pain & symptom management: rqhr response - injectable …saskpalliativecare.org/2013/june 14 -...

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

vomiting after gastric bypass. Obesity Surgery 2005; 15:

707-709