Anticoagulation. MPharm Programme & OSPAP Programme. Tania Jones Senior Lecturer in Pharmacy Practice & Therapeutics

Transcription

1 MPharm Programme & OSPAP Programme Anticoagulation Tania Jones Senior Lecturer in Pharmacy Practice & Therapeutics Lecture MPHM13 / MPHM MPHM13 & MPHM14

2 Objectives Understand the mechanism of action of anticoagulants Explain how anticoagulation is initiated, maintained & monitored Predict interactions with warfarin Main INR ranges, induction doses & significant interactions Understand the place in therapy for newer anticoagulants This lecture is intended to be a refresher of your anticoagulation knowledge. You will be expected to do some further reading to supplement this lecture.

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4 Site of action: Anticoagulants

5 Indications for Anticoagulation Atrial fibrillation/ flutter Venous thrombosis Cerebral vascular accidents (AF) Pulmonary embolism Valvular heart disease Prosthetic heart valves Cardiomyopathies Acute MI/ ACS (short term ) Hereditary or acquired thrombophilias

6 Heparins Parenterally administered Binds to body s own anticoagulant Potentiates anticoagulant effect of antithrombin III Heparins UFH LMWH (heparin) (tinzaparin,enoxaparin)

7 Unfractionated heparin Useful when rapid induction required Short duration Can be administered with Warfarin Not absorbed via GIT Can be reversed with protamine sulfate Indicated for S/C administration when Oral anticoagulants: Contraindicated (e.g. pregnancy) Ineffective (in some cancer patients) Inconvenient (e.g. no access to monitoring facilities)

8 Contraindications Haemophilia Thrombocytopenia Peptic ulcer Recent cerebral haemorrhage Severe hypertension Severe liver disease Side effects Haemorrhage Skin necrosis Hyperkalaemia Heparin induced Thrombocytopenia

9 Heparin Induced Thrombocytopenia (HIT) Immune mediated Platelet count falls between 5-12 days following administration of Heparin Complications include gangrene, arterial thrombosis, MI, stroke, DIC Must discontinue all sources of Heparin and begin alternative anticoagulant E.g. Fondaparinux, danaparoid

10 Low Molecular Weight Heparins Derived from heparin Different fragments have different pharmacokinetic properties Principle mode of action occurs by inactivating factor xa Better bioavailability at lower doses Prolonged biological half life More predictable dose response Treatment of choice for majority of patients with venous thromboembolism

11 Fondaparinux Direct FXa inhibitor licensed for: initial treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) venous thromboembolism prevention in patients undergoing surgery for hip fracture or hip/knee replacement or abdo surgery Prophylaxis of VTE in medical pts Treatment of unstable angina or NSTEMI or STEMI Good subcutaneous bioavailability and predictable dose response No antidote currently available S/C admin

12 Warfarin: Dosing, Monitoring, Interactions

13 Target INRs for Various Indications Indication Target INR Range Acute MI (high risk) Atrial fibrillation Prosthetic valve -- (Depends on type of valve) Mechanical valve + risk factors Mechanical valve with systemic embolism despite adequate anticoagulation Venous thromboembolism

14 Dosing Schedules If rapid anticoagulation is required: Give 5 mg once a day for 2 days and re-measure the person's international normalized ratio (INR) on day three. Subsequent doses depend on the prothrombin time reported as an international normalized ratio (INR). Where an immediate effect is required heparin or a low molecular weight heparin is given concomitantly. This is done in secondary care. It takes 48 to 72 hours for the anticoagulant effect of warfarin to fully develop. For people with atrial fibrillation: There is no need to achieve anticoagulation rapidly; a slow-loading regimen is safe and achieves therapeutic anticoagulation in the majority of people within 3 4 weeks.

15 INR Monitoring Initiating Therapy Check INR within 2-3 days (outpatient). Daily INR/PT in hospital until therapeutic x2 days. Check one week after initiation steady state. Monitor weekly during first month of therapy. Maintenance Therapy: If you have to hold a dose, recheck within 1-2 days If you change a dose, recheck within 1-2 weeks. Routine follow up for stable, reliable patients is every 4 weeks (may consider 6 weeks in some patients), more often (every 1-2 weeks) in less reliable or unstable patients.

16 Duration of treatment Long term conditions e.g. AF need lifelong treatment

17 Drug Interactions: Increase INR Thyroid products Metronidazole Fluconazole/azole 2nd, 3rd generation cephs Broad spectrum ABx Alcohol Amiodarone Azithromycin Statins Omeprazole Phenytoin Bactrim Heparin Gemfibrozil Fluoroquinolones Cimetidine

18 Drug Interactions: Reduce INR Estrogens Vitamin K Alcohol Carbamazepine Barbiturates Phenytoin Rifabutin Rifampicin Ritonavir

19 Drug Interactions: No INR Effect Aspirin Clopidogrel COX 2 inhibitors Glycoprotein IIb/IIIa antagonists (Tirofiban) NSAIDs BUT increased risk of bleeding

20 Interactions with Food and Natural Glucosamine Ginseng Fish Oil Gingko biloba St. John s Wort Chondroiton Vitamin E Seaweed Garlic Ginger Saw Palmetto Products Green (leafy)vegetables Soya Mayonnaise Ice cream Cranberry Green Tea

21 Management of Drug Interactions How should we manage those interactions?

22 Adverse Effects of Warfarin Haemorrhage! Major Life threatening or occurs in critical organ Stopping the bleeding more important than thrombotic risk Minor Can be clinically important Epistaxis, macroscopic haematuria, muscle hematoma Always ID source of bleed

23 Dealing with Emergencies Major Bleed Stop warfarin give Phytomenadione 5-10mg slow I.V inj Prothrombin complex (factors II, VII, IX, X) Fresh frozen Plasma INR>8 No bleeding/minor bleed stop warfarin Restart when INR<5 If other risk factors for bleeding give vit K 500mcg slow I.V inj / 5mg Po Repeat Vit K dose if INR still too high after 24hrs.

24 Other things to watch out for Can you identify the problem in each photo?

25 Newer Oral Treatment Anticoagulants Dabigatran Thrombin inhibitor Second licensed in class (ximelegatran withdrawn) Renally excreted No coagulation monitoring required Rivaroxaban / Apixaban direct inhibitors of free and clot bound FXa inhibit the conversion of prothrombin to thrombin but does not act upon AT. predictable pharmacokinetics and pharmacodynamics rapid onset of action. metabolised by cytochrome P450

26 Novel anticoagulants in AF [update 2014] NICE guidance summary (June 2014) Anticoagulation may be with apixaban, dabigatran etexilate, rivaroxaban or a vitamin K antagonist. Consider anticoagulation for men with a CHA 2 DS 2 -VASc score of 1. Take the bleeding risk into account. Offer anticoagulation to people with a CHA 2 DS 2 -VASc score of 2 or above, taking bleeding risk into account. Discuss the options for anticoagulation with the person and base the choice on their clinical features and preferences. Do not offer stroke prevention therapy to people aged under 65 years with atrial fibrillation and no risk factors other than their sex (that is, very low risk of stroke equating to a CHA 2 DS 2 -VASc score of 0 for men or 1 for women). Do not offer aspirin monotherapy solely for stroke prevention to people with atrial fibrillation.

27 CHA2DS2-VASc score for stroke risk in atrial fibrillation Feature Congestive heart failure 1 Hypertension 1 Age > 75 years 2 Age between years 1 Stroke/TIA/TE 2 Vascular disease (previous MI, peripheral arterial disease or aortic plaque) Diabetes mellitus 1 Female 1 Score 1 CHA2DS2-VASc is the recommended scoring system used by NICE Use the HAS-BLED score to assess the risk of bleeding in people who are starting or have started anticoagulation.

28 Feature Hypertension (Systolic >= 160mmHg) HAS-BLED Score Abnormal renal function 1 Abnormal liver function 1 Age >= 65 years 1 Stroke in past 1 Bleeding 1 Labile INRs 1 Taking other drugs as well 1 Alcohol intake at same time 1 Score if present 1 Score of 3 or more indicates increased one year bleed risk on anticoagulation sufficient to justify caution or more regular review. Risk is for intracranial bleed, bleed requiring hospitalization or a haemoglobin drop > 2g/L or that needs transfusion.

29 Further reading Impossible to cover all anticoagulant issues in a 1 hour lecture! Focus your extended reading on: - Patient counselling for warfarin - Yellow book contents - NPSA safety alerts for warfarin - Other anticoagulants in the BNF not covered in the lecture