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Medicinal Forms

There can be variation in the licensing of different medicines containing the same drug. Powder for solution for infusion ▶Epoprostenol (Non-proprietary) Epoprostenol (as Epoprostenol sodium) 500 microgram Epoprostenol 500microgram powder (pH12) for solution for infusion vials | 1 vial P s (Hospital only) Epoprostenol (as Epoprostenol sodium) 1.5 mg Epoprostenol 1.5mg powder (pH12) for solution for infusion vials | 1 vial P s (Hospital only) ▶Veletri (Actelion Pharmaceuticals UK Ltd) Epoprostenol (as Epoprostenol sodium) 500 microgram Veletri 500microgram powder for solution for infusion vials | 1 vial P £24.44 Epoprostenol (as Epoprostenol sodium) 1.5 mg Veletri 1.5mg powder for solution for infusion vials | 1 vial P £49.24 Powder and solvent for solution for infusion ELECTROLYTES: May contain Sodium ▶Epoprostenol (Non-proprietary) Epoprostenol (as Epoprostenol sodium) 500 microgram Epoprostenol 500microgram powder and solvent (pH10.5) for solution for infusion vials | 1 vial P £58.95 Epoprostenol (as Epoprostenol sodium) 1.5 mg Epoprostenol 1.5mg powder and solvent (pH10.5) for solution for infusion vials | 1 vial P £118.75 ▶Flolan (GlaxoSmithKline UK Ltd) Epoprostenol (as Epoprostenol sodium) 500 microgram Flolan 500microgram powder and solvent (pH12) for solution for infusion vials | 1 vial P £22.22 Epoprostenol (as Epoprostenol sodium) 1.5 mg Flolan 1.5mg powder and solvent (pH12) for solution for infusion vials | 1 vial P £44.76 3.2 Thromboembolism Cardiovascular system Venous thromboembolism Overview Venous thromboembolism includes deep-vein thrombosis and pulmonary embolism and occurs as a result of thrombus formation in a vein. Venous thromboembolism prophylaxis g All patients should undergo a risk assessment to identify their risk of venous thromboembolism and bleeding on admission to hospital. h Commonly used risk assessment tools can be found at www.nice.org.uk/guidance/ ng89/resources. Patients considered to be at high risk of venous thromboembolism include those who are anticipated to have a substantial reduction in mobility, those with obesity, malignant disease, history of venous thromboembolism, thrombophilic disorder, and patients over 60 years of age. Pregnancy and the postpartum period are also risk factors for venous thromboembolism. There are two methods of thromboprophylaxis: mechanical and pharmacological. Options for mechanical prophylaxis are anti-embolism stockings that provide graduated compression and produce a calf pressure of 14–15 mmHg, and intermittent pneumatic compression. g Anti-embolism stockings should be worn day and night until the patient is sufﬁciently mobile; they should not be offered to patients admitted with acute stroke or those with conditions such as peripheral arterial disease, peripheral neuropathy, severe leg oedema, or local conditions (e.g. gangrene, dermatitis). When using pharmacological prophylaxis, in most cases, it should start as soon as possible or within 14 hours of admission. Patients with risk factors for bleeding (e.g. acute stroke, thrombocytopenia, acquired or untreated inherited bleeding disorders) should only receive pharmacological prophylaxis when their risk of venous thromboembolism outweighs their risk of bleeding. Patients receiving anticoagulant therapy who are at high risk of venous thromboembolism should be considered for prophylaxis if their anticoagulant therapy is interrupted, for example during the peri-operative period. h For full guidance on prophylaxis of venous thromboembolism, see NICE guideline 89 (www.nice.org.uk/ guidance/ng89). Surgical patients g To reduce the risk of venous thromboembolism in surgical patients, regional anaesthesia over general anaesthesia should be used if possible. Mechanical prophylaxis (e.g. anti-embolism stockings or intermittent pneumatic compression) should be offered to patients with major trauma, or undergoing cranial, abdominal, bariatric, thoracic, maxillofacial, ear, nose, and throat, cardiac or elective spinal surgery. Prophylaxis should continue until the patient is sufﬁciently mobile or discharged from hospital (or for 30 days in spinal injury, elective spinal surgery or cranial surgery). h Choice of mechanical prophylaxis depends on factors such as the type of surgery, suitability for the patient, and their condition. g Pharmacological prophylaxis should be considered in patients undergoing general or orthopaedic surgery when the risk of venous thromboembolism outweighs the risk of bleeding. h The choice of prophylaxis will depend on the type of surgery, suitability for the patient, and local policy. g A low molecular weight heparin is suitable in all types of general and orthopaedic surgery; heparin (unfractionated) p. 143 is preferred in patients with renal impairment. Fondaparinux sodium p. 136 is an option for patients undergoing abdominal, bariatric, thoracic or cardiac surgery, or for patients with lower limb immobilisation or fragility fractures of the pelvis, hip or proximal femur. Pharmacological prophylaxis in general surgery should usually continue for at least 7 days post-surgery, or until sufﬁcient mobility has been re-established. Pharmacological prophylaxis should be extended to 28 days after major cancer surgery in the abdomen, and to 30 days in spinal surgery. Mechanical prophylaxis with intermittent pneumatic compression should be considered when pharmacological prophylaxis is contra-indicated in patients undergoing lower limb amputation, or those with major trauma or fragility fractures of the pelvis, hip or proximal femur. Patients undergoing an elective hip replacement should be given thromboprophylaxis with either a low molecular weight heparin administered for 10 days followed by low- dose aspirin p. 130 for a further 28 days, or a low molecular weight heparin administered for 28 days in combination with anti-embolism stockings until discharge, or rivaroxaban p. 137. If these options are unsuitable, apixaban p. 133 or dabigatran etexilate p. 146 can be considered as alternatives. If pharmacological prophylaxis is contra-indicated, anti- embolism stockings can be used until discharge. Patients undergoing an elective knee replacement should be given thromboprophylaxis with either low-dose aspirin p. 130 for 14 days, or a low molecular weight heparin administered for 14 days in combination with anti-embolism stockings until discharge, or rivaroxaban. If these options are unsuitable, apixaban or dabigatran etexilate can be considered as alternatives. If pharmacological prophylaxis is contra-indicated, intermittent pneumatic compression can be used until the patient is mobile. h Medical patients The choice of prophylaxis will depend on the medical condition, suitability for the patient, and local policy. g Acutely ill medical patients who are at high risk of venous thromboembolism should be offered pharmacological prophylaxis. Patients should be given either a low molecular weight heparin as a ﬁrst-line option, or fondaparinux sodium as an alternative, for a minimum of 7 days. Patients with renal impairment should be given either a low molecular weight heparin or heparin (unfractionated) and the dose should be adjusted as necessary. Mechanical prophylaxis can be considered when pharmacological prophylaxis is contra-indicated; their use should be continued until the patient is sufﬁciently mobile. In patients admitted with acute stroke, mechanical prophylaxis with intermittent pneumatic compression should be considered, as anti-embolism stockings are unsuitable in these patients; their use should be started within 3 days of the acute stroke and continued for 30 days, or until the patient is sufﬁciently mobile or discharged from hospital. h Thromboprophylaxis in pregnancy g All pregnant women (who are not in active labour), or women who have given birth, had a miscarriage or termination of pregnancy during the past 6 weeks, with a risk of venous thromboembolism that outweighs the risk of bleeding should be considered for pharmacological prophylaxis with a low molecular weight heparin during hospital admission. In pregnant women, prophylaxis should be continued until there is no longer a risk of venous thromboembolism, or until discharge from hospital. Women who have given birth, had a miscarriage or termination of pregnancy during the past 6 weeks, should start thromboprophylaxis with a low molecular weight heparin 4–8 hours after the event, unless contra-indicated, and continue for a minimum of 7 days. Additional mechanical prophylaxis should be considered for women who are likely to be immobilised or have signiﬁcantly reduced mobility and continued until the woman is sufﬁciently mobile or discharged from hospital. Intermittent pneumatic compression should be used as the ﬁrst-line option and anti-embolism stockings as an alternative. h Edoxaban Edoxaban p. 135, an inhibitor of factor Xa, can be given orally for the treatment and prophylaxis of venous thromboembolism, although, it should not be used as an alternative to unfractionated heparin in pulmonary embolism in patients with haemodynamic instability, or who may receive thrombolysis or pulmonary embolectomy. Duration of therapy should be determined by balancing the beneﬁt of treatment with the bleeding risk; shorter duration of treatment (at least 3 months) should be based on transient risk factors i.e. recent surgery, trauma, immobilisation, and longer durations should be based on permanent risk factors or idiopathic deep-vein thrombosis or pulmonary embolism. Treatment of venous thromboembolism For the initial treatment of deep-vein thrombosis and pulmonary embolism a low molecular weight heparin is used; alternatively, heparin (unfractionated) p. 143 is given as an intravenous loading dose, followed by continuous intravenous infusion (using an infusion pump) or (for deep- vein thrombosis only) by intermittent subcutaneous injection. Intermittent intravenous injection of heparin (unfractionated) is no longer recommended. An oral anticoagulant (usually warfarin sodium p. 150 is started at the same time as unfractionated or low molecular weight heparin (the heparin needs to be continued for at least 5 days and until the INR is 2 for at least 24 hours). Laboratory monitoring for heparin (unfractionated), preferably on a daily basis, is essential; determination of the activated partial thromboplastin time (APTT) is the most widely used measure (for heparin (unfractionated). A low molecular weight heparin or, in some circumstances, heparin (unfractionated) is also used in regimens for the management of myocardial infarction and unstable angina. Treatment of venous thromboembolism in pregnancy Heparins are used for the management of venous thromboembolism in pregnancy because they do not cross the placenta. Low molecular weight heparins are preferred because they have a lower risk of osteoporosis and of heparin-induced thrombocytopenia. Low molecular weight heparins are eliminated more rapidly in pregnancy, requiring alteration of the dosage regimen for drugs such as dalteparin sodium p. 140, enoxaparin sodium p. 142, and tinzaparin sodium p. 144. Treatment should be stopped at the onset of labour and advice sought from a specialist on continuing therapy after birth. Extracorporeal circuits Heparin (unfractionated) is also used in the maintenance of extracorporeal circuits in cardiopulmonary bypass and haemodialysis. Haemorrhage If haemorrhage occurs it is usually sufﬁcient to withdraw unfractionated or low molecular weight heparin, but if rapid reversal of the effects of the heparin is required, protamine sulfate p. 1440 is a speciﬁc antidote (but only partially reverses the effects of low molecular weight heparins). Advanced Pharmacy Services Patients with, or at risk of venous thromboembolism may be eligible for the New Medicines Service / Medicines Use Review service provided by a community pharmacist. For further information, see Advanced Pharmacy Services in Medicines optimisation p. 18. Stroke Overview Stroke is associated with a signiﬁcant risk of morbidity and Cardiovascular system mortality. Patients presenting with acute symptoms should be immediately transferred to hospital for accurate diagnosis of stroke type, and urgent initiation of appropriate treatment; patients should be managed by a specialist multidisciplinary stroke team. The following section gives an overview of the initial and long-term management of transient ischaemic attack, ischaemic stroke, and intracerebral haemorrhage. Transient ischaemic attack g Patients suspected of having a transient ischaemic attack should immediately receive aspirin p. 130. Patients with aspirin hypersensitivity, or those intolerant of aspirin despite the addition of a proton pump inhibitor, should receive a suitable alternative antiplatelet. Following a conﬁrmed diagnosis, patients should receive treatment for secondary prevention (see Long-term Management, under Ischaemic Stroke). h Ischaemic stroke Initial management g Alteplase p. 230 is recommended in the treatment of acute ischaemic stroke if it can be administered within 4.5 hours of symptom onset and if intracranial haemorrhage has been excluded by appropriate imaging techniques. It should be given by medical staff experienced in the administration of thrombolytics and the treatment of acute stroke, preferably within a specialist stroke centre. Provided that intracranial haemorrhage has been excluded, treatment with aspirin should be initiated as soon as possible within 24 hours of symptom onset; a proton pump inhibitor should be considered for patients with a history of dyspepsia associated with aspirin. Patients with aspirin hypersensitivity, or those intolerant of aspirin despite the addition of a proton pump inhibitor, should receive an alternative antiplatelet. Anticoagulants are not recommended as an alternative to antiplatelet drugs in acute ischaemic stroke in patients who are in sinus rhythm. However, parenteral anticoagulants may be indicated in patients who are symptomatic of, or at high risk of developing, deep vein thrombosis or pulmonary embolism. h Warfarin sodium p. 150 should not be given in the acute phase of an ischaemic stroke. g Patients with a disabling ischaemic stroke and atrial ﬁbrillation should receive aspirin for 2 weeks before being considered for anticoagulant treatment. Patients already receiving anticoagulation for a prosthetic heart valve who experience a disabling ischaemic stroke and are at signiﬁcant risk of haemorrhagic transformation, should have their anticoagulant treatment stopped for 7 days and substituted with aspirin. Treatment of hypertension in the acute phase of ischaemic stroke can result in reduced cerebral perfusion, and should therefore only be instituted in the event of a hypertensive emergency, or in those patients considered for thrombolysis. h Long-term management g Patients should receive long-term treatment following a transient ischaemic attack or an ischaemic stroke to reduce the risk of further cardiovascular events. Following a transient ischaemic attack or an ischaemic stroke (not associated with atrial ﬁbrillation), long-term treatment with clopidogrel p. 131 [unlicensed in transient ischaemic attack] is recommended. If clopidogrel is contra- indicated or not tolerated, patients can receive modiﬁed- release dipyridamole p. 132 in combination with aspirin; if both aspirin and clopidogrel are contra-indicated or not tolerated, then modiﬁed-release dipyridamole alone is recommended; if both modiﬁed-release dipyridamole and clopidogrel are contra-indicated or not tolerated, then Cardiovascular system aspirin alone is recommended. Patients with ischaemic stroke or transient ischaemic attack associated with atrial ﬁbrillation should be reviewed for long-term anticoagulant treatment (for stroke, see also Initial Management under Ischaemic Stroke). Anticoagulants are not routinely recommended in the long-term prevention of recurrent stroke, except when atrial ﬁbrillation or other indications (such as a cardiac source of embolism, cerebral venous thrombosis or arterial dissection) are present. A high-intensity statin (such as atorvastatin p. 215), should be initiated 48 hours after stroke symptom onset in patients not already taking a statin, irrespective of the patient’s serum-cholesterol concentration. See Dyslipidaemias p. 208 for further information. Patients with acute stroke who are already taking a statin can continue statin treatment. Following the acute phase of ischaemic stroke, blood pressure should be measured and treatment initiated to achieve a target blood pressure of <130/80 mmHg. Beta- blockers should not be used in the management of hypertension following a stroke, unless they are indicated for a co-existing condition. All patients should be advised to make lifestyle modiﬁcations that include beneﬁcial changes to diet, exercise, weight, alcohol intake, and Smoking cessation p. 520. h Intracerebral haemorrhage Initial Management g Surgical intervention may be required following intracerebral haemorrhage to remove the haematoma and relieve intracranial pressure. Patients presenting within 6 hours of symptom onset should be given rapid blood pressure lowering therapy if they have a systolic blood pressure between 150 and 220 mmHg and they do not ﬁt any exclusion criteria. A systolic blood pressure target of 130 to 140 mmHg should be aimed to be attained within 1 hour of starting treatment and maintained for at least 7 days. Rapid blood pressure lowering should also be considered for patients presenting beyond 6 hours of symptom onset or who have a systolic blood pressure greater than 220 mmHg. Rapid blood pressure lowering should not be given to patients who have an underlying structural cause, have a score on the Glasgow Coma Scale of below 6, are going to have early neurosurgery to evacuate the haematoma or have a massive haematoma with a poor expected prognosis. Patients taking anticoagulants should have this treatment stopped and reversed. Anticoagulant therapy has, however, been used in patients with intracerebral haemorrhage who are symptomatic of deep vein thrombosis or pulmonary embolism; placement of a caval ﬁlter is an alternative in this situation. h Long-term management g Specialist advice should be sought for patients with atrial ﬁlbrillation and those at a high risk of ischaemic stroke or cardiac ischaemic events as aspirin and anticoagulant therapy are not normally recommended following an intracerebral haemorrhage. Blood pressure should be measured and treatment initiated where appropriate, taking care to avoid hypoperfusion. Statins should be avoided following intracerebral haemorrhage, however they can be used with caution when the risk of a vascular event outweighs the risk of further haemorrhage. h Advanced Pharmacy Services Patients at risk of, or patients with a history of stroke or transient ischaemic attack, may be eligible for the New Medicines Service / Medicines Use Review service provided by a community pharmacist. For further information, see Advanced Pharmacy Services in Medicines optimisation p. 18. Useful resources Stroke and transient ischaemic attack in over 16s: diagnosis and initial management. National Institute for Health and Care Excellence guideline NG128. May 2019. www.nice.org.uk/guidance/ng128 Oral anticoagulants Overview The main use of anticoagulants is to prevent thrombus formation or extension of an existing thrombus in the slower-moving venous side of the circulation, where the thrombus consists of a ﬁbrin web enmeshed with platelets and red cells. Anticoagulants are of less use in preventing thrombus formation in arteries, for in faster-ﬂowing vessels thrombi are composed mainly of platelets with little ﬁbrin. Coumarins and phenindione The oral anticoagulants warfarin sodium p. 150, acenocoumarol p. 150 and phenindione p. 150, antagonise the effects of vitamin K, and take at least 48 to 72 hours for the anticoagulant effect to develop fully; warfarin sodium is the drug of choice. If an immediate effect is required, unfractionated or low molecular weight heparin must be given concomitantly. These oral anticoagulants should not be used in cerebral artery thrombosis or peripheral artery occlusion as ﬁrst-line therapy; aspirin p. 130 is more appropriate for reduction of risk in transient ischaemic attacks. Unfractionated or a low molecular weight heparin (see under Parenteral anticoagulants p. 127) is usually preferred for the prophylaxis of venous thromboembolism in patients undergoing surgery; alternatively, warfarin sodium can be continued in selected patients currently taking long-term warfarin sodium and who are at high risk of thromboembolism (seek expert advice). Dose The base-line prothrombin time should be determined but the initial dose should not be delayed whilst awaiting the result. Target INR The following indications and target INRs for adults for warfarin take into account recommendations of the British Society for Haematology guidelines on oral anticoagulation with warfarin—fourth edition. Br J Haematol 2011; 154: 311–324: An INR which is within 0.5 units of the target value is generally satisfactory; larger deviations require dosage adjustment. Target values (rather than ranges) are now recommended. INR 2.5 for: . treatment of deep-vein thrombosis or pulmonary embolism (including those associated with antiphospholipid syndrome or for recurrence in patients no longer receiving warfarin sodium) . atrial ﬁbrillation . cardioversion—target INR should be achieved at least 3 weeks before cardioversion and anticoagulation should continue for at least 4 weeks after the procedure (higher target values, such as an INR of 3, can be used for up to 4 weeks before the procedure to avoid cancellations due to low INR) . dilated cardiomyopathy . mitral stenosis or regurgitation in patients with either atrial ﬁbrillation, a history of systemic embolism, a left atrial thrombus, or an enlarged left atrium . bioprosthetic heart valves in the mitral position (treat for 3 months), or in patients with a history of systemic embolism (treat for at least 3 months), or with a left atrial thrombus at surgery (treat until clot resolves), or with other risk factors (e.g. atrial ﬁbrillation or a low ventricular ejection fraction) . acute arterial embolism requiring embolectomy (consider long-term treatment) . myocardial infarction INR 3.5 for: . recurrent deep-vein thrombosis or pulmonary embolism in patients currently receiving anticoagulation and with an INR above 2; Mechanical prosthetic heart valves: . the recommended target INR depends on the type and location of the valve, and patient-related risk factors . consider increasing the INR target or adding an antiplatelet drug, if an embolic event occurs whilst anticoagulated at the target INR. Duration The risks of thromboembolism recurrence and anticoagulant-related bleeding should be considered when deciding the duration of anticoagulation. The following durations of warfarin sodium for the treatment of deep-vein thrombosis and pulmonary embolism reﬂect the recommendations of the British Society for Haematology (Guidelines on Oral Anticoagulation with Warfarin—fourth edition. Br J Haematol 2011; 154: 311–324): . 6 weeks for isolated calf-vein deep-vein thrombosis . 3 months for venous thromboembolism provoked by surgery or other transient risk factor (e.g. combined oral contraceptive use, pregnancy, plaster cast) . at least 3 months for unprovoked proximal deep-vein thrombosis or pulmonary embolism; long-term anticoagulation may be required. Haemorrhage The main adverse effect of all oral anticoagulants is haemorrhage. Checking the INR and omitting doses when appropriate is essential; if the anticoagulant is stopped but not reversed, the INR should be measured 2–3 days later to ensure that it is falling. The cause of an elevated INR should be investigated. The following recommendations (which take into account the recommendations of the British Society for Haematology Guidelines on Oral Anticoagulation with Warfarin—fourth edition. Br J Haematol 2011; 154: 311–324) are based on the result of the INR and whether there is major or minor bleeding; the recommendations apply to adults taking warfarin: . Major bleeding—stop warfarin sodium; give phytomenadione p. 1150 (vitamin K1) by slow intravenous injection; give dried prothrombin complex p. 119 (factors II, VII, IX, and X); if dried prothrombin complex unavailable, fresh frozen plasma can be given but is less effective; recombinant factor VIIa is not recommended for emergency anticoagulation reversal . INR >8.0, minor bleeding—stop warfarin sodium; give phytomenadione (vitamin K1) by slow intravenous injection; repeat dose of phytomenadione if INR still too high after 24 hours; restart warfarin sodium when INR <5.0 . INR >8.0, no bleeding—stop warfarin sodium; give phytomenadione (vitamin K1) by mouth using the intravenous preparation orally [unlicensed use]; repeat dose of phytomenadione if INR still too high after 24 hours; restart warfarin when INR <5.0 . INR 5.0–8.0, minor bleeding—stop warfarin sodium; give phytomenadione (vitamin K1) by slow intravenous Cardiovascular system injection; restart warfarin sodium when INR <5.0 . INR 5.0–8.0, no bleeding—withhold 1 or 2 doses of warfarin sodium and reduce subsequent maintenance dose . Unexpected bleeding at therapeutic levels—always investigate possibility of underlying cause e.g. unsuspected renal or gastro-intestinal tract pathology Peri-operative anticoagulation Warfarin sodium should usually be stopped 5 days before elective surgery; phytomenadione (vitamin K1) by mouth (using the intravenous preparation orally [unlicensed use]) should be given the day before surgery if the INR is 1.5. If haemostasis is adequate, warfarin sodium can be resumed at the normal maintenance dose on the evening of surgery or the next day. Patients stopping warfarin sodium prior to surgery who are considered to be at high risk of thromboembolism (e.g. those with a venous thromboembolic event within the last 3 months, atrial ﬁbrillation with previous stroke or transient ischaemic attack, or mitral mechanical heart valve) may require interim therapy (‘bridging’) with a low molecular weight heparin (using treatment dose). The low molecular weight heparin should be stopped at least 24 hours before surgery; if the surgery carries a high risk of bleeding, the low molecular weight heparin should not be restarted until at least 48 hours after surgery. Patients on warfarin sodium p. 150 who require emergency surgery that can be delayed for 6–12 hours can be given intravenous phytomenadione p. 1150 (vitamin K1) to reverse the anticoagulant effect. If surgery cannot be delayed, dried prothrombin complex p. 119 can be given in addition to intravenous phytomenadione (vitamin K1) and the INR checked before surgery. Combined anticoagulant and antiplatelet therapy Existing antiplatelet therapy following an acute coronary syndrome or percutaneous coronary intervention should be continued for the necessary duration according to the indication being treated. The addition of warfarin sodium, when indicated (e.g. for venous thromboembolism or atrial ﬁbrillation) should be considered following an assessment of the patient’s risk of bleeding and discussion with a cardiologist. The duration of treatment with dual therapy (e.g. aspirin p. 130 and warfarin sodium) or triple therapy (e.g. aspirin with clopidogrel p. 131 and warfarin sodium) should be kept to a minimum where possible. The risk of bleeding with aspirin and warfarin sodium dual therapy is lower than with clopidogrel and warfarin sodium. Depending on the indications being treated and the patient’s risk of thromboembolism, it may be possible to withhold antiplatelet therapy until warfarin sodium therapy is complete, or vice versa (on specialist advice) in order to reduce the length of time on dual or triple therapy. Advanced Pharmacy Services Patients taking oral anticoagulants may be eligible for the New Medicines Service / Medicines Use Review service provided by a community pharmacist. For further information, see Advanced Pharmacy Services in Medicines optimisation p. 18. Parenteral anticoagulants Overview The main use of anticoagulants is to prevent thrombus formation or extension of an existing thrombus in the slower-moving venous side of the circulation, where the thrombus consists of a ﬁbrin web enmeshed with platelets and red cells. Anticoagulants are of less use in preventing thrombus formation in arteries, for in faster-ﬂowing vessels thrombi Cardiovascular system are composed mainly of platelets with little ﬁbrin. Heparin Heparin initiates anticoagulation rapidly but has a short duration of action. It is often referred to as ‘standard’ or heparin (unfractionated) p. 143 to distinguish it from the low molecular weight heparins, which have a longer duration of action. Although a low molecular weight heparin is generally preferred for routine use, heparin (unfractionated) can be used in those at high risk of bleeding because its effect can be terminated rapidly by stopping the infusion. Low molecular weight heparins Low molecular weight heparins (dalteparin sodium p. 140, enoxaparin sodium p. 142, and tinzaparin sodium p. 144) are usually preferred over heparin (unfractionated) in the prevention of Venous thromboembolism p. 124 because they are as effective and they have a lower risk of heparin-induced thrombocytopenia. The standard prophylactic regimen does not require anticoagulant monitoring. The duration of action of low molecular weight heparins is longer than that of heparin (unfractionated) and once-daily subcutaneous administration is possible for some indications, making them convenient to use. Low molecular weight heparins are generally preferred over heparin (unfractionated) in the treatment of deep vein thrombosis and pulmonary embolism, and are also used in the treatment of myocardial infarction, unstable coronary artery disease (see under Acute coronary syndromes p. 226) and for the prevention of clotting in extracorporeal circuits. Dalteparin sodium and tinzaparin sodium (only 20 000 unit/mL syringe) are also licensed for the extended treatment and prophylaxis of venous thromboembolism in patients with solid tumours; treatment is recommended for a duration of 6 months. Treatment should be initiated by healthcare professionals experienced in the treatment of venous thromboembolism. Heparinoids Danaparoid sodium p. 139 is a heparinoid used for prophylaxis of deep-vein thrombosis in patients undergoing general or orthopaedic surgery. Providing there is no evidence of cross-reactivity, it also has a role in patients who develop heparin-induced thrombocytopenia. Argatroban An oral anticoagulant can be given with argatroban monohydrate p. 145, but it should only be started once thrombocytopenia has substantially resolved. Hirudins Bivalirudin, a hirudin analogue, is a thrombin inhibitor which is licensed for unstable angina or non-ST-segment elevation myocardial infarction in patients planned for urgent or early intervention, and as an anticoagulant for patients undergoing percutaneous coronary intervention (including patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention—see also Management of ST-segment elevation myocardial infarction (STEMI) in Acute coronary syndromes p. 226). Heparin flushes The use of heparin ﬂushes should be kept to a minimum. For maintaining patency of peripheral venous catheters, sodium chloride injection 0.9% is as effective as heparin ﬂushes. The role of heparin ﬂushes in maintaining patency of arterial and central venous catheters is unclear. Epoprostenol Epoprostenol (prostacyclin) can be given to inhibit platelet aggregation during renal dialysis when heparins are unsuitable or contra-indicated. It is also licensed for the treatment of primary pulmonary hypertension resistant to other treatment, usually with oral anticoagulation; it should be initiated by specialists in pulmonary hypertension. Epoprostenol is a potent vasodilator. It has a short half-life of approximately 3 minutes and therefore it must be administered by continuous intravenous infusion. Fondaparinux Fondaparinux sodium is a synthetic pentasaccharide that inhibits activated factor X. Other drugs used for Thromboembolism Streptokinase, p. 230 ANTIDOTES AND CHELATORS

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Medicinal Forms

PDF pages 145, 146, 147, 148, 149, 150

Epoprostenol

Overview

Drug Action

Indications And Dose

Pharmacokinetics

Contra Indications

Cautions

Safety

Interactions

Side Effects

Pregnancy

Breast Feeding

Monitoring Requirements

Dose and formulations

Directions For Administration

Medicinal Forms

Clinical care

Treatment Cessation

Dose text by age group

Epoprostenol

Overview

Drug Action

Indications And Dose

Pharmacokinetics

Contra Indications

Cautions

Safety

Interactions

Side Effects

Pregnancy

Breast Feeding

Monitoring Requirements

Dose and formulations

Directions For Administration

Medicinal Forms

Clinical care

Treatment Cessation

Dose text by age group