Heparin
Sodium ROVI^®

Frequency not known (cannot be estimated from the available clinical trial data):

Haemorrhage, epistaxis, contusion, thrombocytopenia, haematuria, adrenal insufficiency, hypoaldosteronism, alopecia, skin necrosis, osteoporosis, hypersensitivity, rebound hyperlipidaemia, hyperkalaemia, hypokalaemia, priapism, injection site reactions, alanine aminotransferase increased, asparate aminotransferase increased.

Erythematous nodules, or infiltrated and sometimes eczema-like plaques, at the site of subcutaneous injections are common, occurring 3-21 days after starting heparin treatment.

Haemorrhage

Haemorrhage is the chief complication that may result from heparin therapy. An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug. It should be appreciated that gastrointestinal or urinary tract bleeding during anticoagulant therapy may indicate the presence of an underlying occult lesion. Bleeding can occur at any site but certain specific haemorrhage complications may be difficult to detect.

Adrenal haemorrhage, with resultant acute adrenal insufficiency, has occurred during anticoagulant therapy. Therefore, such treatment should be discontinued in patients who develop signs and symptoms of acute adrenal haemorrhage and insufficiency. Initiation of corrective therapy should not depend on laboratory confirmation of the diagnosis, since any delay in an acute situation may result in the patient’s death.

Hypersensitivity to the active substance(s) or to any of the excipients listed below:

• Sodium chloride
• Benzyl alcohol
• Sodium hydroxide

This heparin formulation contains the preservative benzyl alcohol and so must not be given to children under 3 years old, premature babies or neonates. As benzyl alcohol may cross the placenta the use of this formulation must be avoided in pregnancy.

Current (or history of) immune-mediated heparin-induced thrombocytopenia.

An epidural anaesthesia during birth in pregnant women treated with heparin is contraindicated.

Regional anaesthesia in elective surgical procedures is contraindicated because the use of heparin may be very rarely associated with epidural or spinal haematoma resulting in prolonged or permanent paralysis.

Generalised or local haemorrhagic tendency.

Heparin should be used with caution in patients with hypersensitivity to low molecular weight heparins.

Care should be taken when heparin is administered to patients with increased risk of bleeding complications, hypertension, renal or hepatic insufficiency.

Heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients such as those with diabetes mellitus, chronic renal failure, preexisting metabolic acidosis, a raised plasma potassium or taking potassium sparing drugs. The risk of hyperkalaemia appears to increase with duration of therapy but is usually reversible. Plasma potassium should be measured in patients at risk before starting heparin therapy and monitored regularly thereafter particularly if treatment is prolonged beyond about 7 days.

Drugs affecting platelet function or the coagulation system should in general not be given concomitantly with heparin.

In patients undergoing peri-dural or spinal anaesthesia or spinal puncture, the prophylactic use of heparin may be very rarely associated with epidural or spinal haematoma resulting in prolonged or permanent paralysis. The risk is increased by the use of a peri-dural or spinal catheter for anaesthesia, by the concomitant use of drugs affecting haemostasis such as non-steroidal anti-inflammatory drugs, platelet inhibitors or anticoagulants and by traumatic or repeated puncture. In decision making on the interval between the last administration of heparin at prophylactic doses and the placement or removal of a peri-dural or spinal catheter, the product characteristics and the patient profile should be taken into account. Subsequent dose should not take place before at least four hours have elapsed. Re-administration should be delayed until the surgical procedure is completed.

Should a physician decide to administer anti-coagulation in the context of peri-dural or spinal anaesthesia, extreme vigilance and frequent monitoring must be exercised to detect any signs and symptoms of neurologic impairment, such as back pain, sensory and motor deficits and bowel or bladder dysfunction. Patients should be instructed to inform immediately a nurse or a clinician if they experience any of these.

Heparin should not be administered by intramuscular injection due to the risk of haematoma.

Due to increased bleeding risk, care should be taken when giving concomitant intramuscular injections, lumbar puncture and similar procedures.

As there is a risk of antibody-mediated heparin-induced thrombocytopenia, platelet counts should be measured in patients receiving heparin treatment for longer than 5 days and the treatment should be stopped immediately in those who develop thrombocytopenia.

Heparin induced thrombocytopenia and heparin induced thrombocytopenia with thrombosis can occur up to several weeks after discontinuation of heparin therapy.

Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for heparin induced thrombocytopenia and heparin induced thrombocytopenia with thrombosis.

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

Heparin sodium ROVI contains benzyl alcohol (10mg/ml) as preservative.

Intravenous administration of benzyl alcohol has been associated with serious adverse events and death in neonates (“gasping syndrome” ). The minimum amount of benzyl alcohol at which toxicity may occur is not known. High volumes should be used with caution and only if necessary, especially in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).