With extensive bleeding, excess heparin is neutralized with protamine sulfate (1 mg protamine sulphate per 100 IU of heparin). 1% protamine sulphate solution is administered intravenously very slowly. Every 10 minutes, you can not administer more than 50 mg (5 ml) of protamine sulfate. Given the rapid metabolism of heparin sodium, the required dose of protamine sulfate decreases with time. To calculate the required dose of protamine sulfate, it can be considered that T1 / 2 of sodium heparin is 30 minutes. When protamine was used, severe anaphylactic reactions with a lethal outcome were noted, and therefore, the drug should be administered only under conditions of separation, equipped to provide emergency medical care for anaphylactic shock. Hemodialysis is ineffective.

Interaction:Pharmaceutical interaction: a solution of heparin sodium is compatible only with 0.9% sodium chloride solution. A solution of sodium heparin is incompatible with the following drug solutions: alteplase, amikacin sulfate, amiodarone, ampicillin sodium, benzylpenicillin sodium, ciprofloxacin, cytarabine, dicarbazine, danorubicin, diazepam, dobutamine, doxorubicin hydrochloride, droperidol, erythromycin, gentamicin sulfate, haloperidol lactate, hyaluronidase, hydrocortisone sodium succinate, dextrose, fat emulsions, idarubicin, kanamycin sulfate, methicillin sodium, netilmicine sulfate, opioids, oxytetracycline hydrochloride, polymyxin B sulfate, sulfafurazole diethanolamine, tetracycline hydrochloride, tobramycin sulfate, cephalothrin sodium, cefaloridine, vancomycin hydrochloride, vinblastine sulfate, labetalol hydrochloride, nicardipine hydrochloride. Pharmacokinetic interaction: heparin sodium expels phenytoin, quinidine, propranolol and benzodiazepine derivatives from the sites of their binding to plasma proteins, which may lead to an increase in the pharmacological effect of these drugs. Sodium Heparin is bound and inactivated by sodium protamine, polypeptides having an alkaline reaction, and tricyclic antidepressants. Pharmacodynamic interaction: the anticoagulant effect of sodium heparin increases with simultaneousapplication with other drugs that affect hemostasis, incl. with antiplatelet agents (acetylsalicylic acid, clopidogrel, prasugrel, ticlopidine, dipyridmine), anticoagulants of indirect action (warfarin, phenylin, syncumar), thrombolytic drugs (alteplase, streptokinase, urokinase), non-steroidal anti-inflammatory drugs (including phenylbutazoneschbuprofen, indomethacin, diclofenac), glucocorticosteroids and dextrin, resulting in increased risk of bleeding. In addition, the anticoagulant effect of sodium heparin can be enhanced when combined with hydroxychloroquine, sulfinpyrazone, probenecid, ethacrynic acid, cytostatics, cefamandole, cefotetan, valproic acid, propylthiouracil.
The anticoagulant effect of sodium heparin decreases with simultaneous use with ACTH, antihistamine drugs, ascorbic acid, ergot alkaloids, nicotine, nitroglycerin, cardiac glycosides, thyroxine, tetracycline and quinine.
Heparin sodium can reduce the pharmacological action of adrenocorticotropic hormone,glucocorticosteroids and insulin.

Special instructions:Treatment in large doses is recommended in a hospital. The control of the number of platelets should be made ahead of the beginning of treatment, on the first day of treatment and at short intervals during the entire period of administration of sodium heparin, especially between 6 and 14 days after initiation of treatment. Immediately stop treatment with a sharp decrease in the number of platelets (see "Side effect").
A sharp decrease in the number of platelets requires further investigation for the detection of heparin-induced immune thrombocytopenia. If this is the case, the patient should be informed that he can not prescribe heparin in the future (even low molecular weight heparin). If there is a high probability of heparin-induced immune thrombocytopenia, heparin should be immediately withdrawn.
When developing heparin-induced thrombocytopenia in patients receiving heparin for thromboembolic disease or in the case of thromboembolic complications, other antithrombotic agents should be used.
Patients with heparin-induced immune thrombocytopenia (white clot syndrome) should not undergo hemodialysis with heparinization.If necessary, alternative methods of treating renal failure should be used.
To avoid overdose, it is necessary to constantly monitor clinical symptoms indicating possible bleeding (bleeding of the mucous membranes, hematuria, etc.). in individuals with a lack of response to heparin or requiring the appointment of high doses of heparin, it is necessary to control the level of antithrombin III. Resistance to sodium heparin is often observed with fever, thrombosis, thrombophlebitis, infectious diseases, myocardial infarction, malignant neoplasms, and also after surgical interventions and with the deficiency of antithrombin III. In such situations, more thorough laboratory monitoring (APTT monitoring) is required.
Although heparin sodium does not penetrate the placental barrier and is not detected in breast milk, when administered at therapeutic doses, should be carefully monitored by pregnant women and breast-feeding mothers.
Special care should be taken within 36 hours after delivery.
It is necessary to conduct appropriate control laboratory tests (clotting time, activated partial thromboplastin time and thrombin time).
In women over 60 years of age, heparin can increase bleeding, and therefore, the dose of sodium heparin should be reduced in this category of patients.
When using heparin in patients with hypertension, one should constantly monitor blood pressure.
Transition to warfarin therapy: to ensure a persistent anticoagulant effect, heparin sodium should be continued in full dosage until a stable target level of INR is reached. After this, the administration of sodium heparin should be discontinued.
Transition to dabigatran therapy: Continuous intravenous administration of sodium heparin should be discontinued immediately after the first dose of dabigatran. With fractional intravenous administration, the patient must take the first dose of dabigatran within 1-2 hours before the scheduled administration of a regular dose of heparin sodium.
Before routine surgical interventions to reduce blood loss during surgery and during the postoperative period, it is usually recommended to cancel oral anticoagulants (warfarin) and antiplatelet drugs (acetylsalicylic acid, clopidogrel, ticlopidine) 7 days before surgery and appoint heparin sodium in therapeutic doses. The administration of heparin sodium in this case ceases 6 hours before the operation and resumes 6 hours after its termination. Intramuscular injections should be excluded when prescribing heparin sodium for medicinal purposes. Puncture biopsies, infiltration and epidural anesthesia and diagnostic lumbar punctures should also be avoided whenever possible. If there is a massive bleeding, you should cancel heparin sodium and to investigate the coagulogram indices. If the results of the analysis are within the limits of the norm, then the probability of development of this bleeding due to the use of sodium heparin is minimal. Changes in the coagulogram tend to normalize after heparin withdrawal.

Effect on the ability to drive transp. cf. and fur:studies to assess the impact of heparin sodium on the ability to drive vehicles and engage in potentially hazardous activities were not conducted.

Form release / dosage:Solution for intravenous and subcutaneous administration of 5000 IU / ml.

Packaging:1 ml, 2 ml and 5 ml of the solution are placed in a glass bottle sealed with a rubber stopper,Rinsed with an aluminum ring (plastic caps are possible); 1 bottle together with instructions for use in a pack of cardboard or 5 bottles per plastic pallet, 1 pallet together with instructions for use in a pack of cardboard.
1 ml per disposable glass syringe with a needle protected with a plastic cap, 1 syringe per plastic tray, 1 pallet together with instructions for use in a cardboard pack.

Storage conditions:Keep in dry the dark place at a temperature of no higher than 25 ° C. Do not freeze.
Keep out of the reach of children.

Shelf life:3 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002569

Date of registration:07.08.2014

The owner of the registration certificate:JODAS EKSPOIM, LLC JODAS EKSPOIM, LLC Russia

Manufacturer: & nbsp

NOVALEK PHARMACEITICAL, Pvt. Ltd. India

Representation: & nbspJodas Expoim, Open CompanyJodas Expoim, Open Company

Information update date: & nbsp2016-01-07

Illustrated instructions

Instructions

Heparin J (Heparin)