Heparin Sodium

Registered South African indications:

• Arterial and venous thrombosis
• Vascular surgery and blood transfusions
• Prophylaxis of thromboembolic complications after surgery

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• Current or history of immune-mediated heparin-induced thrombocytopenia
• Active major haemorrhage, or risk factors thereof
• Generalised or local haemorrhagic tendency
  - Uncontrolled severe hypertension
  - Severe hepatic insufficiency  or disease (including oesophageal varices)
  - Active peptic ulcer
  - Intracranial haemorrhage
  - Injuries and operations on the central nervous system, eyes and ears
  - Women with abortus imminens
  - Hiatus hernia
  - Neoplasm
  - Bacterial endocarditis
  - Retinopathy
  - Bleeding haemorrhoids
  - Cerebral thrombosis
• Septic endocarditis
• Haemophilia or other bleeding disorder
• Active tuberculosis
• Increased capillary permeability
• Locoregional anaesthesia in elective surgical procedures (treatment)
• Insertion of epidural catheter or epidural anaesthesia during birth in pregnant women (treatment)
• Premature babies or neonates (formulations with benzyl alcohol)
• IM injection or major trauma
• Patients who consume large amounts of alcohol
• Surgery of the brain, spinal cord and eye or at sites of increased risk of bleeding
• Lumbar puncture or regional anaesthetic block
• Coadministration with IV diclofenac

Cautions 

• Hypersensitivity to low molecular weight heparin
• Pregnancy
• Severe renal impairment
• Moderate to severe hepatic impairment (Child-Pugh Classes B &C)
• Elderly
• Risk of haemorrhage
• Increased risk of bleeding complications
• Hypertension
• Peridural or spinal anaesthesia or spinal puncture (prophylactic use)
• Use of a peridural or spinal catheter for anaesthesia (prophylactic use)
• Traumatic or repeated puncture
• Intramuscular injection
• Concomitant IM injections
• Diabetes mellitus
• Pre-existing metabolic acidosis
• Raised plasma potassium at pre-treatment
• Long-term use
• Sodium controlled diet (certain formulations)
• Heparin resistance (see additional prescribing points)

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

Treatment of thromboembolic disorders
- Deep vein thrombosis
- Acute arterial embolism or thrombosis
- Thrombophlebitis
- Pulmonary embolism
- Fat embolism

1000 IU (one thousand IU) and 5000 IU (five thousand IU) injection

• IV: 5000-10000 IU (five thousand to ten thousand IU), 4hrly OR 500 IU/kg, dly as a continuous infusion
• SC: Initial: 250 IU/kg; THEN 12hrly with dosage adjusted according to coagulation test results

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Dosages should be adjusted to maintain a thrombin clotting time, whole blood clotting time or activated partial thromboplastin time 1.5 to 2 times that of control on blood withdrawn 4-6 hours after the first injection or commencement of infusion and at similar intervals until the patient is stabilised

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During pregnancy: Standard treatment dosages should be given initially by continuous intravenous infusion, or every 12hrs by SC injection. Intermittent intravenous injections are not advised. Subsequent dosages and/or dosage intervals should be individually adjusted according to changes in thrombin clotting time, whole blood clotting time and/or activated partial thromboplastin time

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25000 IU (twenty five thousand IU)/ml solution for injection

Treatment of thromboembolic disorders
- Deep vein thrombosis
- Pulmonary embolism

• IV: Loading dose: 5000-10000 IU (five thousand to ten thousand IU); Maintenance: 1000-2000 IU (one thousand to two thousand IU)/hr as an infusion
  OR
• SC: Maintenance: 10000-20000 IU (ten thousand to twenty thousand IU), 12hrly
  OR 
• IV: Maintenance; 5000-10000 IU (five thousand to ten thousand IU), 4hrly as an injection

Prophylaxis of thromboembolic disorders

1000 IU (one thousand IU) and 5000 IU (five thousand IU) injection

- Major elective surgery

• SC: 5000 IU (five thousand IU), given 2hrs pre-operatively; THEN 8-12hrly post-operatively for 10-14 days or until patient is ambulant

- Myocardial infarction

• SC: 5000 IU (five thousand IU), 12hrly; Treatment duration: 10 days or until patient is mobile

- Other indications where prophylaxis is needed

• SC: 5000 IU (five thousand IU), 8-12hrly

- Prophylactic dosage in pregnancy

Early pregnancy

• SC: 5000 IU (five thousand IU), 12hrly

Last trimester

• SC: 10000 IU (ten thousand IU), 12hrly

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The dosage should be reduced during labour and the standard prophylactic dosage is suitable in the puerperium

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Formulations may contain the preservative benzyl alcohol. As benzyl alcohol may cross the placenta, the use of these formulations should be avoided in pregnancy. If use is considered essential, the dosage recommendations given above should be followed

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25000 IU (twenty five thousand IU)/ml solution for injection

- Deep vein thrombosis
- Pulmonary embolism

• SC: 5000 IU (five thousand IU), given 2hrs pre-operatively; THEN 8-12hrly post-operatively for 7-10 days for until patient is ambulant

- Prophylaxis during pregnancy (deep vein thrombosis and pulmonary embolism)

• SC: 5000-10000 IU, 12hrly adjusted according to aPTT or anti-Xa assay

- Myocardial infarction

• SC: 12500 IU (twelve thousand and five hundred IU), 12hrly for ≥10 days

- Cardiopulmonary bypass

• IV: Initial: 300 IU/kg; THEN adjusted according to activated clotting time (400-500 seconds)

Prophylaxis of clotting during haemodialysis

• IV: Initial: 1000-5000 IU (one thousand to five thousand IU), as a bolus dose; Maintenance: 1000-2000 IU/hr (one thousand to two thousand IU/hr), as an infusion, adjusted to maintain clotting time >40min

Unstable angina pectoris
Peripheral arterial occlusion

25000 IU (twenty five thousand IU)/ml solution for injection

• IV: Loading dose: 5000 IU (five thousand IU); Maintenance 1000-2000 IU (one thousand to two thousand IU)/hr as an infusion OR 5000-10000 IU (five thousand to ten thousand IU), 4hrly as an injection

Paed. forms avail. in SA and covered in this monograph: inj

Treatment of thromboembolic disorders
- Deep vein thrombosis
- Pulmonary embolism

• Loading dose: IV: 50 IU/kg; Maintenance: 15-25 IU/kg/hr, as an infusion
  OR
• SC: Maintenance: 250 IU/kg, 12hrly
  OR
• IV: Maintenance: 100 IU/kg, 4hrly

Unstable angina pectoris
Peripheral arterial occlusion

• Loading dose: IV: 50 IU/kg; Maintenance:15-25 IU/kg/hr, as an infusion
  OR
• IV: Maintenance: 100 IU/kg, 4hrly

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Manufacturers recommendations for the 1000 IU (one thousand IU) and 5000 IU (five thousand IU) injection:
Standard treatment dosages should be given initially. Subsequent dosages and/or dosage intervals should be individually adjusted according to changes in thrombin clotting time, whole blood clotting time and/or activated partial thromboplastin time

Pregnancy

• Caution
• Anticoagulant treatment of pregnant women requires specialist involvement
• Heparin does not cross the placenta and can be used during all trimesters of pregnancy if clinically needed
• The decision to use heparin in pregnancy should be taken after evaluation of the risk/benefit in any particular circumstance
• Reduced bone density has been reported with prolonged heparin treatment during pregnancy
• Caution should be exercised in relation to the risk of haemorrhage, especially during delivery and epidural anaesthesia
• Due to the risk of spinal haematoma, treatment doses of heparin are contraindicated in patients who receive neuraxial anaesthesia. Therefore, epidural anaesthesia in pregnant women should always be delayed until at least 4-6 hours after intravenous administration of the last treatment dose of heparin, and 8-12 hours after subcutaneous administration of the last treatment dose of heparin. However, prophylactic doses may be used as long as a minimum delay of 4-6 hours is allowed between the last administration of heparin and the needle or catheter placement
• Use in women with threatened abortion is contraindicated
• Heparin contains benzyl alcohol. This preservative may cross the placenta

Breastfeeding

• Compatible
• Heparin is not excreted in human milk and can be used during breastfeeding

Fertility

• There are no clinical studies with heparin regarding fertility

Renal Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; dose adjustment recommended
  Heparin doses must be adjusted according to the patient's coagulation profile (aPTT, anti-Xa, bleeding time)

Hepatic Impairment

• Child-Pugh Class A: No dose adjustment recommended
• Child-Pugh Classes B & C: Caution; dose adjustment recommended
  Avoid large doses; Increase frequency in case of changes in coagulation profile (aPTT, anti-Xa, bleeding time, INR, platelets)

Elderly

• Caution; no dose adjustment recommended
  Lower dosages may be required; Elderly patients physiologically may have higher serum levels and clinical response

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Cardiovascular Disorders

• Haemorrhage

Hepatobiliary Disorders

• Increased transaminases

Genitourinary Disorders

• Priapism

Endocrine and Metabolic Disorders

• Hypoaldosteronism
• Adrenal insufficiency, secondary to adrenal haemorrhage
• Hyperkalaemia
• Release of lipoprotein lipase

Musculoskeletal Disorders

• Osteoporosis (long term use)
• Fractures in vertebrae and ribs

Skin and Subcutaneous Tissue Disorder

• Rash
  - Erythematous
  - Generalised
  - Macular
  - Maculo-papular
  - Papular
  - Pruritic
• Urticaria
• Pruritus
• Injection site reactions
• Erythema
• Skin necrosis
• Erythematous nodules
• Infiltrated and eczema-like plaques

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
  - Urticaria
  - Conjunctivitis  
  - Rhinitis
  - Asthma
  - Cyanosis
  - Tachypnoea
  - Feeling of oppression 10
  - Fever
  - Chills
  - Angioneurotic oedema
  - Anaphylactic shock
• Anaphylactic reaction
• Thrombocytopenia (including non-immune heparin associated thrombocytopenia (type I))
• Heparin-induced thrombocytopenia and thrombosis
• Haematoma
• Activated partial thromboplastin time prolonged beyond therapeutic range

• Analgesics
• Platelet inhibitors
• Acetylsalicylic acid
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Ketorolac
• IV diclofenac
• Anticoagulants
• Epoprostenol
• Clopidogrel
• Ticlopidine
• Streptokinase
• Dipyridamole
• Abciximab
• Eptifibatide
• Agents that interfere with coagulation
• Selective serotonin reuptake inhibitors (SSRIs)
• Thrombolytic agents
• Vitamin K antagonists
• Dextrans
• Activated protein C
• Direct thrombin inhibitors
• Angiotensin-converting enzyme inhibitors
• Angiotensin II receptor antagonists
• Renin inhibitor
• Aliskiren
• Nitrates
• Glyceryl nitrate
• Probenecid
• Cephalosporins
• Cefaclor
• Ceftriaxone
• Cefixime
• Interference with the determination of aminoglycosides by immunoassays

Other interactions

• Tobacco smoke
• Nicotine

None routine. Specific cases may require

• Serum potassium
• Activated partial thromboplastin time (aPTT)
• Anti-Factor Xa
• Platelet function
• Coagulation
• Haemoglobin
• Haematocrit
• Platelet count
• Prothrombin time
• Faecal occult blood test
• Activated clotting time

Additional observations

• Signs and symptoms of
  - Neurologic impairment
  - Bleeding
• Risk factors for bleeding

Heparin resistance

• There is considerable variation in individual anticoagulant responses to heparin
• Heparin resistance, defined as an inadequate response to heparin at a standard dose for achieving a therapeutic goal, occurs in approximately 5-30% of patients. Factors predisposing to the development of heparin resistance, include:
  - Antithrombin III activity less than 60% of normal (antithrombin III-dependent heparin resistance): Reduced antithrombin III activity may be hereditary or more commonly, acquired (secondary to preoperative heparin therapy in the main, chronic liver disease, nephrotic syndrome, cardiopulmonary bypass, low grade disseminated intravascular coagulation or drug induced, e.g. by aprotinin, oestrogen or possibly nitroglycerin)
  - Patients with normal or supranormal antithrombin III levels (antithrombin III-independent heparin resistance)
  - Thromboembolic disorders
  - Increased heparin clearance
  - Elevated levels of heparin binding proteins, factor VIII, von Willebrand factor, fibrinogen, platelet factor 4 or histidine-rich glycoprotein
  - Active infection (sepsis or endocarditis)
  - Preoperative intra-aortic balloon counterpulsation
  - Thrombocytopenia
  - Thrombocytosis
  - Advanced age
  - Plasma albumin concentration ≤ 35g/dl
  - Relative hypovolaemia
• Heparin resistance is also often encountered in acutely ill patients, in patients with malignancy and during pregnancy or the postpartum period
• Agents affecting platelet function or the coagulation system should in general not be given concomitantly with heparin

Heparin is a naturally occurring anticoagulant which prevents the coagulation of blood. It potentiates the inhibition of several activated coagulation factors, including thrombin and factor X (Xa).

Injection (per ml) 1000 iu

• Heparin Sodium Fresenius (Bodene)

Injection (per ml) 5000 iu

• Bio-Heparin (Biotech)
• Heparin Sodium Fresenius  (Bodene)

Injection (per ml) 25000 iu

• Heparin Sodium Fresenius (Bodene)

Injection (per 0.2ml) 5000 iu

• Calciparine (Adcock Ingram) originator

Injection (per 0.5ml) 12500 iu

• Calciparine (Adcock Ingram) originator