fentanyl (Sublimaze, Subsys, Fentanyl Oralet, Actiq, Fentora, Onsolis, Abstral, Lazanda)
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Introduction
Tradenames: Sublimaze, Duragesic. DEA-controlled substance: class 2.
Indications
- treatment of moderate to severe acute pain syndromes
- anesthesia related to pain control
- do not use patches for unstable or acute pain
- for use in opioid tolerant patients
Dosage
Injection: 0.05 mg/mL (2 mL, 5 mL, 20 mL)
Transdermal:* Tradename: Duragesic. (2 generics: Sandoz, Mylan)#
- one patch every 3 days.
Patches: 25, 50, 75 & 100 ug/hr
* reservoir for transdermal fentanyl is the skin removal of patch will NOT remove fentanyl in skin
do not cut patches, improper use may cause leakage[11]
# Sandoz (same as Duragesic) liquid reservoir[7]
Ionsys Works by iontophoresis
Transmucosal lollipops: Tradename: Fentanyl Oralet, Actiq.
- 5-15 ug/kg, max 400 ug.
Lollipops: 200, 300, 400 ug.
Buccal tablet: Tradename: Fentora
- Bioavailability about twice that of Actiq
Tablets: 100, 200, 400, 600, 800 mg
Buccal soluble film formulation for cancer pain: Onsolis
Sublingual: Abstral, Sublys* (spray)
Nasal spray: Lazanda 100 ug/spray[13]
25 ug patch = 45-134 mg morphine PO daily
50 ug patch = 134-224 mg morphine PO daily
75 ug patch = 225-314 mg morphine PO daily
100 ug patch = 315-404 mg morphine PO daily
125. ug patch >= 405 mg morphine PO daily
Patients should be on an equivalent of at least 60 mg of oral morphine daily for at least 1 week prior to using a fentanyl patch[11]
Pharmacokinetics
- intravenous (IV)
- immediate onset of action
- duration of action 30-60 minutes
- metabolized by liver by cyt P450 3A4
- metabolites eliminated in urine
- short 1/2 life, less than morphine or meperidine
- oral
- extensive first-pass metabolism
- oral bioavailability of 33%
- onset of action is 5-10 minutes
- transdermal
- absorption varies with body temperature & the application of heat to the skin surface
- onset of action is 12-24 hours
- steady state reached in 72 hours
- post-removal, steady state concentrations are seen for 24-48 hours
- reservoir is skin
elimination via liver
Adverse effects
- common (> 10%)
- bradycardia, hypotension, respiratory depression, drowsiness, nausea/vomiting (minimal)
- less common (1-10%)
- uncommon (< 1%)
- bronchospasm, circulatory depression, convulsions, pruritus, urticaria, dysesthesia, laryngospasm, depression, delirium, paradoxical CNS excitation, cold & clammy skin, dizziness, biliary spasm, urinary tract spasm
- other
- fentanyl infusions can stimulate chest wall tightness & exacerbate respiratory failure; give prophylactic benzodiazepines
- rash, especially with transdermal delivery
- respiratory depression (dose & tolerance dependent), greater with IV dosing
- dependence (physical &/or psychological)
- constipation
- overdose & death reported from use of transdermal patch[8]
- accidental exposure to fentanyl via transdermal patch, particularly by children[14]
- severe necrotic wounds, extending to bone, amputations with illicit fentanyl containing xylazine (veternary sedative)[22][24]
- fentanyl detected in ~ 2/3 of opioid overdose deaths in southeastern Massachusetts Oct 2014 - March 2015[20]
- 82% involved illicitly manufactured fentanyl.
- 90% without pulse when emergency medical services arrived
- 36% with evidence overdose within seconds or minutes
- 6% with evidence of naloxone administration by bystanders[17]
- illicit fentanyl often contains xylazine (veternary sedative)[22][24]
- multiple doses of naloxone may be needed to revive a patient after a fentanyl overdose[19]
- drug adverse effects of opiates
- drug adverse effects of psychotropic agents
- drug adverse effects of sedatives
Drug interactions
- any drug that inhibits cyt P450 3A4 may increase levels of fentanyl
- any drug that induces cyt P450 3A4 may diminish levels of fentanyl
- benzodiazepines, barbiturates, alcohol in combination increase adverse CNS effects
- MAO inhibitors within 14 days are CONTRAINDICATED
- severe & unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics
- fatal reactions have occurred
- naloxone is a direct opiate antagonist
- scorpion venom in combination increases the toxic effects of the venom
- drug interaction(s) of benzodiazepine with opiates
- drug interaction(s) of antidepressant with opiates
- drug interaction(s) of Z-drugs with opiates
- drug interaction(s) of alcoholic beverage with opiates
- drug interaction(s) of pregabalin with opiates
- drug interaction(s) of gabapentin with opiates
Laboratory
Mechanism of action
- opiate agonist
- phenenylpiperidine derivative
- alters perception to pain at the level of the spinal cord & higher levels of the CNS
- alters emotional response to pain
- causes less of an increase in biliary tract pressure than morphine
Comparative biology
Notes
- only 1/2 of Subsys prescriptions (sublingual spray) marketed for treatment of breakthrough cancer pain are written by oncologists
- general practice physicians, neurologists & even dentists & podiatrists account for almost 1/2 theprescriptions[18]
More general terms
More specific terms
Additional terms
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 5.0 5.1 Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
- ↑ Ferrell B, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ 7.0 7.1 Prescriber's Letter 12(5): 2005 Generic Duragesic (Fentanyl) Patches Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210504&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#Fentanyl http://www.fda.gov/medwatch/safety/2007/safety07.htm#Fentanyl
- ↑ 9.0 9.1 9.2 Lexicomp, select drug information, 2005
- ↑ Prescriber's Letter 13(11): 2006 Fentora: Buccal Fentanyl Tablets Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=221105&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 11.0 11.1 11.2 Prescriber's Letter 14(10): 2007 Safe Use of Fentanyl (Duragesic) Patches Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=231010&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 18(5): 2011 New Formulation: Abstral (Fentanyl) Sublingual Tablets Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=270520&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 13.0 13.1 Prescriber's Letter 18(10): 2011 COMMENTARY: New Formulation: Oxecta (Oxycodone) CHART: Fentanyl Products for Breakthrough Pain CHART: Drugs with REMS and Other Special Prescribing/ Dispensing Requirements Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=271021&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 14.0 14.1 FDA Issues Warning on Fentanyl Patches 04/19/2012 http://www.medscape.com/viewarticle/762326?sssdmh=dm1.777166&src=nl_newsalert
- ↑ Elia J Marketing Pushes Powerful Painkiller Far Off-Label. Physician's First Watch, May 15, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
- ↑ DEA Issues Nationwide Alert on Fentanyl as Threat to Health and Public Safety. March 18, 2015 http://www.dea.gov/divisions/hq/2015/hq031815.shtml
- ↑ 17.0 17.1 SUBSYS (fentanyl sublingual spray) Prescribing Information http://subsysspray.com/assets/subsys/client_files/files/PrescribingInfo.pdf
- ↑ 18.0 18.1 SUBSYS (fentanyl sublingual spray) The First and Only Sublingual Spray for Breakthrough Cancer Pain http://subsysspray.com/?gclid=CPGcrefoq74CFaYF7AodKlYACg
- ↑ 19.0 19.1 Centers for Disease Control & Prevention (CDC) CDC Health Advisory. Oct 26, 2015 Increases in Fentanyl Drug Confiscations and Fentanyl-related Overdose Fatalities. http://emergency.cdc.gov/han/han00384.asp
- ↑ 20.0 20.1 Somerville NJ, O'Donnell J, Gladden RM, et al. Characteristics of Fentanyl Overdose - Massachusetts, 2014-2016. MMWR Morb Mortal Wkly Rep 2017;66:382-386 https://www.cdc.gov/mmwr/volumes/66/wr/mm6614a2.htm
- ↑ NEJM Knowledge+ Internal Medicine Board Review. https://myknowledgeplus.nejm.org/flow/flowjs.html
- ↑ 22.0 22.1 22.2 NEJM Journal Watch. Feb 2, 2021 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
Johnson J, Pizzicato L, Johnson C, Viner K. Increasing presence of xylazine in heroin and/or fentanyl deaths, Philadelphia, Pennsylvania, 2010-2019. Inj Prev. 2021 Feb 3:injuryprev-2020-043968 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33536231 - ↑ 23.0 23.1 Brooks M Fentanyl Vaccine a Potential 'Game Changer' for Opioid Crisis. Medscape. Nov 18, 2022 https://www.medscape.com/viewarticle/984327
Haile CN, Baker MD, Sanchez SA et al An Immunconjugate Vaccine Alters Distribution and Reduces the Antinociceptive, Behavioral and Physiological Effects of Fentanyl in Male and Female Rats. Pharmaceutics 2022, 14(11), 2290 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36365109 Free article https://www.mdpi.com/1999-4923/14/11/2290 - ↑ 24.0 24.1 24.2 24.3 Fiore K What Doctors Should Know About Xylazine in Fentanyl. Naloxone still works but additional support may be needed; wound care a challenge. MedPage Today February 1, 2023 https://www.medpagetoday.com/special-reports/features/102915
Patient information
fentanyl overdose patient information