Download Safety of Fentanyl Patch Prescribing at UMHS

Precision of Transdermal
Fentanyl Prescribing at UMHS
Kate Veltman
Advised by Dr. John Clark
September 6, 2013
IRB HUM00062367
Objectives
• Explore the unique PK/PD profile of transdermal fentanyl
(TDF), the differences between oral opioids and
transdermal fentanyl, and how these differences affect
usage
• Review the FDA black box warning, dosing chart, and
absolute contraindications and determine if these are
supported by outside literature
• Look at the results of a retrospective study examining
transdermal fentanyl prescribing at UMHS and discuss
the implications for patient care
What is TDF?
• Long-acting transdermal opioid designed to be used for
chronic pain control
• Only CII opioid currently on the market in transdermal
form
• Other transdermal pain medications available:
• Buprenorphine (Schedule III)
• Lidocaine (legend, non-controlled)
http://medlibrary.org/lib/images-rx/fentanyl-transdermal-system-1/a7c456e6-403b-4aae-a57660b106bf66a7-01.jpg
TDF versus Oxycontin®
TDF
ER Oxycodone
Dosing schedule
Every 72 hours
Every 12 hours
Tmax
20 to 72 hours
2.1 to 3.2 hours
Half-life
20 to 27 hours
4.5 to 8 hours
6 L/kg
2.6 L/kg
Hepatic impairment
AUC ↑ 120%
AUC ↑ 95%
Renal impairment
AUC ↑ 100%
AUC ↑ 60%
Volume of distribution
Micromedex. Accessed July 24 2013.
Dosing
Current Analgesic
Daily Dosage (mg/day)
25 mcg/hr
50 mcg/hr
75 mcg/hr
100 mcg/hr
Oral Morphine
60-134
135-224
225-314
315-404
IV/IM Morphine
10-22
23-37
38-52
53-67
Oral Oxycodone
30-67
67.5-112
112.5-157
157.5-202
Oral
Hydromorphone
8-17
17.1-28
28.1-39
39.1-51
150-447
448-747
748-1047
1048-1347
20-44
45-74
75-104
105-134
Oral Codeine
Oral Methadone
Duragesic full prescribing information. Revised 7/2012.
Titration and tapering
• Titration
• May increase dose no more than every 3 days
• Increase based on amount of breakthrough meds
needed on days 2 and 3
• 45 mg morphine = 12.5 mcg/hr increase
• Dose interval may be changed to every 48 hours if
wearing off occurs, but dose increase should be
considered first
• Taper
• Decrease by no more than half the current dose no
more frequently than every 6 days
• Withdrawal symptoms may occur
Unique PK profile: Pros and Cons
BENEFITS
• Long-term, constant
pain relief
• Compliance
• No swallowing
DANGERS
• Overdose potential
• Mcg/hr strength
• Patient
understanding
• Requires careful
disposal
• Heat sensitive
Duragesic® and the FDA
• FDA mandated specific dosing guidelines and
contraindications designed to prevent fatal
respiratory depression
•
•
•
•
•
•
Patients who are not opioid tolerant
Acute pain or intermittent pain
Post-operative pain (in- or out-patient)
Mild pain
Respiratory compromise
Severe or acute bronchial asthma
• REMS program participant
Duragesic full prescribing information. Revised 7/2012.
Chronic Pain Management
• WHO guidelines: opioids are mainstay of therapy
• Oral drugs preferred
• Morphine: “gold standard” drug
http://idsportsmed.com/patient_education/45/eeb17d844459b3adc6ce05a5f1559f42
Ripamonti et al. Support Care Cancer. 2006;14:400-407.
Efficacy in pain management
• Equally effective in RCTs comparing to morphine for both
chronic non-cancer and cancer pain1,2
• Surgical pain: higher doses decrease PCA use compared
to placebo3
• Satisfaction, pain control: varies by study3,4
• Shows some benefit over ER morphine in regards to
pain during movement at 24 hours post-op, but not at
12 or 36 hours4
• Open-label crossover: fentanyl had higher satisfaction
and better pain control5
1. Allan et al. SPINE. 2005;30(22):2484-2490. 2. Ahmedzai & Brooks. J Pain Symptom Management. 1997;13(5):254-261. 3. Caplan et
al. JAMA. 1989;261(7):1036-1039. 4. Sevarino et al. Anesthesiology. 1992;77:463-466. 5. Allan et al. BMJ. 2001;322:1-7.
Convenience factors
• Dosed every 72 hours (or every 48 hours)
• Easier administration and compliance > 90%1
• No swallowing required
• Nursing studies show increased nurse
satisfaction when using fentanyl as opposed
to morphine PCA for post-surgical patients2
1. Chiou et al. AJH. 2010;27:31. 2. Lindley et al. JAN. 2009;65:1370.
Safety of TDF
• Serious adverse effects of all strong opioids:
• Constipation
• Nausea/vomiting
• Somnolence
• Respiratory depression and death
1. Allan et al. BMJ. 2001;322:1-7. 2. Weschules et al. PainMed.
2006;7:320-329. 3. Allan et al. SPINE. 2005;30:2484-2490.
Adverse Effects
• Compared to oral morphine, studies generally
show fentanyl is associated with:
• Increased nausea1
• Decreased constipation1,3
• Decreased sleep amount2
• Decreased ability to communicate2
• Increased risk of respiratory depression or
death4
• Participant withdrawal rates tend to be similar in
both groups in studies2,3
1. Allan et al. BMJ. 2001;322:1-7. 2. Weschules et al. PainMed. 2006;7:320-329. 3. Allan
et al. SPINE. 2005;30:2484-2490. 4. Sevarino et al. Anesthesiology. 1992;77:463-466.
Safety of TDF: Respiratory
Depression
• Serious, potentially fatal adverse event
• Bradypnoea: less than 10 breaths per minute1
• High risk in opioid naïve patients
• Can still occur in opioid tolerant patients
• Mechanism:2
• Opioid sensitive chemoreceptors responsible for
breathing rhythm decrease tonic input, causing
decreased breathing rate
• Decreases in tidal volume are observed
• This is partly compensated for by increased PaCO2
1. Bulow et al. Acta Anaesthesiol Scand. 1995;39:835-839. 2. Pattinson. Br
J Anaesth. 2008;100(6):747-758.
Safety of TDF: Respiratory
Depression
• Many studies on use in contraindicated
populations focus on pain score and common
adverse effects; do not monitor respiratory rate
• Japanese study: initiation of TDF in doses above
the recommended minimum (25 mcg/hr)
showed significant respiratory effects1
• This was true whether prescribed by general
physicians or palliative care specialists1
1. Hashizume et al. Kagaku Ryoho. 2007;34:897-902.
Safety of TDF: Respiratory
Depression
• Denmark study: Small RCT evaluating TDF vs morphine
PCA after major upper abdominal surgery
• TDF was applied 1 hour before surgery began and was
left in place for 72 hours
• 3 of 10 patients randomized to 100 mcg/hr TDF
experienced bradypnoea
• One required naloxone due to significantly decreased
PaO2
• All started between 11 and 12 hours after last
intraoperative fentanyl dose
Bulow et al. Acta Anaesthesiol Scand. 1995:39;835-839.
Safety of TDF: Respiratory
Depression
• USA: RCT of 42 patients undergoing major shoulder
surgery, receiving either 75 mcg/hr patch
immediately prior to surgery or morphine PCA post
surgery
• Significant decrease in respiratory rate with TDF
between hours 13 and 24 post-op (p = 0.002)
• Placebo: 16 ± 2 breaths per minute
• TDF: 14 ± 3 breaths per minute
• 3 patients experienced transient bradypnoea of 5 to
7 breaths per minute while sleeping; patients were
awoken and breathing rate increased
Caplan et al. JAMA. 1989;261:1036-1039.
What’s the actual risk?
• IMSN study of 3291 voluntarily reported incorrectly prescribed TDF
prescriptions in Canada, USA, UK and Ireland found:
• 32.8% were wrong dose, strength, or quantity of patches
• 30.5% were dose omission or underdosing
• The major themes of these Rxs were:
• Overdosing, or administered too soon
• Underdosing, or administered too late
• Patient did not need/should not have received medication
• Other
• There were significant risks to these patients
• 8% resulted in harm but not death
• 0.3% resulted in death
ISMP. 2009. Medication incidents related to the use of fentanyl
transdermal systems: An international aggregate analysis.
Study Rationale
• Current prescriptions written at UMHS are not evaluated
by a pharmacist for appropriate use before dispensing
• Unique pharmacokinetic factors of transdermal fentanyl
make incorrect dosing potentially dangerous to the
patient
• It is currently unknown whether patients at UMHS are
receiving prescriptions written in accordance with FDAlisted guidelines and contraindications
• Objective: to determine whether prescribers at UMHS
are appropriately using TDF, and if not, what deviations
from are most common
Methods
• Retrospective descriptive chart review
• 200 patients reviewed, 106 qualified
• Inclusion criteria
• 18 or older
• First TDF prescription written at UMHS
• Filled at least one TDF Rx at UMHS in 2010 or 2011
• Exclusion criteria
• First Rx written by outside hospital or physician
• Lack of proper documentation to determine
previous analgesia
Methods
• Data collected:
• General patient information, including age and
BMI
• Previous analgesia (drug and dosing)
• Length of time on previous analgesia
• Prescriber service
• Presence of contraindications
• Surgical pain
• Non-surgical acute pain
• Intermittent pain or PRN dosing
• Accurate dosing was determined as maximum
daily dose ± 25%
Methods
• Statistical analysis
• Descriptive statistics calculated using SPSS
• Categorical data: chi squared analysis
• Discrete data: regression analysis
• Data was considered significant if p < 0.05
• Analysis included:
• Actual dose as a function of age or BMI
• Accurate dosing as related to various
demographic characteristics
Results
Characteristic
Quantity
(n = 106)
Percentage
Female
50
47%
Age*
55 ± 12 years
N/A
Overweight
50/91
56%
Caucasian
89
83%
Started inpatient
20
19%
* p = 0.022; R = -0.222
Results
Prescriber Service
Prescriber Type
3%
2% 3%
10%
Hem/Onc
Gen Med
NP, 41%
MD,
42%
Surgery
82%
SympAll
Other
PAC,
17%
Results
Analgesia Prior to TDF
35%
30%
32%
27%
25%
20%
15%
10%
10%
12%
12%
5%
0%
2%
4%
Results
Incidences of Prescribing Discrepancies
60%
54%
50%
40%
39%
30%
20%
10%
16%
0%
No breakthrough med
Incorrect dose
Contraindicated
Incidence of Dosing Discrepancies
35%
30%
29%
25%
25%
20%
15%
18%
10%
5%
0%
Not appropriate
Overdose
Underdose
Use In Contraindicated Populations
25%
20%
21%
15%
10%
5%
8%
8%
3%
0%
PRN usage
Acute pain
Surgical pain < 1 week on
opioids
Results
• 19 patients did not qualify for any strength
of TDF based on previous opioid usage and
were evaluated based on:
• Swallowing ability
• Prescribing of breakthrough pain medications
• Initial dosage
Ability to Swallow
Considerable
difficulty
swallowing, 3
Difficulty
swallowing, 3
Able to
swallow, 13
Breakthrough Medication Prescribing
No
breakthrough
meds, 7
Breakthrough
meds, 12
Starting Dose
50 mcg/hr, 2
25 mcg/hr, 2
12 mcg/hr, 15
Conclusions
• The majority of patients (54%) are receiving an incorrect dose
of TDF upon initiation of therapy
• Prescribers are using TDF as a first-line therapy, both for initial
pain control and for long-acting opioids
• Patients not opioid tolerant at any level are receiving TDF
relatively frequently (18% of patients) and do not have clearly
indicated prescriber rationale
• Most patients are being treated for conditions that typically
require long-acting pain medication, with a predominance
(82%) in hematology/oncology
• All types of prescribers are prescribing similarly, and there are
no significant trends suggesting consistent prescribing
Future Direction
• Determine barriers to correct prescribing
• Develop a strategic medication safety plan
to improve patient safety by facilitating
proper prescribing
• Discourage improper prescribing via
prescriber education and other available
tools such as CPOE prompts
Discussion Questions
• Are there any contraindications that appear to be
either unclear or unreasonable?
• Which errors seen at UMHS seem most likely to
cause patient harm?
• What challenges could prescribers be facing that
prevent them from proper prescribing?
• What role can pharmacists play in prevention of
patient harm with use of TDF?