Advertisement

A review of the safety of buprenorphine in special populations

      Abstract

      Rates of opioid misuse and opioid use disorder have been increasing in recent years. Buprenorphine has emerged as an appealing medication for its use not only as treatment for opioid use disorder, but also as an opioid for chronic pain that has a ceiling effect on risks associated with opioid therapy. As other opioid prescribing decreases, buprenorphine prescribing continues to increase. As a result, it is imperative to understand the safety and efficacy of its use in special populations. This review article will explore the safety and efficacy of buprenorphine when used in subjects with hepatic and renal impairment, the elderly, and pregnant women. While manufacturer labeling for buprenorphine products may caution against their use in these populations, further examination of available data indicates that buprenorphine can be used safely and effectively for both chronic pain and/or opioid use disorder in all four of these populations.

      Key Indexing Terms

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of the Medical Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Dowell Deborah
        • Haegerich Tamara
        • Chou Roger
        CDC guideline for prescribing opioids for chronic pain - United States, 2016.
        MMWR Recomm Rep. 2016; 65: 1-49
      1. Drug Enforcement Administration. "Established aggregate production quotas for schedule I and II controlled substances and assessment of annual needs for the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine for 2017." Federal Register 2016-23988 (July 22, 2016). 81 FR 69079. P. 69079-69083. Accessed December 9, 2021.

      2. 2021 Overdose Epidemic Report: Physicians’ Actions to Help End the Nation's Drug-Related Overdose and Death Epidemic - and What Still Needs to be Done.
        American Medical Association, 2021
        • U.S. Department of Health and Human Services
        Pain Management Best Practices Inter-Agency Task Force Report: Updates, Gaps, Inconsistencies, and Recommendations.
        (May) U.S. Department of Health and Human Services, 2019 (Available at:)
        • Rolly G.
        • Versichelen L.
        Buprenorphine as postoperative analgesic.
        Acta Anaesthesiol Belg. 1976; 27 (PMID: 801582): 183-186
        • Jasinski D.R.
        • Pevnick J.S.
        • Griffith J.D.
        Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction.
        Arch Gen Psychiatry. 1978; 35: 501-516https://doi.org/10.1001/archpsyc.1978.01770280111012
      3. Belbuca Buccal Film.
        Endo Pharmaceuticals, Inc., Malvern, PA2015 ([package insert])
      4. Buprenex Injection.
        Indivior Inc., North Chesterfield, VA2019 ([package insert])
      5. Butrans Transdermal Patch.
        Purdue Pharma L.P., Stamford, CT2014 ([package insert])
      6. Bunavail Buccal Film.
        BioDelivery Sciences International, Inc., Raleigh, NC2014 ([package insert])
      7. Sublocade Injection.
        Indivior Inc., North Chesterfield, VA2021 ([package insert])
      8. Suboxone Sublingual Film.
        Reckitt Benckiser Pharmaceuticals Inc., Richmond, VA2010 ([package insert])
      9. Suboxone Sublingual Tablet.
        Reckitt Benckiser Pharmaceuticals Inc., Richmond, VA2011 ([package insert])
      10. Subutex Sublingual Tablet.
        Reckitt Benckiser Pharmaceuticals Inc., Richmond, VA2011 ([package insert])
      11. Zubsolv Sublingual Tablet.
        Orexo US, Inc., Morristown, NJ2016 ([package insert])
        • Boas R.A.
        • Villiger J.W.
        Clinical actions of fentanyl and buprenorphine. The significance of receptor binding.
        Br J Anaesth. 1985; 57: 192-196
        • Lutfy K.
        • Cowan A.
        Buprenorphine: a unique drug with complex pharmacology.
        Curr Neuropharmacol. 2004; 2: 395-402https://doi.org/10.2174/1570159043359477
        • Bettinger J.
        • Quevedo H.B.
        • Cleary J.
        Emerging pharmacologic mechanisms of buprenorphine to explain experience of analgesia versus adverse effects.
        J Opioid Manag. 2021; 17: 21-31https://doi.org/10.5055/jom.2021.0639
        • Walsh S.L.
        • Preston K.L.
        • Stitzer M.L.
        • Cone E.J.
        • Bigelow G.E.
        Clinical pharmacology of buprenorphine: ceiling effects at high doses.
        Clin Pharmacol Ther. 1994; 55 (PMID: 8181201): 569-580https://doi.org/10.1038/clpt.1994.71
        • Cone E.J.
        • Gorodetzky C.W.
        • Yousefnejad D.
        • Buchwald W.F.
        • Johnson R.E.
        The metabolism and excretion of buprenorphine in humans.
        Drug Metab Dispos. 1984; 12 (PMID: 6149907): 577-581
        • Rodighiero V.
        Effects of liver disease on pharmacokinetics.
        Clin Pharmacokinet. 1999; 37: 399-431https://doi.org/10.2165/00003088-199937050-00004
        • Nasser A.F.
        • Heidbreder C.
        • Liu Y.
        • et al.
        Pharmacokinetics of sublingual buprenorphine and naloxone in subjects with mild to severe hepatic impairment (child-pugh classes A, B, and C), in hepatitis C virus-seropositive subjects, and in healthy volunteers.
        Clin Pharmacokinet. 2015; 54: 837-849https://doi.org/10.1007/s40262-015-0238-6
        • McCance-Katz E.F.
        • Moody D.E.
        • Morse G.D.
        • et al.
        Interactions between buprenorphine and antiretrovirals. I. The nonnucleoside reverse-transcriptase inhibitors efavirenz and delavirdine.
        Clin Infect Dis. 2006; 43 (PMID: 17109309): S224-S234https://doi.org/10.1086/508187
        • McCance-Katz E.F.
        • Moody D.E.
        • Prathikanti S.
        • Friedland G.
        • Rainey P.M.
        Rifampin, but not rifabutin, may produce opiate withdrawal in buprenorphine-maintained patients.
        Drug Alcohol Depend. 2011; 118: 326-334
        • McCance-Katz E.F.
        • Moody D.E.
        • Smith P.F.
        • et al.
        Interactions between buprenorphine and antiretrovirals. II. The protease inhibitors nelfinavir, lopinavir/ritonavir, and ritonavir.
        Clin Infect Dis. 2006; 43: S235-S246https://doi.org/10.1086/508188
        • McCance-Katz E.F.
        • Moody D.E.
        • Morse G.D.
        • et al.
        Interaction between buprenorphine and atazanavir or atazanavir/ritonavir.
        Drug Alcohol Depend. 2007; 91 (Epub 2007 Jul 23. PMID: 17643869; PMCID: PMC3272856): 269-278https://doi.org/10.1016/j.drugalcdep.2007.06.007
        • Fihlman M.
        • Hemmila T.
        • Hagelberg N.M.
        • et al.
        Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.
        Eur J Clin Pharmacol. 2016; 72: 1363-1371
        • Kapil R.P.
        • Cipriano A.
        • Michels G.H.
        • et al.
        Effect of ketoconazole on the pharmacokinetic profile of buprenorphine following administration of a once-weekly buprenorphine transdermal system.
        Clin Drug Investig. 2012; 32 (PMID: 22845044): 583-592https://doi.org/10.1007/BF03261913
        • Tegeder I.
        • Lotsch J.
        • Geisslinger G.
        Pharmacokinetics of opioids in liver disease.
        Clin. Pharmacokinet. 2012; 37: 17-40
        • Summerfield R.J.
        • Allen M.C.
        • Moore R.A.
        • Sear J.W.
        • McQuay H.J.
        Buprenorphine in end stage renal failure.
        Anaesthesia. 1985; 40: 914
        • Hand C.W.
        • Sear J.W.
        • Uppington J.
        • Ball M.J.
        • McQuay H.J.
        • Moore R.A.
        Buprenorphine disposition in patients with renal impairment: single and continuous dosing, with special reference to metabolites.
        Br J Anaesth. 1990; 64 (PMID: 2328175): 276-282https://doi.org/10.1093/bja/64.3.276
        • Filitz J.
        • Griessinger N.
        • Reinhard S.
        • Likar R.
        • Schuttler J.
        • Koppert W.
        Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentrations in chronic pain patients treated with transdermal buprenorphine.
        Eur J Pain. 2012; 10: 743
        • Bhutto A.
        • Morley J.E.
        The clinical significance of gastrointestinal changes with aging.
        Curr Opin Clin Nutr Metab Care. 2008; 11 (PMID: 18685464): 651-660https://doi.org/10.1097/MCO.0b013e32830b5d37
        • Blechman M.B.
        • Gelb A.M.
        Aging and gastrointestinal physiology.
        Clin Geriatr Med. 1999; 15: 429-438
        • Mangoni A.A.
        • Jackson S.H.
        Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications.
        Br J Clin Pharmacol. 2004; 57: 6-14https://doi.org/10.1046/j.1365-2125.2003.02007.x
        • Milton J.C.
        • Hill-Smith I.
        • Jackson S.H.
        Prescribing for older people.
        BMJ. 2008; 336: 606e609
        • Scott-Warren V.
        • Maguire S.
        Physiology of ageing.
        Anaesth Intensive Care Med. 2017; 18
        • Likar R.
        Transdermal buprenorphine in the management of persistent pain: safety aspects.
        Ther Clin Risk Manag. 2006; 2: 115-125
        • Webster L.R.
        • Camilleri M.
        • Finn A.
        Opioid-induced constipation: rationale for the role of norbuprenorphine in buprenorphine-treated individuals.
        Subst Abuse Rehabil. 2016; 7 (Published 2016): 81-86https://doi.org/10.2147/SAR.S100998
        • Griessinger N.
        • Sittl R.
        • Likar R.
        Transdermal buprenorphine in clinical practice–a post-marketing surveillance study in 13,179 patients.
        Curr Med Res Opin. 2005; 21: 1147-1156
        • Harris S.C.
        • Morganroth J.
        • Ripa S.R.
        • Thorn M.D.
        • Colucci S.
        Effects of buprenorphine on QT intervals in healthy subjects: results of 2 randomized positive- and placebo-controlled trials.
        Postgrad Med. 2017; 129: 69-80
        • Steiner D.
        • Munera C.
        • Hale M.
        • et al.
        Efficacy and safety of buprenorphine transdermal system (BTDS) for chronic moderate to severe low back pain: a randomized, double-blind study.
        Pain. 2009; 10: S51
        • Steiner D.
        • Sitar S.
        • Wen W.
        • et al.
        Efficacy and safety of the seven-day buprenorphine transdermal system in opioid-naïve patients with moderate to severe chronic low back pain: an enriched, randomized, double-blind, placebo-controlled study.
        Pain Symptom Manag. 2011; 42: 903-917
        • James I.
        • O'Brien C.
        • McDonald C.
        • et al.
        A randomized, doubleblind, double-dummy comparison of the efficacy and tolerability of low-dose transdermal buprenorphine (BuTrans SevenDay Patches) with buprenorphine sublingual tablets (Temgesics) in patients with osteoarthritis pain.
        J Pain Symptom Manag. 2010; 40: 266-278
        • Atkinson T.J.
        • Fudin J.
        • Pandula A.
        • Mirza M.
        Medication pain management in the elderly: unique and underutilized analgesic treatment options.
        Clin Ther. 2013; 35: 1669-1689https://doi.org/10.1016/j.clinthera.2013.09.008
        • Patrick S.W.
        • Schumacher R.E.
        • Benneyworth B.D.
        • Krans E.E.
        • McAllister J.M.
        • Davis M.M.
        Neonatal abstinence syndrome and associated health care expenditures: United States, 2000–2009.
        JAMA. 2012; 307 (Epub 2012 Apr 30. PMID: 22546608): 1934-1940https://doi.org/10.1001/jama.2012.3951
        • Patrick S.W.
        • Davis M.M.
        • Lehmann C.U.
        • Cooper W.O.
        Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012.
        J Perinatol. 2015; 35 ([published erratum appears in J Perinatol 2015;35:667]): 650-655
        • Virginia Department of Health
        Pregnancy-Associated Deaths from Drug Overdose in Virginia, 1999-2007: A Report from the Virginia Richmond Mortality Review Team.
        VDH, Richmond (VA)2015
        • Maryland Department of Health and Mental Hygiene
        Maryland Maternal Mortality Review 2016 Annual Report.
        DHMH, Baltimore (MD)2016
        • Jones H.E.
        • Heil S.H.
        • Baewert A.
        • et al.
        Buprenorphine treatment of opioid-dependent pregnant women: a comprehensive review.
        Addiction. 2012; 107 (0 1): 5-27https://doi.org/10.1111/j.1360-0443.2012.04035.x
        • Opioid Use and Opioid Use Disorder in Pregnancy
        ACOG Committee Opinion Number 711.
        The American College of Obstetricians and Gynecologists & The American Society of Addiction Medicine, 2017
        • American Society of Addiction Medicine
        Treating Pregnant People with Opioid Use Disorder. ASAM COVID-19 Task Force Recommendations: Caring for Patients During the COVID-19 Pandemic.
        The American Society of Addiction Medicine, 2020
        • Jones H.E.
        • Kaltenbach K.
        • Heil S.H.
        • et al.
        Neonatal abstinence syndrome after methadone or buprenorphine exposure.
        N Engl J Med. 2010; 363: 2320-2331
        • Jones H.E.
        • Finnegan L.P.
        • Kaltenbach K.
        Methadone and buprenorphine for the management of opioid dependence in pregnancy.
        Drugs. 2012; 72: 747-757https://doi.org/10.2165/11632820-000000000-00000
        • Substance Abuse and Mental Health Services Administration
        Clinical Guidance for Treating Pregnant and Parenting Women With Opioid Use Disorder and Their Infants.
        Substance Abuse and Mental Health Services Administration, Rockville, MD2018 (HHS Publication No. (SMA) 18-5054)
        • Lind J.N.
        • Interrante J.D.
        • Ailes E.C.
        • et al.
        Maternal use of opioids during pregnancy and congenital malformations: a systematic review.
        Pediatrics. 2017; 139 (and also Jumah et al)e20164131https://doi.org/10.1542/peds.2016-4131
        • Debelak K.
        • Morrone W.R.
        • O'Grady K.E.
        • Jones H.E.
        Buprenorphine + naloxone in the treatment of opioid dependence during pregnancy-initial patient care and outcome data.
        Am J Addict. 2013; 22 (PMID: 23617867): 252-254https://doi.org/10.1111/j.1521-0391.2012.12005.x
        • Wiegand S.L.
        • Stringer E.M.
        • Stuebe A.M.
        • Jones H.
        • Seashore C.
        • Thorp J.
        Buprenorphine and naloxone compared with methadone treatment in pregnancy.
        Obstet Gynecol. 2015; 125 (FebPMID: 25569005): 363-368https://doi.org/10.1097/AOG.0000000000000640
        • Jumah N.A.
        • Edwards C.
        • Balfour-Boehm J.
        • et al.
        Observational study of the safety of buprenorphine+naloxone in pregnancy in a rural and remote population.
        BMJ Open. 2016; 6 (PMID: 27799240; PMCID: PMC5093362)e011774https://doi.org/10.1136/bmjopen-2016-011774
        • Lindemalm S.
        • Nydert P.
        • Svensson J.O.
        • et al.
        Transfer of buprenorphine into breastmilk and calculation of infant drug dose.
        J Hum Lact. 2009; 25: 199-205
        • Ilett K.F.
        • Hackett L.P.
        • Gower S.
        • et al.
        Estimated dose exposure of the neonate to buprenorphine and its metabolite norbuprenorphine via breastmilk during maternal buprenorphine substitution treatment.
        Breastfeed Med. 2012; 7: 269-274
        • Feghali M.
        • Venkataramanan R.
        • Caritis S.
        Pharmacokinetics of drugs in pregnancy.
        Semin Perinatol. 2015; 39: 512-519