Bemiparin Sodium

Registered South African indications:

• Prevention of thromboembolic disease in patients undergoing general and orthopaedic surgery
• Prevention of clotting in the extracorporeal circuit during haemodialysis
• The treatment of established deep vein thrombosis, with or without pulmonary embolism

Contraindications

• Hypersensitivity to the active ingredient or any of is excipients
• Hypersensitivity to heparin or substances derived from pigs
• Severe hepatic impairment
• History of confirmed or suspected immunologically mediated heparin-induced thrombocytopenia (HIT)
• Active haemorrhage or increased risk of bleeding due to impairment of haemostasis
• Severe impairment of pancreas function
• Injuries to and operations on the central nervous system, eyes and ears
• Disseminated intravascular coagulation (DIC) attributable to heparin-induced thrombocytopenia
• Acute endocarditis and endocarditis lenta
• Organic lesion with high risk of bleeding (e.g. active peptic ulcer, haemorrhagic stroke, cerebral aneurysm or cerebral neoplasms)
• Locoregional anaesthesia in elective surgical procedures in patients receiving heparin for treatment rather than for prophylaxis
   

Cautions

• Renal impairment
• Mild to moderate hepatic impairment
• Intramuscular injection of bemiparin
• Intramuscular injection of other agents during bemiparin administration
• Use of dosage regimens of other low molecular weight heparins
• Mixing with any other injections or infusions
• Uncontrolled arterial hypertension
• History of gastro-duodenal ulcer disease
• Thrombocytopenia
• Nephrolithiasis and/or urethrolithiasis
• Choroid and retinal vascular disease, or any other organic lesion with an increased risk of bleeding complications
• Diabetes mellitus
• Pre-existing metabolic acidosis
• Raised plasma potassium
• History of heparin-induced thrombocytopenia, with or without thrombosis
• Use in patients undergoing epidural or spinal anaesthesia or lumbar puncture

Forms avail. in SA and covered in this monograph: inj

General surgery with risk of venous thromboembolism

• SC: Initial: 2500 IU (two thousand five hundred IU), 2hrs before surgery OR 6hrs after surgery; Subsequent days: 2500 IU (two thousand five hundred IU), every 24hrs

Orthopaedic surgery with high risk of venous thromboembolism

• SC: Initial: 3500 IU (three thousand five hundred IU) , 2hrs before surgery OR 6hrs after surgery; Subsequent days: 3500 IU (three thousand five hundred IU), every 24hrs

Prophylactic treatment must be followed in accordance with the medical practitioner’s opinion during the period of risk or until the patient is mobilised.

As a general rule, it is considered necessary to maintain prophylactic treatment for at least 7 – 10 days after the surgical procedure and until the risk of thromboembolic disease has decreased.

Prevention of the thromboembolic disease in non-surgical patients

• SC: 2500 IU (two thousand five hundred IU) OR 3500 IU (three thousand five hundred IU), dly (see notes below)

The dose should be according to whether the set of risk factors of the patients defines them as mild or high-risk thromboembolic patients.

Prophylactic treatment must be continued, according to the medical practitioner’s criteria, during the risk period or until the complete mobilisation of the patient.

Prevention of clotting in the extracorporeal circuit during haemodialysis
- For patients undergoing repeated haemodialysis of no longer than 4 hours in duration and with no risk of bleeding

• IV: <60kg: 2500IU (two thousand five hundred IU), bolus, single dose, into the arterial line at the beginning of the dialysis session
   
• IV: ≥60kg: 3500IU (three thousand five hundred IU), bolus, single dose,  into the arterial line at the beginning of the dialysis session

Treatment of deep vein thrombosis

• SC: 115 IU/kg (one hundred and fifteen IU per kg), dly
  Recommended duration: 7 +/- 2 days
  
  The daily dose generally corresponds - depending on the body weight range - to the following doses and volumes of the product in pre-filled syringes:

In the absence of any contra-indication, oral anticoagulation should be commenced 3-5 days after beginning beriparim sodium first administration, and the dose adjusted so as to keep the International Normalised Ratio (INR) value between 2-3 times the control value. Beriparin sodium administration can be stopped as soon as the said INR value is achieved

Oral anticoagulation should be continued for at least 3 months

Not established for use in children

Pregnancy

• Caution
• Safety in pregnancy has not been established
• Bemiparin is not recommended for use by women who are pregnant

Breastfeeding

• Caution; not recommended
• Mothers who receive bemiparin should be advised to avoid breastfeeding

Renal impairment

• Caution; no information available

Hepatic impairment

• Mild to moderate: Caution; no information available
• Severe: Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Not yet classified (NC)

Central Nervous System Disorders

• Epidural and spinal haematoma (following epidural or spinal anaesthesia and lumbar puncture)
• Neurological impairment
• Prolonged or permanent paralysis

Gastrointestinal Disorders

• Bleeding complications

Genitourinary Disorders

• Bleeding complications

Musculoskeletal Disorders

• Osteoporosis (associated with long-term heparin treatment)

Skin and Subcutaneous Tissue Disorders

• Bleeding complications
• Cutaneous allergic reactions (urticaria, pruritus)
• Injection site haematoma and pain
• Injection site ecchymosis
• Injection site cutaneous necrosis

Immune, Blood and Lymphatic System Disorders

• Transient thrombocytopenia (type I)
• Severe thrombocytopenia (type II)
• Anaphylactic reactions (nausea, vomiting, fever, dyspnoea, bronchospasm, glottis oedema, hypotension, urticaria, pruritus)

• Vitamin K antagonists
• Other anticoagulants
• Acetylsalicylic acid and other salicylates
• Nonsteroidal anti-inflammatory drugs
• Ticlopidine
• Clopidogrel and other platelet inhibitors
• Glycoprotein llb/Illa antagonists
• Systemic glucocorticoids
• Dextran
• Potassium-sparing medicines
• IV Nitroglycerine

• Elevations of transaminases (AST, ALT) and gamma-GT levels
• Serum electrolytes

Method of administration
Subcutaneous injection technique:

• The pre-filled syringes are ready for immediate use and must not be purged before the subcutaneous injection.
• When bemiparin is administered subcutaneously, the injection should be given in the subcutaneous cell tissue of the anterolateral or posterolateral abdominal waist, alternately on the left and right sides
• The needle should be fully inserted, perpendicularly and not tangentially, into the thick part of a skin fold held between the thumb and the forefinger; the skin fold should be held throughout the whole injection
• Do not rub the injection site

Hyperkalemia Risk:

• Bemiparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia
• The risk of hyperkalaemia appears to increase with the duration of therapy
• Serum electrolytes should be measured in patients at risk before starting bemiparin therapy and monitored regularly thereafter particularly if treatment is prolonged beyond about 7 days

Heparin-induced thrombocytopenia:

• Bemiparin is to be used with extreme caution in patients with a history of heparin-induced thrombocytopenia, with or without thrombosis
• The risk of heparin-induced thrombocytopenia may persist for several years. If a history of heparin-induced thrombocytopenia is suspected, the decision to use bemiparin in such a case must be made only in consultation with an expert in the field
• Thrombocytopenia (type I) at the beginning of therapy with bemiparin with platelet counts between 100,000/mm3 and 150,000/mm3 due to platelet activation has been observed
• Antibody-mediated severe thrombocytopenia (type II) with platelet counts clearly below 100,000/mm3 has been observed
• This effect usually occurs within 5 to 21 days after the beginning of treatment; in patients with a history of heparin-induced thrombocytopenia this may occur sooner
• Platelet counts are recommended before administration of bemiparin, on the first day of therapy and then regularly every 3-4 days and at the end of therapy with bemiparin
• In practice, treatment must be discontinued immediately and an alternative therapy initiated if a significantly reduced platelet count is observed (30 to 50 %) associated with positive or unknown results of in-vitro tests for anti-platelet antibody in the presence of bemiparin
• Cases of cutaneous necrosis, sometimes preceded by purpura or painful erythematous blotches have been reported with bemiparin. In such cases, treatment should be discontinued immediately

Known symptoms of overdosage and particulars of its treatment:

• Bleeding is the main symptom of overdose. Bemiparin should be discontinued
• In case of major haemorrhages, administration of protamine sulphate may be needed
• Protamine sulphate exerts a partial decrease on anti Xa activity for 2 hours after its intravenous administration, at a dose of 1,4 mg of protamine sulphate each 100 IU anti Xa administered

Bemiparin sodium is a low molecular weight heparin (LMWH). Heparin acts as a catalyzer of the ATIII enzyme, accelerating the formation of the neutralizing complex with thrombin and blocking the enzyme activity of coagulation factors. ATIII inhibits both thrombin and the active form of other coagulation factors (XII, XI, IX and X), as well as plasmin. However, inhibition of thrombin and FXa is particularly significant and clinically relevant. Fractionation of the heparin molecule (4000 – 7000 daltons) has allowed for selecting the fractions with a lower MW (LMWHs), which retain the anti Xa activity, but have a reduced anti IIA activity. The anti Xa activity of Bemiparin ranges between 80 and 120 anti Xa IU per mg and the anti IIA activity ranges between 5 and 20 anti IIA IU per mg, calculated in relation to dry matter. The anti Xa/IIA ratio is approximately 8.

Injection 2500 IU/0.2 ml

• Hibor (Litha)

Injection 3500 IU/0.2 ml

• Hibor (Litha)

Injection 5000 IU/0.2 ml

• Hibor (Litha)

Injection 7500 IU/0.3 ml

• Hibor (Litha)

Injection 10000 IU/0.4 ml

• Hibor (Litha)