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1
Breakthrough Cancer Pain (BTCP)
and Its Treatment
•
•
•
•
INSYS Therapeutics is sponsoring this presentation
I am a paid speaker presenting on behalf of INSYS Therapeutics
This promotional, non-CME program is intended for healthcare professionals who
are involved in the management of breakthrough pain in cancer patients 18 years
of age and older who are already receiving and who are tolerant of opioid therapy
for their underlying persistent cancer pain
This is an on-label promotional program, and the information provided is
consistent with FDA guidelines
www.subsysspray.com
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
2
Types of Pain
Nociceptive Pain
Neuropathic Pain
Somatic
Visceral
Skin, muscle, bone
Internal organs or viscera
Nerve damage/injury
Diffuse
Gnawing
Cramping
Aching
Pins and needles
Tingling
Burning
Shooting
Sharp
Aching
Stabbing
Throbbing
Pressure
Referenced with permission from the NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) for Adult Cancer Pain V.2.2014. ©
National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed March 17, 2016. To view the most recent and complete
version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK ®, NCCN®, NCCN GUIDELINES®, and all other
NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc..
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
3
Persistent Pain in Cancer
Persistent pain in cancer survivors is often underreported, under-recognized, and under-treated1
Causes of Chronic, Persistent Pain in Cancer Patients
Pain Related
to Cancer
Pain of metastatic disease2
• Compression
• Obstruction
• Fracture
• Hemorrhage
• Tumor-related neuropathic pain
• Bone, soft tissue, visceral, or
leptomeningeal metastases
1.
2.
Antineoplastic
Therapies1,2
Procedural or Surgical
Chemotherapy
Hormonal therapy
Radiotherapy
The British Pain Society’s Cancer Pain Management. The British Pain Society website.
www.britishpainsociety,org. Published January 2010. Accessed May 13, 2014.
Parala-Metz A, Davis M. Cleveland Clinic Center for Continuing Education. Cancer pain. 2013.
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
4
Components of Cancer Pain
Cancer Pain
Intermittent
Intermittent
Bursts of pain without underlying
persistent daily pain5
1.
2.
3.
4.
5.
Moderate to severe pain that
Common
Short Acting
lasts throughout
the day Opioids
(>12 h)2,3
Oxycodone IR
Oxymorphone IR
Hydromorphone IR
Morphine IR
Common NSAIDS
Ibuprofen
Naproxen
SAO + NSAID
Bennett D et al. Pharm Ther. 2005;30(5):296-301.
Portenoy RK, Hagen NA. Pain. 1990;41(3):273-281.
Portenoy RK et al. Pain. 1999;81(1-2):129-134.
Hwang SS et al. Pain. 2003;101:55-64.
Referenced with permission from the NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) for Adult Cancer Pain
V.2.2016. © National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed March 17, 2016. To view the most
recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK ®, NCCN®,
NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc..
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
5
Components of Cancer Pain
Cancer Pain
Intermittent
Intermittent
Bursts of pain without underlying
persistent daily pain5
1.
2.
3.
4.
5.
Persistent
Pain that lasts throughout
the day (>12 h)1,2
Common Long Acting Opioids
Morphine ER
Oxycodone
ER
Common
NSAIDS
Hydromorphone
ER
Ibuprofen
Hydrocodone
Naproxen ER
Oxymorphone
SAO + NSAID ER
Fentanyl Patch
Bennett D et al. Pharm Ther. 2005;30(5):296-301.
Portenoy RK, Hagen NA. Pain. 1990;41(3):273-281.
Portenoy RK et al. Pain. 1999;81(1-2):129-134.
Hwang SS et al. Pain. 2003;101:55-64.
Referenced with permission from the NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) for Adult Cancer Pain
V.2.2016. © National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed March 17, 2016. To view the most
recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK ®, NCCN®,
NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc..
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
6
Components of Cancer Pain
Cancer Pain
Intermittent
Intermittent
Intermittent
Persistent
Bursts of pain without underlying
persistent daily pain5
TIRFs
Fentanyl Sublingual Spray
OTFC Lozenge
Fentanyl Citrate Tablet
Fentanyl Citrate Nasal Spray
Fentanyl Citrate Buccal Soluble Film
Pain that lasts throughout
the day (>12 h)1,2
Breakthrough
Transient exacerbation
of pain or episodic pain
Common NSAIDS
that “breaks through” regularly scheduled
Ibuprofen
opioid treatment1-5
Naproxen
• Typically severe intensity
SAO + NSAID
• In patients with persistent pain otherwise
controlled by around-the-clock opioids
1. Bennett D et al. Pharm Ther. 2005;30(5):296-301. 2. Portenoy RK, Hagen NA. Pain. 1990;41(3):273-281. 3. Portenoy RK et al. Pain. 1999;81(1-2):129134. 4. Hwang SS et al. Pain. 2003;101:55-64. 5. Referenced with permission from the NCCN Clinical Practice Guidelines In Oncology (NCCN
Guidelines®) for Adult Cancer Pain V.2.2016. © National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed March 17, 2016. To
view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK ®, NCCN®, NCCN
GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc..
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
7
The CDC Guideline for Prescribing Opioids and the American Society
of Clinical Oncologist (ASCO) Guidance on Opioid Therapy
CDC Guideline for Prescribing Opioids for Chronic Pain
(released March 18, 20161):

Recommendations for primary care clinicians that
opioids should not be first-line or routine therapy for
chronic pain outside of active cancer, palliative, and endof-life care
ASCO Policy Statement on Opioid Therapy: Protecting Access to
Treatment for Cancer-Related Pain (released March 23, 20162):

Cancer Patients Are a Special Population and should be
largely exempt from regulations restricting access to or
limiting doses of prescription opioids

There is strong evidence of under treatment of cancerrelated pain

Among patients with cancer, opioid agents remain an
essential part of many pain treatment plans
1 CDC
Guideline for Prescribing Opioids for Chronic Pain – United States, 2016
Policy Statement issued May 23, 2016
2 ASCO
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
8
Characterization of BTCP
Characteristics can vary widely among patients1-6
Severity1-6
•
Often severe or excruciating
Time to peak pain intensity
(median)1,2,4-6
•
<1 to 10 minutes
Duration (median)1,4-6
•
15 to 60 minutes
Episodes per day (median)1-6
•
1 to 7 episodes per day
Idiopathic or incident-related
(predictable or unpredictable)
4.
1. Portenoy RK, Hagen NA. Pain. 1990;41(3):273-281.
5.
2. Portenoy RK et al. Pain. 1999;81(1-2):129-134.
3. Zeppetella G et al. J Pain Symptom Manage. 2000;20(2):87-92. 6.
Davies A et al. J Pain Symptom Manage. 2013;46:619-628.
Portenoy RK et al. J Opioid Manage. 2010;6:97-108.
Hwang SS et al. Pain. 2003;101:55-64.
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
9
Breakthrough Cancer Pain (BTCP) negatively affects a
majority of chronic cancer pain patients
In a pooled analysis of 19 studies, about 60% of
chronic cancer pain patients experienced BTCP 1
• Prevalence rates range from 39.9% to 80.5%
Patients with BTCP have a 5X greater burden on
healthcare costs2
1.
2.
Deandrea S et al. J Pain Symptom Manage. 2014;47(1):57-76.
Fortner et al. J of Pain, 2002;3(1): 38-44
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
10
Limitations of Short Acting Opioids (SAOs) and
Long Acting Opioids (LAOs) when treating BTCP
Short-acting oral opioids may not
provide timely relief
Increasing the dose of ATC
medication may:
• Increase the risk of opioid
tolerance
• Increase side effects such as
constipation, sleepiness, and
confusion
Bennett D et al. Part 2: Management. Pharm Ther. 2005;30(6):354-361.
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
11
Idealized Treatment
The ideal treatment for
BTCP would match the
temporal characteristics
of BTCP as much as
possible
Unlike SAOs and LAOs,
TIRF Medications offer
rapid onset of analgesic
effect
1.
2.
3.
Bennett D et al. Part 2: Management. Pharm Ther. 2005;30(6):354-361.
Zeppetella G. Opioids for the management of breakthrough cancer pain in adults: a systematic review undertaken as part
of an EPCRC opioid guidelines project. Palliat Med. 2011;25(5):516-524.
Smith H. A comprehensive review of rapid-onset opioids for breakthrough pain. CNS Drugs. 2012;26(6):509-535.
Please see Indication, Important Safety Information and Limitations of Use on slides 12-15
12
The First and Only Sublingual Spray
for Breakthrough Cancer Pain
SUBSYS® is indicated for the management of breakthrough pain in adult cancer patients who are
already receiving and who are tolerant to around-the-clock opioid therapy for their underlying
persistent cancer pain. Patients considered opioid tolerant are those who are taking around-theclock medicine consisting of at least 60 mg of oral morphine daily, at least 25 mcg of transdermal
fentanyl/hour, at least 30 mg of oral oxycodone daily, at least 8 mg of oral hydromorphone daily or
an equianalgesic dose of another opioid daily for a week or longer. Patients must remain on aroundthe-clock opioids when taking SUBSYS.
This product must not be used in opioid non-tolerant patients because life-threatening respiratory
depression and death could occur at any dose in patients not on a chronic regimen of opioids. For
this reason, SUBSYS is contraindicated in the management of acute or postoperative pain.
SUBSYS is intended to be used only in the care of cancer patients and only by oncologists and pain
specialists who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer
pain.
Limitations of Use
As part of the Transmucosal Immediate-Release Fentanyl (TIRF) REMS Access Program,
SUBSYS may be dispensed only to outpatients enrolled in the program. For inpatient administration
(e.g., hospitals, hospices, and long-term care facilities that prescribe for inpatient use) of SUBSYS,
patient enrollment is not required.
www.subsysspray.com
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
13
Important Safety Information
WARNING: RISK OF RESPIRATORY DEPRESSION, MEDICATION ERRORS, ABUSE POTENTIAL
Respiratory Depression
Fatal respiratory depression has occurred in patients treated with transmucosal immediate-release fentanyl products such as SUBSYS®,
including following use in opioid non-tolerant patients and improper dosing. The substitution of SUBSYS for any other fentanyl product
may result in fatal overdose.
Due to the risk of respiratory depression, SUBSYS is contraindicated in the management of acute or postoperative pain including
headache/migraine and in opioid non-tolerant patients.
Death has been reported in children who have accidentally ingested transmucosal immediate-release fentanyl products. SUBSYS must be
kept out of reach of children. [see Patient Counseling Information (17.3) and How Supplied/Storage and Handling (16.1)].
The concomitant use of SUBSYS with CYP3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause
potentially fatal respiratory depression [see Drug Interactions (7)].
Medication Errors
Substantial differences exist in the pharmacokinetic profile of SUBSYS compared to other fentanyl products that result in clinically
important differences in the extent of absorption of fentanyl that could result in fatal overdose.
- When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products to SUBSYS. [see Dosage and
Administration (2.1), Warnings and Precautions (5.2), and Clinical Pharmacology (12.3)].
- When dispensing, do not substitute a SUBSYS prescription for other fentanyl products.
Abuse Potential
SUBSYS contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid
analgesics. SUBSYS can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing
or dispensing SUBSYS in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion.
Because of the risk for misuse, abuse, addiction, and overdose, SUBSYS is available only through a restricted program required by the Food
and Drug Administration, called a Risk Evaluation and Mitigation Strategy (REMS). Under the Transmucosal Immediate-Release Fentanyl
(TIRF) REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in
the program. [See Warnings and Precautions (5.10)] Further information is available at www.TIRFREMSaccess.com or by calling
1-866-822-1483.
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
14
Important Safety Information Continued
Contraindications
•
•
•
SUBSYS® is contraindicated in opioid non-tolerant patients.
SUBSYS is contraindicated in the management of acute or postoperative pain including headache/migraine. Life-threatening
respiratory depression and death could occur at any dose in opioid non-tolerant patients.
SUBSYS is contraindicated in patients with known intolerance or hypersensitivity to any of its components or the drug fentanyl.
Anaphylaxis and hypersensitivity have been reported in association with the use of other oral transmucosal fentanyl products.
Warnings and Precautions
•
•
•
•
•
Clinically significant respiratory depression can occur. Monitor patients accordingly. Respiratory depression is the chief hazard of
opioid agonists, including fentanyl, the active ingredient in SUBSYS. Respiratory depression is more likely to occur in patients with
underlying respiratory disorders and elderly or debilitated patients, usually following large initial doses in opioid non-tolerant
patients, or when opioids are given in conjunction with other drugs that depress respiration.
In cancer patients with mucositis, exposure to SUBSYS was greater than in patients without mucositis. For patients with Grade 1
mucositis, the increased maximum serum concentration and overall exposure requires closer monitoring for respiratory depression
and central nervous system depression, particularly during initiation of therapy with SUBSYS.
For patients with Grade 2 mucositis or higher, avoid use of SUBSYS unless the benefits outweigh the potential risk of respiratory
depression from increased exposure
SUBSYS is not bioequivalent with other fentanyl products. Do not convert patients on a mcg per mcg basis from other fentanyl
products. When dispensing, DO NOT substitute a SUBSYS prescription for any other fentanyl product. The substitution of the
same dose of SUBSYS for the same dose of any other fentanyl product may result in a fatal overdose.
Patients and their caregivers must be instructed that SUBSYS contains a medicine in an amount which
can be fatal to a child. Death has been reported in children who accidentally ingested transmucosal immediate-release fentanyl
products. Patients and their caregivers must be instructed to keep both used and unused dosage units out of the reach of children.
All used units should be disposed of immediately after uses as they represent a special risk to children.
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
15
Important Safety Information Continued
Warnings and Precautions
•
The concomitant use of SUBSYS® with other CNS depressants, including other opioids, sedatives or hypnotics, general anesthetics, phenothiazines,
tranquilizers, skeletal muscle relaxants, sedating antihistamines, and alcoholic beverages may produce increased depressant effects (e.g.,
respiratory depression, hypotension, and profound sedation). Concomitant use with strong and moderate inhibitors of CYP450 3A4 isoform (e.g.,
erythromycin, ketoconazole, and certain protease inhibitors) may increase fentanyl levels, resulting in increased depressant effects. Patients on
concomitant CNS depressants must be monitored for a change in opioid effects. Consideration should be given to adjusting the dose of SUBSYS if
warranted.
•
Patients taking SUBSYS must be warned that opioid analgesics impair the mental and/or physical ability required for the performance of
potentially dangerous tasks (e.g., driving a car or operating machinery). Warn patients taking SUBSYS of these dangers and counsel them
accordingly.
•
Because potent opioids can cause respiratory depression, titrate SUBSYS with caution in patients with chronic obstructive pulmonary disease or
preexisting medical conditions predisposing them to respiratory depression. In such patients, even normal therapeutic doses of SUBSYS may
further decrease respiratory drive to the point of respiratory failure.
•
Administer SUBSYS with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention such as those
with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient with a head injury
and should be used only if clinically warranted
•
Use SUBSYS® with caution in patients with bradyarrhythmias.
•
SUBSYS is not recommended for use in patients who have received MAO inhibitors within 14 days because severe and unpredictable potentiation
by MAO inhibitors has been reported with opioid analgesics.
Drug Interactions
•
Monitor patients for opioid toxicity who begin therapy with, or increase the dose of, inhibitors of CYP450 3A4, or stop therapy with, or decrease
the dose of, inducers of CYP450 3A4
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
16
SUBSYS® Spray Technology
SUBSYS is a unique compact single-unit
spray device delivering a small volume
of oral solution, 0.1 mL (2-3 drops)
Formulated to be disbursed over the
broad permeable sublingual mucosa to
allow for rapid absorption of fentanyl
across the sublingual mucosa
• Nonionized fentanyl – in a form
ready for absorption – sprayed as a
fine mist over a broad, permeable
sublingual mucosa
• Sugar free – xylitol, which does not
promote dental caries added as a
sweetener
• Does not require saliva to
administer, but must first swallow
any saliva present
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
Xylitol professional information/ www.xylitol.org. Accessed 8/3/2016
Burt BA. The use of sorbitol- and xylitol-sweetened chewing gum in caries control. J Am Dent Assoc. 2006;137(2):190-196.
17
Pharmacokinetics: Extent of Absorption
Fentanyl Plasma Concentrations of SUBSYS® Compared to Actiq®
• Absolute bioavailability*† (AUC0-∞) of SUBSYS was 76% vs 51% for Actiq
• SUBSYS achieved roughly 50% more bioavailability than Actiq
*Absolute bioavailability is (AUC0-∞)
calculated as a percentage of IV which is
100%.
†Fentanyl
pharmacokinetic profile and
bioavailability depend on the fraction of
the dose that is absorbed through the
sublingual mucosa and the fraction
swallowed from the gastrointestinal tract.
Monitor patients with Grade 1 mucositis
closely for signs of respiratory and central
nervous system depression particularly
during initiation of therapy with SUBSYS.
The use of SUBSYS should be avoided in
patients with Grade 2 and more severe
mucositis unless the benefits are expected
to outweigh the risk of respiratory depression.
In a study that compared the relative bioavailability of SUBSYS and Actiq (oral transmucosal fentanyl citrate) in 21 healthy adult subjects, the
rate and extent of fentanyl absorption were considerably greater with SUBSYS (34% greater maximum plasma concentration [C max] and 38%
greater systemic exposure [AUCinf]).
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
Parikh N, Goskonda V, Chavan A, Dillaha L. Single-dose pharmacokinetics of fentanyl sublingual spray and oral transmucosal fentanyl
citrate in healthy volunteers: a randomized crossover study. Clin Ther. 2013;35(3):236-243.
Actiq® (oral transmucosal fentanyl citrate) is a trademark of Cephalon Inc. or its affiliates.
Data on file, INSYS Therapeutics.
18
Pharmacokinetics: Rate and Extent
of Absorption
Fentanyl Plasma Concentrations of SUBSYS® Compared to Actiq®
A = 5 minutes, SUBSYS blood levels were approximately that of Actiq at 15 minutes
B = At 10 minutes, SUBSYS blood levels were approximately that of Actiq at 60 minutes
In a study that compared the
relative bioavailability of
SUBSYS and Actiq (oral
transmucosal fentanyl citrate)
in 21 healthy adult subjects,
the rate and extent of fentanyl
absorption were considerably
greater with SUBSYS
(34% greater maximum plasma
concentration [Cmax] and 38%
greater systemic exposure
[AUCinf]).
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
Parikh N, Goskonda V, Chavan A, Dillaha L. Single-dose pharmacokinetics of fentanyl sublingual spray and oral transmucosal fentanyl
citrate in healthy volunteers: a randomized crossover study. Clin Ther. 2013;35(3):236-243.
Actiq® (oral transmucosal fentanyl citrate) is a trademark of Cephalon, Inc. or its affiliates.
19
Efficacy: Pain Relief
Primary endpoint, Summed Pain Intensity Difference at 30 minutes post
treatment (SPID30), was achieved
Pain Relief was also achieved at all time points starting at 5 minutes (5, 10,
15, 30, 45, 60 minutes)
A randomized, double-blind, placebo-controlled
study designed to determine the efficacy of
SUBSYS. Study enrolled 130 adult opioidtolerant patients with BTCP. Ninety-eight
patients entered the double-blind period and 96
patients were evaluable. The dose range studied
was from 100 mcg per dose to 1600 mcg per
dose. Patients rated Pain Relief (PR) using a 5point categorical scale (1=no relief, 2=a little
relief, 3=moderate relief, 4=a lot of relief,
5=complete relief). P- value = < 0.0001 for all
time points measured. Pain Intensity Difference
(PID) was calculated as the difference in pain
intensity at each time interval relative to the
baseline pain intensity. Summed Pain Intensity
Difference (SPID) was calculated as the
cumulative sum of PID scores across time. The
primary endpoint was the Summed Pain
Intensity Difference at 30 minutes post dose
(SPID30).
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
Rauck et al. Curr Med Res Opin. 2012;28(5):859-870.
20
Efficacy: Treatment Satisfaction
Questionnaire
Mean scores for all four TSQM domains improved between start of titration period and
the start of the double-blind period
• 9 out of 10 patients reported satisfaction with onset versus 2 out of 10 with previous medication*
• 9 out of 10 patients reported overall satisfaction† with SUBSYS
*Baseline medications were primarily traditional immediate-release opioids. Ten percent of baseline medications were TIRFs.
†A Treatment Satisfaction Questionnaire for Medication (TSQM) scale was used to assess the satisfaction with previous rescue
medications used for BTCP at baseline and SUBSYS following the titration period. TSQM was a secondary end-point
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
Rauck et al. Curr Med Res Opin. 2012;28(5):859-870.
21
SUBSYS® Safety Profile
Adverse events
associated with SUBSYS
were consistent with
those expected with
fentanyl treatment:
nausea, somnolence,
dizziness, vomiting,
pyrexia, diarrhea, and
peripheral edema
<1% discontinuation rate
due to application site
irritation, somnolence,
and constipation
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
22
Finding an effective Dose
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
23
How to use SUBSYS®
Patient Effective Dose Distribution in Clinical Trial
In clinical trials:
75% of patients found an effective SUBSYS dose between 600-1600 mcg
•
Only 4% of patients found an effective dose of 100 mcg
No correlation was found between the around-the-clock dose and the effective
SUBSYS dose
•
The oral morphine equivalent daily around-the-clock dose was 180 mg median (324 mg mean)
*Effective dose defined
as a dose used
consecutively to treat 2
BTCP episodes with
adequate pain relief
and acceptable side
effects for patients
entering double-blind
period of clinical trials.
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
Rauck et al. Pain Management. (Epub ahead of print)
24
Relationship Between Transdermal Fentanyl
Patch and SUBSYS Effective Dose
Safety Profile of patients on SUBSYS as adjunct therapy to transdermal fentanyl patch vs other
around-the-clock opioids was similar
More than 90% (n=29) of patients on transdermal fentanyl patch reported satisfaction with
onset of action of SUBSYS vs 21% of other BTCP treatments
More than 90% (n=29) of patients found a mean effective dose of SUBSYS between 550 mcg
and 1000 mcg
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
Alberts et al. Pain Management . 2012;28(5):859-870.
25
Services provided by the INSYS Patient Support Services are designed to
maximize the satisfaction and success of each SUBSYS patient.

New: A Patient Support Specialist will call each new patient to help them and their
caregivers with their questions and needs for:




Product and insurance related information,
How to use the device and finding an effective dose,
Increased communication with their HCP,
Support with all available INSYS resources and programs

Free Trial Offer for commercially insured patients*

Prior Authorization Assistance through the INSYS Patient Services Center or one of the INSYS
Pharmacy Network Partners

$0 copay programs for both commercial and government insured patients*

Free compassionate patient assistance product for patients denied coverage from
commercial or government insurance*

Educational tools and resources such as Patient Starter Kits
Patients may also call directly to speak with a Patient
Support Specialist by calling:
1-844-309-3834
* Limitations and restrictions may apply
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
26
Letter of Medical Necessity: Required Information
Letter of Medical Necessity (LMN) is drafted by the Health Care Provider providing justification for the
requested treatment as the preferred option for their patient*. LMN’s are unique to a patient and should
contain the following elements:
HCP Identification and Patient History
Provide following information:
•
HCP Specialty
•
Duration of patient treatment
•
Name of medication, strength, and units requested
•
Diagnosis description along with duration of diagnosis
•
Names of Tried and/or Failed treatments
•
Provide rationale for preferred treatment over Payor preferred treatment
Statement of Medical Necessity
Why does the patient require this treatment?
•
Justification as to why the HCP has determined this is the appropriate line of treatment for his/her patient
•
Expand on each statement to give supporting medical evidence
Include the requirements outlined in the Payor’s Prior Authorization denial letter
Conclusion
•
Conclude letter with rationale for treatment and potential consequences
if the request is denied
* HCPs with questions regarding LMNs should and will be directed to INSYS Medical
Affairs. INSYS sales personnel should and will not participate in the drafting of LMNs.
27
SUBSYS® Is Available Via Transmucosal
Immediate-Release Fentanyl (TIRF) REMS
The goal of the TIRF REMS Access program is to mitigate the risk of misuse, abuse,
addiction, overdose, and serious complications due to medication errors
The Risk Evaluation and Mitigation Strategy (REMS) program is an FDA-approved
program designed to ensure informed risk-benefit decisions before initiating
treatment, and while patients are treated to ensure appropriate use of Transmucosal
Immediate-Release Fentanyl (TIRF) medicines
Enrollment is easy
•
•
Log on to www.TIRFREMSaccess.com to create an account and register
If you are unable to enroll online, please call the TIRF REMS Access program call center at
1-866-822-1483 for further assistance
Direct your patients to an enrolled pharmacy where SUBSYS can be obtained
•
Enrolled pharmacies can be found by calling 1-866-822-1483
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
28
Summary
SUBSYS® is a unique spray technology distributing 0.1 mL of nonionized fentanyl
in a fine mist across the sublingual mucosa
Conveniently‡ administered in seconds and easy to dispose of after use
Does not require saliva to administer, but must first swallow any saliva present
SUBSYS achieved a greater rate and extent of absorption vs Actiq®
Pain Relief achieved at all time points measured starting at 5 minutes (5, 10, 15, 30,
45, and 60 minutes)
Easy to find an effective dose with the widest range of doses up to 1600 mcg
3 out of 4 patients found an effective SUBSYS dose between 600 and 1600 mcg
A Patient Support Specialist can ensure each patient has education, support and
access to all SUBSYS Cares programs and resources
Please see full Prescribing Information, including Boxed Warning and Medication Guide for SUBSYS.
Parikh N, Goskonda V, Chavan A, Dillaha L. Single-dose pharmacokinetics of fentanyl sublingual spray and oral
transmucosal fentanyl citrate in healthy volunteers: a randomized crossover study. Clin Ther. 2013;35(3):236-243.
Rauck et al. Curr Med Res Opin. 2012;28(5):859-870.
Actiq® (oral transmucosal fentanyl citrate) is a trademark of Cephalon, Inc. or its affiliates.
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