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Pain & Symptom Management: RQHR Response - Injectable Drug Shortage Carmen L. Johnson, MD CCFP, ABFP, AAHPM, AAPM, ABAM, ABRPM (Pain Medicine) Medical Director – Palliative Care Services
Pain & Symptom Management: RQHR Response - Injectable
Drug Shortage
Carmen L. Johnson, MD CCFP, ABFP, AAHPM, AAPM, ABAM, ABRPM (Pain Medicine)
Medical Director – Palliative Care Services
Disclosures
Speakers Bureau, Purdue Pharma
Speakers Bureau, Pallium
Dedication
Dr. Martha Santamaria
Dr. Lawrence Librach
Learning Objectives
Why sudden nationwide shortage of
injectable meds?
RQHR response to drug shortages
Drugs affected, shortage severity
Determinants in choosing alternate
medications
Medications we chose
Learning Objectives
How did we do?
Prescribing changes
Any other lessons?
Time savings
Cost savings
Future drug use
Headlines
February 20, 2012
Sandoz Canada, a leading maker of
injectable drugs, announced it has
suspended or discontinued production of
some drugs, prompting fears of a shortage
of critical medications. CBC Online
Headlines
Caught Health Care Professionals Off Guard
Larissa Feldman’s Montreal drugstore was
among those left in the lurch by the sudden
stoppage . . . . “This morning, we’ve tried to
order some of these products . . . . [Much]
to our surprise, there was none available,”
Feldman said. CBC Online
Headlines
February 20, 2012
‘Significant reduction in output’
The company [Sandoz] said it was expecting “a
significant reduction in output” and was halting
production lines to upgrade operations after
quality-control assessments by the [US] Food and
Drug Administration warned the factory fell short of
FDA standards.
CBC News
Headlines
March 4, 2012
To exacerbate supply concerns, a fire
Sunday in the ceiling above the boiler room
of Sandoz’s Boucherville plant has halted
production.
CBC Online
Headlines
March 6, 2012
Health Canada
“We’ve seen an interruption of the supply,
and principally of injectable medications for
hospitals .... Elective surgeries are being
cancelled... and there’s widespread
concern.” Dr. Robert Cushman.
CBC News
Headlines
Drugs affected:
Painkillers
Antibiotics
Anaesthetics
Headlines
March 6, 2012
Health Canada plans to fast-track new
sources of certain medications . . . we do
have arrangements with similar
organizations like the [Food and Drug
Administration] in the U.S.
CBC News
Headlines
Little Did The
Canadian Public
Know ! . . .
Headlines
Drug Shortage Crisis - United States
“The U.S. is experiencing a rapidly
increasing frequency of drug shortages . . .”
Pharmacy and Therapeutics –
Pub Med Central
National Institute of Health, November 2011
Headlines
USA drug shortages
Generic cancer drugs
Heart medications
Pain medications
Morphine
Hydromorphone
Shortages Reported
Intravenous (IV) electrolytes
Anaesthetic agents
Furosemide
Amino acids
Headlines
March 6, 2012
In Canada, hospitals turn to sharing their supplies
Myrella Roy, . . . Canadian Society of Hospital
Pharmacists, says, “hospitals typically have a few
weeks of inventory on hand.... So, when they are
notified that a particular drug or number of drugs
may be in short supply, they can only fall back on
a few weeks worth of inventory”.
Canadian Press
Headlines
Week of March 5, 2012
Officials with Alberta Health Services
asked doctors to conserve injectable
medications. Cancer patients received
oral anti-nausea medications instead of
injections.
CBC News
Headlines
March 13, 2012
DRUG SHORTAGES COULD
MEAN
1890’s STYLE SURGERY!
CBC News
Headlines
Canadians will face medicine from the
1890s or no surgery at all if a
shortage of injectable drugs
continues, the head of the Canadian
Medical Association says. No
anaesthesia, no antibiotics.
CBC News
Headlines
March 13, 2012
Canceled or postponed elective
surgeries reported in Quebec.
CBC News
Impact on Symptom Management
Injectable drugs:
Mainly patients end of life – difficulty
swallowing
Hospital
Community, hospice, home care program
Major Drug Categories
Painkillers
Anti-nausea
Anti-seizure
Sedation
Secretion control
RQHR Emergency Meeting February 2012
Pharmacy newsletter weekly or biweekly
Drugs shorted and their alternates
Newsletters continuing today
Categories:
grey – depleted
red – less than 2 weeks
yellow – use judiciously
Drugs Affected
Pain – morphine, hydromorphone
Nausea – gravol, ondansetron, haloperidol
(esp. community)
Seizures – midazolam, phenobarb,
dexamethasone
Drugs Affected
Sedation – midazolam, haloperidol,
methotrimeprazine (community)
Secretions – glycopyrrolate, atropine,
hyoscine
Mar. 15/12 – Apr. 19/13 (56 wks)
Drug - Nausea # of Weeks Short
dimenhydrinate 56
ondansetron 30
Both on shortage list same week – 12 wks
Mar. 15/12 – Apr. 19/13 (56 wks)
Drug - Pain # of Weeks Short
fentanyl 34
morphine 17
hydromorphone 15
ketorolac 13
fentanyl & morphine on list same week – 1 wk
fentanyl & hydromorphone on list same week – 1 wk
morphine & hydromorphone on list same week – 6 wks
Mar. 15/12 – Apr. 19/13 (56 wks)
Drug - Secretion # of Weeks Short
atropine 4
glycopyrrolate 18
hyoscine 3
atropine & glycopyrrolate on list same week – 1 wk
atropine/glycopyrrolate/hyoscine on list same week – 0 wks
Mar. 15/12 – Apr. 19/13 (56 wks)
Drug - Sedation # of Weeks
Short
midazolam 26
propofol 5
ketamine
29
midazolam & propofol on list same week – 3 wks
Mar. 15/12 – Apr. 19/13 (56 wks)
Drug - Seizures # of Weeks Short
midazolam 26
phenytoin 14
midazolam & phenytoin on list same week – 9 wks
Mar. 15/12 – Apr. 19/13 (56 wks)
Drug - # of Weeks
Short
dexamethasone 1
Mar. 15/12 – Apr. 19/13 (56 wks)
Drug - # of Weeks
Short
haloperidol community only
Determinants Alternative Meds
Safety, efficiency
Bioavailability (buccal, rectal, transdermal)
Onset duration of action
Determinants Alternative Meds
Duration of effect
Dosage frequency
Comfort – rectal meds – gel caps
PAIN/DYSPNEA
Analgesics
MS Contin – matrix – rectal ok
M-Esselon – time release beads
Hydromorph Contin – time release beads
Oxyneo - matrix, not for rectal use
PAIN/DYSPNEA
Rectal Admin
MS Contin
IR morphine
IR hydromorphone
IR oxycodone
PAIN/DYSPNEA
Methadone Suspension/Tabs
Very lipophilic
Complete absorption 30 min
vomiting patients
Buccally or rectally
PAIN/DYSPNEA
Methadone Suspension/Tabs
Immediate & long term analgesic effects
Immediate 4-6 hr analgesia
Repeated dosing – longer action analgesic
Dose - 1-3 times daily
PAIN/DYSPNEA
Methadone Suspension/Tabs cont’d
Long half life
Reservoir in fat tissue
If buccal volume problematic
dose more frequently - smaller amounts
increase concentration
switch – rectal route
PAIN/DYSPNEA
Methadone Sub-Q Injection
Chronic shortage
From UK, Health Canada
RQHR: pharmacy manpower shortage
to mix methadone for sub-Q use
PAIN/DYSPNEA
Fentanyl Transdermal Patches
Difficult to titrate
Not useful on cachectic patients
Several hours therapeutic
PAIN
Dexamethasone
Good pain reliever, esp. bone
Neuropathic model of pain
Reduces inflammatory markers
Modulates pH
Reduces noxious pain transmission
PAIN
Dexamethasone
Inflammation/edema brain
Reduces seizure risk
Anti-emetic, appetite stimulant
No info on rectal use
PAIN
NSAIDs
Diclofenac supp 50-100mg TID
Indomethacin supp 50-100mg BID
Naproxen supp 500mg BID
Ketoprofen supp 50-100mg BID
No decrease seizure risk – brain edema
GASTRITIS
Omeprazole
Can be given PR
AGITATION/DELERIUM
Antipsychotics 1st
- sub-Q important - nursing safety
Benzodiazepines 2nd
- can increase agitation
AGITATION/DELERIUM
Anti-Psychotics
Haloperidol sub-Q
- PCU supply - hospital priority
- unavailable community
- no info PR
Prochlorperazine 10mg supp
Chlorpromazine sub-Q
AGITATION
Anti-Psychotics cont’d …
Methotrimeprazine sub-Q
- not always available
Methotrimeprazine 10mg PO unavailable
- 25mg available
AGITATION
Benzodiazepines – used rarely
Can increase agitation/falls
Midazolam sub-Q for emergencies
Ativan SL or PR or sub-Q
SECRETIONS
Anti-cholinergic
Usually atropine, glycopyrrolate
Glycopyrrolate shorted
- doesn’t cross BBB
- better for delirium
All others can exacerbate delirium
Atropine –cardiac resuscitation
SECRETIONS
Anti-cholinergic cont’d…
Amitryptiline PR 25-50mg Q4H PRN
Meclizine 25mg PR Q4H PRN
compounded
Scopolamine patch 1.5mg Q3 days
Hyoscine 10mg S/Q Q2H PRN
NAUSEA/VOMITING
Anti-dopaminergic
Prochlorperazine 10 supp Q6H PRN
Promethazine 12.5 - 50mg supp Q8H
Haloperidol 0.5 mg – 1 mg po q4h prn
Could use haloperidol sub-Q on PCU
NAUSEA/VOMITING
Anti-cholinergics – nausea with movement
Scopolamine patch 1.5mg Q3 days
Meclizine – compounded
NAUSEA/VOMITING
5HT3 antagonists
Ondansetron PO – EDS
frequent dosing - short ½ life
Mirtazapine PO wafer Q HS
once a day dosing
sleep, pain (5HT2)
appetite stimulant, mood
SEIZURES
Barbituates
Phenobarbitol sub-Q not available community
Phenobarbitol sub-Q – limited hospital
SEIZURES
Anti-convulsants
Carbamazapine 100mg PR Q8H
Sodium channel blocker
Valproic acid 500mg PR Q8H
Gabaergic, sodium, calcium channel blocker
Both need frequent dosing
SEIZURES
Benzodiazapines
Midazolam:
reserved acute seizure
short half life
requires frequent dosing
$$
SEIZURES
Benzodiazapines
Ativan 2mg sub-Q or PR Q6H
Ativan SL not effective – swallowed
Clonazepam 2mg PR Q8H
- usually BID
- long half life
HOW DID WE DO?
No formal data
Perceptions
HOW DID WE DO?
Pain control adequate
Nausea/vomiting - better
Secretion – adequate
HOW DID WE DO?
Reduction complaints
reduced over sedation
Less confusion
HOW DID WE DO?
Methadone:
Very well tolerated
Very effective for dyspnea/pain
Palliative Care Unit Statistics (3A)
March 2011 – February 2013
Prescribing changes
S/Q opioid usage
CHANGES IN PRESCRIBING
CHANGES IN PRESCRIBING
CHANGES IN PRESCRIBING
CHANGES IN PRESCRIBING
Methadone Changes in Prescribing Orders
0
200
400
600
800
Methadone Scheduled 308 739
Methadone prn 7 16
2011-12 2012-13
CHANGES IN PRESCRIBING
Hydromorphone Total Oral Mg Used
0
20,000
40,000
60,000
80,000
2011 14,703 16,086 30,789
2012 22,656 47,384 70,040
HM SR HM IR Total HM
CHANGES IN PRESCRIBING
Morphine Total Oral Mg Used
0
5,000
10,000
15,000
2011 7,940 4,790 12,730
2012 7,950 5,730 13,680
Morphine SR Morphine IR Total Morphine
CHANGES IN PRESCRIBING
Oxycodone Total Oral Mg Used
0
500
1,000
1,500
2011 330 1,055 1,385
2012 0 915 915
Oxycodone SR Oxycodone IR Total Oxycodone
CHANGES IN PRESCRIBING
Methadone Total Oral Mg Used
0
50,000
100,000
150,000
200,000
250,000
Methadone 85,800 209,701
2011 2012
CHANGES IN PRESCRIBING
Total S/Q Medications Used
0
50,000
100,000
2011-12 16,905 76,850
2012-13 14,340 72,846
Morphine S/Q Hydromorphone S/Q
WHAT OTHER LESSONS? Time savings? Cost savings?
NURSING MED ADMIN TIMES
Looked at drug admin times
Different drugs/routes
NURSING MED ADMIN TIMES
Analgesics
Sub-Q Line Insertion/Priming
gather supplies, initiate sub-Q line min:sec
(most have sub-Q line – PRN meds) 8:00s
hydromorphone sub-Q med 3:45s x6 22:30s day
buccal methadone 2:15s x3 6:45s day
Time saved/pt 15:45s day
NURSING MED ADMIN TIMES
Analgesics cont’d …
Buccal methadone vs hydromorphone sub-Q
5 patients x 15:45s day
= 1:18:45s day
NURSING MED ADMIN TIMES
Analgesics cont’d …
min:sec
hydromorphone sub-Q med 3:45s x6 22:30s day
rectal methadone (ped feed tube) 3:30s
rectal methadone – TID 3:30s x3 10:30s day
Time saved/pt 12:00s day
NURSING MED ADMIN TIMES
Analgesics cont’d …
min:sec
hydromorphone sub-Q med 3:45s x6 22:30s day
rectal methadone – BID 3:30s x2 7:00s day
Time saved/pt 15:30s day
NURSING MED ADMIN TIMES
Analgesics cont’d …
Rectal methadone vs hydromorphone sub-Q
5 patients x 12:00s - 15:30s
= 1 hour – 1:17:30s
NURSING MED ADMIN TIMES
Anti-emetics
ondansetron sub-Q 3:45 x3 11:15s
sub-Q line insertion/priming 8 min
Nursing time used: 19 min 15 sec 1st day
mirtazapine RD daily 2:15s
NURSING MED ADMIN TIMES
Anti-Seizure
midazolam sub-Q Q4H 3 min 18 min/day
clonazepam gel tab PR BID 6 min 12 min/day
clonazepam – long half-life
midazolam – short half-life, break through seizures
COST SAVINGS
Analgesics
Morphine Injection Hydromorphone
Injection
Methadone
Oral Solution
10mg/ml = 43 cents 2mg/ml = 55 cents 10mg/ml = 37 cents/ml
15mg/ml = 44 cents 10mg/ml = $1.11
50mg/ml = $3.99 50mg/ml = $6.68
COST SAVINGS
Analgesics
MS Contin Hydromorph Contin Methadone Tablets
15mg = $.104 3mg = $.6845 1mg = 17 cents
30mg = $.14 4.5mg = $.8757 5mg = 57 cents
60mg = $.26 6mg = $1.0265 10mg = 90 cents
100mg = $.9968 12mg = $1.779 25mg = $1.70
200mg = $3.816 24mg = $3.285
30mg = $3.9355
COST SAVINGS
Analgesics
Fentanyl Patches
12 = $1.02 - $1.69
25 = $1.05 - $3.00
50 = $1.35 - $4.75
75 = $1.73 - $6.65
100= $2.35 - $8.45 (generic vs. brand)
COST SAVINGS
Analgesics
Morphine IR Hydromorph IR Oxycodone IR
5mg = 14 cents 1mg = 15 cents 5mg = 9 cents
10mg = 19 cents 2mg = 22 cents 10mg = 15 cents
20mg = 34 cents 4mg = 22cents 20mg = 15 cents
30mg = 44 cents 8mg = 52 cents
COST SAVINGS
Benzodiazepines
Clonazepam Tablet Midazolam Injection
.25mg = 7 cents 1mg/ml x 2ml = $.78 - $1.56
.5mg = 7 cents 1mg/ml x 5ml = $1.56 - $3.90
2mg = 13 cents 5mg/ml x 1ml = $.41 – $1.94
5mg/ml x 2ml = $2.65
Gel caps and lubricants very low -
not a factor
5mg/ml x 10ml = $8.82
COST SAVINGS
Anti-emetics
Mirtazapine RD 15mg $0.0833
Ondansetron Inj 4mg/2mL $0.68/vial
Ondansetron Inj 8mg/4mL $1.25/vial
Haloperidol 5mg/ml $1.10ml
Methotrimeprazine 25mg/ml $3.25ml
COST SAVINGS
Secretions
Hyoscine butyl bromide 20mg/ml $4.34/ml
Scopolamine patch 1.5mg $3.96
Amitryptiline 25mg $0.13
Amitryptiline 50mg $0.25
COST SAVINGS
Secretions
Atropine 0.6mg/ml $0.825/ml
Glycopyrrolate 0.2 mg/ml $7.46/2ml
Glycopyrrolate 0.2mg/ml $53.80/20ml
FUTURE
Cost Saving and Time Saving Benefits
1) Methadone as 1st line agent for dyspnea/pain
2) Clonazepam
3) Mirtazapine
LEARNING OBJECTIVES
Have Learned:
Why sudden nationwide shortage of injectable
meds
RQHR response to drug shortages
Drugs affected, shortage severity
Determinants in choosing alternate
medications
Medications we chose
LEARNING OBJECTIVES
Have Learned:
How did we do?
Prescribing changes
Any other lessons?
- time savings, cost savings
Future drug use
THANK YOU TO:
Dr. Martha Santamaria – Antonio Pedro
University Hospital
Dr. Lawrence Librach – University of
Toronto
Bev Cross, RN, Nurse Educator, RQHR
Dr. Alana Kilmury, Palliative Care Physician
RQHR
THANK YOU TO:
RQHR Pharmacy team
Regina Palliative Care Team Members
Kathleen Richlen-Tilden, PhD
Terrilynn Lowes, Marcia Sehn, Admin
Assistants
REFERENCES
CBC News Online
Pub Med Central, US National Library of
Medicine, National Institutes of Health,
Pharmacy and Therapeutics. Vol. 36(11); Nov
2011; PMC 3278171
Twycross R, Wilcock A (eds). Palliative Care
Formulary, 4th Ed., Palliativedrugs.com Ltd,
United Kingdom, 2012
REFERENCES
Pereira JL, Associates. The Pallium Palliative
Pocketbook: a peer-reviewed, referenced resource.
1st Ed., The Pallium Project, Edmonton, Canada, 2008
Walsh D, et al. Palliative Medicine, 1st Ed., Saunders
Elsevier, Philadelphia, 2009
Stahl SM, Stahl’s Essential Psychopharmacology, 3rd
Ed., Cambridge University Press, New York, 2008
REFERENCES
Kim S, Shin I, Kim J, Kim Y, Kim K, Kim Ki, Yang S, Yoon
J: Effectiveness of mirtazapine for nausea and insomnia in
cancer patients with depression. Psychiatry and Clinical
Neurosciences 2008; 62: 75-83
Chang F, Ho S, Sheen M: Efficacy of mirtazapine in
preventing intrathecal morphine-induced nausea and
vomiting after orthopaedic surgery. Anaesthesia 2010; 65:
1206-1211
Teixeira F, Novaretti T, Pilon B, Pereira P, Breda, M:
Mirtazapine (Remeron TM) as treatment for non-mechanical
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