Making therapeutic decisions
with ongoing drug shortages
Dr. Roland Halil, BSc(Hon), BScPharm, ACPR, PharmD
Pharmacist, Bruyere Academic Family Health Team
Assistant Professor, Department of Family Medicine, University of Ottawa
rhalil@bruyere.org
November, 2013
Faculty/Presenter Disclosure
• Faculty: Dr. Roland Halil
• Program: 51st Annual Scientific Assembly
• Relationships with commercial interests:
– Not Applicable
Disclosure of Commercial
Support
• This program has received No Commercial Support
Mitigating Potential Bias
• Not Applicable
Objectives
• Understand contributory factors to drug
shortages in North America
• Promote a logical process for selecting
alternative drug therapy.
– Promote a process for applying population level
evidence to individual patients.
– List the 4 steps in rationalizing drug therapy choices
using EBM.
• List resources in determining most recent drug
shortages in Canada.
Drug Shortages
• Multifactorial
– FDA driven crack-down on manufacturing quality
• Globalization of manufacturing
– Raw material shortages
– Small number of suppliers / shrinking profit
margins
– Increasing demand
– “Just-in-time” inventory management
1) Drug Shortages. A Guide for Assessment and Patient Management. CPhA 2010
2) Darrell Issa (CA-49), Chairman U.S. House of Representatives Committee on Oversight and Government
Reform. FDA’s Contribution to the Drug Shortage Crisis. U.S. HOUSE OF REPRESENTATIVES, 112TH
CONGRESS, COMMITTEE ON OVERSIGHT AND GOVERNMENT REFORM, JUNE 15TH, 2012
Don’t Panic!
The (Relatively) Good News
• Most shorted drugs are:
– Injectables
• Less commonly used in primary care
– Can be obtained within a reasonable delay
• Most patients can ‘make do’
– Competing manufacturers can handle part of the
demand to increase supply
– Therapeutic alternatives exist
• Four Steps of Rational Prescribing
• A logical process for finding alternatives
Options
• First, lay out therapy options:
– Drug A
– Drug B
– Drug C
– Non-drug options D, E, & F
– No treatment
• (Always an option!)
Rational Prescribing
Needs a Process to Provide Structure
1.
2.
3.
4.
Efficacy
Toxicity
Cost
Convenience
1. What’s it going to do
for me?
2. What’s the catch?
3. How much is this
going to run me?
4. How much work is
this going to be?
1. Efficacy – Ask About…
1. Hard outcomes:
a) Reduction in mortality?
b) Reduction in morbidity?
2. Surrogate outcomes:
•
Clinically relevant?
3. Then, “What is the quality of this evidence?”
•
•
•
•
•
Meta-analysis?
Randomized Controlled Trial?
…
Case series?
Anecdotal evidence?
1. Efficacy
• If there is no efficacy, why waste your time on
the potential toxicity, cost and inconvenience
of a drug?
• If there is proven efficacy at the population
level, then balance this against the potential
toxicity to the individual.
2. Toxicity – Ask About…
Bothersome
Common
Rare
Severe
Not legal
Who cares
2. Toxicity
• Age is important:
• Newer agents =
• Older agents =
Less Safety Data
More Safety Data
• N.B. RCTs are usually powered to show
differences in efficacy, not always toxicity.
– Efficacy endpoint: ~ 1 in 5000
– Toxicity endpoint: ~ 1 in 20,000
• So, might need > 4 RCTs to see statistical
signals of toxicity after a drug reaches market.
3. Cost – Ask About…
• Patient cost vs Societal cost
• Covered by provincial drug plan?
– By private plans?
4. Convenience – Ask About…
• What is the likelihood of compliance?
1. Frequency of administration?
–
Daily vs QID?
2. Special restrictions?
–
–
PO vs IV?
Home vs Office vs Hospital therapy?
3. Many interactions?
4. Special monitoring requirements?
5. Constraints in supply?
A simple example:
Metformin
Januvia®
VS
Efficacy
1. HARD Outcomes
–
Mortality benefit
– Metformin – reduction in CV events (UKPDS-34 trial)
– Januvia - none
–
Morbidity benefit
– Metformin – reduction in microvascular complications
– Januvia - none
Efficacy
2. SURROGATE Outcomes
a) Hgb-A1c reduction
• Metformin ~ 1% - 2%
• Januvia® ~ 0.5% - 0.8%
b) Insulin Sparing Effects
• Metformin - yes
• Januvia® - none
c) Weight neutral
• Metformin – yes
• Januvia - yes
Toxicity
• Metformin
– ?Rare cause of lactic acidosis?
• 0.03 cases / 1000 pt-yrs
– ~ 50% fatal
• Never clearly implicated
– GI upset / diarrhea
• Start low, go slow!
– B12 / folate deficiency /
anemia (6 - 8/100)
• Reduced absorption – easy to
supplement
– Anorexia
• usually transient
• Januvia®
– ?Unknown
• ?Pancreatitis
– Too few patients examined
–
–
–
GI upset
edema
?elevated risk of
infection?
Cost & Convenience
• Metformin
• Januvia®
– ~ $33 / 100 days(^)
– ~ $315 / 100 days(^)
– $ 0.0587 / tab(*)
– Covered by ODB
– $ 2.8948 / tab(*)
– Covered by ODB
– QD to TID po
– Once daily po
(*) – Ontario Drug Benefit e-Formulary. Accessed Oct 26/12
(^) – Rxfiles.ca Hypoglycemic Comparison Charts. Aug 2012
A simple example:
Metformin
Januvia®
VS
•
•
•
•
Life saving
Well tolerated
Dirt-cheap
A classic!
• Young and sexy
What if Metformin 500mg tablets
were in short supply?
1. Do nothing and wait
2. Rx 850mg tabs of metformin
– No ODB coverage
3. Rx Janumet 850/50mg tabs
– (Januvia + metformin) – ODB covered
4. Rx sitagliptin (Januvia®) instead
5. Rx other therapies instead
– Eg. glyburide, gliclazide, acarbose, etc.
Clinical scenario 1
• 60 y.o. female patient
• PMHx
– Diabetes type 2 (1998)
– NSTEMI (2009)
• Meds
– Bisoprolol 5mg qhs
– ASA 81mg daily
– Simvastatin 20mg qhs
• BP: 148/98; HR 60 bpm
• eGFR 80mL/min, urACR = 10
• K+ = 4.0; LDL = 1.5
• This patient is missing
an:
– ACE inhibitor!
Choosing ACEinh
•
•
•
•
•
•
•
•
Enalapril (Vasotec)
Ramipril (Altace)
Quinapril (Accupril)
Perindopril (Coversyl)
Lisinopril (Prinivil/Zestril)
Benazepril (Lotensin)
Trandolapril (Mavik)
Fosinopril (Monopril)
• Efficacy
– All equivalent
• Cardio- and Nephroprotection
• BP reduction
• Toxicity
– All equivalent
• Hyperkalemia, ARF,
angioedema
• Convenience
– All QD-BID
Cost
• Any except PERINDOPRIL (Coversyl®)
– Not yet generic, although covered under ODB
–
–
–
–
–
Perindopril
Enalapril
Fosinopril
Ramipril
Lisinopril
$0.63- $1.10 per tab
$0.20 - $0.35 per tab
$0.23- $0.27 per tab
$0.17 – $0.25 per cap
$0.13 - $0.19 per tab
• N.B. In cases of shortage or high costs, higher
strength tabs could be cut in ½ or ¼.
Drug Shortage Resources
• www.vendredipm.ca/
• www.fridaypm.ca/
– By SigmaSanté
• A non-profit organization
that negotiates goods &
services for healthcare
organizations in Montreal
& Laval regions
• www.drugshortages.ca/
– Government of Canada
& Province of Alberta
• Multi-Stakeholder
Steering Committee on
Drug Shortages to
advance collaborative
work on drug shortages.
• www.ashp.org/menu/DrugShortages
• American Society of Health-System Pharmacists database
Summary
• Drug shortages are likely here to stay.
– Step 1: assess indication
– Step 2: assess options
– Step 3: choose best option using a logical process
• Applying EBM requires a process
– It distills out high quality information
• (Efficacy)
– It protects patients from unnecessary harm (and you from
medico-legal harm!)
• (Toxicity)
– It saves time
• (Cost and Convenience)
Suggested Readings: On Shortages
• University of Saskatchewan – MedSask - Primer on drug shortages
–
http://medsask.usask.ca/
• CPhA (Canadian Pharmacists Association) - Drug Shortages - A Guide for
Assessment and Patient Management
–
http://www.pharmacists.ca/cpha-ca/assets/File/cpha-on-the-issues/DrugShortagesGuide.pdf
• CSHP (Canadian Society of Hospital Pharmacists) - CSHP Speaks Up on Drug
Shortages
–
–
–
–
–
http://www.cshp.ca/advocacy/CSHPspeaks/drugShortages_e.asp
http://www.cshp.ca/advocacy/CSHPspeaks/docs/CMA_CPhA_CSHPnewsrelease_jan2013.pdf
http://www.cshp.ca/advocacy/CSHPspeaks/docs/survey_backgrounder_Jan2013.pdf
http://www.cshp.ca/dms/dmsView/1_Drug-shortages---OVRDIS-Update-Mar%2712.pdf
http://www.cshp.ca/dms/dmsView/1_Standing-Com-on-Health-Mar%2712---CSHP-Speaking-NotesFINAL.pdf
• U.S. House of Representatives Committee on Oversight and Government
Reform - FDA’s Contribution to the Drug Shortage Crisis (June 2012)
–
http://oversight.house.gov/wp-content/uploads/2012/06/6-15-2012-Report-FDAs-Contribution-to-theDrug-Shortage-Crisis.pdf
QUESTIONS?