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Not 4 Me

Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca. Not 4 Me. Handouts provided, as there is always some tall person that decides to sit in the front!. 3 rd ANNUAL EDUCATION DAY Morgan Creek Golf Club, Surrey Saturday November 3rd, 2012 12:35 – 13:25.

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Not 4 Me

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  1. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Not 4 Me Handouts provided, as there is always some tall person that decides to sit in the front! 3rd ANNUAL EDUCATION DAY Morgan Creek Golf Club, Surrey Saturday November 3rd, 201212:35 – 13:25 BRUCE KENNEDY BSc.(Pharm.) M.B.A. Clinical Pharmacy Specialist – Palliative Care Bruce.Kennedy@fraserhealth.ca

  2. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca T3 Composition Codeine 30 mg Caffeine 15 mg Acetaminophen 300 mg Brands: Tylenol No. 3 Generics: Novo-gesic C30, Acet 30 (PMS), Ratio-Lenoltec No 3 Atasol 30 (often used in hospital) is similar, but slightly different; - has same codeine content 30 mg, - has extra acetaminophen content 325 mg, - has 30 mg caffeine citrate (but this provides same net caffeine of 15 mg as the others)

  3. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Ibuprofen 400 mg when studied in 5456 patients had a NNT of 2.5 ! (in moderate to severe pain. Versus Placebo, pain relief over 4 to 6 hours Terrible NNT Codeine 60 mg NNT = 16.7 Lower confidence level 11, higher 48 i.e. “at best 1 in 11, at worst 1 in 48” get 50% pain relief In 1305 pts studied only 15% have 50% pain reduction* Worst analgesic on Oxford chart* Some studies - no better than placebo** Acute Pain Systematic Reviews*** Addition of 60 mg codeine to acetaminophen added but 5 to 12% additional benefit NNT is Number Needed to Treat(for 1 in the group to get 50% pain relief) When codeine was studied in 1305 patients – only 196 or 15% received a 50% reduction in their pain !! (Oxford League Table – checked Oct 30, 2012) *Oxford League Table of Analgesic Efficacy 2007– Number Needed to Treat (NNT) http://www.medicine.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/lftab.html ** J Clin Pharmacol 1984;24:96-102 An appraisal of codeine as an analgesic single-dose analysis, Br. J Anesthesia 2002 94(6):710-14 Predicting postop analgesia outcomes: NNT league tables or procedure-specific evidence? ***Pain 1997 Paracetamol with and without codeine in acute pain: a quantitative systematic review, BMJ 1996 Analgesic efficacy and safety of paracetamol-codeine combination versus paracetamol alone:a systematic review

  4. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine needs conversion to be an effective analgesic http://www.pharmgkb.org/images/pathway/codeineMorphine-pk.png

  5. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Yet Same Occurrence of Adverse Effects 170 mg codeine doses 18 patients: 9 Poor Metabolizers (PM), 9 Extensive Metabolizers (EM) No differences in adverse effects, but PM’s – only 0.17% morphine conversion (and no pain benefit) versus EM’s – 3.9% conversion into morphine 23 X difference ! Pain 1998 76:27-33 Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation

  6. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca When you age… CYP450 activity very low at birth CYP2D6 less than 1% activity in very young CYP2D6 still less than 25% when < 5 years old So then changes your 2D6 capability 2008 Australian Prescriber June 31(3):63-5 Pediatric analgesia

  7. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine pediatric use;impactful Canadian deaths Newborn Breastfeeding case – Aug 2006 Mom took codeine 60 mg + 1000 mg acetaminophen q12h x 2 days then 30 mg and 500 mg q12h x 14 more days Mom ultra rapid metabolizer, infant EM Two year old adenotonsillectomy – Aug 2009 Healthy 13 Kg, Hx snoring, sleep apnea Codeine 10 - 12.5 mg q4-6h. Died 9 am Post-op Day 3 Ultrarapid metabolism-> morphine toxicity Four year old tonsillectomy - reported April 2012 Died at home after only 4 age-appropriate doses of 8 mg The 2012 article also describes one death of a 5 year old boy in the US, and a near miss in Canada 2006 Lancet 368:704 Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. 2007 Canadian Family Physician Jan;53:33-5 Safety of codeine during breastfeeding 2009 NEJM 361:8 Aug 20 Codeine, ultrarapid-metabolism genotype and post operative death 2012 Pediatrics More codeine fatalities after tonsillectomy in North American children 129:e1-e5

  8. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Another pediatric case report 3 yr old admitted to ER with mom with cough/fever Taking long acting cough mixture with codeine, acetaminophen, ibuprofen, ivy extract x 6 days 2 & ½ hours later father finds twin brother dead in bed. (massive aspiration of gastric contents, diffuse cerebral edema) Misdosing 10 drops, not 0.5 mL using dosing spoon Each drop dose could vary from 12 to 23 mg codeine (instead of intended daily codeine dose of 10 mg) Both twins were ultrarapid metabolizers->morphine toxicity Surviving twin ventilated x 3 days, had severe hypotension 2009 Eur J Pediatr 168:819-824 Drug dosing error – severe clinical course of codeine intoxictation in twins 2009 Int J Legal Med 123:387-94 Fatal and severe codeine intoxication in 3 year old twins – interpretation of drug and metabolite concentrations

  9. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine’s routine use is not recommended in children Removed from Toronto’s Hospital for Sick Children’s formulary UK commission for Human Medicines says not suitable to use OTC codeine medicines in children under 18 years of age Canadian physicians calling for halt to use; UBC Ob Gyn MD Dr Peter von Dadelszen wants T3 banned Globe & Mail Aug 22, 2008, Mar 31, 2009 CMAJ 2010 article – is it time to phase out codeine? Vancouver pediatrician Dr Noni MacDonald Dr Stuart MacLeod CMAJ section editor, Public Health • FH May 4, 2012(- was a rather weak response – and merely a “be aware” type of direction)Good Afternoon All, • You have most likely heard of this matter through other means, however I wish to take this opportunity to alert you to the impact these recent reports may have on practice in Fraser Health. • The main concern is that there may be Pre-Printed Orders (PPOs) which promote the use of codeine for children.  Until policy decisions are made regarding codeine use in children, there are several interim actions that can be taken to mitigate the risk: •  Check pediatric/obstetric practice areas to identify and revise obstetric and post tonsillectomy PPO’s following guidelines in attached memo •  Identify and revise other at-risk PPOs • The codeine risk among the general pediatric population is controversial however, the programs should review and determine the most appropriate course of action for the general pediatric population. • C    Collaboration between Program and Pediatric Clinical Pharmacy Specialists (CPS) is paramount to ensure that areas which have at risk PPOs can be identified and revised. • Please  share this information through your program clinicians to ensure that the PPO review and revisions occur as soon as possible. • If you have any questions, please feel free to contact me. • Thank you, •  Janice  • Janice Munroe BSc.Pharm.Fraser Health Medication Safety CoordinatorLower Mainland Pharmacy Services 2010 Oct 4th UK Medicines and Healthcare products Regulatory Agency OTC cough syrupshttp://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con096756.pdf 2010 Nov 23 Cdn Medical Assn Journal Has the time come to phase out codeine? p1825

  10. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Ceiling effect T3: 3 ingredients, 3 ceiling’seach likely different depending on individual’s tolerance and pain Acetaminophen maximum 4 g/day (or less ~2.5 g-some patients) Codeine maximum Max dose: 240* to 800 mg/day Likely about 7 mg/kg Max single dose60* to 120 mg MAX DOSE/DAY Literature reports variable *Martindale 36th Ed 2009

  11. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca WHO Ladder – Cancer Pain Pain persisting, or increasing Step 3 Opioid for severe pain+/- Step 1 choices Step 2 Opioid for moderate pain+/- Step 1 choices Step 1 Non-opioid +/- adjuvants

  12. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca What Dr Twycross is saying now • It is perhaps practical to skip Step 2 in countries where palliative care is well established • Some pediatric PC services omitted Step 2 many years ago • No absolute pharmacological need for starting with a weak opioid before progressing to a strong opioid • Exception: Lack of access in some countries to strong opioids such as morphine Palliative Care Formulary Canadian Edition 2010 www.palliativebooks.com

  13. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine requires cautious and reduced dosing in both renal and hepatic impairment I’d say avoid completely in renal impairment, same for morphine – especially if dosing regularly Dosing adjustment in renal impairment: GFr 10-50 mL/minute: Administer 75% of dose*,** GFr <10 mL/minute: Administer 50% of dose*,** Dosing adjustment in hepatic impairment: “Probably necessary”** Reduced hepatic blood flow or enzyme dysfunction - can significantly will affect conversion rate of codeine into morphine *2007 Drug Prescribing in Renal Failure 5th Ed Aronoff GR, Bennett WM, et al **http://www.merck.com/mmpe/lexicomp/codeine.html

  14. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Prodrug Conversion Conversion delays pain relief onset Primary use of T#3 = p.r.n. dosing and is when onset of effect is important C -> M Goodman & Gillman’s The Pharmacological Basis of Therapeutics 2001 p 1946,1985

  15. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Drug Interactions - another problem 2D6 drug inhibitors impact codeine’s conversion; delays pain relief reduces max blood level reduces pain relief increases toxicity risk CYP2D6 – involved in 11 to 25% of all drugs Many common drugs Less Drugs Less Interactions

  16. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine Drug Interactions *2012 Feb Pharmacy Practice Top Rx Drugs of 2011 Cytochrome Drug Interaction Table v.5 2009 http://medicine.iupui.edu/clinpharm/ddis/

  17. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Other common drugspotentially interacting with codeine Inhibitors Amiodarone, cimetidine, chlorpheniramine, cocaine, diphenhydramine, duloxetine, fluoxetine, hydroxyzine, methotrimeprazine, methadone, metoclopramide Substrates Carvediolol, dextromethorphan, fluoxetine, fluvoxamine, haloperidol, lidocaine, metoclopramide, nortriptyline, ondansetron, propranolol, tamoxifen, tramadol Inducers Dexamethasone, rifampin And this is not a complete list. Consult pharmacist, or current drug interaction text

  18. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Life threatening codeine intoxication with drug interaction 62 yr old, lymphocyctic leukemia Dyspnea, fever, cough ER: ceftriaxone, clarithromycin,voriconazole, codeine 25 mg tid Day 4 unresponsive Ultra rapid metabolizer plussecondary codeine metabolism route inhibited by clarithromycin & voriconazole Morphine levels 20 - 80 X higher than expected NEJM 2004 351:2837-31 Codeine intoxication associated with ultra rapid CYP 2D6 metabolism Erratum NEJM 2005;352:638

  19. Apparently 1 million grams in a metric ton Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine Canada’s estimated 2012 need is 30 tons This is 5.7% of the world’s consumption For 0.49% of the world’s population Per capita we are #1 codeine consumers Is globally the most widely used narcotic • Canada’s Population: 34,781,799 • 37th largest of 229 countries • 0.49 % of world • World Population: 7,077,969,692 2010 Morphine need was but 3.5 tons The International Narcotics Control Board http://www.incb.org/incb/narcotic_drugs_reports.htmlhttp://www.xist.org/earth/population1.aspxprovides daily population figures

  20. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Canada’s Needed Opioids for 2012 Jokes: Cannabis needs for BC are likely less than the national average here in BC In fact don’t we export from here? Imagine the tax revenues if were legalized Oct 2, 2012 update: Estimated Requirements of narcotic drugs www.incb.org/incb/en/narcotic-drugs/estimates/nacotic-drugs-estimates.html

  21. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Round and Round Hydromorphone Morphine extracted Hydrocodone Codeine synthesized (Lab) Converts back to Morphine in body 95 % of global morphine is used to make codeine through a semi-synthetic manufacturing process Per http://www.incb.org/pdf/technical-reports/narcotic-drugs/2010/Narcotic_drugs_publication_2010.pdf

  22. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Genotyping Costs $$$, Unable to obtain as only available in research labs • “It might be good if physicians would know about the CYP2D6 genotype before administering codeine” Frequency of CYP2D6 phenotypes in White Populations The Pharmacogenomics Journal 2007;7:257-65 Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D62004 NEJM 351:27:2867-9 Genes and the response to drugs 2010 Oct 4 Cdn Press Consider abandoning codeine until more safety research is done www.canadianhealthcarenetwork

  23. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Genetic Variations 144 variants of 2D6 exist* Results in significant unpredictablity Unattainable to know patient’s CYP2D6 enzyme activity Drug effect, titration requires monitoring • Ultrarapid metabolizers (UM’s) • Have like dual convertor chambers (allele’s) • 30 mg codeine in a UM has same effects as 45 mg in an EM (1.5 fold increase in morphine concentration) • ~ 3% of many Caucasian populations • Up to 30 to 45 x higher codeine metabolites conc than PM’s • Good responders to codeine maybe UM’s! *www.cypalleles.ki.se The Pharmacogenomics Journal 2007;7:257-65 Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 Pharmacogenomics 2008;9(9):1267-84 Gideon Koren Pharmacogenetic insights into codeine analgesia: implications to pediatric codeine use

  24. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca If you use this slide in your presentation, mentioning the source author graciously appreciated ! Codeine (in Caucasians) Between all three of these groups it totals 46% of the Caucasian populationshould be selecting an alternative drug other than codeine ! *2011 Clinical Pharmacology & Therapeutics 89(5);May:662-673 Pharmacogenetics: from bench to byte- an update of guidelines. **1997 American J Human Genetics 60:284-5

  25. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca in Surrey?... Stats Canada 2006 Census Data2006 The Oncologist 11;126-35 Interethnic differences in genetic polymorphisms in the U.S. population: clinical implications, *Tylenol #3 Prescribing Info July14, 2008

  26. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine 6 to 12 T3/day not working Patient not identified as poor metabolizer Patient presumed to be opioid-tolerant New opioid gets started too high – converted at “equianalgesic dose” – but codeine wasn’t getting converted before False Tolerance in Poor MetabolizersToxicity with Opioid Switch

  27. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca T3 Massively (OVER) used Poor from a population based approach A combination product containing codeine makes poor sense to provide reliable pain relief, yet it’s the main Canadian prescription pain relief product T#3 (1971) released before we knew about; This 2D6 codeine enzyme non-conversion issue (1989) The WHO ladder (1986) Before T3 - using 292’s, meperidine (How good an idea was that???) Dosing, Use, Practicalities Overview

  28. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine dependency A weak opioid - yet the wide availability of over-the-counter (OTC) codeine products is impactful Now many internet resources, methods to extract morphine from OTC and Rx codeine products; Youtube.com - Cold Water Extraction (CWE) videos performing Internet bulletinboards Heroinhelper.com 2 methods to extract from OTC acetaminophen/ASA products Opiophile.org Provide methods called “Homebake” in New Zealand and Australia Sophisticated methods using several chemicals including chloroform Does support of T3 use - support T1 abuse? T3, T1 safety

  29. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Acetaminophen Combination ProductsRisk Toxicity Local SDM – Murrayville Square you will see 53 acetaminophen single ingredient products, of which only 8 were regular strength • FDA (USA) very concerned as during 1990 to 1998 - 56,000 ER room visits, 26,000 hospitalizations, 458 deaths EACH YEAR related to acetaminophen associated overdoses • From 1998 to 2003, acetaminophen was the leading cause of acute liver failure • 48% of acetaminophen-related cases associated with accidental overdose • Prescription combination products frequently used: Vicodin (acetaminophen and hydrocodone) is #1 Rx prescribed drug above all other prescription products in U.S., since 1997! http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM164897.pdf http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM170188.pdf Lee WM. The case for limiting acetaminophen-related deaths: smaller doses and unbundling the opioid-acetaminophen compounds Clinical Pharmacology & Therapeutics Sep 3, 2010 289-291

  30. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Acetaminophen Combination ProductsRisk Toxicity Reminder: Make the point about what a wimpy dose 325 mg acetaminophen is in hospital • US acetaminophen product sales: 28 billion doses • 11 billion Rx containing acetaminophen products (182 million Rx’s in 2005) • 8 billion single dose acetaminophen e.g. Tylenol – 92% is 500 mg strength • 9.7 billion combination OTC (e.g. Nyquil, Theraflu) • FDA (2009)38 member expert panel voted and advised to • Eliminate prescription acetaminophen products completely! (20 votes, 10/20 high priority) • FDA (Feb 13/11) now recommend 325 mg per dosage limit in prescription products http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM164897.pdf http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM170188.pdf Lee WM. The case for limiting acetaminophen-related deaths: smaller doses and unbundling the opioid-acetaminophen compounds Clinical Pharmacology & Therapeutics Sep 3, 2010 289-291 http://www.fda.gov/Drugs/DrugSafety/ucm239821.htm

  31. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Which product does not contain Acetaminophen? (471 do in Canada) Acetazone Actified Plus Arthritis pain extended relief Balminil Cough & Flu Benadryl Total Dayquil D Dristan ND caplets Hot Lemon relief Midol Night-Time Nyquil Sinus Liquicaps Pamprin Extra Strength Sinutab Theraflu Cold & Flu Triaminic cough & sore throat softchews 2009 = 435 2010 = 446 2012 = 471

  32. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Caffeine “Why is it there?” Regulatory fit/rules evasion- no duplicate Rx Helps headaches – 5,427,000* of them? Causes GI upset, effect on sleep Caffeine withdrawal could occur Adds unneeded drug-interaction-allergy risk, caffeine interacts with other drugs, smoking Little to no therapeutic role, esp. pain * Number of prescriptions in 2011 in Canada for acetaminophen, caffeine and codeine

  33. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca If codeine and T3 are suboptimal What should we consider instead? Relieve Pain – Help patients

  34. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Morphine 200 X stronger affinity for mu receptor than codeine It’s the most significant active component of codeine Provides predictability. No worries about the PM’s Poor (0-19*%) *South African’s EM’s Extensive (71- 100%) UM’s Ultra-rapid (0-29**%) **Ethiopian’s Why wait? Onset requires no 2D6 conversion Use a small dose – 2.5 mg PO to start Study importation of codeine into Ethiopia! The Pharmacogenomics Journal 2007;7:257-65 Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6

  35. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Hydromorphone Less histamine release risk than either codeine or morphine Codeine & morphine have a dose-related histamine releasing effect Meperidine<Codeine<Morphine<Oxycodone<Hydromorphone<Fentanyl Pharmacists Letter 2006 Opioid Intolerance Decision Algorithm Document #220201Martindale’s The Complete Drug Reference 36th Ed 2009 Codeine p 37

  36. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Oxycodone, Tramadol • Options; • however are also metabolized by the same Cytochrome P450 2D6 enzyme • Best to avoid when response to codeine suspected to be poor or excessive 2006 Progress in Neuro-Psychopharmacology & Biological Psychiatry 30:1356-58 Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer 2011 Clinical Pharmacology & Therapeutics 89(5);May:662-673 Pharmacogenetics: from bench to byte- an update of guidelines

  37. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca If you use this slide in your presentation, mentioning the source author graciously appreciated ! Oxycodone 2011 Clinical Pharmacology & Therapeutics 89(5);May:662-673 Pharmacogenetics: from bench to byte- an update of guidelines

  38. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca If you use this slide in your presentation, mentioning the source author graciously appreciated ! Tramadol 2011 Clinical Pharmacology & Therapeutics 89(5);May:662-673 Pharmacogenetics: from bench to byte- an update of guidelines

  39. Intent is short-term, but on initiation use becomes long-term • 1997-2008. Ontario seniors age 66 and older reviewed • Low-risk short stay surgeries: cataract surgery, TURP, varicose vein stripping, laparoscopic cholecystectomy 2012 Arch Intern Med(5):425-30. Long-term analgesic use after Low-Risk Surgery

  40. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Ibuprofen 400 mg when studied in 5456 patients had a NNT of 2.5 ! (in moderate to severe pain. Versus Placebo, pain relief over 4 to 6 hours http://www.medicine.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/lftab.html NSAID’s • Use short term, whenever possible • Ibuprofen 400 mg NNT is 2.5 • Could combine with acetaminophen • NNT is 1.5 to 1.6 when combining • Ibuprofen with acetaminophen • 100 mg with 250 mg, 200 mg with 500 mg or400 mg ibuprofen with 1000 mg acetaminophen • But Bandolier comments that this common possible combination poorly studied • Unfortunately! http://www.medicine.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/lftab.html Bandolier Investigating over-the-counter oral analgesics http://www.medicine.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/OTC%20analgesics1.html

  41. Reverse Ladder Concept • Consider • Timeframes • Monitoring for stepping down What goes up, must come down? 2011 Anaesth Int Care 39;804-23. Acute pain management in opioid-tolerant patients: a growing challenge http://www.medicine.ox.ac.uk/bandolier/booth/painpag/wisdom/493HJM.html http://www.painbc.ca/content/pain-bc-conference-2012-evolution-pain-management

  42. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine’s lack of effect in PM’s gets “masked” in T3Acetaminophen carries the pain relief load - so PM’s are not easily recognized clinically Is inexpensive No discharge prescription required No opioid abuse or addiction issues Safer with chronic use, when used within daily limits E.g. 4 g per day, less as indicated Acetaminophen

  43. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Acetaminophen Benefit Reminder: Make the point about what a wimpy dose 325 mg acetaminophen is in hospital NNT Figures = Number Needed to Treat (to achieve 50% pain relief in 1 patient) Oxford League Table of Analgesic Efficacy – Number Needed to Treat http://www.medicine.ox.ac.uk/bandolier/booth/painpag/acutrev/analgesics/lftab.html Acute pain, single dose studies, study size 138 to 2759 people

  44. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Codeine: any other Therapeutic Roles? Diarrhea: Loperamide (Imodium) far better Need 200 mg codeine PO for same effect as 4 mg of loperamide Needs conversion to morphine to work for diarrhea!* At doses effective for antidiarrheal effect – risks central (unwanted) adverse effects, such as sedation, analgesia Cough: Codeine no more effective than alternatives; morphine, methadone and likely dextromethorphan. (UK reg – not in children!) 1997 Clin Pharm Ther Effect of codeine in GI motility in relation to CYP2D6. (61), 459-66 2010 Oct 4th UK Medicines and Healthcare products Regulatory Agency OTC cough syrupshttp://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con096756.pdf

  45. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Prescriptions In Canada 525 Million total of all prescriptions per year 27.5 Million of these (4.7%) are for analgesics 5.4 Million (20% of all analgesics) just for Acetaminophen/Caffeine/Codeine - makes it the 18th most commonly issued Rx in Canada # patient recipients British Columbia #1, Manitoba: #1, Ontario #2 Other provinces likely very similar 2011 Feb Pharmacy Practice Top Rx Drugs of 2011 PharmaCare Trends 2009/2010 http://www.health.gov.bc.ca/pharmacare/pdf/PCareTrends2009-10.pdf

  46. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca 2011- 2008 figures are for combined brand Tylenol #3 and generics. 2007 and prior represents just figures for brand name Tylenol #3

  47. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Alternatives to T#3 To provide approximately the same pain relief (*); 13 cents! • 1-2 ¢ • 2 ¢ • 3 ¢ • 3 ¢ • 9 ¢ • 6-11 ¢ • 9-18 ¢ • 500 - 1000 mg of Acetaminophen • 200 mg of Ibuprofen • 500 mg Acetaminophen + 200 mg Ibuprofen • ½ tablet of a generic Percocet • 3.3 mg Oxycodone • Morphine 2.5 to 5 mg tablet • Hydromorphone 0.5 to 1 mg tablet * Maybe – Depends on several factors, assuming you are a normal (extensive) metabolilzer. Other factors, type, source of pain can also play a roleThis is a rough guide – assess patient, particularly prior to use of opioids

  48. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca KEY LEARNING POINTS • Codeine is a poor analgesic • Benefit, if occurs, is unpredictable • Combined with acetaminophen increases outpatient risk of accidental overdose with other acetaminophen products • Use the alternatives!

  49. Slide created by Bruce Kennedy, Palliative Care Pharmacist, bruce.kennedy@fraserhealth.ca Not 4 Me Bruce Kennedy Clinical Pharmacy Specialist Bruce.Kennedy@fraserhealth.ca 604-614-6328 Thank You ! Link to another presentation I did with some other interesting pain aspects can be found here: http://www.painbc.ca/sites/default/files/pdf_files/Prescribing%20Opioids%20in%20Multiethnic%20%26%20Genetically%20Diverse%20BC.pdf

  50. Still to DO • Practice the 45 minute time frame • See about eliminating some slides • Fix animation • Check spelling • Keep or eliminate the caffeine slide? • Watch that 12 year old speech: Have you ever wondered….? • Caffeine – safety… Caffeine content is unknown at Morgan Creek here – however see me, (or Dr Laugh) if you would like to volunteer for a study. • Read, review that newer 2012 article (both of Dr Ross) • Remove old stuff on the sides

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