Pain Management & Opioid Analgesics

1. Pain Management & Opioid Analgesics

2. Objectives Determine proper opioid dosing Differentiate between specific opioid analgesics and be able to convert between agents Discuss basal and bolus doses for PCA Discuss adverse reactions of opioids Review the Sole Provider program Discuss how to properly write a prescription for a controlled substance

3. Pain • Definition • An unpleasant sensory & emotional experience associated with actual or potential tissue damage or described in terms of such damage • Types • Nociceptive • Somatic – bone pain, skin, soft tissue trauma • Visceral – ab pain due to tumor invasion • Neuropathic – post herpetic neuralgia, post-mastectomy, phantom limb

4. Choosing Analgesic Therapy • What type of pain? • Nociceptive vs. neuropathic • Acute vs. chronic • Mild vs. severe • What route should be used? • What agent should be used? • Type, severity of pain • Pt characteristics – side effects, elderly, allergy, co-morbid conditions, tolerance, previous narcotics used • Insurance, cost

5. WHO Ladder of Analgesics www.anzsgm.org/vgmtp/Pain/analgesia_ladder.htm

6. Non-opioid analgesics • Aspirin • NSAIDs • Acetaminophen • Adjuvants • Antidepressants – amitriptyline, duloxetine • Anticonvulsants – carbamazepine, gabapentin, pregabalin • Anesthetics – lidocaine patch (12 hours on, 12 hours off)

7. Potency of Opioids Weak Agonists Strong Agonists Morphine Oxycodone Hydromorphone (Dilaudid) Fentanyl (Duragesic, Sublimaze) Methadone (Dolophine) Meperidine (Demerol) • Propoxyphene (Darvon, Darvocet) • Codeine • Hydrocodone/APAP (Vicodin, Lortab, Lorcet, Norco) • Tramadol

8. Tramadol • Synthetic analog of codeine but is NOT controlled • Weak agonist/low affinity at mu receptor and also weak SNRI (which inhibits pain transmission in the spinal cord) • Use with caution in pt on TCAs, MAOIs, SSRIs as it may lower seizure threshold • Max dose is 400 mg/day but 300 mg/day if >75yo; renal dosing if CrCl<30 • Tramadol is 5-10 times less potent than morphine and reported to cause less respiratory depression • Approximately 50 mg tramadol = 60 mg codeine

9. Considerations in choosing opioids • Renal impairment • Preferred oral agent: hydromorphone • Use with caution: morphine, codeine • Avoid meperidine • Metabolites can accumulate and cause seizures • Other cautions with meperidine • Avoid in pts with CHF, hepatic insufficiency, elderly • Avoid use in pts on MAOIs (phenelzine, selegeline, linezolid) in past 14 days

13. PCA Dosing When initiating PCA for first time (no conversion from outpatient med), the initial demand dose is 50% of the basal rate • Dosing considerations • For opioid-naïve patients, use lower end of range • Pain Assessment • Respiratory Assessment • Sedation Assessment

14. PCA dosing initial • 62 yo patient s/p TAH has been moved to PACU. You have been asked to start the patient on a PCA. Which of the following is an appropriate order: • Morphine PCA 1 mg/ml: LD 2 mg, 1 mg demand dose, lock out 10 min, no basal • Dilaudid PCA 1mg/ml: LD 2 mg, 1 mg demand dose, lock out 10 min, no basal • Fentanyl patch 25 mcg q72 hours

15. Conversions* Decreasing IV potency as you go down the table *When switching between opioids, there is NOT a complete cross tolerance. If patient is controlled, consider decrease the dose by 1/2 to 1/3 to avoid side effects. **conversion ratio is highly variable

16. For CHRONIC pain: 25 mcg/hr fentanyl patch = oral morphine 50 mg/24h

17. Fentanyl patch • NOT for acute pain or post-op pain • Absorbed through the skin, producing a drug depot in the upper skin layers, then diffusing into systemic circulation • Can have variable responses between patients (i.e. cachetic, elderly) • Watch for drugs that inhibit its metabolism • Ketoconazole, erythromycin, diltiazem, grapefruit juice

18. Morphine:methadone conversion

19. Breakthrough Dosing • Use immediate-release opioids • Chronic oral meds • Give 10 – 20% of the total daily dose q4hprn • Example – MS Contin 60 mg PO q12h – should give 10 – 20 mg q4h prn of morphine immediate release • IV dosing (PCA dosing) • 10% of the 24 hr requirement, then: • Divide by 4 if giving every 15 minutes • Ex: 100 mg morphine daily  2.5 mg IV q15 min

20. Dose Adjustment • Increasing the opioid dosage • For moderate to severe pain, increase by 50 – 100% • For mild to moderate pain, increase by 25 – 50% • Convert to oral as early as possible: • Pain is controlled • GI function intact • IV to oral dosage calculation • Calculate total daily IV use • Calculate breakthrough dose • 10-20% of total daily dose of regularly scheduled opioid every 4 h as needed

21. Conversion problem Pt is taking Percocet 5/325 two tabs q6h What dose of oxycodone ER (OxyContin) would you start the patient? What dose of morphine ER (MS Contin)? What dose of fentanyl patch?

22. Conversion problem 8 tabs Percocet = 40 mg oxycodone per day Oxycodone ER (OxyContin) = 20mg q12h

23. Conversion Problem • MS Contin conversion • 40 mg pooxycodone= 20 mg pooxycodone x 30 mg po morphine • X = 60 mg po morphine daily = MS Contin 30 mg q12h • If you want to decrease dose to allow for decreased cross-tolerance, decrease dose by 1/2 to 1/3 = 30 to 40 mg morphine daily = MS Contin 15 mg q12h • Fentanyl patch • 30 – 60 mg po morphine daily = 25 mcg fentanyl patch

24. Conversion problem In the previous problem, your patient was stable on MS Contin 30 mg q12h Your attending wants to change over to the fentanyl patch How do you time the transition from MS Contin to the patch?

25. Conversion problem • In the previous problem, your patient was stable on MS Contin 30 mg q12h • Your attending wants to change over to the fentanyl patch • How do you time the transition from MS Contin to the patch? • It takes about 12 hrs for onset of fentanyl patch • Give patient one last dose of MS Contin at the same time the patch is applied

26. Example of conversion from oral med to PCA • Pt taking OxyIR 20 mg PO q4h • Pt’s pain is well-controlled • Want to convert to hydromorphone PCA • What would be a basal dose (in mg/hr)? • What would be the bolus/demand dose?

27. Example of conversion of oral med to PCA • Pt taking OxyIR 20 mg q4h • Convert total oral daily dose (120 mg oxycodone) to oral hydromorphone • 120 mg pooxycodone= 20 mg pooxycodone x 7.5 mg pohydromorphone • X = 45 mg pohydromorphone • Convert to IV • 45 mg pohydromorphone = 7.5 mg po x 1.5 mg IV • x = 9 mg IV hydromorphone daily

28. Example of conversion to PCA • Basal rate • 9 mg daily total = 0.4 mg per hour • May want to decrease basal by 1/2 to 1/3 to account for incomplete cross tolerance • Basal dose of 0.2 to 0.3 mg per hour • Bolus/demand dose is usually 10% of the daily dose divided by 4 • (0.10 x 9 mg) / 4 = 0.2 mg q 15 minutes • Titrate based on use & pt’s response

29. Example of PCA conversion to oral med Pt on post-op morphine PCA with basal of 1 mg/hr and bolus of 1 mg q15 minutes Pt used 40 bolus injections in 24 hours What dose of oral morphine (basal & breakthrough) should be used? What dose of oral oxycodone (basal & breakthrough) should be used?

30. Example of PCA conversion to oral med • Total daily use of IV morphine • 1 mg/h x 24 h + 40 bolus = 64 mg/24 hour • Convert to oral morphine • 64 mg IV morphine = 1 mg IV morphine x 3 mg po morphine • X = 192 mg po morphine • MS Contin 100 mg q12h (basal) • Morphine IR 30 mg q4h prn for breakthrough • 10 – 20% of daily dose q4h (10 – 20% of 200 mg is 20 to 40 mg)

31. Example of PCA conversion to oral med • Converting to pooxycodone • 192 mg po morphine = 30 mg po morphine x 20 mg pooxycodone • X = 128 mg pooxycodone • Decrease daily dose by 1/2 or 1/3 to allow for incomplete cross tolerance • Total daily dose of oxycodone = 64 to 85 mg • OxyContin dose (basal): 60 mg q12h or can use 30 to 40 mg q12h if want to account for incomplete cross tolerance • Oxycodone IR (breakthrough): 5-10 mg q4h prn

32. Side Effects Constipation – worsens with dose increases Sedation, fatigue – wears off within 1 week Dizziness – wears off, may require slower titration Nausea – usually wears off; switching products may help Hallucinations – more common at higher doses Itching - anti-histamine; rotate narcotics Respiratory depression – rare side effect with chronic dosing; more common with IV, epidural

33. Respiratory Depression • 0.2 – 2 mg naloxone IV, IM, SC • Repeat doses every 2 to 3 min prn • Total dose up to 10 mg • After reversal, may need to readminister dose at a later interval (20 to 60 minutes) depending on the type/duration of opioid

34. Assessment Scales Respiratory Sedation 1 = agitated, restless 2 = cooperative, oriented 3 = asleep, easily arousable 4 = asleep, arouses to voice 5 = no response to verbal stimuli 6 = no response to pain Stop PCA & give naloxone for score 5 & 6 • Should be counted for at least 30 seconds • If RR <12/min, then count for full minute • If RR <10/min, stop PCA • If RR <4/min, give naloxone

35. Constipation • Need a stool softener • Docusate 100 mg: 1 to 2 caps po twice daily • Need a stimulant laxative • Senna: usual dose is 1 tab at bedtime or twice daily but can titrate up to 4 tabs three times daily prn • Bisacodyl 5 mg: 1 to 2 tabs twice daily prn

36. Constipation www.toonpool.com

37. Opioid “Allergy” • “Pseudoallergy” caused by histamine release – most commonly seen with codeine, morphine, meperidine • Pt c/o flushing, itching, hives, sweating • Mild hypotension • Use H2RA • Decrease dose • Switch to a more potent opioid (i.e. fentanyl, hydromorphone)

38. Opioid “Allergy” • Pts with “true” allergy • Breathing, speaking, swallowing difficulties • Swelling of face, lips, mouth, tongue, pharnyx, or larynx • Severe hypotension • Switch to a different class • Phenylpiperidines: meperidine, fentanyl • Diphenylheptanes: methadone, propoxyphene • Morphine group: morphine, codeine, hydrocodone, oxycodone, hydromorphone, nalbuphine, butorphanol

39. Sole Provider Program • Purpose • To monitor patients exhibiting signs of drug-seeking behavior, insufficient analgesia, evidence of non-optimization in care options, psychosocial issues, or other complex pharmaceutical care issues • Narcotic prescriptions only • The primary care provider can be the Sole Provider or choose to refer a patient to a Sole Provider • Opioid “contract” signed between patient and Sole Provider physician • Pharmacy informed and note put in CHCS • Sole Provider committee will monitor for violations

40. Sole Provider Program • NNMC Intranet • Site Map • Pharmacy

41. Sole Provider Program

42. Writing Prescriptions Link on Pharmacy Website Write legibly Write out your DEA number Spell out the quantity to be dispensed C-IIs are not refilled (new Rx required) & require separate prescriptions Use DoD Form 1289 for controlled substances

43. DEA numbers Retail and mail-order pharmacies are no longer accepting the NNMC DEA number Must apply for own practitioner DEA number Active military physicians (MD, DO, DDS, DMD, and DPM) are fee exempt and may be licensed in any state to obtain a DEA registration DEA number is to be used solely for DoD beneficiaries prescriptions and may not be used for off-duty employment

44. DEA numbers • To apply for DEA number: • Contact the Credentialing Office to complete the correct paperwork • Contact person: Rebekah Byrd at 319-4157

45. Med Errors to Avoid • Roxanol v Roxicodone oral solutions • Roxanol (morphine) v Roxicodone (oxycodone) • Correct strengths • PCA strength • Morphine: 1 mg/ml and 5 mg/ml • Hydromorphone: 1 mg/ml and 0.2 mg/ml • Fentanyl patch • For inpatients, double check if patient has patch on from home

46. References Pharmacotherapy: A Pathophysiologic Approach. 6th edition: Chapter 58. End of Life/Palliative Education Resource Center Micromedex Drug Facts and Comparisons Equianalgesic Dosing of Opioids for Pain Management. Pharmacist’s Letter 2004. Opioid Intolerance Decision Algorithm. Pharmacist’s Letter 2006. Clinical Pharmacology

47. References Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, American Pain Society, 5th Ed. 2003 Grammaitoni AR et al. Clinical Application of Opioid Equianalgesic Data. Clin J Pain 2003; 19(5): 286-297. McPherson M.L. Demystifying Opioid Conversion Calculations: A Guide for Effective Dosing. 2010.

48. Questions?