1. SAFE AND EFFECTIVE PRESCRIBING - 2 Safe prescribing a case study and Anticoagulation key messages Dr Ian Coombes, Senior Clinical Lecturer University of Queensland Schools of Medicine and Pharmacy Safe Medication Practice Unit, Queensland Health Dr Ian Coombes, Senior Clinical Lecturer University of Queensland Schools of Medicine and Pharmacy Safe Medication Practice Unit, Queensland Health The University of Queensland

2. Session Objectives (week 2)  At the end of these tutorials students should have:  An increased awareness of common prescribing error traps  Enable students to apply key principles of safe prescribing  Facilitate students writing regular in hospital prescription  Understand key points for safe prescribing of anticoagulants

3. To recap – why interns make mistakes

4. How a patient with documented ADR to cephalosporin received two more doses {From Reason’s Swiss Cheese Model} Verbal order by Surgeon for antibiotic in OT Transcribed by Registrar to medical notes/record Phone call – Nurse to ward call dr (outlier) Prescribed by Dr (1 st term junior) Prepared by Nurse 1 (busy) Check Nurse 2 (agency) Patient (asleep) Given by RN Severe anaphylaxis, dialysis, steroids, antihistamines

5. Re-exposure to Cephalosporin  Patient Factors  Sedated, post op  Task Factors  Writing a prescription some one else ordered  Practitioner Factors  Hungry, tired, late, inexperienced, ill-informed  Team Factors  What team? – Outlied patient, ward call doctor  Workplace Factors  Medicine charts – ADRs/Allergies on front of chart – order on inside  Organisation Factors  Did not invest in safety systems or training for safe prescribing  Patient Factors  ADR/ alert bracelets  Task Factors  Reduce delegation of tasks  Practitioner Factors  Drs hours + training + support  Team Factors  Safe prescribing – lead by consultants  Workplace Factors  Medicine charts – ADR on chart where prescribing + administration  Organisation Factors  Acknowledge and Invested in safety + system change + education

6. So What is a Prescribing?

7. The Prescribing process Patient Coombes I, PhD 7 Mainly Snr doctors Mainly Jnr Doctors And or nursing staff

8. Key stage of prescribing for junior doctors is… COMMUNICATING information about:  drug  form  route  dose  frequency  administration time/s  administration of IV meds  duration of therapy in a CLEAR, UNDERSTANDABLE form to:  other doctors  nurses  pharmacy staff

9. Case Study – Mr AD  68 y.o. 60 kg ♂ presents to ED  PC: SOB pyrexial and sputum  HoPC: 2/52 increased, cough, sputum, fever 7 days of amoxycillin from local (private Dr) no response  Exam: BP 110/70; HR 90; RR 19, bi-basal chest crackles  Creatinine, urea other E, LFTs Normal  PMH: RA (10 yrs); HT (20 yrs),  Dx: URTI  Social Hx: lives alone  ADR: Erythromycin – severe Hives, rash – 2005

10.  68 y.o. 60 kg ♂ presents to ED  PC: SOB pyrexial and sputum  HoPC: 2/52 increased, cough, sputum, fever 7 days of amoxycillin from local (private Dr) no response  Exam: BP 110/70; HR 90; RR 19, bi-basal chest crackles  Creatinine, urea other E, LFTs Normal  PMH: RA (10 yrs); HT (20 yrs),  Dx: URTI  Social Hx: lives alone  ADR: Erythromycin – severe Hives, rash – 2005 Your Registrar asks you to write up Mr AD’s drug chart (DOB: 01/4/40; UR:155566; date: today; ward: medical)  Captopril oral 25mg BD  Diltiazem SR oral 240mg mane  Methotrexate oral 10 mg weekly on Sunday morning  Co-amoxiclav oral1 TDS  Clarithromycin oral 500mg BD

11. Write up the medicines the person should have Pass to the Person Next to You

12. Is Everything OK? Imagine you are a junior nurse at 8 a.m. on Friday  Name - care with “sound alikes” -Piroxicam + Proscar (trade)  Drug Form – immediate vs sustained release -e.g. Diltiazem sustained release vs standard  Combinations – Co-amoxiclav – contains penicillin  Strengths - if unsure,(1 tablet) make a clinical decision  Route - oral, IV, IM, SC, IT – can they take it?  Dose - multiple/partial tablets & decimal points -e.g. digoxin 62.5 micrograms, 5.0 units insulin  Frequency - explicit standard terms – NB: weekly medication (cross out unnecessary days)  Times to be entered by doctor when prescribing?

13. ADR – Erythromycin = Hives  Marks: Patient name = 5 marks  All drug names – clear = 4 marks  All routes – clear = 4 marks  All doses + frequencies = 4 marks  SR form of Diltiazem = 4 marks (no SR = -4!)  Weekly methotrexate – block out = 10 marks (Did not block out -10 mark  Did not prescribe Clarithromycin = 10 marks, (DID prescribe = -20 mark

14. ADRs  Class effects (macrolide antibiotics) :common trap  BEWARE trade names and combination drugs  Document all relevant ADR details on chart BEFORE prescribing!  ADR details in medical chart/notes as well  Ask patient, carer, previous notes  Check with patient and chart and front of medical record file BEFORE prescribing

15. Sustained release drugs What if the patient gets 4 x 60 mg tablets ?

16. Hypotensive = bradycardic

17. Weekly medicines  Medicines to be taken once a week:  Ie Methotrexate for arthiritis  Alendronate for osteoporosis  Significant risk that your order may be misinterpreted by nursing staff and patient may receive daily = pancytopenia

18. Ceasing Medications Prevent transcription errors but still legible for records Physically block further administration Sign and Date, State reason for ceasing

19. Reducing the risk of adverse events  Always  include a detailed drug history in the consultation  Only  use drug treatment when there is a clear indication  Stop  drugs that are no longer necessary  Check  dose and response, especially in the young, elderly and those with renal, hepatic or cardiac disease

20. Medication Assessment/ Review Does the patient need this drug ? Is this drug the most effective and safe ? Is this dosage the most effective and safe ? If side effects are unavoidable does the patient need additional drug therapy for these side effects? Will drug administration impair safety or efficacy ? Are there any drug interactions ? Will the patient comply with prescribed regimen ?

21. Summary  Accidents happen everywhere  The best people make mistakes  Same “simple” mistake - different consequences  Everyone is responsible for patient safety  Writing an order is as important as making the decision what to prescribe  If in doubt check!

22. Anticoagulants - Objectives  Anticoagulation Why, where, when and when NOT to!  Heparins Low Molecular Weight Heparin (LMWH) Standard Unfractionated Heparin Heparinoids (eg danaparoid)  Warfarin  Anticoagulation and Surgery  Reversal

23. Anticoagulation: The classic balance between risk and benefit of medication The margin for error is relatively small

24. Past Incidents  “Most frequent cause of preventable drug related harm” (Quality in Australian Health Care Study)  Inadequate anticoagulation and emboli  Warfarin omission on discharge – embolic events  Out-of-hours dosing - bleeds  Drug interactions resulting in enhanced (eg bleeds) or inadequate effects  LMWH dosing and bleeds

25.  Anticoagulation  Indications?

26. Primary prevention: Atrial Fibrillation (AF), left ventricular dilatation, mural thrombus DVT/PE in hospitalised patients (medical and surgical) Secondary prevention: Thromboembolic events (DVT, PE) Acute coronary syndrome (ACS) Peripheral vascular disease (PVD) Post CVA; AF Adjunctive treatment: Myocardial infarction (MI) Indications for anticoagulation?

27.  Anticoagulation   Contraindications?

28. Contraindications to Anticoagulation?  Bleeding disorders, including haemophilia  Uncontrolled active bleeding  Major trauma or recent surgery  Thrombocytopenia (including HITTS)*  Cerebral haemorrhage  Peptic ulcer  Severe uncontrolled hypertension  Severe hepatic disease  Bacterial endocarditis  *heparin/LMWH contraindicated

29. Anticoagulation ProphylaxisTreatment Initial  Mostly fractionated heparin  Occasionally unfractionated heparin  Very occasionally warfarin (eg AF) Subsequent  Mostly warfarin  Occasionally heparin if warfarin contraindicated (eg pregnancy)

30. Prophylaxis: LMWH  HIGH RISK: - 40 mg sub-cut 12 hrs pre-op, then once/day for 7-10 days or until mobilised (NB: continue up to 30/7 for total hip replacement surgery)  MODERATE RISK: - 20 mg sub-cut 2 hrs pre-op, then once/day for 7-10 days or until mobilised  MEDICAL PATIENTS: - 40 mg/day sub-cut for 6-14 days or until mobilised  PROLONGED PROPHYLAXIS (eg hip replacement): - 40 mg/day sub-cut for up to 30 days  HAEMODIALYSIS: - 0.5-1 mg/kg (via arterial line) at start of session

31. Treatment: LMWH (enoxaparin)  ESTABLISHED DVT: - 1 mg/kg BD (inpatients) - 1.5 mg/kg/day (outpatients)  High risk patients  1 mg/kg BD more beneficial - Start warfarin on the same day as heparin  Overlap with LMWH for a minimum of 5 days and until INR has been therapeutic for at least 2 consecutive days  Unstable angina & non-Q-wave MI: - 1 mg/kg BD for 2-8 days - + aspirin 100–325 mg/day

32.  Low Molecular Weight Heparin  Any benefits compared with conventional intravenous (IV) unfractionated heparin?

33. Benefits of LMWH  Predictable dosing  Must weigh the patient or calculate LBW  No monitoring of APTT required  Can treat in the community as outpatient  No pump required

34.  Low Molecular Weight Heparin  Risks?

35. LMWH – No Panacea!  7% of QH high risk incidents related to enoxaparin!  Sub-cut vs IV  not seen as “special” drug  Inaccurately promoted as “safe” alternative to heparin because it “doesn’t need monitoring”

36. Risks of LMWH RisksAction

37. Risks of LMWH RisksAction Must know weight Must know baseline renal function (CrCl) Care with dose timing eg peri-procedural Reversal can be difficult

38. LMWH and Renal Impairment  AVOID if possible!  Dose adjustment if CrCl < 30 mL/min - Prophylaxis: 20mg once daily - Treatment: 1mg/kg once daily

39. Low Molecular Weight Heparin RisksAction Must know weight lean body weight (max 100kg and min 40kg) Must know baseline renal function (CrCl) < 30mL/min = use IV heparin and monitor APTT Care with dose timing eg peri-procedural t ½ = 12 hrs (care with upcoming surgery or starting post-op) Reversal can be difficultpartially reversed with protamine

40. Case Study I  67 y.o. ♂  Mr AD - UR: 123 456 - DOB: 25/02/41 - 32 Pharmy Lane, Drugsville  Admitted 5 days ago - SOB, PND  PMHx: - IHD; AMI ’98; HF; T2DM; HT; RA  Dx - Worsening heart failure, 2 o to NSAID and sub-optimal therapy  Weight: 70 kg  Creatinine: 180 micromol/L (normally 120)  Observations - HR 75 - BP 145/90  ADR - penicillin (angioedema? 1999)

41. Prescribing Anticoagulation  Patient develops DVT  No thrombophilia found  Ward round decision: –Start heparin – how and what? –has renal impairment – CrCL = 30mL/min –Iv heparin with aptt monitoring

42. Heparin Reversal  Protamine combines with heparin to form a stable, inactive complex  1mg protamine neutralises 100 units heparin if given within 15 min of heparin  At  risk of allergic reaction to protamine: - Patients having undergone procedures where protamine used, e.g. coronary angioplasty, cardiopulmonary bypass - Diabetics treated with protamine insulin - Patients allergic to fish - Vasectomised or infertile men (may have antibodies to protamine)

43. IV unfractionated heparin Key Messages  IV indications: - ACS or in place of warfarin maintenance e.g. if patient having surgery and warfarin stopped - Surgery e.g. Neuro/vascular surgery - PE/ DVT (as an alternative to LMWH)  Organise baseline APTT and full blood count  Check if patient recently prescribed/administered - enoxaparin / LMWH - fibrinolytic agent (thrombolysis) - warfarin and antithrombotics  Weight adjusted bolus and initial rate of infusion based on indication  For monitoring, use nomogram (based on indications)  Significant inter-patient variability

44. Task: Initiating Warfarin  Assess individual benefit vs risk - Consider age, weight, other Rx, indication, duration, co-morbidities….  Baseline INR to exclude coagulopathy  Start on first day of heparin therapy  Overlap warfarin with full heparin dose - For a minimum of five (5) days and - INR therapeutic for at least two (2) consecutive days

45.  Target INR – documented?  Indication specified  Duration of treatment  Daily INRs initially – subsequent monitoring  Consider drug interactions  Patient education imperative  Warfarin guidelines available for PDA Warfarin - Key Messages http://qheps.health.qld.gov.au/qhmms/docs/wafarin_guidelines_pda.pdf

46. Risks of Warfarin  INR > 4 ≈ 10 x bleeding risk vs INR 2–3  Bleeds associated with time INR > target  Some patients will bleed INR < 2  Associated risks: - Anti-platelet therapy - Change in any medication - Falls - Surgery - Lack of monitoring - Any illness

47. Guidelines  Risk factors for increased sensitivity to warfarin - Interacting rx - Hx bleeding - Baseline INR > 1.4  Starting nomogram  Target INR ranges  Minimum durations  Warfarin management peri-operatively  Warfarin reversal  Warfarin drug interactions

48. Case Study II  69 y.o. ♂ patient with Ca. prostate + Hx COPD  Admitted with bleeding peptic ulcer  Recent chest infection managed by GP  U&E / LFTs – NAD  Regular Rx (as per discharge 4/12 ago): - Marevan ® (warfarin) 2 x 1mg daily (long term for recurrent DVTs)  INR 5.8 (usually stable at 2-2.5, checked monthly) - MS Contin ® (morphine controlled release) 30mg BD - Flixotide ® (fluticasone) MDI, 1 puff BD - Ventolin ® (salbutamol) MDI 1-2 Q4-6hrs PRN  What is going on?

49. Key Messages  INR may increase or decrease for many reasons, for example: - Poor concordance/compliance - Changes to medications  Drug interactions  Addition/removal of medicine  Change in dose

50. Case Study II Cont…  GP had started roxithromycin (Rulide ® ) 300mg/day for 10 days  GP concerned with the potential interaction, i.e. inhibition of warfarin metabolism, so he checked INR day 2 post roxithromycin initiation: - INR  2.5  Effect delayed by ≈ 72 hours  NOT detected by day 2 INR! NB Augmentin ® (amoxycillin + clavulanate) will also potentially raise INR

51. Warfarin and Surgery  Depends on patient and risk:  Low risk (uncomplicated AF) - Stop 4-5 days prior - Check INR day of procedure - Re-start USUAL dose ASAP - Employ thrombo-prophylaxis as per hospital policy  High risk – SEEK ADVICE - Cease warfarin 4-5 days prior - 2-3 days before surgery, commence treatment dose of IV heparin or LMWH subcutaneously - Re-start USUAL dose ASAP (cover with a heparin) - Cease heparin (IV heparin or LMWH) 48 hours after the target INR is reached

52. WARFARIN REVERSAL (end of bed chart) INR > therapeutic range but < 5 and NO bleeding withhold review INR and dose INR 5 – 9 and NO bleedingwithhold give vitamin K, 1-2mg orally (0.5-1mg IV) review INR and dose INR > 9 and NO bleeding Low risk of bleed withhold give vitamin K up to 5mg orally (0.5-1mg IV) review INR and dose High risk of bleed withhold give vitamin K 1mg IV consider Prothrombinex™-HT, FFP review INR and dose Any clinically significant bleeding where warfarin- induced coagulopathy considered a contributing factor SEEK SENIOR ADVICE cease warfarin give vitamin K 5-10mg IV Prothrombinex™-HT, FFP review INR frequently < 5 and bleeding stops

53. Key Messages  Anticoagulation - Most frequent high risk drugs you will prescribe  Assess risks and benefits  enoxaparin - no panacea - Need to know renal function, weight, timing  Prescribing can not be too explicit  If in doubt, ASK!  Information available includes - Guidelines for anticoagulation using warfarin (end of bed) - Heparin Intravenous Infusion Order & Administration Form - Your friendly pharmacist!