Low Molecular Weight Heparins (LMWH) Shared Care Guideline for the use of Enoxaparin and Dalteparin in the Treatment and Prophylaxis of Venous Thromboembolism Introduction Low Molecular Weight Heparins (LMWH s) such as enoxaparin and dalteparin are now widely used for a number of licensed and unlicensed indications including the prevention and treatment of venous (and sometimes arterial) thromboses in selected patient groups. The availability of LMWH s which are administered by subcutaneous injection only once or twice means that patients can often self administer their anticoagulant. This guideline is only for use in patients whose GFR is 30mls/min or above. Patients with severe renal impairment require additional monitoring and will be managed by the acute trust until further guidance can be written and approved. Barnsley Hospital use dalteparin (Fragmin) for the treatment and prophylaxis of DVT in patients with a solid tumours, and for bridging anticoagulation (off license indication) only. Enoxaparin (Clexane) is used for all other indications, and the information provided in this document reflects this. Pharmacology LMWH s bind to anti-thrombin III leading to inhibition of the specific coagulation factors IIa and Xa. This results in anticoagulant and antithrombotic activity, but without significant effects on platelet aggregation, binding of fibrinogen to platelets, or changes to global coagulation tests such as APTT or prothrombin time. Enoxaparin (Clexane) Licensing information Licensed for prophylaxis of venous thrombosis in surgical patients (for 7-10 days) and high risk medical patients (for 6-14 days). Recommended for prophylaxis of venous thrombosis (by NICE) for hip fracture patients and those following hip arthroplasty for 35 days. Licensed for the treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) until oral anticoagulant treatment therapeutic. Not licensed for, but is used in pregnancy for the prevention and treatment of venous thrombosis in pregnancy, and for treatment of antiphospholipid syndrome. Not licensed for, but may be used for the treatment of deep vein thrombosis or pulmonary embolism in injectable drug users, patients with cancer, or those in whom it was not possible to stabilise oral anticoagulation. Not licensed for, but may be used for thromboprophylaxis of thrombosis associated with central lines. Not licensed for, but may be used for prophylaxis of below knee deep venous thrombosis in patients immobilised in lower-limb casts. Preparations available: Clexane pre-filled syringes 100mg/ml in syringe sizes equating to the following doses: 20mg, 40mg, 60mg, 80mg and 100mg. (Syringes are graduated and when using a mg/kg calculation, doses should be prescribed to the nearest multiple of 2.5mg). Clexane pre-filled syringes 150mg/ml in syringe sizes equating to the following doses: 120mg and 150mg. Page 1 of 8
Dosage and administration Indication Dose Duration of Treatment Treatment of venous thromboembolism in the following patient groups: Patients with cancer or receiving cancer therapies Injectable drug users Patients in whom it has not been possible to stabilise oral anticoagulation NOT pregnancy see below 1.5mg/kg given by subcutaneous injection ONCE. The dose is usually reduced to 1.2mg/kg after the first 6 weeks. First event: 3 6 months as instructed Recurrent idiopathic event: long term For ongoing risk factors such as cancer or if inability to stabilise on long term oral anticoagulation: consider continuing long term while risk factors are Treatment of venous thromboembolism in pregnancy (based on early pregnancy bodyweight) Prevention of venous thromboembolism or treatment of antiphospholipid syndrome in pregnancy (based on early pregnancy bodyweight) (higher doses may be divided into two separate injections) Prevention of venous thromboembolism in orthopaedic patients (hip fracture, hip arthroplasty, or high risk patients immobilised in lower limb cast) Prophylaxis of thromboses associated with central venous lines or other medical reasons Given by subcutaneous injection: Antenatal: less than 50kg: 40mg s/c twice 50-69kg: 60mg s/c twice 70-89kg: 80mg s/c twice 90-110kg: 100mg s/c twice over 110kg: 1mg/kg twice Postnatal 1.5mg/kg OD Given by subcutaneous injection: <50kg = 20mg OD 50-90kg = 40mg OD 91 130kg = 60mg OD 131 170kg = 80mg OD >171kg = 0.6mg/kg/day (High prophylactic dose for women weighing 50 90kg = 40mg BD) Given by subcutaneous injection: 40mg OD Given by subcutaneous injection: 40mg OD prevalent. Throughout pregnancy and for at least 6 weeks post partum, should be continued until a total of at least 6 months treatment has been given. Advice on adjustment to dosage in preparation for labour will be provided by haematologists Throughout pregnancy and for 6 weeks post partum. Consideration can be given to stopping at term in antiphospholipid syndrome associated with recurrent miscarriages. For a total of 35 days, or until lower limb cast removed For the duration that the central line is in-situ (or the duration of the risk) For women requiring the standard 6 weeks of enoxaparin prophylaxis in the post-natal period, the full supply will be made by Barnsley Hospital. Page 2 of 8
Dalteparin (Fragmin) Licensing information Licensed for the extended treatment and prophylaxis of DVT or PE in patients with solid tumors. Not licensed for, but used in bridging anticoagulant treatment in patients undergoing procedures (not expected to impact on Shared Care). Preparations available: Fragmin is available as single-dose syringes in the following strengths/doses: 12, 500 units/ml as 2,500units/0.2mL syringes 25,000 units/ml as 5,000units/0.2mL; 7,500units/0.3mL; 10,000units/0.4mL; 12,500units/0.5mL; 15,000units/0.6mL; 18,000units/0.72mL Fragmin also comes as a graduated syringe (10,000units/mL) and injections for subcutaneous and intravenous use: 10,000units/4mL; 10,000units/mL and 100,000units/4mL. Dosage and administration Indication Dose Duration of Treatment Extended treatment and prophylaxis of Initial dose is once for 30 days, using the following doses: 6 months, including the initial 30 days. Treatment DVT or PE in patients with solid tumors. Body-weight 40 45kg, 7500 units beyond this period has not yet been evaluated. Body-weight 46 56kg, 10000 units Body-weight 57 68kg, 12500 units Body-weight 69 82kg, 15000 units Body-weight 83kg and over, 18000 units then once for a further 5 months, using the reduced maintenance doses below: Body-weight 40 56kg, 7500 units Body-weight 57 68kg, 10000 units Body-weight 69 82kg, 12500 units Body-weight 83 98kg, 15000 units Body-weight 99kg and over 18000 units In the case of chemotherapy-induced thrombocytopenia: Plt count 50,000-100,000mm 3 reduced Dalteparin by 2,500 units until plt. count >100,000mm 3 Plt. count <50,000mm 3 discontinue Dalteparin until platelets recover to >50,000mm 3 Page 3 of 8
Prescriber Resposibilities: Whichever prescriber is supplying LMWH on prescription will be responsible for supplying sharps bins for safe disposal of the used needles. Responsibilities of the specialist initiating treatment Summary To assess the suitability of the patient for treatment. To discuss the benefits and side effects of treatment with the patient/carer and the need for long term monitoring if applicable. To monitor platelet counts for the emergence of Heparin Induced Thrombocytopenia (HIT) within the first 14 days of treatment. To prescribe for the first 28 days of LMWH treatment To ask the GP whether they are willing to participate in shared To provide the GP with a summary of information relating to the individual patient to support the GP in undertaking reduced shared care (See Shared care request form in Appendix A). To advise the GP of any dosage adjustments required, monitoring required, when to refer back, and when and how to stop treatment (if appropriate). To monitor the patient for adverse events and report to the GP and where appropriate Commission on Human Medicines/MHRA (Yellow card scheme). To provide the GP with contact details in case of queries. Baseline Tests Include platelet counts, full blood count and U&E s for patients at risk of hyperkalaemia (e.g. patients with diabetes mellitus, or taking potassium supplements or potassium sparing diuretics). Routine Tests Routine monitoring of serum potassium levels may be required for patients at risk of hyperkalaemia. These should be done on a monthly basis. Disease monitoring The frequency of review of the patient will depend on the indication and likelihood of continuing treatment on a long term basis. The review period must be specified on the shared care referral request. Responsibilities of other prescribers Acceptance of Responsibility by the Primary Care Clinician It is optional for GPs to participate in taking on responsibility for shared care for the patient. GPs will take on shared care only if they are willing and able. Summary To reply to the request for shared care as soon as possible. To prescribe and adjust the dose as recommended by the specialist. To ensure there are no interactions with any other medications initiated in primary To continue monitoring as agreed with secondary care (guideline should include details of monitoring requirements and what to do when each of the defined parameters alters). To refer back to the specialist where appropriate. For example: o Patient or general practitioner is not comfortable to continue with the existing regime due to either change in condition or drug side effects. o Advice in respect of concordance. Discontinue the drug as directed by the specialist if required To identify adverse events if the patient presents with any signs and liaise with the hospital specialist where necessary. To report adverse events to the specialist and where appropriate LMWH the Shared Commission care Guideline on Human Medicines/MHRA (Yellow card scheme). Page 4 of 8
Clinical Particulars BNF therapeutic 2.8.1 Parenteral Anticoagulants class Contraindications History of Heparin Induced Thrombocytopenia Significant hepatic impairment Active gastric or duodenal ulceration or oesophageal varices Haemophilia and other inherited bleeding disorders / major bleeding disorders Thrombocytopenia with platelets <50 x 10 9 /l Recent cerebral haemorrhage Severe hypertension Recent neurosurgery or eye surgery Acute bacterial endocarditis Hypersensitivity to enoxaparin Adverse Drug Heparin induced thrombocytopenia HIT usually presents between 5 Reactions and and 14 days after starting therapy. This should be considered if platelet associated count falls below normal range, or to less than 50% of baseline platelet Precautions count. BHNFT will undertake monitoring for HIT during first 2 weeks of therapy, if indicated. If patient develops thrombocytopenia, skin reaction or new thrombosis within 14 days of starting therapy, HIT should be considered. Refer as emergency to MAU for assessment and treatment. Hyperkalaemia: Heparin inhibits aldosterone secretion and may cause hyperkalaemia (patients with diabetes, chronic renal failure, acidosis, raised potassium or taking potassium-sparing drugs most susceptible). Risk increases with duration of therapy. Haemorrhage Thrombocytopenia (monitoring for HIT required by secondary care as above) Injection site reactions (consider change to alternative LMWH) Osteoporosis (risk lower with enoxaparin than with unfractionated heparin) Skin necrosis and hypersensitivity reactions Monitoring When the appropriate monitoring for HIT and hyperkalaemia have been performed (and results are satisfactory) the responsibility for re-prescribing the drug and further monitoring for hyperkalaemia (if appropriate in higher risk patients) will pass to the patient s practice. The practice will be informed of this transfer of prescribing responsibilities and the patient provided with a further 2 weeks supply of drug by the hospital pharmacy. Monitoring of enoxaparin and dalteparin for heparin-induced thrombocytopenia (HIT) is not required in some patient groups (e.g. pregnant patients receiving LMWH for prophylaxis), whereas others usually require only limited monitoring for the first 2 weeks of treatment. This will be carried out by BHNFT. Occasional patients require ongoing monitoring for hyperkalaemia. Patients at high risk of developing hyperkalaemia and renal impairment include those with pre-existing renal impairment, patients taking medications such as ACE inhibitors, angiotensin receptor blockers and aldosterone antagonists, and patients taking medication which may alter renal blood flow. Interactions Systemic salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), clopidogrel, dipyridamole (increased risk of bleeding), ACE inhibitors (increased risk of hyperkalaemia), dextran, ticlopidine, systemic glucocorticoids, thrombolytics, anticoagulants. This is not a comprehensive list. Please see current BNF for complete information. Page 5 of 8
Communication Specialist to GP The specialist will inform the GP when they have initiated LMWH. When the patient is near completing the satisfactory initiation period, the specialist will write to the GP to request they take over prescribing and where possible give an indication as to the expected length of treatment. The Specialist will also send a Shared care request form to support the GP in undertaking reduced shared (Appendix A) GP to specialist If the GP has concerns over the prescribing of LMWH, they will contact the specialist as soon as possible. Contact names and details Contact Details Consultant Haematologists: Dr J. P. Ng Dr D. Chan-Lam Consultant Obstetricians: Telephone number 01226 730000 01226 730000 Email Miss N Khanem Medicines Information: 01226 432857 Gilliansmith2@nhs.net or medicinesinformation@nhs.net References 1. Summary of Product Characteristics (SPC) for enoxaparin (Clexane) accessed via www.medicines.org.uk/emc 2. Summary of Product Characteristics (SPC) for dalteparin (Fragmin) accessed via www.medicines.org.uk/emc 3. BNF number 61 accessed via www.bnf.org Development Process This guidance has been produced by Gillian Smith, Medicines Information Pharmacist, and Dr J P Ng, Consultant Haematologist, Barnsley Hospital NHS Foundation Trust, following an AMBER classification status of enoxaparin by the Barnsley Area Prescribing Committee. This guideline has been subject to consultation and endorsement by the Area Prescribing Committee on 11 th December 2013 and by the LMC on 8 th April 2014. The Guideline was adapted from the Sheffield shared care guideline for the use of enoxaparin, and was produced in Consultation with the following Specialists: Dr D. Chan-Lam Consultant Haematologist, BHNFT Miss N Khanem, Consultant Obstetrician, BHNFT Dr Y Myint, Consultant Anaesthetist and Chair of the Venous Thromboembolism Committee, BHNFT Page 6 of 8
Appendix A Shared Care request form (Amber) Specialist to complete when requesting GP to enter a shared care arrangement. GP to return signed copy of form. Both parties should retain a signed copy of the form in the patient s record. From (Specialist): Patient Details To (GP): Name: Address: ID Number: DOB: Diagnosed condition: Amber Drug details Drug name: Enoxaparin / Dalteparin (delete as appropriate) Dose: By subcutaneous injection Date of initiation: Length of treatment: 3 months / 6 months/ 12 months / long term / other (please specify) (circle as appropriate) U&E monitoring requirements:(tick as appropriate): High risk - high risk of hyperkalaemia or renal impairment monitor monthly Monitoring Low risk only needs to be done periodically as deemed necessary by clinical condition The patient will be reviewed by the Consultant on: The patient should be reviewed by the GP by: The following baseline tests have been carried out: Parameter BHNFT Reference Range Result Date test done FBC Platelets 150 400 x 10 9 /L RBC 4.33 5.6 x 10 12 /L Hb 13.2 16.9 g/dl (males) 11.9 14.9 g/dl (females) U&E s Sodium 133 146 mmol/l Potassium Creatinine Urea 3.5 5.3 mmol/l 51 96 micromol/l 2.5 7.8 mmol/l The following monitoring should be undertaken by the GP: Parameter Date next test due Frequency U&E s FBC Monthly if high risk, as required if low risk (see above) Periodically as deemed necessary by clinical condition Page 7 of 8
Communication Consultant Telephone number: Fax number: Email address: Specialist Nurse Telephone number: Fax number: Email address: Confirmation of acceptance of shared care Specialist (Doctor/Nurse) name: Specialist (Doctor/Nurse) signature: Date: I, Dr.., can confirm I : accept the request to participate in shared care for the patient named above. reject the request to participate in shared care for the patient named above. The reason for this being.. GP signature: Date: Page 8 of 8