Step two:
Moderate pain
Tramadol
Opioid combinations
Acetaminophen or aspirin with
•Codeine
•Hydrocodone
•Oxycodone
Plus/minus adjuvants
Dose limiting toxicity
Adjuvants
Primarily for neuropathic pain
Antidepressants
Tricyclics
Venlafaxine, Duloxitene
Anticonvulsants
Gabapentin, pregabalin, carbamazepine
Antiarrhythmics
Lidocaine, mexilitene
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
Opioids
Opioids
Short acting oral agents
Long acting oral agents
Equianalgesic dose conversions
Opioid infusions
PRN dosing and dose escalation
Methadone
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
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
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
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
Long acting oral agents
Morphine
Cost relative to
MS 200 mg/day
Morphine ER
~$40/mo
Kadian, Avinza
~$680-770/mo
Oxycontin
~$600/mo
Hydromorphone (Exalgo)
~$3200/mo
Oxymorphone (Opana/ER)
~$550/mo
Methadone
~$20/mo
Should be prescribed along with short acting agent for
breakthrough pain
Equianalgesic
Dosing
Equianalgesic
Dosing
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
Step 1: Calculate total daily oral morphine
equivalent (OME) for each medication using
equianalgesic ratios.
Calculate OME of each
medication
Oxycodone ER 240 mg/day
Oxy: MS ratio = 2:3
OME is 360 mg
Calculate OME of each
medication
Hydrocodone 10 mg, 2 tabs QID = 80 mg
Hydrocodone: MS ratio = 1:1
OME = 80 mg
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
Calculate total
daily OME
Oxycodone
Hydrocodone
Hydromorphone
Total OME
360 mg
80 mg
320 mg
760 mg
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 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 3: Convert to equivalent
parenteral morphine dose
500 mg po morphine * 1/3 ≈ 167 mg iv morphine
167 mg iv morphine per day/24 hours ≈ 7 mg iv morphine/hour
Step 4: Calculate
equianalgesic dose of i.v.
hydromorphone
7 mg iv morphine/hour*1.5/10 ≈
1 mg iv hydromorphone/hour
Or use a calculator
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?
Step 5: Add loading dose equal to
1-2 times the hourly dose
Time to steady state takes 3-5 half lives
or 12-20 hours for most opioid infusions
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 Cmax