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PHARMACY COVERAGE GUIDELINES
SECTION:
DRUGS
ORIGINAL EFFECTIVE DATE:
LAST REVIEW DATE:
LAST CRITERIA REVISION DATE:
ARCHIVE DATE:
12/02/11
03/16/17
02/25/17
TRANSMUCOSAL IMMEDIATE RELEASE FENTANYL FORMULATIONS:
ABSTRAL® (fentanyl citrate) sublingual tablet
ACTIQ® (fentanyl citrate) transmucosal lozenge
FENTORA® (fentanyl citrate) buccal tablet
LAZANDA® (fentanyl citrate) nasal spray
SUBSYS® (fentanyl) sublingual spray
Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as
outlined in the member's specific benefit plan. This Pharmacy Coverage Guideline must be read in its
entirety to determine coverage eligibility, if any.
This Pharmacy Coverage Guideline provides information related to coverage determinations only and
does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the
member are responsible for all decisions regarding the appropriateness of care. Providers should provide
BCBSAZ complete medical rationale when requesting any exceptions to these guidelines.
The section identified as “Description” defines or describes a service, procedure, medical device or drug
and is in no way intended as a statement of medical necessity and/or coverage.
The section identified as “Criteria” defines criteria to determine whether a service, procedure, medical
device or drug is considered medically necessary or experimental or investigational.
State or federal mandates, e.g., FEP program, may dictate that any drug, device or biological product
approved by the U.S. Food and Drug Administration (FDA) may not be considered experimental or
investigational and thus the drug, device or biological product may be assessed only on the basis of
medical necessity.
Pharmacy Coverage Guidelines are subject to change as new information becomes available.
For purposes of this Pharmacy Coverage Guideline, the terms "experimental" and "investigational" are
considered to be interchangeable.
BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered service marks of the
Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield
Plans. All other trademarks and service marks contained in this guideline are the property of their
respective owners, which are not affiliated with BCBSAZ.
Description:
Transmucosal immediate release (oral and nasal) formulations of the opioid analgesic fentanyl are indicated only
for the management of breakthrough cancer pain in individuals, who are already receiving around-the-clock opioid
pain medication for cancer pain and who are tolerant to opioid therapy for their persistent cancer pain.
Substantial differences exist in the pharmacokinetic profiles of each product formulation that result in clinically
important differences in extent of absorption of fentanyl. The formulations are not interchangeable on a mcg for
mcg basis. There are no dose conversion directions available on any other fentanyl product; this includes oral,
transdermal, or parenteral formulations.
Page 1 of 8
PHARMACY COVERAGE GUIDELINES
SECTION:
DRUGS
ORIGINAL EFFECTIVE DATE:
LAST REVIEW DATE:
LAST CRITERIA REVISION DATE:
ARCHIVE DATE:
12/02/11
03/16/17
02/25/17
TRANSMUCOSAL IMMEDIATE RELEASE FENTANYL FORMULATIONS (cont.)
Use of transmucosal immediate release (oral and nasal) formulations of fentanyl is subject to a Risk Evaluation
and Mitigation Strategies (REMS) program that requires provider, patient, and dispensing pharmacy be enrolled
into the program. Only providers and Pharmacies enrolled into the REMS may prescribe and dispense the drug,
respectively, to individuals who are also in the program. A REMS program attempts to manage known or
potentially serious risks associated with a drug product and is required by the Food and Drug Administration
(FDA) for some drugs to ensure that the benefits of a drug outweigh its risks.
Providers, pharmacies, and individual patients must be enrolled in the shared Transmucosal Immediate-release
Fentanyl (TIRF) Risk Evaluation and Mitigation Strategy (REMS) Access Program in order to prescribe, dispense,
and receive TIRF products. The TIRF REMS web site can be accessed at: www.TIRFREMSaccess.com
Abstral sublingual tablet contains fentanyl citrate intended for oral sublingual administration. It is designed to be
placed under the tongue and allowed to completely dissolve. It is available as 100 mcg, 200 mcg, 300 mcg, 400
mcg, 600 mcg, and 800 mcg strengths.
Actiq transmucosal lozenge contains fentanyl citrate formulated as a solid drug matrix on a handle intended for
oral transmucosal administration and is designed to dissolve slowly in the mouth. It is available as 200 mcg, 400
mcg, 600mcg, 800 mcg, 1200 mcg, and 1600 mcg strengths.
Fentora buccal tablet contains the opioid fentanyl citrate intended for buccal mucosal administration. It is
designed to be placed and retained within the buccal cavity for a sufficient period of time to allow disintegration of
the tablet and absorption of fentanyl across the oral mucosa. It is available as 100 mcg, 200 mcg, 400 mcg, 600
mcg, and 800 mcg strengths.
Lazanda nasal spray is a liquid formulation of fentanyl citrate intended for intranasal transmucosal administration.
It is formulated to deliver a spray of 100 mcL of solution containing 100 mcg or 400 mcg of fentanyl base,
depending on product strength. It is supplied in a 5.3 mL bottle containing 8 meter dosed sprays.
Subsys sublingual spray contains fentanyl base and is intended for sublingual administration. It is formulated in
blister packages that contain single spray units of fentanyl base. It is available in 100 mcg, 200 mcg, 400 mcg,
600 mcg, 800 mcg, 1200 mcg, and 1600 mcg dosage strengths.
Definitions:
Opioid Tolerance: determined by documentation of any ONE of the following:
 Individual is taking at least 60 mg of oral morphine daily
 Individual is using at least 25 mcg of transdermal fentanyl/hour
 Individual is taking at least 30 mg of oral oxycodone daily
 Individual is taking at least 8 mg of oral hydromorphone daily
 Individual is taking at least 25 mg of oral oxymorphone daily
 Individual is taking at least 60 mg of oral hydrocodone daily
 Individual is taking an equal analgesic dose of another opioid for a week or longer
Page 2 of 8
PHARMACY COVERAGE GUIDELINES
SECTION:
DRUGS
ORIGINAL EFFECTIVE DATE:
LAST REVIEW DATE:
LAST CRITERIA REVISION DATE:
ARCHIVE DATE:
12/02/11
03/16/17
02/25/17
TRANSMUCOSAL IMMEDIATE RELEASE FENTANYL FORMULATIONS (cont.)
Drug related events:
Ineffective / failure
Use of a drug employing optimal doses (FDA-recommended doses) for optimal duration; where the condition
being treated has not improved or worsened
A request for branded agent due to generic drug failure or ineffectiveness will be assessed for potential
approval with documentation of use of optimal dose / duration of the generic product and meeting other
criteria within the coverage guideline. When the drug in question is a combination product, there must be
documentation of failure / ineffectiveness of concurrent use (each ingredient used at the same time) of
individual generic components. When the drug in question is a low dose formulation, there must be
documentation of failure / ineffectiveness of low dose generic formulation.
Adverse Drug Event: Allergic reaction / Hypersensitivity / Intolerance
Use of a drug produced a significant reaction where continued use of the drug places the individual at risk for
either lack of improvement or worsening of the condition being treated or at risk for harm and the concern is
documented in medical record. A significant adverse drug event is when an individual’s outcome is death,
life-threatening, hospitalization (initial or prolonged), disability resulting in a significant, persistent, or
permanent change, impairment, damage or disruption in the individuals’ body function/structure, physical
activities or quality of life, or requires intervention to prevent permanent impairment or damage.
Allergic reaction / hypersensitivity – may or may not involve the active ingredient. When the active
ingredient is involved, use of same or a chemically similar agent places the individual at risk for harm
when the same or chemically similar agent is used. The subsequent reaction may be the same as the
original reaction or a more exaggerated response may be seen, potentially placing the individual at even
greater risk for harm.
If the reaction occurred from the active/main generic ingredient; request for branded agent with same
active ingredient will not be considered unless it is proven (documented) that active ingredient did not
cause reaction and the request meets other criteria within the coverage guideline
Intolerance – these events represent circumstance(s) where use of a drug produced a significant
reaction and continued use may result in non-adherence to proposed therapy and this concern is
documented in medical record
Contraindication
Use of a drug that is not recommended by the manufacturer or FDA labelling
Use of any drug in the face of a contraindication is outside of the FDA and manufacturer’s labelled
recommendation and is considered investigational or experimental
Non-adherence
Individual does not follow prescribe regimen that places the individual at risk for lack of improvement or
worsening of the condition being treated and this concern is documented in medical record
Page 3 of 8
PHARMACY COVERAGE GUIDELINES
SECTION:
DRUGS
ORIGINAL EFFECTIVE DATE:
LAST REVIEW DATE:
LAST CRITERIA REVISION DATE:
ARCHIVE DATE:
12/02/11
03/16/17
02/25/17
TRANSMUCOSAL IMMEDIATE RELEASE FENTANYL FORMULATIONS (cont.)
Precertification:
Precertification (Prior Authorization) is required for members with a Blue Cross Blue Shield of Arizona (BCBSAZ)
pharmacy benefit for medication(s) or product(s) indicated in this guideline.
This Pharmacy Coverage Guideline does not apply to FEP or other states’ Blues Plans.
Information about medications that require precertification is available at www.azblue.com/pharmacy.
Some large (100+) benefit plan groups may customize certain benefits, including adding or deleting precertification
requirements.
All applicable benefit plan provisions apply, e.g., waiting periods, limitations, exclusions, waivers and benefit
maximums.
Criteria:
See “Resources” section for FDA-approved dosage.

Precertification for transmucosal immediate release (oral and nasal) fentanyl formulations requires completion
of the specific request form in its entirety. All requested data must be provided. Once completed the form
must be signed by the prescribing provider and faxed back to BCBSAZ Pharmacy Management at (602) 8643126 or emailed to [email protected]. Incomplete forms will be returned.

Initial therapy: FDA-approved product labeling (indication, age, dosage, testing, contraindications,
exclusions, etc.) of Abstral or Actiq or Fentora or Lazanda or Subsys is considered medically when ALL of
the following criteria are met:
1. Individual is
 18 years of age or older for Abstral, Fentora, Lazanda or Subsys
 16 years of age or older for Actiq
2. Individual has medical record documentation of a confirmed diagnosis of cancer
3. Individual is experiencing breakthrough cancer-related pain
4. Absence of ALL of the following contraindications:
 Use in the emergency department
 Known or suspected gastrointestinal obstruction, including paralytic ileus
 Hypersensitivity to Fentanyl or other component of the product
 Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative
equipment

Continuation of coverage (renewal request): Abstral or Actiq or Fentora or Lazanda or Subsys is
considered medically necessary with documentation of ALL of the following:
Page 4 of 8
PHARMACY COVERAGE GUIDELINES
SECTION:
DRUGS
ORIGINAL EFFECTIVE DATE:
LAST REVIEW DATE:
LAST CRITERIA REVISION DATE:
ARCHIVE DATE:
12/02/11
03/16/17
02/25/17
TRANSMUCOSAL IMMEDIATE RELEASE FENTANYL FORMULATIONS (cont.)
1. The individual has benefited from therapy but remains at high risk
2. The condition has not progressed or worsened while on therapy
3. Individual has not developed any contraindications or other exclusions to its continued use

Abstral, Actiq, Fentora, Lazanda, and Subsys for all other indications not previously listed is considered
experimental or investigational based upon:
1.
2.
3.
4.
Lack of final approval from the Food and Drug Administration, and
Insufficient scientific evidence to permit conclusions concerning the effect on health outcomes, and
Insufficient evidence to support improvement of the net health outcome, and
Insufficient evidence to support improvement of the net health outcome as much as, or more than,
established alternatives, and
5. Insufficient evidence to support improvement outside the investigational setting.
This includes but is not limited to the following:
 Management of chronic pain caused by a condition or diagnosis other than cancer
Resources:
Transmucosal immediate release fentanyl (TIRF) Risk Evaluation and Mitigation Strategy 12-2014
Abstral. Package Insert. Revised 12-2016 by manufacturer Reviewed 02-25-2017.
Actiq. Packet Insert. Revised 12-2016 by manufacturer. Reviewed 02-25-2017.
Fentora. Packet Insert. Revised 02-2017 by manufacturer. Reviewed 02-25-2017.
Subsys. Packet Insert. Revised 12-2016 by manufacturer. Reviewed 02-25-2017.
Lazanda. Packet Insert. Revised 03-2015 by manufacturer. Reviewed 02-27-2017.
Abstral. Package Insert. Revised July 2013 by manufacturer Reviewed 05-08-2014.
Actiq. Packet Insert. Revised December 2011 by manufacturer. Reviewed 05-08-2014.
Fentora. Packet Insert. Revised February 2013 by manufacturer. Reviewed 05-08-2014.
Lazanda. Packet Insert. Revised November 2013 by manufacturer. Reviewed 05-08-2014, 02-25-2017.
Subsys. Packet Insert. Revised July 2013 by manufacturer. Reviewed 05-08-2014.
Refer to package inserts for complete information on initial dosing, dose titration, and maintenance dosing. Brief
overview on dosing:
Page 5 of 8
PHARMACY COVERAGE GUIDELINES
SECTION:
DRUGS
ORIGINAL EFFECTIVE DATE:
LAST REVIEW DATE:
LAST CRITERIA REVISION DATE:
ARCHIVE DATE:
12/02/11
03/16/17
02/25/17
TRANSMUCOSAL IMMEDIATE RELEASE FENTANYL FORMULATIONS (cont.)
Indication
Recommended Dose
Abstral is an opioid agonist indicated for the management of
breakthrough pain in cancer patients 18 years of age and
older 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,
for one week or longer, around-the-clock medicine consisting
of at least 60 mg of oral morphine per day, at least 25 mcg
per hour of transdermal fentanyl, at least 30 mg of oral
oxycodone per day, at least 8 mg of oral hydromorphone per
day, at least 25 mg oral oxymorphone per day, at least 60 mg
oral hydrocodone per day, or an equianalgesic dose of
another opioid daily for a week or longer. Patients must
remain on around-the-clock opioids while taking Abstral.
Limitations of Use

Not for use in opioid non-tolerant patients.

Not for use in the management of acute or postoperative
pain, including headache/migraine, dental pain, or in the
emergency department.

As a part of the TIRF REMS Access program, Abstral
may be dispensed only to outpatients enrolled in the
program. For inpatient administration of Abstral (e.g.,
hospitals, hospices, and long-term care facilities that
prescribe for inpatient use), patient and prescriber
enrollment is not required.
Actiq is an opioid agonist indicated for the management of
breakthrough pain in cancer patients 16 years of age and
older 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,
for one week or longer, around-the-clock medicine consisting
of at least 60 mg of oral morphine per day, at least 25 mcg of
transdermal fentanyl per hour, at least 30 mg of oral
oxycodone per day, at least 8 mg of oral hydromorphone per
day, at least 25 mg oral oxymorphone per day, at least 60 mg
oral hydrocodone per day, or an equianalgesic dose of
another opioid daily for a week or longer. Patients must
remain on around-the-clock opioids while taking Actiq.
Limitations of Use

Not for use in opioid non-tolerant patients.

Not for use in the management of acute or postoperative
pain, including headache/migraine or dental pain.






Page 6 of 8
Patients must require and use around-the-clock opioids
when taking Abstral.
Use the lowest effective dosage for the shortest
duration consistent with individual patient treatment
goals.
Individualize dosing based on the severity of pain,
patient response, prior analgesic experience, and risk
factors for addiction, abuse, and misuse.
Administer on the floor of the mouth directly under the
tongue and allow to completely dissolve.
Initial dose of Abstral: 100 mcg.
No more than two doses can be taken per breakthrough
pain episode.
Individually titrate to a tolerable dose that provides
adequate analgesia.
Wait at least 2 hours before treating another episode of
breakthrough pain with Abstral.
Limit consumption to treat four or fewer breakthrough
pain episodes per day once a successful dose is found.
When opioid therapy is no longer required, consider
discontinuing Abstral along with a gradual downward of
other opioids to minimize possible withdrawal effects.
Patients must require and use around-the-clock opioids
when taking Actiq.
Use the lowest effective dosage for the shortest
duration consistent with individual patient treatment
goals.
Individualize dosing based on the severity of pain,
patient response, prior analgesic experience, and risk
factors for addiction, abuse, and misuse.
Initial dose of Actiq: 200 mcg. Prescribe an initial supply
of six 200 mcg Actiq units.
Individually titrate to a tolerable dose that provides
adequate analgesia using single Actiq dosage unit per
breakthrough cancer pain episode.
No more than two doses can be taken per breakthrough
pain episode.
Wait at least 4 hours before treating another episode of
breakthrough pain with Actiq.
Limit consumption to four or fewer units per day once
successful dose is found.
When opioid therapy is no longer required, consider
PHARMACY COVERAGE GUIDELINES
SECTION:
DRUGS
ORIGINAL EFFECTIVE DATE:
LAST REVIEW DATE:
LAST CRITERIA REVISION DATE:
ARCHIVE DATE:
12/02/11
03/16/17
02/25/17
TRANSMUCOSAL IMMEDIATE RELEASE FENTANYL FORMULATIONS (cont.)

discontinuing Actiq along with a gradual downward of
other opioids to minimize possible withdrawal effects.
As a part of the TIRF REMS Access program, Actiq may
be dispensed only to outpatients enrolled in the program.
For inpatient administration of Actiq (e.g., hospitals,
hospices, and long-term care facilities that prescribe for
inpatient use), patient and prescriber enrollment is not
required.
Fentora is an opioid agonist indicated for the management of
breakthrough pain in cancer patients 18 years of age and
older 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,
for one week or longer, around-the-clock medicine consisting
of at least 60 mg of oral morphine per day, at least 25 mcg
per hour of transdermal fentanyl, at least 30 mg of oral
oxycodone per day, at least 8 mg of oral hydromorphone per
day, at least 25 mg oral oxymorphone per day, at least 60 mg
of oral hydrocodone per day, or an equianalgesic dose of
another opioid daily for a week or longer. Patients must
remain on around-the-clock opioids while taking Fentora.
Limitations of Use

Not for use in opioid non-tolerant patients.

Not for use in the management of acute or postoperative
pain, including headache/migraine, or dental pain.

As a part of the TIRF REMS Access program, Fentora
may be dispensed only to patients enrolled in the TIRF
REMS Access program. For inpatient administration of
Fentora (e.g., hospitals, hospices, and long-term care
facilities that prescribe for inpatient use), patient and
prescriber enrollment is not required.
Lazanda is an opioid agonist indicated for the management of
breakthrough pain in cancer patients 18 years of age and
older who are already receiving and who are tolerant to
opioid therapy for their underlying persistent cancer pain.
Limitations of Use:
Lazanda may be dispensed only to patients enrolled in the
TIRF REMS Access program.
















Patients must require and use around-the-clock opioids
when taking Fentora.
Use the lowest effective dosage for the shortest duration
consistent with individual patient treatment goals.
Individualize dosing based on the severity of pain, patient
response, prior analgesic experience, and risk factors for
addiction, abuse, and misuse.
Initial dose of Fentora: 100 mcg.
Initiate titration using multiples of 100 mcg Fentora tablet.
Limit patient access to only one strength of Fentora at
any one time.
Individually titrate to a tolerable dose that provides
adequate analgesia using single Fentora tablet.
No more than two doses can be taken per breakthrough
pain episode.
Wait at least 4 hours before treating another episode of
breakthrough pain with Fentora.
Place entire tablet in buccal cavity or under the tongue;
tablet is not to be split, crushed, sucked, chewed or
swallowed whole.
When opioid therapy is no longer required, consider
discontinuing Fentora along with a gradual downward of
other opioids to minimize possible withdrawal effects.
Patients must require and use around-the-clock opioids
when taking Lazanda.
Initial dose of Lazanda for all patients is 100 mcg.
Individually titrate to an effective dose, from 100 mcg to
200 mcg to 400 mcg, and up to a maximum of 800 mcg,
that provides adequate analgesia with tolerable side
effects.
Dose is a single spray into one nostril, a single spray into
each nostril (2 sprays), or two sprays into each nostril (4
sprays); no more than four doses per 24 hours.
Wait at least 2 hours before treating another episode of
breakthrough pain with Lazanda.
During any episode, if adequate pain relief is not
achieved within 30 minutes, the patient may use a
rescue medication as directed by their healthcare
provider.
Page 7 of 8
PHARMACY COVERAGE GUIDELINES
SECTION:
DRUGS
ORIGINAL EFFECTIVE DATE:
LAST REVIEW DATE:
LAST CRITERIA REVISION DATE:
ARCHIVE DATE:
12/02/11
03/16/17
02/25/17
TRANSMUCOSAL IMMEDIATE RELEASE FENTANYL FORMULATIONS (cont.)
Subsys is an opioid agonist indicated for the management of
breakthrough pain in cancer patients 18 years of age and
older 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,
for one week or longer, around-the-clock medicine consisting
of at least 60 mg of oral morphine per day, at least 25 mcg of
transdermal fentanyl per hour, at least 30 mg of oral
oxycodone per day, at least 8 mg of oral hydromorphone per
day, at least 25 mg oral oxymorphone per day, at least 60 mg
oral hydrocodone per day, or an equianalgesic dose of
another opioid daily for a week or longer. Patients must
remain on around-the-clock opioids when taking Subsys.
Limitations of Use

Not for use in opioid non-tolerant patients.

Not for use in the management of acute or postoperative
pain, including headache/migraine, dental pain, or in the
emergency room.

As a part of the Transmucosal Immediate-Release
Fentanyl (TIRF) REMS ACCESS Program, Subsys may
be dispensed only to outpatients enrolled in the program.
[see Warnings and Precautions (5.7)]. For inpatient
administration of Subsys (e.g. hospitals, hospices, and
long-term care facilities that prescribe for inpatient use),
patient and prescriber enrollment is not required.









Patients must require and use around-the-clock opioids
when taking Subsys.
Use the lowest effective dose for the shortest duration
consistent with individual patient treatment goals.
Individualize dosing based on the severity of pain, patient
response, prior analgesic experience, and risk factors for
addiction, abuse, and misuse.
Initiate treatment with 100 mcg except patients already
using Actiq.
Individually titrate to a tolerable dose that provides
adequate analgesia using a single Subsys dose per
breakthrough cancer pain episode.
No more than two doses can be taken per breakthrough
pain episode.
Wait at least 4 hours before treating another episode of
breakthrough pain with Subsys.
Limit consumption to four or fewer doses per day once
successful dose is found.
When opioid therapy is no longer required, consider
discontinuing Subsys along with a gradual downward
titration of other opioids to minimize possible withdrawal
effects.
Page 8 of 8