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1 Guidance on the use of Warfarin Version 1 September 2015

SH CP 185

Guidance on the use of warfarin

Version: 1

Summary: Warfarin – Guidance and information checklist on the use of Warfarin

Keywords: Anticoagulation, Prescription Chart, Warfarin prescription, Warfarin.

Target Audience: Medical Staff, Nursing Staff, Pharmacists, Mental Health Practitioners

Next Review Date: September 2018

Approved &

Ratified by:

Physical Health Drugs and

Therapeutics Committee

Medicines Management Committee

Date of meeting: July 2015 2 September 2015

Date issued: September 2015

Authors: Janet Beith Principal Pharmacist Lymington

Director: Lesley Stevens, Medical Director


Version Control

Change Record

Date Author Version Page Reason for Change

June 2015

Janet Beith 1 Entire document Transfer of HPFT CP 19 Anticoagulation Guidelines onto SHFT template. Check of content and reformat

Reviewers/contributors -

Name Position Version Reviewed & Date

Stephen Bleakley Deputy Chief Pharmacist V1 July 2015

Dr Giles Durward Consultant Physician Lymington V1 June 2015

Physical Health Drugs and Therapeutics Committee

Trust wide representation V1 July 2015

Medicines Management Committee Trust wide representation V1 August 2015


Contents

Page

1 Introduction 4

2 Initiating warfarin

4

3 Warfarin Duration and INR Ranges

5

4 Drugs and food interactions with warfarin

6

5 Management of Bleeding and Excessive Anticoagulation

7

6 Discharging Patients on Warfarin

8

7 References

9

Appendices

Appendix 1 Information checklist for patients

10

Appendix 2 Warfarin Prescription Chart

11

Appendix 3 Dietary Advice for Patients taking Warfarin

12


Guidance on the use of warfarin 1. Introduction

These guidelines have been developed to assist staff in dealing with patients on warfarin. Staff are also reminded to consult their local acute hospital who may advise further on dosing and monitoring requirements. Anticoagulation may be with a vitamin K antagonist, such as warfarin. Alternatives such as apixaban, dabigatran etexilate, or rivaroxaban are available with similar efficacy and lower intracranial bleeding risk.

2. Initiating warfarin1

Always prescribe warfarin on the inpatient drug chart (or electronic prescribing system if available) AND on the separate warfarin treatment prescription chart, if in use. Always state the indication for warfarin and target INR.

Establish Baseline FBC, LFT’s, U&E’s and clotting screen.

Check if a thrombophilia screen should be performed. In known cases of protein C or protein S deficiency start enoxaparin or unfractionated heparin when initiating warfarin.

Counsel the patient about warfarin therapy and ensure they have an opportunity for questions before discharge. Document using the checklist.

Refer to surgical guidelines for restarting warfarin post operatively.

After administration of warfarin an effect on the INR occurs usually within 2 to 3 days (depending on the loading dose). There are various different schedules for initiating warfarin therapy. A common example is given below.

In patients with atrial fibrillation and no recent neurovascular event, a slow loading regimen with warfarin or initiation with a new oral anticoagulant (NOAC) is a suitable alternative.

Days 1 and 2 Day 3 Day 4

INR Dose INR Dose

Give 5mg each evening if baseline INR <1.4

<1.5 10mg 1.5 to 2.0 5mg 2.1 to 2.5 3mg 2.6 to 3.0 1mg >3.0 0mg and seek advice on further management

<1.6 10mg 1.6 to 1.7 7mg 1.8 to 1.9 6mg 2.0 to 2.3 5mg 2.4 to 2.7 4mg 2.8 to 3.0 3mg 3.1 to 3.5 2mg 3.6 to 4.0 1mg >4.0 0mg and seek advice on further management

ACUTE INDUCTION (e.g. DVT or PE treatment)

Suggested dosing schedule:

Day 1: Warfarin 5mg at 6pm

Day 2: Warfarin 5mg at 6pm

Days 3, 4 and 5: Blood test at 9-10am.

Adjust dose according to table below.

Warfarin at 6pm


Atrial Fibrillation (AF)2

The CHA2DS2-VASc stroke risk score should be used to assess stroke risk in people with any of

the following: symptomatic or asymptomatic paroxysmal, persistent or permanent atrial fibrillation atrial flutter a continuing risk of arrhythmia recurrence after cardioversion back to sinus rhythm. Deep Vein Thrombosis/Pulmonary Embolism Refer to DVT management guidelines of local acute Trust Pregnancy Anticoagulation in pregnancy should be discussed on an individual basis with a senior obstetrician, haematologist and if appropriate a cardiologist. Prosthetic Heart Valve If prosthetic heart valve is in situ, the new oral anticoagulants (NOAC) should not be used,

anticoagulate with warfarin

3. Warfarin duration and INR ranges1,2

Indications Target INR/Range

Duration

Atrial Fibrillation 2.5 (2.0 - 3.0) Long Term/indefinite

Cardiomyopathy 2.5 (2.0 - 3.0) Long Term/indefinite

Cardioversion * 3.0 (2.5 – 3.5) pre 2.5 (2.0 – 3.0) post

Minimum 3 weeks pre and minimum 4 weeks post. Seek Cardiologist advice on individual basis.

Mechanical Prosthetic Heart Valve (MHV)

Aortic 3.0 (2.5 - 3.5) Indefinite

Mitral 3.5 (3.0 - 4.0) Indefinite

Mural Thrombosis 2.5 (2.0 - 3.0) 3 months

Arterial Thromboembolism 3.5 (3.0 - 4.0) Discuss with haematologist

Calf DVT 2.5 (2.0 - 3.0) 3 months **

Proximal DVT 2.5 (2.0 - 3.0) 6 months**

Prophylaxis of postoperative deep vein thrombosis

2.5 (2.0 - 3.0) 3 months

Pulmonary Embolus (PE) 2.5 (2.0 - 3.0) 6 months

Recurrence of venous thromboembolism (when 2.5 (2.0 - 3.0) Consider long-term

SLOW INDUCTION (e.g. for AF patients):

Suggested dosing schedule

Patients with atrial fibrillation not requiring treatment with heparin should be

started on warfarin 2 mg daily after a baseline INR is ascertained to be <1.4.

Check INR at 2 weeks.

http://www.cardiosource.org/Science-And-Quality/Clinical-Tools/Atrial-Fibrillation-Toolkit.aspx


no longer on oral anticoagulants)

Recurrence of venous thromboembolism (whilst on oral anticoagulants and INR therapeutic)

3.5 (3.0 - 4.0) Consider long-term

Antiphospholipid Syndrome (Arterial thrombosis) seek advice

2.5 (2.0 - 3.0) or 3.5 (3.0 - 4.0)

Consider long-term

Antiphospholipid Syndrome (Venous Thrombosis)

2.5 (2.0 - 3.0) Consider long-term

* Target INR of 3.0 leads to fewer cancellations of the procedure.

** Shortening treatment to 3 months for proximal, and 6 weeks for distal DVT, will be recommended if circumstances indicate that the risk benefit ratio favours this, e.g. if a reversible precipitating factor is present, and there are risk factors for bleeding (age > 65 years). Long–term treatment of venous thromboembolism will be considered for:

recurrent unprovoked thromboses

a single idiopathic event associated with significant thrombophilia (antiphospholipid antibodies, antithrombin deficiency, combined defects)

Patients with cancer (consider Enoxaparin as LMWHs are superior to warfarin in this scenario).

a life-threatening even

4. Drugs and foods interacting with warfarin

Warfarin has many potential interactions with other medicines and foods and even a slight variation in dose can have potentially serious outcomes, including life threatening bleeds. Patient education is essential. A review of high INR results has shown that a significant proportion of patients become over-coagulated while in hospital due to a predictable drug interaction. The following table contains the most commonly prescribed interacting medicines. This list is not exhaustive. Consult the BNF for further details or your ward pharmacist.

Increase in INR or risk of bleeding.

Action

Anti-infectives. Antibiotics: Azithromycin, ciprofloxacin, clarithromycin, co-trimoxazole, doxycycline, erythromycin, isoniazid metronidazole.

Monitor INR in all patients who are clinically unwell regardless of agent chosen

Antifungals: Fluconazole, itraconazole, miconazole (significantly oral gel), voriconazole.

Medicines that affect bleeding.

Aspirin, clopidogrel, dabigatran, dipyridamole, levothyroxine, NSAIDs, prasugrel, rivaroxiban, SSRIs, tramadol, venlafaxine, ‘flu vaccine (give by deep SC injection rather than IM).

These may not affect INR but will increase risk of bleeding.

Medicines raising warfarin levels.

Allopurinol, amiodarone, bezafibrate, corticosteroids (especially high doses), cytotoxics, fenofibrate, omeprazole, simvastatin, tamoxifen, tibolone.

Monitor INR.

Food and drink interactions

Binge drinking of alcohol, cranberry juice. Avoid with warfarin. Avoid major changes in diet.


The most significant interactions occur with NSAIDs, amiodarone and antibiotics. As a general rule, monitor INR more frequently in patients started on these medicines.

Decrease in INR Action

Various Azathioprine, carbamazepine, carbimazole, mercaptopurine, phenobarbital, phenytoin, rifampicin, St John’s Wort.

Monitor INR and increase warfarin dose as needed

5. Management of bleeding and excessive anticoagulation1

The following recommendations are based on published guidance. It should, however, be

noted that full reversal of warfarin with vitamin K may result in prolonged oral anticoagulant

resistance and therefore full consideration of the degree of reversal required must always be

decided on an individual patient basis. Recommendations from local acute trusts may be in

place and further advice from their haematologists should be sought in the event of any query.

Patients with mechanical heart valves must not be given vitamin K without first

discussing the case with a cardiologist/cardiac surgeon.

Major bleeding

Stop warfarin Give phytomenadione (vitamin K) 5mg by slow intravenous injection if available Transfer patient to acute hospital for reversal of Oral Anticoagulation No bleeding/Minor bleeding – see below for summarised information from BNF 2.8.2

Minor bleeding No bleeding

INR > 8.0

Stop Warfarin Give phytomenadione (vitamin K) 1-3mg by slow intravenous injection Repeat dose of phytomenadione if INR still too high after 24 hours Restart Warfarin when INR < 5.0

Stop Warfarin Give phytomenadione 1-5mg by mouth using IV 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

Stop Warfarin Give phytomenadione (vitamin K) 1-3mg by slow intravenous injection Restart Warfarin when INR < 5.0

Withhold 1 or 2 doses of Warfarin and reduce subsequent maintenance dose

Any INR above 5 should be reported as a medicines error on the Ulysses (safeguarding)

system.

Unexpected bleeding at therapeutic levels – always investigate possibility of underlying cause.

The decision to reinstitute warfarin should be made on an individual basis and may have to be

discussed with the haematologists.


6. Discharging patients on warfarin1,3

Warfarin in Southampton and Hampshire CCGs is managed by the GP and any new patient

should be discharged into the care of their GP.

There are anticoagulant clinics at the acute Trusts, which can be accessed by referral to the Haematology Consultant and are for patients with complicated medical conditions, drug interactions or for specialist advice. Before discharge, make sure that the patient understands the reason for being on warfarin. The patient must be informed of the following risks and the need to be on warfarin in the face of these. Warfarin increases the risk of intracranial haemorrhage two to five fold. From randomised trials and observational studies this is estimated from 0.1 to 0.9% per year (approx. 1 in 200 patients). The rate of serious extracranial bleeding ranges from 0.4 to 2% (approx. 1 in 50). At discharge ensure the following:

INR is stable within the therapeutic range (exceptions may include AF and some other conditions following agreement from the Haematologist and GP, under these circumstances the transfer of information to the GP is especially important) Counselling checklist has been completed and patient/carer has a full understanding of their warfarin treatment. This should include education about bleeding risks, interaction of warfarin with other medication and diet, duration of treatment who to contact in the event of bleeding and who will continue the management of their warfarin

Patient has been given all relevant information booklets including

Oral Anticoagulant Therapy Pack (New patients only FULLY COMPLETED)

Treatment booklet (FULLY COMPLETED).

Trust dietary advice leaflet. To ensure continuation of optimal anticoagulation the General Practitioner (GP) must be given information without delay. Fax a copy of the completed warfarin prescription chart to the GP on the day the patient is discharged. This is the responsibility of the person discharging the patient This should include the following information:

Indication for warfarin

Target INR

Precise duration of treatment

Dose on discharge

Date of previous INR

Date or time period to next INR

Whose responsibility it is to follow up or discontinue treatment.

(It is very important to ensure that a follow-up INR has been arranged at the GP practice or hospital.) Although this information should be faxed to the General Practitioner without delay, the

discharge summary must outline the management plan in detail.


7. References:

1. Keeling, D., Baglin, T., Tait, C., Watson, H., Perry, D., Baglin, C., ... & Makris, M. (2011).

Guidelines on oral anticoagulation with warfarin–fourth edition. British journal of

haematology, 154(3), 311-324.

2. National Institute for Health and Care Excellence. Atrial fibrillation: the management of atrial

fibrillation. June 2014 CG 180

3. National Patient Safety Agency. Patient Safety Alert. Actions that can make anticoagulants

safer. 28th March 2007


Appendix 1

INFORMATION CHECK LIST FOR PATIENTS ON WARFARIN

The following information must be given to the patient when commencing warfarin. Initial counselling should be given and documented by the person who prescribes the warfarin or, by agreement for a specific patient, the pharmacist. Further information including patient education must be reinforced by a nurse or pharmacist and supported by written information. The checklist must be completed and reinforced prior to discharge and a copy given to the patient. This is the responsibility of the person arranging the discharge.

INITIATION OF WARFARIN Prescribers signature Date The indication for taking warfarin has been explained including the length of treatment & who will stop it or when it should be reviewed

The risk/benefit of taking warfarin has been discussed.

Risk of poor warfarin control to include compliance, not missing doses, taking too much warfarin, importance of attending for blood tests.

The risk of bleeding or thrombosis associated with poor control.

How warfarin works, how to recognise a minor or major bleed and what action to take.

For patients newly started on warfarin – This has been discussed with GP/warfarin clinic and mechanism for follow up INR arranged

EDUCATION Nurse Signature Date

Who to contact in an emergency

The importance of reporting changes in medication, diet or lifestyle to the person monitoring the blood tests.

The need to inform other healthcare professionals that warfarin taken, e.g. dentist, pharmacist or physiotherapist.

Taking the correct dose at the correct time (Usually 6pm)

What to do if you miss a dose

Starting new or stopping current medication

Tablet colour & strengths explained

Dietary advice given including Trust leaflet

Alcohol No more than 2 units per day.

Lifestyle including hobbies/leisure

Avoiding over the counter or herbal medicines including dietary supplements without advice from Doctor or Pharmacist

DISCHARGE CHECK

New patients have an ‘Oral Anticoagulant Therapy’ pack that is FULLY completed. To include a dietary advice leaflet.

All patients need a FULLY completed updated booklet

Dosing advice in mg given in writing & explained verbally.

Follow up INR arranged

Completed treatment chart has been faxed to GP

Checklist completed & signed (Copy given to patient)

I understand the risks and benefits of taking warfarin. I confirm that I have had the chance to discuss and understand the information that I have been given. Signed: ----------------------------------------------------------------- Date: ---------------------------------------


Southern Health NHS Foundation Trust Warfarin Prescription Chart

Hospital: ……………………………….. Patient details or addressograph: Ward: ................................................ Surname: ………………………….. Consultant: ................. First Name: …………………......…

Reason for anticoagulation: ………………................ INR Target Range: _________ to ____________ Duration: ....................................................................D.O.B.: ……………………….......... Pre-op warfarin dose, if applicable………...…...…...... NHS No.: …………………............

Date Prothrombin

Ratio (INR) Dose Doctor’s

Signature of Prescription

Nurse’s Signature

(when given)

TAB. WARFARIN mg. at pm














DISCHARGE INFORMATION TO THE GP:

Please ensure this warfarin prescription chart is faxed to the GP on the day that the patient is discharged.

Dose on discharge: ……….………………………. Date next INR due: ………………………........... Duration of treatment: ……………………………. Who will stop the warfarin? …........................ Blood test at: Hosp/GP/Walk in clinic/Comm. Nurse. Who will adjust dose: Hospital/GP

(delete as necessary)

Please contact the medical team if this patient's INR goes above. …....... or falls below ...….... Please ensure that the Oral Anticoagulant treatment booklet is FULLY completed

Concurrent interacting Drugs


Appendix 3 DIETARY ADVICE FOR PATIENTS TAKING WARFARIN

A well balanced diet is important to health. A balanced diet means eating a variety of healthy foods including pulses, grains, fruits and vegetables. When taking warfarin you should avoid sudden or drastic changes to your diet as this can lead to changes in your INR (blood test). If you are planning to make changes to your diet you should discuss them with the person monitoring your INR, as the dose you take may need to be changed.

It is important to eat regular meals and to avoid binging or starving FATS Aim to reduce high fat content foods containing saturated fats and cholesterol. Saturated fats are found in animal products such as red meats, in dairy products such as butter, cream and cheese and in some plant oils. Cholesterol is found mainly in animal and dairy products. Changing suddenly to a low fat diet will affect your INR result and again will need to be discussed with the person monitoring your INR.

HERBAL REMEDIES Some herbal remedies have properties that can either increase or decrease the action of oral anticoagulation and should be avoided e.g. St John’s Wort, Danshen, Ginko biloba to name but a few. It is always best to discuss this with the person monitoring your blood tests before considering herbal remedies.

CRANBERRY JUICE & CRANBERRY TABLETS There have been some reports that large quantities of cranberry juice and cranberry tablets will raise the INR. One or two small glasses per day are probably all right. Again the message is consistency. Do not change the amount that you would usually drink or suddenly start to drink it.

ALCOHOL Alcohol can significantly raise the INR result. It is usually safe to drink 1 or 2 units on a regular basis, if it is consistent. It is important not to binge drink. This will put you at serious risk of haemorrhage. A unit is equivalent to half a pint of beer, a glass of wine (125ml) or a pub measure of spirit. DIETARY SUPPLEMENTS. Many dietary supplements contain Vitamin K. If these were required it would be better if they were taken following medical advice. Other vitamins such as vitamin E can affect your INR result. Calcium supplements taken 2 or 3 times a day can reduce the absorption of oral anticoagulation. Fish oils such as Cod liver oil and omega 3 can have an effect on the INR.

It is important that the person monitoring your INR is aware if you start or stop taking dietary supplements.


VITAMIN K Vitamin K plays an important role in the blood clotting process. It is needed for them to be effective by a number of the clotting factors. Most oral anticoagulants work by preventing vitamin K from acting on these clotting factors, slowing the clotting process down. It is important to eat regularly without making big changes to your diet so that the vitamin K made by the body is kept at a constant level. Vitamin K is also present in some of the foods that we eat. It is mainly found in dark green leafy vegetables. Eating too much can reduce or reverse the action of oral anticoagulants. It is important to include these foods in your diet but to maintain a consistent amount of foods containing vitamin K so that fluctuations in the INR do not occur.

It is recommended that you eat five servings of fruit and vegetables per day, but no more than three servings of dark green vegetables per week. Do not eat these dark green vegetables all on the same day but spread them evenly through the week. These vegetables include broccoli, cabbage, Brussel sprouts, spring greens and spinach greens and spinach.

FOODS CONTAINING HIGH AMOUNTS OF VITAMIN K

Portion size guide Pork or beef liver (4oz or 100g) Avocado (½ medium sized) Asparagus (10 spears) Broccoli (6-7 small/medium florets) Brussels sprouts (12 sprouts)

Cabbage (4 heaped dessert spoons) Watercress (¼ bunch) Kale (3 heaped dessert spoons) Spinach (3 rounded dessert spoons)

IF THERE IS ANY DOUBT ABOUT ANYTHING MENTIONED IN THIS ADVICE PLEASE DISCUSS WITH THE PERSON MONITORING YOUR INR.

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