Heparin Sodium ROVI 5,000 IU/ml

/ Kamada

Heparin sodium must be individually dosed.
The dosage depends on the coagulation parameters the nature and course of the disease, the patient’s response, adverse reactions, and the patient’s weight and age.
Differences in sensitivity to heparin and a possible change in heparin tolerance during the course of treatment need to be considered.
Prophylaxis of thromboembolism (low-dose treatment)
Subcutaneous injection is recommended for the prophylaxis of thromboembolism. Pre-filled syringes with an appropriate dosage are available for this. General dosage recommendation for the prophylaxis of thromboembolism:
– Pre- and postoperative prophylaxis of thromboembolism

Preoperatively 5,000-7,500 IU subcutaneously approximately 2 hours before the operation. Postoperatively, depending on the risk of thrombosis, usually 5,000 IU subcutaneously every 8-12 hours or 7,500 IU subcutaneously every 12 hours until the patient is mobilised or until vitamin K antagonists have an adequate effect. Laboratory monitoring (coagulation parameters) for dose adjustment may be required in individual cases.
– Prophylaxis in non-surgical medicine
(e.g. prolonged bed rest, increased thrombotic tendency in the patient, diseases with an increased risk of thrombosis.)

Depending on the risk of thrombosis, generally 5,000 IU subcutaneously every 8-12 hours or 7,500 IU subcutaneously every 12 hours.
The dosage must be adapted to the risk of thrombosis and the level of activity of the coagulation system and can be determined by monitoring coagulation parameters.
As part of the treatment of venous or arterial thromboembolic disorders
Continuous intravenous administration is recommended if there are clots in blood vessels.
Dosage in adults
Generally start with 5,000 IU heparin sodium as an intravenous bolus, followed by a continuous infusion of 1,000 IU heparin sodium per hour using an infusion pump.
Dosage in children
Initially 50 IU/kg body weight, then 20 IU/kg body weight per hour.
If a continuous intravenous infusion is not possible, subcutaneous therapy (in 2-3 separate doses) may be used as an alternative, with close monitoring of therapy (e.g. 10,000-12,500 IU of heparin sodium every 12 hours).
Close monitoring of therapy accompanied by assay of coagulation parameters is absolutely essential in all cases. Monitoring of therapy and dose adjustment are generally based on activated partial thromboplastin time (aPTT), which should be around 1.5-2.5 times the normal value. It is recommended that the aPTT be checked 1-2 hours, 6 hours, 12 hours and 24 hours after the start of treatment in the case of continuous intravenous heparin administration, and 6 hours after administration of the second dose in the case of subcutaneous administration.
– Treatment of venous thromboembolism
Initially, 5,000 IU heparin sodium should be administered intravenously as a bolus, followed by an intravenous infusion of generally 1,000 IU heparin sodium per hour. The dosage should be adjusted according to the aPTT values, aiming to prolong the aPTT to 1.5-2.5 times the initial value (within the first 24 hours if possible).
The treatment should take place for at least 4 days or continued until adequate oral anticoagulation has been achieved.
– As part of the treatment of unstable angina and non–Q-wave myocardial infarction
In general, 5,000 IU heparin sodium as an intravenous bolus, followed by a continuous infusion of 1,000 IU per hour. The dose is based on the aPTT, which should be prolonged to 1.5-2.5 times the normal value.
Heparin sodium should be administered for at least 48 hours.
– As concomitant therapy in thrombolysis with fibrin-specific thrombolytics (e.g. r-tPA) for the treatment of acute myocardial infarction
Initially, 5,000 IU heparin sodium as an intravenous bolus, followed by an intravenous infusion of 1,000 IU per hour.
The infusion should be adjusted according to aPTT values to prolong them to about 1.5-2.5 times the initial value. Heparin sodium should be given for 48 hours.
In the case of thrombolysis with non-fibrin-specific thrombolytics (e.g. streptokinase), a subcutaneous injection of 12,500 IU heparin sodium may also be administered every 12 hours, starting 4 hours after thrombolysis.
The exact dosage of the concomitant heparin therapy depends on the type of thrombolytic and should be undertaken according to the data on the individual thrombolytic agents.
It is important to ensure accurate monitoring of the coagulation status in all cases.
Anticoagulation in treatment or surgery with an extracorporeal circulation
Haemodialysis
Individual dosage depending on the results of the coagulation tests and type of machine.
Heart/lung machine
The dosage depends on the type of heart/lung machine and the length of the operation and should be managed individually.
Method of administration
Subcutaneous and intravenous injection or intravenous infusion.
Administration of the subcutaneous injection
The injection should be administered with a fine injection needle held perpendicular to the body axis, into a raised fold of abdominal skin or on the anterior aspect of the thigh; the injection must be strictly subcutaneous. Any drops adhering to the injection needle should be removed before the injection, as introducing heparin sodium into the injection channel can result in superficial bruising and in rare cases local allergic irritation.
Notes:
To minimise disruption of lymph drainage, the drug should be administered into the upper arm in patients with surgical clearance of lymph nodes in the abdominal/urogenital regions.
As heparin is bound by platelet components (PF4), as a result of which the effect is neutralised, blood taken for coagulation tests and mixed with citrate should be centrifuged and decanted as soon as possible after sampling in order to separate blood cells and blood plasma.
The treating physician decides on the duration of administration.
Regular monitoring of the activated partial thromboplastin time (aPTT) and platelet count are necessary with heparin therapy.

Prevention of thromboembolic disorders.
– As part of the treatment of venous or arterial thromboembolic disorders (including the early treatment of heart attacks as well as unstable angina pectoris).
– For anticoagulation during treatment or operation with an extracorporeal circulation (e.g. heart/lung machine, haemodialysis).
Prevention of thromboembolic disorders.
– As part of the treatment of venous or arterial thromboembolic disorders (including the early treatment of heart attacks as well as unstable angina pectoris).
– For anticoagulation during treatment or operation with an extracorporeal circulation (e.g. heart/lung machine, haemodialysis).

– Hypersensitivity to the active substance heparin, Benzyl alcohol or to any of the excipients.
– Acute or previous history of heparin-induced allergic thrombocytopenia (type 2).
– Disorders associated with a bleeding diathesis, e.g. thrombocytopenia, coagulopathies, severe hepatic, renal or pancreatic disorders.
– Disorders in which there is a suspected lesion of the vascular system, e.g. gastrointestinal ulcers, hypertension (>105 mmHg diastolic), cerebral haemorrhage, trauma or surgical operations involving the central nervous system (CNS), eye operations, retinopathies, vitreous haemorrhage, aneurysm of the cerebral arteries, infectious endocarditis.
– Threatened miscarriage.
– Spinal anaesthesia, epidural anaesthesia, lumbar puncture.
– Organ lesions associated with a bleeding tendency.

The drug must not be used in preterm or newborn babies because of the benzyl alcohol content.

Should not be used in the case of:
– suspected malignancy with a bleeding tendency.
– renal or ureteric calculi.
– chronic alcoholism.

Particularly careful medical monitoring is necessary:
– during pregnancy, especially in the case of prolonged use .
– in elderly patients, especially in women.
– during concomitant treatment with fibrinolytics or oral anticoagulants, with antiplatelet drugs (e.g. aspirin, ticlopidine, clopidogrel) and/or glycoprotein IIb/IIIa receptor antagonists.
– during concomitant use of medicinal products that increase the serum potassium level. Serum potassium levels should be monitored in at-risk patients (e.g. because of diabetes, impaired renal function or use of medicinal products that increase the serum potassium level).

During treatment with heparin sodium, intramuscular injections should be avoided because of the risk of haematomas.
If thromboembolic complications occur during heparin administration, type 2 heparin-induced thrombocytopenia must be considered in the differential diagnosis and the platelet count monitored.
In infants, children and patients with renal and/or hepatic failure, careful monitoring and testing of coagulation parameters are essential; this also applies to the prophylaxis of thromboembolism (low-dose treatment).
Patients on heparin therapy (of over 22,500 IU/day) should avoid putting themselves at risk of injury.
Heparin can increase and prolong menstrual bleeding. If there is unusually heavy or acyclic bleeding, an organic cause requiring treatment should be excluded by a complementary gynaecological examination.
In isolated cases, the occurrence of spinal and epidural haematomas has been reported in temporal association with spinal or epidural anaesthesia for unfractionated and fractionated low-molecular-weight heparin, especially in the case of intravenous administration or the administration of doses above those recommended for low-dose prophylaxis of thromboembolism (above 15,000 IU unfractionated heparin per day subcutaneously). These haematomas may lead to neurological complications of varying severity and even persistent or
permanent paralysis. should therefore be used only after a detailed individual benefit-risk assessment if neuraxial anaesthetic procedures are planned or have already taken place.
According to a recommendation by the German Society of Anaesthesiology and Intensive Care Medicine, a puncture-free interval of 4 hours should be left as a safety precaution between the last administration at a prophylactic dose (low-dose) and re-insertion or removal of a spinal/epidural catheter. Thereafter, at least 1 hour should be allowed to elapse before the further administration of low-dose the drug.
Patients should be carefully monitored neurologically after the use of a neuraxial anaesthetic procedure, watching particularly for persistent sensory or motor deficits. If a haematoma in the region of the spinal cord is suspected clinically, suitable diagnostic or therapeutic measures should be initiated immediately.
Notes on laboratory investigations:
The platelet count should be checked:
– before the start of heparin administration.
– on the 1st day after the start of heparin administration.
– then regularly every 3-4 days during the first 3 weeks.
– at the end of heparin therapy.

Heparin can distort the results of many laboratory investigations, e.g. the erythrocyte sedimentation rate, erythrocyte fragility and complement fixation tests. Heparin can affect the prothrombin time; this needs to be considered when switching to coumarin derivatives.
The results of thyroid function tests may be distorted during heparin therapy (e.g. false high T3 and T4 levels).
contains benzyl alcohol
Benzyl alcohol has been associated with the risk of serious adverse reactions (gasping syndrome) in newborn babies and infants.
In infants (under 3 years of age), the medicinal product should not be used for longer than a week because of accumulation.
Large quantities of benzyl alcohol should be used only with caution and when absolutely necessary because of the risk of accumulation and toxicity (metabolic acidosis), especially in individuals with hepatic or renal impairment and during pregnancy and lactation.

Blood and lymphatic system disorders
Very common: Depending on the heparin dosage, increased incidence of bleeding, especially from skin, mucous membranes, wounds, gastrointestinal and urogenital tract.
Common: At the start of treatment, type 1 heparin-induced thrombocytopenia not mediated by antibodies (platelet count: 100,000-150,000/μl), without thrombosis.
Hepatobiliary disorders
Very common: Elevation of serum transaminases (AST, ALT), gamma-glutamyl transpeptidase (gamma-GT), LDH and lipase.
General disorders and administration site conditions
Common: Local tissue reactions at the injection site (induration, redness, discoloration and small haematomas).

Antiplatelet drugs (aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor, dipyridamole in high doses), fibrinolytics, other anticoagulants (coumarin derivatives), oral factor Xa inhibitors (apixaban, rivaroxaban), thrombin inhibitors (bivalirudin, argatroban, dabigatran), hirudin (desirudin), non-steroidal anti-inflammatory drugs (phenylbutazone, indometacin), glycoprotein IIb/IIIa receptor antagonists, high-dose penicillin, dextrans:
Clinically significant increased effect and increased risk of bleeding.
Cytostatics
Increase in the effect of heparin: doxorubicin probably attenuates the effect.
Nitroglycerin, administered intravenously
A clinically significant reduction in the effect of heparin can arise with the intravenous administration of nitroglycerin. After nitroglycerin is stopped, there may be a sharp rise in the aPTT. Close monitoring of the aPTT and adjustment of the heparin dose are necessary during
the concomitant infusion of nitroglycerin.
Ascorbic acid, digitalis, tetracyclines, smoking
Inhibition of the effect of heparin.
Medicinal products bound to plasma proteins (e.g. propranolol)
Increase in the effect through displacement from plasma protein binding sites.
Medicinal products that increase the serum potassium level
Medicinal products that increase the serum potassium level must only be used concomitantly with Heparin Sodium if there is particularly careful medical monitoring.
Basic medicinal products (tricyclic antidepressants, antihistamines and quinine)
Reciprocal reduction in the effect through salt formation with heparin.

Pregnancy
Heparin does not cross the placenta. To date, experience in pregnant women has not demonstrated any foetal/neonatal toxicity of heparin. Animal studies have also not shown any evidence of reproductive toxicity.
There are, however, reports of an increased risk of miscarriages and premature births. Treatment- or disease-induced complications in pregnant women cannot be ruled out. Daily high-dose heparin administration over a period of more than 3 months can increase the risk of osteoporosis in pregnant women.
Epidural anaesthesia is contraindicated during birth in women treated with anticoagulants. Anticoagulant treatment is also contraindicated if there is a bleeding tendency such as with threatened miscarriage.
If necessary, use of heparin during pregnancy can be considered.
Lactation
Heparin is not excreted in human milk. Heparin can be used during breast-feeding. Daily high- dose administration of heparin over a period of more than 3 months can increase the risk of osteoporosis in breast-feeding women.

a) Symptoms of an overdose
Bleeding, in most cases from the skin and mucous membranes, wounds, gastrointestinal and urogenital tract (epistaxis [nosebleed], haematuria, melaena, haematomas, petechiae). A fall in blood pressure, decrease in haematocrit or other symptoms may be signs of occult bleeding.
b) Treatment of overdose Mild bleeding
Reduce the heparin dose if necessary.
Moderate non–life-threatening bleeding
Suspend the heparin therapy.
More serious, life-threatening bleeding
Reverse the effect of heparin with protamine after excluding other causes of bleeding (e.g. consumption coagulopathy, factor deficiency).
Protamine should be administered only in the case of life-threatening bleeding, as there is an increased risk of thromboembolic complications once the heparin has been completely neutralised. The patient must be monitored and treatment continued in intensive care.
The antidote protamine is an arginine-rich protein which is usually used in the form of a chloride or sulphate. As a general rule, 1 mg of protamine neutralises the effect of about 100 IU of heparin (1 IU of protamine neutralises 1 IU of heparin). The half-life of heparin and the route of administration need to be borne in mind for the treatment, i.e.
– 90 minutes after intravenous heparin administration, only 50% of the calculated protamine dose should be given.
– 3 hours after intravenous administration only 25% should be given.

In the event of over-titration, protamine can itself cause an increased bleeding tendency through various mechanisms. If protamine is injected intravenously too quickly, there may be a fall in blood pressure, bradycardia, dyspnoea and a feeling of oppression. Protamine is eliminated from the bloodstream more rapidly than heparin. The neutralisation effect must therefore be monitored by regular assays of the activated partial thromboplastin time (aPTT). Heparin is not dialysable.