ORAL TRANSMUCOSAL AND NASAL FENTANYL
UTILIZATION MANAGEMENT CRITERIA
DRUG CLASS:
Opioid Agonists
BRAND (generic) NAMES:
Abstral® (fentanyl) sublingual tablet
100, 200, 300, 400, 600, 800 mcg
Actiq® (fentanyl citrate) oral transmucosal lozenge
200, 400, 600, 800, 1200, 1600 mcg
Fentora® (fentanyl) buccal tablet
100, 200, 300, 400, 600, 800 mcg
Lazanda® (fentanyl) nasal spray
100, 300, 400 mcg/spray (8 sprays/bottle)
Subsys® (fentanyl) sublingual spray
100, 200, 400, 600, 800 mcg
FDA-APPROVED INDICATIONS
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 opioid
therapy for their underlying persistent cancer pain.
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 aroundthe-clock opioid therapy for their underlying persistent cancer pain.
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 aroundthe-clock opioid therapy for their underlying persistent cancer pain.
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.
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 opioid
therapy for their underlying persistent cancer pain. Patients must remain on around-the-clock
opioids when taking Subsys.
BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered marks of the Blue Cross and Blue Shield Association, an
association of independent Blue Cross and Blue Shield Plans. BCBSNC is an independent licensee of the Blue Cross and Blue Shield
Association. All other marks are the property of their respective owners.
Last Revision Date: January 2017
Page 1
Limitations of Use:
Abstral, Actiq, Fentora, Lazanda, and Subsys may be dispensed only to patients enrolled in the
TIRF REMS ACCESS program.
COVERAGE AUTHORIZATION CRITERIA
Actiq, Abstral, Fentora, Lazanda, and Subsys may be eligible for coverage when the
following criteria are met:
1. Patient has breakthrough pain due to cancer; AND
2. Patient is utilizing an around-the-clock, long-acting opioid product, in
combination with the requested fentanyl product; AND
3. Patient is considered opioid tolerant as defined by taking the following opioid
equivalent dosages for one week or longer,
 at least 60 mg oral morphine/day,
 at least 25 mcg transdermal fentanyl/hour,
 at least 30 mg of oral oxycodone daily,
 at least 8 mg oral hydromorphone daily,
 at least 25 mg oral oxymorphone daily, or
 an equianalgesic dose of another opioid; AND
4. Patient must be 16 years of age or older if requesting Actiq; OR
5. Patient must be 18 years of age or older if requesting Abstral, Fentora,
Lazanda, and Subsys.
6. For members on the Basic Open Formulary, before approval of a restricted
access agent is given, two non-restricted access agents must be tried. Please
consult the formulary list as these agents may change over time.
7. Non-formulary medications named in this criteria are subject to a trial of up to
TWO, clinically appropriate, formulary alternatives prior to approval (see NonFormulary Exception Criteria for details)
Fentanyl products outlined in this policy are NOT covered:
1. When used in the management of acute or postoperative pain (including
headache/migraine or dental pain).
2. When the patient is not taking an around-the-clock, long-acting opioid.
3. When the patient is not opioid-tolerant
QUANTITY LIMITS
Abstral (fentanyl) sublingual tablet
100, 200, 300, 400, 600, 800 mcg
Actiq (fentanyl citrate) oral transmucosal
lozenge
200, 400, 600, 800, 1200, 1600 mcg
Fentora (fentanyl) buccal tablet
100, 200, 300, 400, 600, 800 mcg
Lazanda (fentanyl) nasal spray
100 mcg/spray, 300 mcg/spray, 400
mcg/spray (8 sprays/bottle each strength)
Subsys (fentanyl) sublingual spray
100, 200, 400, 600, 800 mcg
4 tablets per day; 120 tablets per 30 days
4 lozenges per day; 120 tablets per 30 days
4 tablets per day; 120 tablets per 30 days
1 spray bottle per day; 30 spray bottles per
30 days
4 spray units per day: 120 spray units per 30
days
BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered marks of the Blue Cross and Blue Shield Association, an
association of independent Blue Cross and Blue Shield Plans. BCBSNC is an independent licensee of the Blue Cross and Blue Shield
Association. All other marks are the property of their respective owners.
Last Revision Date: January 2017
Page 2
For patients who are still in the titration process of determining their effective dose, quantities
greater than program quantity limits per product may be approved when clinical rationale is
documented for exceeding the program quantity limits.
CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS
Fentanyl citrate lozenges (Actiq)
Fentanyl citrate buccal tablets (Fentora)
Fentanyl sublingual tablets (Abstral)
Fentanyl nasal spray (Lazanda)
Fentanyl sublingual spray (Subsys)
Fentanyl is a Schedule II opioid agonist controlled substance, with an abuse liability similar to
other opioid analgesics. Fentanyl can be abused in a manner similar to other opioid agonists,
legal or illicit. This should be considered when prescribing or dispensing fentanyl in situations
where the physician or pharmacist is concerned about an increased risk of misuse, abuse or
diversion.
Schedule II opioid substances which include morphine, oxycodone, hydromorphone,
oxymorphone, and methadone have the highest potential for abuse and risk of fatal overdose
due to respiratory depression.
Fentanyl is indicated only for the management of breakthrough cancer pain in patients with
malignancies who are already receiving and who are tolerant to opioid therapy for their
underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking,
for one week or longer:
 at least 60 mg oral morphine/day,
 at least 25 mcg transdermal fentanyl/hour,
 at least 30 mg of oral oxycodone daily,
 at least 8 mg oral hydromorphone daily,
 at least 25 mg oral oxymorphone daily, or
 an equianalgesic dose of another opioid.
Fentanyl is intended to be used only in the care of opioid tolerant cancer patients and only by
healthcare professionals who are knowledgeable of and skilled in the use of Schedule II opioids
to treat cancer pain.
Because life-threatening hypoventilation could occur at any dose in patients not taking chronic
opiates, fentanyl is contraindicated in the management of acute or postoperative pain. This
product must not be used in opioid non-tolerant patients, including those with only intermittent or
“as needed” (PRN) prior exposure.
Patients and their caregivers must be instructed that fentanyl products contain a medicine in an
amount which can be fatal in children, in individuals for whom it is not prescribed, and in those
who are not opioid tolerant. Patients and their caregivers must be instructed to keep all tablets
and lozenges out of the reach of children, and opened units properly discarded.
The concomitant use of fentanyl with strong and moderate cytochrome P450 3A4 inhibitors may
result in an increase in fentanyl plasma concentrations, and may cause potentially fatal
BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered marks of the Blue Cross and Blue Shield Association, an
association of independent Blue Cross and Blue Shield Plans. BCBSNC is an independent licensee of the Blue Cross and Blue Shield
Association. All other marks are the property of their respective owners.
Last Revision Date: January 2017
Page 3
respiratory depression.
The substitution of Actiq, Fentora, Subsys, Abstral, or Lazanda for any other fentanyl product
may result in fatal overdose. When prescribing, do not convert patients on a mcg per mcg basis
from one transmucosal fentanyl product to another. Carefully consult approved dosing
recommendations. When dispensing, do not substitute one transmucosal fentanyl prescription
for other transmucosal fentanyl products. Substantial differences exist in the pharmacokinetic
profile of the transmucosal fentanyl products that result in clinically important differences in the
extent of absorption of fentanyl. As a result of these differences, the substitution of one fentanyl
product for any other fentanyl product may result in fatal overdose.
*See full prescribing information for complete boxed warning.
DOSAGE AND ADMINISTRATION
Abstral (fentanyl sublingual tablet)
 Patients must require and use around-the-clock opioids when taking Abstral
 Initial dose of Abstral: 100 mcg.
 Individually titrate to a tolerable dose that provides adequate analgesia.
 No more than two doses can be taken per breakthrough pain episode.
 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.
 Administer on the floor of the mouth directly under the tongue and allow to completely
dissolve.
Actiq (fentanyl oral transmucosal lozenge)
 Patients must require and use around-the-clock opioids when taking Actiq.
 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.
Fentora (fentanyl buccal tablet)
 Patients must require and use around-the-clock opioids when taking Fentora.
 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.
BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered marks of the Blue Cross and Blue Shield Association, an
association of independent Blue Cross and Blue Shield Plans. BCBSNC is an independent licensee of the Blue Cross and Blue Shield
Association. All other marks are the property of their respective owners.
Last Revision Date: January 2017
Page 4
Lazanda (fentanyl nasal spray)
 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 or a single spray into each nostril (2 sprays).
 Maximum dose is a single spray into one nostril or single spray into each nostril per
episode; 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.
Subsys (fentanyl sublingual spray)
 Patients must require and use around-the-clock opioids when taking Subsys.
 Initial dose of Subsys: 100 mcg.
 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.
*See full prescribing information for complete dosage and administration information*
REFERENCES
Abstral (fentanyl sublingual tablet). Prescribing Information. Galena Biopharma, Inc. 2011.
Actiq (fentanyl citrate oral transmucosal lozenge). Prescribing Information. Cephalon. 2007.
Fentora (fentanyl buccal tablet). Prescribing Information. Cephalon. 2009.
Lazanda (fentanyl nasal spray). Prescribing Information. Depomed, Inc. 2013.
Subsys (fentanyl sublingual spray). Prescribing Information. INSYS Therapeutics, Inc. 2014.
POLICY IMPLEMENTATION/UPDATE INFORMATION
January 2017: Reviewed for ASO Net Results and Essential formularies; non-formulary
verbiage added.
June 2016: Addition made of new to market strength; Lazanda 300 mcg/spray
April 2015: Historical revision
Non-Discrimination and Accessibility Notice
Discrimination is Against the Law
BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered marks of the Blue Cross and Blue Shield Association, an
association of independent Blue Cross and Blue Shield Plans. BCBSNC is an independent licensee of the Blue Cross and Blue Shield
Association. All other marks are the property of their respective owners.
Last Revision Date: January 2017
Page 5
• Blue Cross and Blue Shield of North Carolina (“BCBSNC”) complies with applicable
Federal civil rights laws and does not discriminate on the basis of race, color, national
origin, age, disability, or sex.
• BCBSNC does not exclude people or treat them differently because of race, color,
national origin, age, disability, or sex.
BCBSNC:
 Provides free aids and services to people with disabilities to communicate
effectively with us, such as:
- Qualified interpreters
- Written information in other formats (large print, audio, accessible electronic
formats, other formats)
 Provides free language services to people whose primary language is not English,
such as:
- Qualified interpreters
- Information written in other languages
• If you need these services, contact Customer Service 1-888-206-4697, TTY and
TDD, call
1-800-442-7028.
• If you believe that BCBSNC has failed to provide these services or discriminated in
another way on the basis of race, color, national origin, age, disability, or sex, you
can file a grievance with:
 BCBSNC, PO Box 2291, Durham, NC 27702, Attention: Civil Rights
Coordinator- Privacy, Ethics & Corporate Policy Office, Telephone 919-7651663, Fax 919-287-5613, TTY 1-888-291-1783 [email protected]
• You can file a grievance in person or by mail, fax, or email. If you need help filing a
grievance, Civil Rights Coordinator - Privacy, Ethics & Corporate Policy Office is
available to help you.
• You can also file a civil rights complaint with the U.S. Department of Health and
Human Services, Office for Civil Rights, electronically through the Office for Civil
Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or
by mail or phone at: U.S. Department of Health and Human Services 200
Independence Avenue, SW Room 509F, HHH Building Washington, D.C. 20201 1800-368-1019, 800-537-7697 (TDD). Complaint forms are available at
http://www.hhs.gov/ocr/office/file/index.html.
• This Notice and/or attachments may have important information about your
application or coverage through BCBSNC. Look for key dates. You may need to take
action by certain deadlines to keep your health coverage or help with costs. You have
the right to get this information and help in your language at no cost. Call Customer
Service 1-888-206-4697.
BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered marks of the Blue Cross and Blue Shield Association, an
association of independent Blue Cross and Blue Shield Plans. BCBSNC is an independent licensee of the Blue Cross and Blue Shield
Association. All other marks are the property of their respective owners.
Last Revision Date: January 2017
Page 6
ATTENTION: If you speak another language, language assistance services, free of charge, are
available to you. Call 1-888-206-4697 (TTY: 1-800-442-7028).
ATENCIÓN: Si habla español, tiene a su disposición servicios gratuitos de asistencia lingüística.
Llame al 1-888-206-4697 (TTY: 1-800-442-7028).
注意：如果您講廣東話或普通話， 您可以免費獲得語言援助服務。請致電 1-888-206-4697
(TTY：1-800-442-7028）。
CHÚ Ý: Nếu bạn nói Tiếng Việt, có các dịch vụ hỗ trợ ngôn ngữ miễn phí dành cho bạn. Gọi số
1-888-206-4697 (TTY: 1-800-442-7028).
주의: 한국어를 사용하시는 경우, 언어 지원 서비스를 무료로 이용하실 수 있습니다.
1-888-206-4697 (TTY: 1- 800-442-7028)번으로 전화해 주십시오.
ATTENTION : Si vous parlez français, des services d'aide linguistique vous sont proposés
gratuitement. Appelez le 1-888-206-4697 (ATS : 1-800-442-7028).
‫ اتصل برقم‬.‫ فإن خدمات المساعدة اللغوية تتوافر لك بالمجان‬،‫ إذا كنت تتحدث اللغة العربية‬:‫ملحوظة‬
.1-800-442-7028 :‫ المبرقة الكاتبة‬.1-888-206-4697
LUS CEEV: Yog tias koj hais lus Hmoob, cov kev pab txog lus, muaj kev pab dawb rau koj. Hu
rau
1-888-206-4697 (TTY: 1-800-442-7028).
ВНИМАНИЕ: Если вы говорите на русском языке, то вам доступны бесплатные услуги
перевода. Звоните 1-888-206-4697 (телетайп: 1-800-442-7028).
PAUNAWA: Kung nagsasalita ka ng Tagalog, maaari kang gumamit ng mga serbisyo ng tulong
sa wika nang walang bayad. Tumawag sa 1-888-206-4697 (TTY: 1-800-442-7028).
સુચના: જો તમે ગુજરાતી બોલતા હો, તો નન:સુલ્કુ ભાષા સહાય સેવાઓ તમારા માટે ઉપલબ્ધ છે . ફોન
કરો
1-888-206-4697 (TTY: 1-800-442-7028).
ចំណំ៖ ប្រសិនបរើបោកអ្នកនិយាយជាភាសាខ្មែរ បសវាកម្ែជំនួយខ្ននកភាសាមាននតលជ់ ូនសប្មារ់បោកអ្នកបោយម្ិនគិតថ្លៃ។
សូម្ទំនាក់ទនំ ងតាម្រយៈបលម៖ 1-888-206-4697 (TTY: 1-800-442-7028)។
ACHTUNG: Wenn Sie Deutsch sprechen, stehen Ihnen kostenlos sprachliche
Hilfsdienstleistungen zur Verfügung. Rufnummer: 1-888-206-4697 (TTY: 1-800-442-7028).
ध्यान दें: यदद आप दिन्दी बोलते िैं तो आपके दलए मफ्ु त में भाषा सिायता सेवाएं उपलब्ध िैं। 1-888-206-4697
(TTY: 1-800-442-7028) पर कॉल करें ।
້ າພາສາ ລາວ, ການບ
່ໍ ເສ
ໂປດຊາບ: ຖ
້ າວ
່ າທ
່ ານເວ
ໍ ິ ລການຊ
່ ວຍເຫ
້ ານພາສາ, ໂດຍບ
່ າ,
ຼື ອດ
ັ ຽຄ
ແມ
່ ນມ
້ ອມໃຫ
້ ທ
່ ານ. ໂທຣ 1-888-206-4697 (TTY: 1-800-442-7028).
ີ ພ
注意事項：日本語を話される場合、無料の言語支援をご利用いただけます。1-888-2064697（TTY: 1-800-442-7028）まで、お電話にてご連絡ください。
BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered marks of the Blue Cross and Blue Shield Association, an
association of independent Blue Cross and Blue Shield Plans. BCBSNC is an independent licensee of the Blue Cross and Blue Shield
Association. All other marks are the property of their respective owners.
Last Revision Date: January 2017
Page 7