Opioid Calculations: Asking The Right Questions To Find The

Opioid Calculations: Asking the Right
questions to Find the Best Answers
Cheryl K Genord, R.Ph.
Clinical Pharmacy Specialist, Pain Management
Objectives
• Understand the five step process to switch a
patient from one opioid to another opioid.
• Describe different types of break-through pain
and recommend an opioid regimen to treat these
pains.
• Determine an appropriate strategy to change an
opioid regimen, including both the regularly
scheduled and rescue opioids.
2
Case Study
• Patient is taking Oxycontin 60mg tid want
to convert to Morphine extended release.
• Oxycodone 20mg = Morphine 30 mg po
Medication
IV Eq PO
• Oxycodone 60mg =
Eq
Morphine
10
30
Morphine 90 mg po
3
Codeine
-
200
Fentanyl
0.1
-
Hydrocodone
-
30
Hydromorpho
ne
1.5
7.5
Oxycodone
-
20
Simple Calculations
• Is that all there is to Opioid Conversions
• If there was this would be a pretty short
presentation
• Where Calculations meets Art
4
Five Step Approach
Step 1
Globally
assess the
patient
Step 2
Determine
total daily
dose of
current
opioids
McPherson ML. ASHP Bethesda, MD. 2010.
5
Step 3
Decide which
opioid
analgesic will
be used and
calculate a
proper dose
Step 4
Individualize
dosage based
on info from
Step 1
Step 5
Patient follow
up and
reassessment
Step 1
• Don’t jump to calculator, assess first!
P • Precipitating and Palliating
Q • Quality
R • Region
S • Severity
T • Temporal
U • You
6
McPherson ML. ASHP Bethesda, MD. 2010.
Precipitating and palliating
• What brings on or worsens the pain
• What relieves the pain
– Pharmacologic
• What was the response
• Any side effects
– Non-Pharmacologic
• What Medications have been tried to treat
the pain
7
Quality
• Pain description in patients own words
– Stabbing, shooting, throbbing, aching,
gnawing
8
Region and radiation
• Where is the Pain?
• Does the pain move anywhere?
9
Severity
• Rating Scale
– Pain right now, worse, best, average, one
hour after you take the medication.
10
Temporal
• Is the pain constant?
• Does the pain come and go – how many
times a day
• How long does it last?
11
U - You
• How does the pain affect your life?
• Your ability to sleep, your appetite, your
ability to ambulate
12
Step 2 Determine daily usage
• Time to play Sherlock Holmes
• Important to I spy with my little
eye
• Whole Truth and Nothing But
the Truth
13
Step 3 – Decide which opioid will be used
and calculate new dose
• Decide which opioid to switch to:
– Renal Function
– Potential for drug interactions
– Patient Specific Factors
•
•
•
•
Patient ability to swallow or apply a transdermal system
Nature of pain
Patient’s previous history of response
Safety concerns
– Formulary, financial limitations
– Availability of dosage
• Get those Calculators ready! WAAAAAAIT
14
Basics of opioid Metabolism
• Production of both inactive and active
metabolism
• Opioids differ in how they are metabolized
• People differ in how they metabolize opioids
• Extensive first-pass in liver
– Phase 1 (modification reactions)
• CYP enzymes (3A4, 2D6)
– Phase 2 (conjugation reactions)
• Glucuronidation
15
metabolic Pathways
Opioid
Phase
1
Phase 2
Metabolites*
Morphine
-
glucuronidation
M3G, M6G
Codeine
CYP2D6
glucuronidation
C6G, morphine
Hydrocodone
CYP2D6
-
hydromorphone
-
glucuronidation
H3G
Oxycodone
CYP2D6,
CYP3A4
-
oxymorphone,
noroxycodone
Methadone
CYP3A4,
CYP2B6
-
-
Fentanyl
CYP3A4
-
-
Hydromorphone
16
Clinical Implications
• Most opioids metabolized by CYP enzymes
– Substantial drug interaction potential
• Cannot predict patient response
– Need to individualize therapy
– Opioid trials for tolerability/analgesic assessment
• Confounding medical conditions
– Hepatic/renal impairment
– Accumulation of active metabolites and increased
ADE’s
17
Smith HS. Mayo Clin Proc. July 2009;84(7):613-624.
18
Smith HS. Mayo Clin Proc. July 2009;84(7):613-624.
19
Morphine
• Morphine  M3G (55%) and M6G (10%)
• Morphine not altered significantly in renal insufficiently, but
metabolites will accumulate
• M6G 2-4x more potent than morphine, with higher levels in
CNS
• M3G lacks analgesic properties but has neuroexcitatory
effects
• Effects of M6G and M3G magnified in kidney disease
• Avoid use in renal dysfunction, especially hemodialysis
• Bioavailability increased in cirrhotics
• Monitor response in hepatic dysfunction
– Suggest increasing dosing interval
20
Smith HS. Mayo Clin Proc. July 2009;84(7):613-624
Johnson SJ. Pain Treatment Topics. June 2007
Codeine
• Codeine (prodrug)  C6G (81%) and morphine
(10%)
• All compounds renally excreted and can
accumulate
• CYP2D6 poor/rapid metabolizers do not respond
well to codeine
– Poor: no conversion into morphine (no analgesia)
– Rapid: too much conversion (intoxication)
• Chronic codeine dosing is proposed to accumulate
to toxic levels in ⅔ of HD patients
• Avoid codeine in patients with renal dysfunction,
on dialysis, or with severe hepatic dysfunction
21
Smith HS. Mayo Clin Proc. July 2009;84(7):613-624
Johnson SJ. Pain Treatment Topics. June 2007
Hydrocodone/Hydromorphone
• Hydrocodone (prodrug) metabolized into
hydromorphone via 2D6
– Poor metabolizers experience little analgesia
• Hydromorphone  H3G (37%)
• H3G no analgesic properties but can cause
neuroexcitation (≈M3G)
• Renally excreted/accumulate in dysfunction
• Water soluble, small VD, low molecular
weight
– Re-dosing after HD may be appropriate
• Avoid hydrocodone in hepatic failure
22
Smith HS. Mayo Clin Proc. July 2009;84(7):613-624
Johnson SJ. Pain Treatment Topics. June 2007
Oxycodone
• Oxycodone  noroxycodone (3A4) and oxymorphone
(2D6)
• Primary effects governed by parent drug
• Renal impairment increases concentration of
oxycodone by 50%
• High efficiency dialyzers enhance plasma clearance
by 48%
• Re-dosing after HD may be appropriate
• Dose reductions 30-50% in severe hepatic impairment
23
Smith HS. Mayo Clin Proc. July 2009;84(7):613-624
Johnson SJ. Pain Treatment Topics. June 2007
Methadone/Fentanyl
•
•
•
•
Fully synthetic, structurally unrelated to morphine
Do not produce active metabolites
Inactive metabolites by (3A4)
Exerts both analgesic and toxic effects through parent
compound
– Methadone acts also on NMDA receptors
• Fentanyl affected more by  hepatic blood flow than
impairment
– Can be used in hepatic dysfunction
• Avoid methadone in severe hepatic failure
– Risk of accumulation
• Minimal, if any, adjustments for renal dysfunction
24
Smith HS. Mayo Clin Proc. July 2009;84(7):613-624
Johnson SJ. Pain Treatment Topics. June 2007
Step 3 – Decide which opioid will be used
and calculate new dose
• It is time to get those Calculators ready!
• Look back at least 24 hours and obtain average
daily dose of all opioids
• Convert all opioids to equivalent units using the
Equianalgesic Dosing Table
• Using knowledge of drug therapy selection and
patient specific factors, switch it up!
– Renal/Hepatic impairment
– Drug Interaction
– Patient specific factors
• Determine what to use – Long acting and/or short
acting or both
25
McPherson ML. ASHP Bethesda, MD. 2010.
Titrating opioid Regimens with Around the
clock and rescue
Types of Breakthrough Pain
• Spontaneous –no precipitation stimulus – occurs without warning
and is acutely severe. (neuropathic)
– Immediate release opioids plus co-analgesics
• Incident pain – volitional
– Patient precipitated movement
– Immediate release opioids on as needed basis prophylactically
– Rescue dose = 10%-15& of daily dose q4hprn
• Incident pain – nonvolitional
– Sneezing, bladder spasm, coughing
– Immediate release opioids on as needed basis
– Rescue dose = 10%-15% of daily dose q4hprn
• End of Dose
– Pain that recures before the next schedulce dose
– Increase dose and/or frequency in ATC opioid
McPherson ML. ASHP Bethesda, MD. 2010.
26
Conversion Examples
• Morphine 20mg IV:
– ____ mg PO morphine
• Oxycodone 60mg PO:
– ____ mg PO hydrocodone
• Hydromorphone 2.25mg IV:
– ____ mg IV fentanyl
• Hydrocodone 30mg PO:
– ____ mg IV morphine
27
Medication
IV Eq
PO Eq
Morphine
10
30
Codeine
-
200
Fentanyl
0.1
-
Hydrocodone
-
30
Hydromorphone
1.5
7.5
Oxycodone
-
20
Fentanyl Patch Conversion
Drug
• USA
Daily Dosage
PO MS
60-134
135-224
225-314
315-404
IV MS
10-22
23-37
38-52
53-67
PO Oxy
30-67
68-112
113-157
158-202
PO HM
8-17
18-28
29-39
40-51
IV HM
1.5-3.4
3.5-5.6
5.7-7.9
8-10




Fentanyl
25 mcg/h
Drug
• CAN
28
50 mcg/h
75 mcg/h
100 mcg/h
Daily Dosage
PO MS
60-134
135-224
225-314
315-404
IV MS
20-44
45-60
61-75
76-90
PO Oxy
30-67
68-112
113-157
158-202
PO HM
8-16
17-28
29-39
40-51
IV HM
4-8.4
8.5-14.4
14.5-19.5
19.6-25.5




Fentanyl
Janssen Pharmaceuticals, Inc; Oct 2011
25 mcg/h
50 mcg/h
75 mcg/h
100 mcg/h
What about Chronic pain conversions
• Hydromorphone
– Conversion ratio of parenteral hydromorphone
to oral hydromorphone of 1:2
• Morphine
– Conversion ratio of pareteral morpine to oral
morphine of 1:3
29
Step 4 Individualize dosage
• After calculations, time to individualize!
• Three options:
– No change, increase, decrease
• Things to consider (from “PQRSTU”)
–
–
–
–
–
–
Type of pain (cancer, acute, chronic, neuropathic)
Age of patient
Location/status of patient
Worsening or improving
Incomplete cross tolerance (0-50%)
Breakthrough needs (10-15% of total per dose)
• More art than science
• Divide total dose for the new dosing interval
30
McPherson ML. ASHP Bethesda, MD. 2010.
Incomplete Cross Tolerance
• Tolerance – continued exposure to a drug
reduces its effectiveness.
• When switching opioid – see increase in
opioid sensitivity
• When converting from one opioid to
another –reduce the calculated dose by
25-50%
31
What to do increase, decrease or keep the
dose the same
• Increase the calculated dose
– Severe cancer pain in hospital
• Same as calculated dose
– Did not switch to a different opioid
– Old opioid has not been used for more than one
week
• Decrease the calculated doses
– Cross Tolerance
– Elderly patient
– Going home
32
Pop Quiz - Individualize dosage
72 yo w/osteoarthritis & difficulty swallowing
– Hydrocodone/APAP tablets to elixir
27 yo POD2 s/p ACL reconstruction
– Fentanyl IV to hydrocodone/APAP
55 yo w/ evolving metastatic breast cancer
– MS-IR to long acting oxycodone
94 yo, ECF resident w/ chronic back pain
– Oxycodone to hydromorphone
63 yo w/ shoulder pain, developed rash
– MS-IR to oxycodone
33
Step 5 Reassess
• Reassess pain with a patient monitoring
plan
• Fine tune the total daily dose
– Adjustments in both short and long acting
Subjective Parameters
Objective Parameters
Monitoring for
therapeutic
effectiveness
-Pain rating
-Performance of ADLs,
sleep, ambulate
-Sleeping longer
-ambulating further
-Limiting use of rescue opioids
Monitoring for
potential toxicity
-Complaints of
constipation, nausea,
sedation, confusion, hives
-Level of arousal/sedation
-Respiratory rate
-Pinpoint pupils
-Bowel movement frequency
34
McPherson ML. ASHP Bethesda, MD. 2010.
Acute Pain
• What Stronger?
– Percocet (Oxycodone) 5/325 2 tab
– Norco (Hydrocodone) 5/325 2 tab
– Morphine 3 mg IV
– Hydromorphone 0.5 mg
35
Genord’s Opioid Analgesic Potency Classes
36
Chronic Pain/Longer term Acute Pain/Acute
on Chronic Pain
• Time to use what we learnt
37
Case 1
• DG is a 62yo man recently diagnosed with colon caner
admitted for surgical resection of the lesion. Post op
he was given hydromorphone 1-2 mg IV q4h.
– Day 1 hydromorphone 12 mg IV
– Day 2 hydromorphone 11mg IV
– Day 3 hydromorphone 8 mg IV
• He reports his pain as 3 after taking hydromorphone.
• On day 4 he is preparing for discharge. CR has a
history of itching with oxycodone and morphine. Oral
Hydromorphone has been effective in the past.
• What oral opioid regimen should be tried prior to
discharge.
38
Case 1
• Step 1 Assess
– DG has used less on day 2 than day 1.
– Good pain control with hydromorphone
– Pain is consistent with normal post op course.
– He has used po hydromorphone in the past
and it has been effective.
• Step 2 Total Daily Dose
– 24 hours day 2 – Hydromorphone 8mg IV.
(TDD)
39
Case 1
• Step 3 Determine new opioid and calculate new dose
– Morphine and Oxycodone makes pt itch so transition to po
hydromorphone
– Calculate equianalgesic dose
X mg TDD oral HM
7.5 mg oral HM
________________ = _______________
8 mg IV HM
1.5 mg IV HM
X = 40 mg
• Step 4 – Individualize
– Well controlled – no need to increase
– Pain is getting better every day expect reduce dose requirement each
day.
– No need to decrease dose for incomplete cross tolerance
– Hydromorphone is available in 2,4,and 8mg tab. Dosed as q4h
– 4 mg q4h (24 mg TDD)
40
Case 2
• LP is a 68 yo man with end-stage lung cancer. He is
receiving MS Contin 120mg Q12h as well as Percocet
5/325 1-2 q4h prn. LP tells you that when he
experiences unanticipated unprovoked pain he takes 2
Percocet tab about 4 times per day. This pain occurs at
different times during the day and is achy and throbbing
in nature. The Percocets are not effective (PS 8 down to
6). LP is growing weaker and is now experiencing
shortness of breath occasionally as well
• What would you recommend?
41
Case 2
• Step1
– Patient is having spontaneous/incidental pain
that does not seem to be neuropathic in
nature.
– Pain does not seem to be end of dose pain
– Percocet 2 tablets has been used for this
pain.
• Step 2
– Morphine 240mg/day
– Percocet 40mg/day
42
Case 2
• Step 3 Determine new opioid and calculate new dose
Breakthrough pain – 10%-15% total daily dose – 24-32mg of
Morphine = 16-24 mg of Oxycodone
Percocet is too low at 10mg dose.
• Step 4 – Individualize
– Before looking at increasing long-acting need to get
breakthrough dose appropriate
• Morphine 30mg IR
– If patient becomes weaker could switch to oral solution –
too weak to swallow concentrated solution could be instilled
in the buccal cavity
43
Questions
44