1. Step two: Moderate pain Tramadol Opioid combinations Acetaminophen or aspirin with Codeine Hydrocodone Oxycodone Plus/minus adjuvants Dose limiting toxicity Tramadol Opioid combinations Acetaminophen or aspirin with Codeine Hydrocodone Oxycodone Plus/minus adjuvants Dose limiting toxicity

2. Adjuvants Primarily for neuropathic pain Antidepressants Tricyclics Venlafaxine, Duloxitene Anticonvulsants Gabapentin, pregabalin, carbamazepine Antiarrhythmics Lidocaine, mexilitene Primarily for neuropathic pain Antidepressants Tricyclics Venlafaxine, Duloxitene Anticonvulsants Gabapentin, pregabalin, carbamazepine Antiarrhythmics Lidocaine, mexilitene

3. Step 3: Severe pain Pure opioids Morphine Hydromorphone Oxycodone Fentanyl Oxymorphone Methadone No ceiling effect Variable toxicity at very high dose Plus/minus adjuvants, non-opioids, steroids Pure opioids Morphine Hydromorphone Oxycodone Fentanyl Oxymorphone Methadone No ceiling effect Variable toxicity at very high dose Plus/minus adjuvants, non-opioids, steroids

4. Opioids

5. Short acting oral agents Long acting oral agents Equianalgesic dose conversions Opioid infusions PRN dosing and dose escalation Methadone Short acting oral agents Long acting oral agents Equianalgesic dose conversions Opioid infusions PRN dosing and dose escalation Methadone

6. Short acting oral agents Peak analgesic effect 60-90 minutes Expected duration of 3-4 hours Typical prescribed interval is Q 4-6 hours AHCPR recommends dosing interval of 3-4 hours Peak analgesic effect 60-90 minutes Expected duration of 3-4 hours Typical prescribed interval is Q 4-6 hours AHCPR recommends dosing interval of 3-4 hours

7. Short acting pure opioids oral dosing Routine (not prn) schedule important for continuous pain relief PRN dose should be 10-15% of total daily dose Every 1 hour administration of single agent is safe if pain not controlled Routine (not prn) schedule important for continuous pain relief PRN dose should be 10-15% of total daily dose Every 1 hour administration of single agent is safe if pain not controlled

8. Example 1 prn dosing Oxycodone 30 mg q 4 hours 180 mg daily dose 10-15 % = 18-24 mg Oxycodone 15-30 mg Q 3 hour prn May give 30 mg in 1 hour if needed Oxycodone 30 mg q 4 hours 180 mg daily dose 10-15 % = 18-24 mg Oxycodone 15-30 mg Q 3 hour prn May give 30 mg in 1 hour if needed

9. Example 2 Pseudo-prn dosing Oxycodone 30 mg q 4 hour Oxycodone 30 mg q 4 hours prn Patient uses all prn doses consistently Total daily dose 360 mg New schedule: Oxycodone 60 mg q 4 hours Oxycodone 30-60 mg q 4 hour prn Oxycodone 30 mg q 4 hour Oxycodone 30 mg q 4 hours prn Patient uses all prn doses consistently Total daily dose 360 mg New schedule: Oxycodone 60 mg q 4 hours Oxycodone 30-60 mg q 4 hour prn

10. Long acting oral agents Morphine Morphine ER Kadian, Avinza Oxycontin Hydromorphone (Exalgo) Oxymorphone (Opana/ER) Methadone Should be prescribed along with short acting agent for breakthrough pain Morphine Morphine ER Kadian, Avinza Oxycontin Hydromorphone (Exalgo) Oxymorphone (Opana/ER) Methadone Should be prescribed along with short acting agent for breakthrough pain ~ $40/mo ~ $680-770/mo ~ $600/mo ~ $3200/mo ~ $550/mo Cost relative to MS 200 mg/day Cost relative to MS 200 mg/day ~ $20/mo

11. Equianalgesic Dosing

12. Fred is a 58 y.o. man with pancreatic cancer diagnosed 9 months ago. Opioid regimen: Norco 10/325, 4-8 tabs per day Oxycodone extended release120 mg twice daily 4 mg dilaudid 1-2 tabs per hour for “breakthrough pain” How do you convert him to a parenteral hydromorphone infusion? Fred is a 58 y.o. man with pancreatic cancer diagnosed 9 months ago. Opioid regimen: Norco 10/325, 4-8 tabs per day Oxycodone extended release120 mg twice daily 4 mg dilaudid 1-2 tabs per hour for “breakthrough pain” How do you convert him to a parenteral hydromorphone infusion? Equianalgesic Dosing

13. Equianalgesic dosing Step 1: Calculate total daily oral morphine equivalent (OME) for each medication using equianalgesic ratios.

15. Calculate OME of each medication Oxycodone ER 240 mg/day Oxy: MS ratio = 2:3 OME is 360 mg Oxycodone ER 240 mg/day Oxy: MS ratio = 2:3 OME is 360 mg

16. Calculate OME of each medication Hydrocodone 10 mg, 2 tabs QID = 80 mg Hydrocodone: MS ratio = 1:1 OME = 80 mg Hydrocodone 10 mg, 2 tabs QID = 80 mg Hydrocodone: MS ratio = 1:1 OME = 80 mg

17. Calculate OME of each medication Hydromorphone 4 mg ~ 20 tabs per day Hydromorphone 80 mg/day Hydromorphone: MS ratio = 1:4 OME is 320 mg Hydromorphone 4 mg ~ 20 tabs per day Hydromorphone 80 mg/day Hydromorphone: MS ratio = 1:4 OME is 320 mg

18. Calculate total daily OME Oxycodone 360 mg Hydrocodone 80 mg Hydromorphone 320 mg Total OME 760 mg Oxycodone 360 mg Hydrocodone 80 mg Hydromorphone 320 mg Total OME 760 mg

19. Equianalgesic dosing Equianalgesic tables and calculators vary Individual variation and incomplete cross tolerance between opioids exists Tables and calculators are only guidelines 30-50% decrease in calculated dose is prudent Equianalgesic tables and calculators vary Individual variation and incomplete cross tolerance between opioids exists Tables and calculators are only guidelines 30-50% decrease in calculated dose is prudent

20. Equianalgesic dosing Step 2: Reduce calculated dose by 1/3 to 1/2 based on patient variability 760 mg x 2/3 ≈ 500 mg po morphine Step 2: Reduce calculated dose by 1/3 to 1/2 based on patient variability 760 mg x 2/3 ≈ 500 mg po morphine

21. 500 mg po morphine * 1/3 ≈ 167 mg iv morphine 167 mg iv morphine per day/24 hours ≈ 7 mg iv morphine/hour Step 3: Convert to equivalent parenteral morphine dose

22. 7 mg iv morphine/hour*1.5/10 ≈ 1 mg iv hydromorphone/hour Step 4: Calculate equianalgesic dose of i.v. hydromorphone

23. Or use a calculator

25. You order dilaudid 1 mg iv per hour continuous 2 hours later the nurse calls to tell you is pain is no better. What happened? What do you do? You order dilaudid 1 mg iv per hour continuous 2 hours later the nurse calls to tell you is pain is no better. What happened? What do you do?

26. Time to steady state takes 3-5 half lives or 12-20 hours for most opioid infusions Step 5: Add loading dose equal to 1-2 times the hourly dose

27. Opioid infusions PRN dosing Fred is given 2 mg iv hydromorphone followed by 1 mg/hour continuous infusion What is the appropriate PRN dose? PRN should be 50-150% hourly rate 1 mg hydromorphone PRN How often? PRN dosing interval is based on time to C max Fred is given 2 mg iv hydromorphone followed by 1 mg/hour continuous infusion What is the appropriate PRN dose? PRN should be 50-150% hourly rate 1 mg hydromorphone PRN How often? PRN dosing interval is based on time to C max