BNF. BACKGROUND FOR USE

Transcription

1 797FM.2 ORAL ANTICOAGULANTS WARFARIN, ACENOCOUMAROL AND PHENINDIONE, WHEN DOSES ARE ADJUSTED BY THE ANTICOAGULATION CLINIC AND PRESCRIBED BY THE GENERAL PRACTITIONER (GP) Shared Care Protocol This protocol provides prescribing and monitoring guidance for oral anticoagulant therapy with warfarin, acenocoumarol or phenindione. It should be read in conjunction with the Summary of Product Characteristics (SPC) available on and the BNF. BACKGROUND FOR USE This agreement outlines the ways in which the responsibilities for prescribing of oral anticoagulation with warfarin, acenocoumarol or phenindione are shared where the anticoagulation monitoring service recommends doses and the GP prescribes them. Sharing of care assumes communication between the anticoagulant monitoring service, GP and patient. The intention to share care should be explained to the patient by both the patient s GP and healthcare professional initiating treatment. It is important that patients are consulted about treatment and are in agreement with it. Patients treated with oral anticoagulants are under regular follow-up, which provides an opportunity to discuss drug therapy. It is the responsibility of both the anticoagulation monitoring service and the GP to maintain competencies relevant to their roles. The anticoagulation monitoring service is responsible for ongoing audit of the quality assurance components of the service. The doctor who prescribes the medication legally assumes clinical responsibility for the drug and the consequences of its use. SUPPORTING INFORMATION The vitamin K antagonist oral anticoagulant of choice is warfarin. A small number of patients are intolerant of warfarin and many of these are able to switch to direct oral anticoagulant (DOAC) drugs. Patients unable to tolerate warfarin who are unsuitable for DOAC drugs should have a risk assessment performed regarding the advisability of continued anticoagulation. Patients who definitely require ongoing vitamin K antagonist treatment should be switched to acenocoumarol. Phenindione should very rarely, if ever, be required see section on equivalent doses under Switching Therapy. Licensed indications Prophylaxis of embolism in rheumatic heart disease Warfarin Acenocoumarol Phenindione Prophylaxis in atrial fibrillation Prophylaxis after insertion of prosthetic heart valves Prophylaxis and treatment of venous thrombosis and pulmonary embolism Transient ischaemic attacks Not licensed Guideline 797FM.2 1 of 11 Uncontrolled if printed

2 ROLES AND RESPONSIBILITIES Where the anticoagulation monitoring service is not the patient s GP, the responsibilities for care specified in this shared care protocol for oral anticoagulation apply. In this situation the anticoagulation monitoring service should request shared care using the form provided in the local shared care document. GP or hospital will refer the patient to an anticoagulation monitoring service provider. Specialist 1. Determine the need for anticoagulation. 2. If rapid anticoagulation is required, initiate oral anticoagulation treatment after providing written and verbal counselling advice on warfarin. 3. If slow anticoagulation is required, refer the patient to the anticoagulation monitoring service of their choice and inform the GP. 4. With the referral provide a clinical plan on how long anticoagulation treatment is required and the INR range needed. Anticoagulant Monitoring Service 1. Confirm receipt of the referral to the referee and the patient s GP. 2. Provide written and verbal counselling advice on warfarin. 3. Initiate and/or take over management of oral anticoagulant treatment. 4. If the anticoagulation monitoring service is initiating the warfarin: Provide first prescription for warfarin, titrate the dose and establish patient on a stable dose of oral anticoagulant. 5. Where a dose change warrants a change in prescription of warfarin that cannot be met with patient s existing warfarin supply, the anticoagulation monitoring service provider must make the supply. 6. Provide the patient with a patient-held yellow oral anticoagulant therapy record book, or equivalent, with clear details of the reason for anticoagulant therapy, target INR range and duration of therapy, and issue an oral anticoagulant alert card for them to keep on their person at all times. 7. Advise GP of the strengths of tablets to prescribe. (Same day dosing using whole tablets should be prescribed wherever possible National Patient Safety Agency (NPSA) guidance should be followed.) 8. Provide ongoing monitoring of INRs and appropriate dosing and follow-up. Communicate in writing the INR results, dose prescribed and date of next INR test promptly to the patient and patient s GP within 24 hours. 9. Discuss and regularly review benefits and side effects of treatment with the patient. To assess treatment at regular intervals and conduct annual treatment review. To check patient is well controlled (i.e. degree of INR control should be more than 65% of time in therapeutic range in last 6-12 months excluding first 6 weeks of treatment) and no contraindications to continuing treatment apply and to communicate results to the patient s GP. 10. In cases of over-anticoagulation, administer oral vitamin K in accordance with British Committee for Standards in Haematology (BCSH) guidelines and clinic protocols. 11. All patients with an INR >5.0 should be investigated for the cause of the raised INR. For every patient with a recorded INR >8 a significant event report giving details of possible cause, management and outcome is to be completed Any Qualified Provider (AQP) contract requirement. 12. Responsibility for the decision to discontinue warfarin or phenindione resides with the anticoagulation monitoring service provider in consultation with the referring clinician and patient s GP. 13. Where necessary, advise GP on when treatment has been stopped. 14. The anticoagulation monitoring service provider must actively follow-up any patient who does not attend within the agreed time period in the anticoagulation service specification. 15. If a patient does not attend (DNA) on 2 or more consecutive occasions or more than 42 days in a DNA period, the anticoagulation monitoring service will inform the patient s GP in writing. 16. Report adverse events on the yellow card system if appropriate. 17. Ensure clear arrangements for back-up, advice and support are in place. Guideline 797FM.2 2 of 11 Uncontrolled if printed

3 General Practitioner Specific Responsibilities 1. Unless initiated in secondary care before referral, the prescriber should have a documented discussion with the patient regarding the need for oral anticoagulation as well as the risks and benefits of long term treatment with warfarin. 2. Prior to referral, carry out a full clinical review and undertake initial FBC, coagulation screen, U&Es and LFTs and communicate results to the anticoagulation monitoring service. There is a standardised referral form that can be imported into the GP s clinical system and which is to be used when referring to any anticoagulant monitoring service clinic to ensure capture of all essential information. Refer patient for initiation of treatment by the anticoagulation monitoring service chosen by the patient following a holistic assessment of the patient s suitability for anticoagulation. The prescriber must assess the appropriateness of treatment against the patient s current health and social status taking into account the patient s preferences. 3. The current chosen anticoagulation monitoring service provider should be recorded in the patient s notes. 4. Prescribe oral anticoagulant once patient is initiated on treatment. 5. Ensure that the patient s INR is being regularly transferred and recorded in their medical records. 6. Inform anticoagulation monitoring service if the situation regarding need for anticoagulation changes according to specialist advice. 7. Monitor for clinical conditions that may lead to a deterioration in health and INR stability and alert anticoagulation monitoring service in the event of any significant changes in patient s clinical condition. 8. The anticoagulation monitoring service will communicate annual review of anticoagulation to the GP. This should be recorded in the patient s notes. (Read code Annual Risk Assessment 66Q2 applies.) 9. When co-prescribing, choose medicines least likely to interact with the oral anticoagulant, as per the interaction chart Appendix 1. If there is a known potential interaction following any medication changes that may affect the stability of the patient s INR, either refer the patient back to the anticoagulant clinic for an appropriate INR follow-up or make arrangements for an INR check to be made and communicate results to anticoagulation monitoring service. 10. Discontinue treatment on advice of specialist or anticoagulation monitoring service. Document this. 11. Alert the anticoagulation monitoring service if a decision to stop oral anticoagulant treatment has been made or if the patient leaves the practice. 12. Liaise with the patient to report any significant adverse events to the anticoagulation monitoring service clinic. Patient Responsibilities 1. Attend anticoagulation monitoring service regularly and if unable to attend re-organise appointments as soon as is practical. 2. Regular INRs are required at least every 12 weeks (at least every 8 weeks if prosthetic heart valve patients). 3. Patients who are self-managing their INRs agree to be reviewed as specified by the anticoagulation monitoring service. 4. Where the GP advises an increased frequency of tests due to interacting drugs, it is the patient s responsibility to have an INR test done as advised and, if requested, to arrange an urgent appointment with the anticoagulation monitoring service. 5. Report any missed doses when attending for an INR check. 6. Advise anticoagulation monitoring service about any changes in prescribed medication or medical condition and check with the anticoagulation monitoring service or community pharmacist before taking or stopping any over the counter medicines or supplements. 7. Share any concerns that they may have in relation to treatment with oral anticoagulant with their anticoagulation monitoring service or GP. 8. Report to the anticoagulation monitoring service or GP if they do not have a clear understanding of their treatment. 9. Take oral anticoagulants as directed and stated in the yellow oral anticoagulant therapy record book or equivalent handheld record. 10. Report any adverse effects to their anticoagulation monitoring service and/or GP whilst treated with oral anticoagulant. Guideline 797FM.2 3 of 11 Uncontrolled if printed

4 Hospital Pharmacy Duration of Supply At initiation of treatment, it is standard practice to issue 28 tablets of warfarin 1 mg and 3 mg strengths. Warfarin is usually supplied in original packs which are not split. CONTRAINDICATIONS AND PRECAUTIONS see Atrial Fibrillation Treatment Absolute Contraindications Known large oesophageal varices. Significant thrombocytopenia (platelet count <50 x 10 9 /L) - refer to haematologist. Within 72 hours of major surgery with risk of severe bleeding - defer and re-assess risk postoperatively. Previously documented hypersensitivity to either the drug or excipients consider cardiology opinion. Acute clinically significant bleed - defer and re-assess suitability for restarting warfarin as soon as acute bleed is over and within 1-3 months. Decompensated liver disease or deranged baseline clotting screen (INR >1.5) refer to gastroenterology/hepatology. Pregnancy or within 48 hours postpartum - seek urgent haematological advice. Severe renal impairment (GFR <30 ml/min/1.73 m 2 ). Relative Contraindications Previous history intracranial haemorrhage. Recent major extracranial bleed within the last 6 months where the cause has not been identified or treated decision for oral anti-thrombotic therapy should be deferred. Recent documented peptic ulcer (PU) within last 3 months decision for oral anti-thrombotic therapy should be deferred until treatment for PU completed. In all cases with history of PU, give PPI cover whilst on anti-thrombotic. Recent history of recurrent and severe falls in patient at higher bleeding risk. A patient at higher bleeding risk is assessed by having 3 or more of the following risk factors: Age >65 years. Previous history bleed or predisposition to bleeding (e.g. diverticulitis). Uncontrolled hypertension. Severe renal impairment (i.e. serum creatinine >200 umol/l, egfr <30 ml/min/1.73 m 2 or on dialysis). Acute hepatic impairment (e.g. bilirubin >2 x ULN + LFTs >3 x ULN), chronic liver disease (e.g. cirrhosis). Low platelet count <80 x 10 9 /L or a thrombocytopenia or anaemia of undiagnosed cause. On concomitant drugs associated with an increased bleeding risk, e.g. selective serotonin reuptake inhibitors (SSRIs), oral steroids, non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate or other immune-suppressant agents. Dementia or marked cognitive impairment with poor medicines compliance and no access to carer support. Chronic alcohol abuse especially if associated with binge drinking. DOSAGE AND TIME TO RESPONSE (see also references 1 and 2) Patients that do not require rapid anticoagulation, e.g. atrial fibrillation and atrial flutter, can be given a slow loading regimen, e.g. 2-3 mg warfarin daily for a week. Subsequent doses are determined by the INR and sensitivity to warfarin. Most patients should achieve therapeutic anticoagulation (i.e. within desired therapeutic range) within 3-4 weeks. Individuals have different dosage requirements of warfarin. The response in individuals cannot be predicted. This is partly due to patients different metabolism of warfarin and partly due to other factors, such as disease states and interacting drugs. The average dose of warfarin required daily is around 4-6 mg but may vary markedly because of several factors. Warfarin should be given once daily, ideally at approximately the same time each day. Guideline 797FM.2 4 of 11 Uncontrolled if printed

5 Once stabilised on warfarin, the frequency of INR monitoring will be dictated by the latest INR reading taking into account their recent INR trend and dosing history see below. SWITCHING THERAPY Acenocoumarol (Sinthrome ) 1 mg is equivalent to warfarin 1.5 to 2 mg. Phenindione 50 mg is equivalent to warfarin 3 mg. Patients currently on phenindione who are allergic to or unable to take a coumarin (warfarin/acenocoumarol) should be referred for consideration of a novel oral anticoagulant (NOAC) drug. Phenindione dose Dosage conversion table 3 Approximate dosage conversions Acenocoumarol (Sinthrome ) dose Warfarin dose 20 mg 0.5 mg 1 mg 35 mg 1.0 mg 2 mg 50 mg 1.5 mg 3 mg 70 mg 2.0 mg 4 mg 80 mg 2.5 mg 5 mg 100 mg 3.0 mg 6 mg 120 mg 3.5 mg 7 mg 135 mg 4.0 mg 8 mg 150 mg 4.5 mg 9 mg 170 mg 5.0 mg 10 mg The risk of potential adherence problems or confusion would need to be taken into account when switching therapies (e.g. elderly, cognitively impaired, language problems) and every effort should thus be made to ensure that the dosing regimen is as simple as possible. MONITORING SCHEDULE by GP It is recommended as good practice to consider checking BP, FBC and U&Es at least annually to fulfil GP s responsibilities listed above (see points 7, 8 and 10). The following parameters relate to the clinical care of patients anticoagulated with vitamin K antagonists (baseline assessments are compulsory for referral but ongoing monitoring requirements are recommended but not essential): Parameter Frequency of test Action Clinical review Baseline assessment (compulsory) and then annually LFTs and baseline clotting screen Pre-treatment only FBC U&E BP Pre-treatment then annually Pre-treatment then annually Pre-treatment then 6 monthly Change in patient s clinical condition, particularly associated with changes in renal function, may necessitate more frequent testing. Guideline 797FM.2 5 of 11 Uncontrolled if printed

6 MONITORING SCHEDULE by anticoagulant monitoring service A full clotting screen is recommended prior to initiation of oral anticoagulation (prothrombin time/inr plus activated partial thromboplastin time (APTT)). A baseline INR <1.5 is required for initiation of oral anticoagulation to proceed. Refer to haematology in the event of abnormal results (baseline INR >1.4; prolonged APTT). The frequency of INR monitoring following commencement of warfarin will initially need to be every 5-7 days until stabilised on treatment. For ongoing monitoring in whom there is no change in medical status or drug therapy, the frequency of monitoring can be guided by the criteria shown below or use of computerised decision support software (CDSS) One INR high One INR low One INR therapeutic Two INRs therapeutic Three INRs therapeutic Four INRs therapeutic Five INRs therapeutic Recall in 7 to 14 days (stop treatment for 1 to 3 days) (max. 1 week in prosthetic valve patients) Recall in 7 to 14 days Recall in 1 to 2 weeks Recall in 2 to 3 weeks Recall in 3 to 4 weeks Recall in 4 to 5 weeks Recall in 6 to 8 weeks More than 5 INRs therapeutic: Recall period can be increased in a step-wise fashion to a maximum of 12 weeks between appointments if stable (maximum 8 weeks for prosthetic valve patients). SIDE EFFECTS Haemorrhage; other side effects reported include hypersensitivity rashes, alopecia, diarrhoea, unexplained drop in haematocrit, purple toes, skin necrosis, jaundice, hepatic dysfunction; also nausea, vomiting and pancreatitis. NOTABLE DRUG INTERACTIONS (REFER TO BNF AND SPC) See Appendix 1. BACK-UP INFORMATION/ADVICE A list of anticoagulant monitoring clinics is available on the CCG websites. If haematological advice is needed: Contact Details Wycombe Hospital Stoke Mandeville Hospital Haematology Hospital Pharmacy Medicines Information (secretaries) In an emergency contact, consultant haematologist on-call (leave message for consultant call back) In an emergency, contact consultant haematologist on-call REFERENCES 1. Joint Formulary Committee (2015). British National Formulary. 69 th edition. London: British Medical Association and Royal Pharmaceutical Society of Great Britain. 2. British Committee Standards Haematology Guidelines on Oral Anticoagulation (warfarin) fourth edition. 3. Guy s and St. Thomas NHS Foundation Trust Medicines Information Centre May Guideline 797FM.2 6 of 11 Uncontrolled if printed

7 See also: Guideline 191FM Guideline 775FM Protocol for Over-anticoagulation with Warfarin Guidelines for the Treatment of Atrial Fibrillation (AF) Title of Guideline Oral Anticoagulants Warfarin, Acenocoumarol and Phenindione When Doses are Adjusted by the Anticoagulation Clinic and Prescribed by the GP Guideline Number 797FM Version 2 Effective Date January 2017 Review Date April 2018 Original Version Produced January 2009 Approvals: Medicines Management Sub Committee 8 th December 2016 Bucks Area Prescribing Committee 14 th December 2016 Clinical Guidelines Subgroup 12 th January 2017 Author/s Jonathan Pattinson, Consultant Haematologist Satinder Bhandal, Anticoagulation Pharmacist Sarah Crotty, Interface Pharmacist, AV & CCCG Maria Smith Senior Pharmacist Advisor, AV & CCCG Medicines Management Team, AV & CCCG Haematology, BHNHST SDU(s)/Department(s) responsible for updating the guideline Uploaded to the Intranet 2 nd February 2017 Buckinghamshire Healthcare NHS Trust/Aylesbury Vale and Chiltern Clinical Commissioning Groups Guideline 797FM.2 7 of 11 Uncontrolled if printed

8 Appendix 1 Recommendations for prescribing commonly used drugs in Primary Care that potentially interact with warfarin 1. ANTIBACTERIAL AND ANTIFUNGAL DRUGS Antifungals Oral cephalosporins Macrolide antibiotics Metronidazole Oral penicillins Quinolone antibiotics Rifampicin Tetracyclines Trimethoprim Clinically important interaction with significant increases in INR seen with fluconazole and miconazole (including stat doses, buccal and topical formulations). Fluconazole has dose related effect on INR (approx. 20% to >50% warfarin dose reductions needed). Reduce dose by at least 20% if co-prescribing fluconazole and, in all cases, check INR day 2-4. Nystatin and amphotericin are possible alternative non-interacting options. Most cephalosporins, such as cefalexin (1 st generation) and cefaclor (2 nd generation), do not normally interact with warfarin, although some of the 2 nd and 3 rd generation cephalosporins have been associated with independent bleeding risks, as they can act as vitamin K antagonists and cause thrombocytopenia. Usually no interaction seen with azithromycin although, very rarely, unpredictable raised INRs have been reported. There is, however, good evidence that azithromycin usually offers a non-interacting and safer alternative to clarithromycin and erythromycin. It is good practice to check INR on day 3-5 from start of treatment. Established and potentially serious interaction seen with clarithromycin but it is unpredictable and not common. All patients requiring clarithromycin should have INR checked within day 2-4 because the reaction, when it occurs, is rapid and usually causes a marked increase on INR. Increases in INR are usually seen with erythromycin although they are not always clinically significant. Marked increases in INR can, however, occur. Reduce dose by 20% in high risk patients only (those sensitive to warfarin, i.e. <3 mg/day and/or if age >75 years), but in all cases check INR day 3-5. An established and clinically important interaction seen. The effect on INR can be markedly increased and prolonged by metronidazole. If concurrent use cannot be avoided, recommend reducing dose by at least 30% and check INR within 3-5 days and then weekly for 3-4 weeks following discontinuation of drug. No clinically significant interaction normally occurs but raised INRs are occasionally seen in the elderly and patients sensitive to warfarin. Check INR within 3-5 days if patient is >75 years of age and on 3 mg warfarin/day or if intensive/prolonged treatment >7 days required. Occasional but unpredictable increases in INR, which can be marked, seen with ciprofloxacin and ofloxacin. Check INR between days 3-5 of concurrent use. Rifampicin causes a marked reduction in anticoagulant effect within 5-7 days of starting treatment and persists for at least 7-10 days after the rifampicin has been stopped in most patients. Warfarin dose usually at least doubled and in some cases increased 5 6 fold to compensate. Increase warfarin dose by 50% and check INR within 3 days of starting concurrent use. Normally no interaction seen but rarely unpredictable and possibly marked increases in INR can occur. Check INR within 3-5 days of starting treatment. Normally no interaction occurs but very occasionally transient increases in INR have been observed. Check INR only in those sensitive to warfarin requiring more than a 3 day antibiotic course. Guideline 797FM.2 8 of 11 Uncontrolled if printed

9 2. OTHER COMMONLY PRESCRIBED DRUGS Allopurinol Amiodarone Aspirin and other antiplatelet drugs Beta-blockers Carbamazepine and oxcarbazepine Colestyramine Corticosteroids Fibrates Flu vaccine H 2 antagonists Non-selective NSAIDs Selective NSAIDs Proton pump inhibitors Wide individual variability in level of interaction seen. Impossible to predict who is likely to be affected. Check INR within 3-5 days of initiating treatment and 2-3 weeks later. Significant increase in INR seen in all patients. Reduce warfarin dose by approx 25-30% and check INR within 4-7 days. Weekly monitoring recommended for first 4 weeks of starting amiodarone. Interaction persists for many weeks following drug withdrawal (6-16 weeks). Low dose aspirin (75 mg daily) does not appear to interact directly to a clinically relevant extent but ALL antiplatelet drugs are associated with an independent increased risk of bleeding. Bleeding risks associated with aspirin use are dose related. Consider PPI cover if combination with aspirin unavoidable. Risks of bleeding similar with clopidogrel. Systemic absorption of topical salicylate preparations does occur and may increase effect of warfarin clinical significance depends upon area of application and frequency of use. Anticoagulation not usually affected by beta-blockers, except possibly with propranolol. If co-prescribing propranolol, check INR within 1-2 weeks of starting drug. Carbamazepine can cause a marked reduction in INR. Doses of warfarin usually need to be doubled to compensate for interaction. Check INR within 7 10 days and monitor INR every 1-2 weeks for following 4 6 weeks. Oxcarbazepine appears to be a relatively non-interacting alternative. Can significantly reduce the INR. Separating the administration of the two drugs by at least 3-6 hours has been shown to minimise the interaction. Check INR within 5-7 days of starting treatment. Effect of steroids on INR unpredictable and usually dose related. High dose steroids can cause marked INR increases. (Also independent bleeding risk associated with steroid use.) Check INR within 5 10 days of use. All fibrates increase the effects of warfarin (established and clinically serious interaction). Reduce dose by 30 50% and check INR within 3 5 days. In practice, both transient increases and decreases in INR have been seen in some patients. It would be prudent to check the INR within 7 10 days following vaccination, especially in high risk individuals. Avoid cimetidine. Interactions with other H 2 antagonists are rare but, as isolated reports of unpredictable raises in INR have been observed, it would be prudent to check INR within 2 weeks of concurrent use. Avoid piroxicam. Slight moderate increases in INR can occur with other NSAIDs although not usually clinically significant, especially if being used prn for acute pain of <5 days duration. Ibuprofen, diclofenac and naproxen are associated with lower GI bleeding risks. Plasma concentrations of topical NSAIDs are low compared to oral therapy. Consider H 2 antagonist/ppi cover if co-prescribing oral NSAID necessary. Check INR within 7 10 days of concurrent use. Good evidence supports celecoxib as being the least likely COX II NSAID to interact with warfarin. However, as there are isolated reports of raised INRs with both celecoxib and some other NSAIDs, check INR within 10 days of concurrent use. No documented interactions have been observed with meloxicam. Omeprazole usually causes only modest increases in INR but, rarely, unpredictably more marked effect on INR is seen. Lansoprazole causes slight, usually clinically insignificant, decreases in INR. Check INR within 7 10 days of starting or stopping either drug. Isolated drug interactions have been reported with pantoprazole. Guideline 797FM.2 9 of 11 Uncontrolled if printed

10 Paracetamol and tramadol Phenytoin SSRI antidepressants Statins Tamoxifen Thyroid and antithyroids Tricyclic antidepressants No interaction seen with occasional, when required, doses of paracetamol, but regular daily use is associated with increases in INR in a dose dependent manner. Full extent of interaction associated with chronic concurrent use takes 7-14 days to develop. Check INR within 7-14 days if prescribed for regular use. With tramadol, unpredictable interaction infrequently seen but clinically significant if it occurs. Check INR within 5 7 days. Can cause marked increases in INR. Warfarin may also affect serum phenytoin levels. Check INR weekly for first few weeks following starting/stopping treatment and also monitor for phenytoin toxicity. No interaction usually occurs with SSRIs, but unpredictably raised INRs seen occasionally with fluoxetine, venlaxine and sertraline. Citalopram is the least likely SSRI to affect INR. SSRIs also associated with independent bleeding risk because of their effect on platelet function. Check INR within days of starting an SSRI. Simvastatin and, less frequently, atorvastatin can cause modest but occasionally clinically significant increases in INR. Check INR within days. As rosuvastatin also has potential to affect INR, check INR within 7 days. Full extent of interaction in all cases may take 3-4 weeks to develop. No interactions have been seen with pravastatin. Established clinically important interaction which affects some but not all patients. Marked increases in INR seen - at least 50% dose reductions in warfarin required if interaction occurs. Check INR within 3-5 days and then weekly for first 4-6 weeks of starting treatment. Starting treatment or increasing the dose in a patient stabilised on warfarin will increase INR. Conversely, antithyroid drugs will decrease INR. Check INR in all cases within 2-3 weeks of starting or changing therapy. Amitriptyline and other tricyclics can cause unpredictable, modest increases or decreases in INR, but these can make stable INR control difficult to achieve. Check INR within days if concurrent use unavoidable. Guideline 797FM.2 10 of 11 Uncontrolled if printed

11 Appendix 2 Buckinghamshire Shared Care Agreement Form For use when prescribing one or more amber protocol drug This form is used to agree shared care between the specialist, patient and GP as follows: 1. Specialist to estimate date of GP prescribing continuation. 2. Specialist to provide pre-treatment counselling and discuss patient responsibilities. 3. Specialist and patient to complete and sign the shared care agreement form. 4. Copy to be filed in patient s hospital notes. 5. Agreement form, drug specific protocol and responsibilities to be faxed to the GP and copies given to patient. 6. GP to complete and sign agreement form. If unwilling to share care, provide reason. 7. Scan copy of shared care agreement form, protocol and responsibilities into patient s notes. 8. Fax signed copy back to specialist. For completion by specialist Drug(s).. Indication Date of first prescription by specialist Patient weight (kg).... Estimated date for prescribing to be continued by the GP Specialist additional comments/advice We accept: The Buckinghamshire shared care responsibilities and The requirements defined in the drug specific shared care protocol(s) Patient name, NHS number and address or sticker Contact details Signature and date AQP clinic service and site location GP name and practice Tel Fax Tel Fax To the GP: If unwilling to share care - please define reason(s) below:.... Guideline 797FM.2 11 of 11 Uncontrolled if printed