DVT Primary Care Prescribing Pathway

DVT Primary Care Prescribing Pathway Scope Classification Author Health Economy Wide Guideline East Lancashire Medicines Management Board (Reviewed December 207) Authorised by ELMMB Date February 208 Reviewed December 207 Review Date February 2020 Supporting references: Guideline: DVT Primary Care Prescribing Pathway Version Number 7 (final), February 208 Review date February 2020

DVT Primary Care Prescribing Pathway www.elmmb.nhs.uk Introduction East Lancashire Clinical Commissioning Groups (CCG), working with local hospital specialists, has designed a clinical pathway for the diagnosis and management of DVT in primary care. The pathway supports clinicians to manage patients presenting with a suspected DVT and provides advice which is in line with the relevant NICE guidance and good clinical practice. Background to DVT Venous thromboembolism (VTE) is a condition in which a blood clot (a thrombus) forms in a vein, most commonly in the deep veins of the legs or pelvis. This is known as deep vein thrombosis, or DVT. The thrombus can dislodge and travel in the blood, particularly to the pulmonary arteries. This is known as pulmonary embolism, or PE. Failure to diagnose and treat DVTs correctly can result in fatal PE. However, diagnosis of DVT is not always straightforward. Primary care management of DVT The primary care prescribing pathway guidance document should be read in conjunction with the relevant service specifications covering DVT assessment and management in primary care. To assist clinicians diagnosing and treating DVT the pathway includes reference to the two-level Wells score, and the place of D-dimer testing and ultrasound imaging along with treatment of adults with suspected or confirmed DVT who are suitable for treatment with oral rivaroxaban (Xarelto ). The pathway does not cover children or young people aged under 8, or women who are pregnant or breastfeeding. The pathway will assume that prescribers will use a drug's summary of product characteristics to inform decisions made with individual patients. The Guideline consists of a number of parts: DVT Patient Pathway DVT patient pathway informed by NICE guidance Rivaroxaban for DVT Treatment Prescribing information DVT Investigation & Treatment Proform 0908_v7

DVT PATHWAY for GP s in East Lancs. Patient with suspected DVT presents to Healthcare Professional Full History (including provocation factors) clinical assessment and 2 level Wells Score Low and Medium probability WELLS 0- High probability WELLS 2 or more Take blood sample for Quantitative D Dimer and arrange follow-up appointment on the next working day Take blood sample for Quantitative D Dimer and refer for ultrasound scan. Negative Positive- Assess the patient and commence on Rivaroxaban 5mg bd if appropriate* See counselling below. Give alert card. If a proximal leg vein ultrasound scan cannot be carried out within 4 hours of being requested give an interim dose of anticoagulant Assess the patient and commence on Rivaroxaban 5mg bd if appropriate* See counselling below. Give alert card. Refer for Doppler Scan Positive USS Negative USS Unprovoked DVT Refer to NICE Clinical Guideline www.nice.org.uk Negative DVT unlikely Stop Treatment Counselling Checklist for Rivaroxaban. Patient alert card go through each point, -Dose and duration of treatment -Possible side effects and what to do -Impact on dental treatment -Advice on planning pregnancy or becoming pregnant -Effect on sports and travel -When and how to seek medical help 2. Importance of compliance 3. Non-reversibility of rivaroxaban and bleeding risk 4. Missed dose advice 5. Avoid OTC aspirin/ibuprofen where possible 6. Take with food 7. Need to request GP to arrange further supply 8. Expect dose change from 5mg twice daily to Positive Continue Rivaroxaban based on dosing below Continue Rivaroxaban at appropriate dose see dosing footnote Ileofemoral DVT Refer to vascular services. NB. If bloods miss afternoon pick-up refer to Emergency Dept or Urgent Care DVT unlikely Stop Treatment. If D-Dimer positive and ultrasound scan negative Repeat scan in 6-8 days. Rivaroxaban Dosing 5mg bd review 2 days Then 20mg od for 3 months In patients with moderate (creatinine clearance 30-49 ml/min) or severe (creatinine clearance 5-29 ml/min) renal impairment A reduction of the dose from 20 mg once daily to 5 mg once daily should be considered if the patient's assessed risk for bleeding outweighs the risk for recurrent DVT and PE. The recommendation for the use of 5 mg is based on PK modelling and has not been studied in this clinical setting [NB. Issue 4 tablets as in interim dose] *If Rivaroxaban is contraindicated or clinically unsuitable then refer to Emergency Dep or Urgent Care

Notes - All patients presenting with VTE should have a full clinical history and examination undertaken with the aim of detecting underlying conditions contributing to the development of thrombosis and assessing suitability for antithrombotic therapy - Unselective screening for cancer in patients with DVT is not recommended - Patients who have a negative or inadequate initial scan but who have a persisting clinical suspicion of DVT or whose symptoms do not settle should have a repeat ultrasound scan - After deep vein thrombosis affecting a lower limb, the use of well fitted below-knee graduated elastic compression stockings for two years should be encouraged to reduce the risk of post-phlebitic syndrome INDICATIONS for Rivaroxaban covered by this document: Treatment of DVT and prevention of recurrent DVT and pulmonary embolism (PE) following an acute DVT in adults. Rivaroxaban (Xarelto ) patient alert card and patient information The prescriber must provide a patient alert card to each patient prescribed rivaroxaban (Xarelto ) 5mg or 20mg (contained within the patient booklet A Patient s Guide to Deep Vein Thrombosis Treatment available from the manufacturer or CCG). The patient alert card will inform treating physicians and dentists about the patient s anticoagulation treatment and will contain emergency contact information. Please instruct patients to carry the patient alert card with them at all times and present it to every health care provider. Counselling checklist Patient alert card go through each point, keep at hand dose & duration of treatment possible side effects and what to do impact on dental treatment advice on planning pregnancy or become pregnant affect on sports and travel when and how to seek medical help Importance of compliance Non-reversibility of rivaroxaban & bleeding risk Missed dose advice DVT DOSING RECOMMENDATIONS WEEK TO 3 - Initially treat with 5mg twice daily with food for the first three weeks. WEEK 4 ONWARDS - The initial treatment is followed by 20mg once daily with food for another 3 months (3 x 28 tablets of 20mg). (See separate dose adjustment advice for renal impairment on page 5) Duration of treatment 3 months treatment - Confirmed proximal DVT continue the maintenance dose of rivaroxaban for 3 months. Short-term treatment (3 months) is recommended for those with transient risk factors such as recent surgery and trauma. After 3 months treatment at maintenance dose, assess the risks and benefits of continuing treatment. Unprovoked proximal DVT - Consider extending beyond 3 months if their risk of VTE recurrence is high and there is no additional risk of major bleeding. Discuss with the patient the benefits and risks of extending their treatment.

Longer duration of treatment - Consider longer treatment for permanent risk factors or idiopathic (unprovoked) deep vein thrombosis if their risk of VTE recurrence is high and there is no additional risk of major bleeding. Discuss with the patient the benefits and risks of extending their treatment. Seek advice from haematology if unsure. General risk factors for VTE recurrence Thrombophilia History/family history of VTE Pregnancy/recent childbirth Bedridden > 3days Age > 60 years Recent surgery in last 4 wks IV drug user Smoker Obesity Travel >4hrs in last 5 wks HRT or oral contraception Cancer Acute medical illness Patients with renal impairment Normal or mild renal impairment egfr >50 ml/min/.73m 2 Moderate to severe renal impairment egfr 5 49 ml/min/.73m 2 Day - 2 Day 22 and onwards Day - 2 Day 22 and onwards 5 mg twice daily for 3 weeks then 20 mg once daily for 3 months (3 x 28 days) 5 mg twice daily for 3 weeks then 20 mg once daily for 3 months (3 x 28 days). A reduction of dose to 5mg once daily should be considered if assessed risk of bleeding outweighs risk of recurrent DVT and PE. Renal impairment egfr <5 ml/min/.73m 2 Not recommended Patients with renal impairment are at a higher risk of haemorrhage. Rivaroxaban (Xarelto ) should also be used with caution in patients with renal impairment taking concomitant potent inhibitors of CYP3A4 (e.g. systemic azole- antimycotics (such as ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (e.g. ritonavir), or dronaderone. INITIATION OF RIVAROXABAN WHILST AWAITING A SCAN/QUANTITATIVE D-DIMER RESULTS DVT is likely - For those patients in whom the diagnosis of a DVT is likely based on the two-level Wells score, and for whom a proximal leg vein ultrasound scan is not available within 4 hours, week (4 x 5mg tablets) treatment with rivaroxaban should be initiated (as well as performing a D- dimer test). For those patients in whom the diagnosis of a DVT is likely based on the two-level Wells score, and for whom a proximal leg vein ultrasound scan is available within 4 hours, a prescription for week (4 x 5mg tablets) treatment with Rivaroxaban should be issued with instructions only to have dispensed and start treatment if the scan is positive. GP communication with the patient must be within the same day. Check renal function. Remember to stop treatment if the diagnosis of DVT is disproved. DVT is unlikely - For those patients in whom the diagnosis of a DVT is unlikely based on the two-level Wells score, and for whom a proximal leg vein ultrasound scan is not available within 4 hours, but a D-dimer test is positive, week (4 x5mg tablets) treatment with rivaroxaban should be initiated. For those patients in whom the diagnosis of a DVT is unlikely based on the two-level Wells score, and for whom a proximal leg vein ultrasound scan is available within 4 hours, but a D-dimer test is

positive, a prescription for week (4 x5mg tablets) treatment with Rivaroxaban should be issued with instructions only to have dispensed and start treatment if the scan is positive. GP communication with the patient must be within the same day. Check renal function. Remember to stop treatment if the diagnosis of DVT is disproved. Missed dose Twice daily treatment period (5mg twice a day for the first three weeks): If a dose is missed, the patient should take rivaroxaban (Xarelto) immediately to ensure intake of 30mg rivaroxaban (Xarelto ) per day. Continue with the regular 5mg twice daily intake on the following day. Once daily treatment period (beyond three weeks): If a dose is missed, the patient should take rivaroxaban (Xarelto ) immediately and continue on the following day with the once daily intake as recommended. The dose should not be doubled within the same day to make up for a missed dose. REVIEW OF PATIENTS Once a diagnosis of DVT is confirmed patients should be reviewed near the end of their 3 month treatment duration. For those patients who continue onto longer durations of treatment, they should be reviewed at least every 3-6 months, depending on the individual clinical circumstances.

A. Patient information Name Address GP DOB NHS No. Tel B. Pre-test probability of DVT Two level Wells Score D. Suitable for primary care management with rivaroxaban? Clinical feature Points Active cancer in last 6/2 Paralysis, paresis or recent leg plaster Recently bedridden for 3/7 or more, or major surgery within 4/52 Tenderness along the distribution of the deep venous system Entire leg (calf and thigh) swollen Calf swelling 3 cm larger than asymptomatic side Pitting oedema confined to/worse in the symptomatic leg Collateral superficial veins (non- varicose) Previously documented DVT An alternative diagnosis is at least as -2 likely as DVT Total score =.. Clinical feature YES proceed to consider treatment NO - due to one or more of the following reasons (or another reason) REFER TO SECONDARY CARE IMMEDIATELY Pregnancy or breastfeeding/post-partum Age <8 years Currently on warfarin or low molecular weight heparin (LMWH e.g. tinzaparin) Symptoms of PE Potential bleeding lesions e.g. GI ulcers, GU, pulmonary, intracranial/spinal or GI bleed <4/52 ago, varices, CNS vascular abnormalities, aneurysm, trauma/surgery, vascular retinopathy, bronchiectasis (not exclusive list) Hepatic disease associated with coagulopathy Congenital or acquired bleeding disorders Tick DVT likely 2 points or more Systolic BP >80 or diastolic BP >5 DVT unlikely point or less Active cancer within 6 months (refer for LMWH consideration e.g. tinzaparin) Anticipated compliance problems even with support (e.g. mental illness or alcohol/drug misuse) C. Blood taken sample for quantitative D Dimer Yes/No Severe renal impairment (CKD stage 5) egfr <5 ml/min/.73 m 2 Azole antifungals (e.g. fluconazole, itraconazole etc.) or HIV protease inhibitor or dronaderone

E. Treating venous thromboembolism (VTE) Rivaroxaban dosing: Renal function Day Dosing schedule Normal or mild renal impairment egfr >50 ml/min/.73m 2 Day - 2 Day 22 and onwards 5 mg twice daily for 3 weeks then 20 mg once daily for 3 months (3 x 28 days) Moderate to severe renal impairment egfr 5 49 ml/min/.73m 2 Day - 2 Day 22 and onwards 5 mg twice daily for 3 weeks then 20 mg once daily for 3 months (3 x 28 days). A reduction of dose to 5mg once daily should be considered if assessed risk of bleeding outweighs risk of recurrent DVT and PE. Renal impairment egfr <5 ml/min/.73m 2 Not recommended Advice: Missed dose during day 2, two 5 mg tablets may be taken at once (max 30mg/day) F. Duration of treatment 3 months treatment - Confirmed proximal DVT continue the maintenance dose of rivaroxaban for 3 months. Short-term treatment (3 months) is recommended for those with transient risk factors such as recent surgery and trauma. After 3 months treatment at maintenance dose, assess the risks and benefits of continuing treatment. Longer duration of treatment - Consider longer treatment for permanent risk factors or idiopathic (unprovoked) deep vein thrombosis if their risk of VTE recurrence is high and there is no additional risk of major bleeding. Discuss with the patient the benefits and risks of extending their treatment. Seek advice from haematology if unsure. Experience with rivaroxaban in this indication for more than 2 months is limited. Duration.. General risk factors for VTE recurrence for reference Thrombophilia Age > 60 years Obesity History/family history of VTE Recent surgery in last 4 wks Travel >4hrs in last 5 wks Smoker Oral contraception IV drug user Bedridden > 3 days Pregnancy / recent childbirth HRT Acute medical illness Cancer G. Mechanical prophylaxis Proximal deep vein thrombosis Offer below-knee graduated compression stockings with an ankle pressure greater than 23 mmhg (Class 3 stockings, or class 2 stockings if these are poorly tolerated) to patients with proximal DVT a week after diagnosis or when swelling is reduced sufficiently and if there are no contraindications and:

Advise patients to continue wearing the stockings for at least 2 years Ensure that the stockings are replaced two or three times per year or according to the manufacturer's instructions Advise patients that the stockings need to be worn only on the affected leg or legs. H. Results & Observations Scan Results Date Result Date of first scan No DVT Confirmed DVT Date of repeat scan (if applicable) No DVT Confirmed DVT

DVT Pathway Primary Care - July 207 POPULATIONS POTENTIALLY AT HIGHER RISK OF BLEEDING Any unexplained fall in haemoglobin or blood pressure should lead to a search for a bleeding site. Several sub- groups of patients are at increased risk of bleeding and should be carefully monitored for signs and symptoms of bleeding complications: Patients with hepatic impairment: Rivaroxaban (Xarelto ) is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients with Child Pugh B and C. Patients concomitantly receiving other medicinal products: - Use of rivaroxaban (Xarelto ) is not recommended with systemic azole-antimycotics (such as ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (e.g. ritonavir), or dronaderone. Take care with drugs affecting haemostasis such as NSAIDs, acetylsalicylic acid, platelet aggregation inhibitors or other antithrombotic agents. Consider GI prophylaxis with a daily proton pump inhibitor (PPI), especially in those on drugs affecting haemostasis, older persons and/or those with additional risk factors. Patients with other haemorrhagic risk factors such as: - uncontrolled severe arterial hypertension (locally defined as systolic BP >80 or diastolic BP >5) - active ulcerative gastrointestinal disease - recent gastrointestinal ulcerations - vascular retinopathy - recent intracranial/intracerebral or genitourinary haemorrhage - intraspinal or intracerebral vascular abnormalities - recent brain, spinal or ophthalmological surgery - bronchiectasis or history of pulmonary bleeding - congenital or acquired bleeding disorders. PREGNANCY/BREASTFEEDING Rivaroxaban (Xarelto ) is contraindicated during pregnancy and breastfeeding. Women of child-bearing potential should avoid becoming pregnant during treatment with Rivaroxaban (Xarelto ). PERIOPERATIVE MANAGEMENT If an invasive procedure or surgical intervention is required, rivaroxaban (Xarelto ) should be stopped at least 24 hours before the intervention, if possible and based on the clinical judgement of the physician. If the procedure cannot be delayed the increased risk of bleeding due to rivaroxaban (Xarelto ) should be assessed against the urgency of the intervention. Rivaroxaban (Xarelto ) should be restarted as soon as possible after the invasive procedure or surgical intervention provided the clinical situation allows and adequate haemostasis has been established. OVERDOSE Due to limited absorption a ceiling effect with no further increase in average plasma exposure is expected at supratherapeutic doses of 50mg rivaroxaban (Xarelto ) and above. The use of activated charcoal to reduce absorption in case of overdose may be considered. HOW TO MANAGE BLEEDING COMPLICATIONS There is currently very limited clinical experience with the use of products in individuals to reverse the effects of rivaroxaban (Xarelto ). Should bleeding complications arise in a patient receiving rivaroxaban (Xarelto ), the next rivaroxaban (Xarelto ) administration should be delayed or treatment discontinued as appropriate. Individualised bleeding management may include: Symptomatic treatment, such as mechanical compression, surgical intervention, fluid replacement Haemodynamic support; blood product or component transfusion For life-threatening bleeding that cannot be controlled with the above measures, administration of a specific procoagulant reversal agent should be considered, such as prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (APCC) or recombinant factor VIIa (r-fviia). Due to the high plasma protein binding rivaroxaban (Xarelto ) is not expected to be dialysable. REPORTING SUSPECTED ADVERSE REACTIONS Rivaroxaban (Xarelto ) is a black triangle drug and all suspected reactions (including those not considered to be serious) should be reported through the Yellow Card Scheme. 9