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Injectable Naltrexone for Smoking Cessation

April 1, 2015 . 11,023 views . View Full Issue (Volume 4, Issue 7) . Print this page

By: Jacqueline Meaney, PharmD Candidate c/o 2015, University at Buffalo: School of Pharmacy and Pharmaceutical Sciences

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Extended release naltrexone (XR-NTX), marketed as once-monthly IM Vivitrol®, is currently FDA approved for use in treating both alcohol and opiate dependence. Naltrexone is a mu-opioid receptor antagonist that blocks the euphoric effect of heroin and prescription opioids. Naltrexone may be useful as a tool for smoking cessation because previous studies have demonstrated a link between opioids and nicotine. Cigarette smoking continues to be the leading cause of preventable death in the United States, and as such, naltrexone may provide an additional option for patients who want to quit smoking or for patients who need an adjunct to their current smoking cessation regimen.2

Oral naltrexone has been studied for smoking cessation and has yielded mixed results.2-14 Oral naltrexone was not shown to be effective for nicotine dependence in patients receiving naltrexone for alcohol addicion,14 and was shown to be no more effective than placebo when used in combination with the nicotine patch.5 In contrast, other studies have demonstrated the efficacy of oral naltrexone when used with and without the nicotine patch,11 and an additional study found that oral naltrexone was only effective for nicotine dependence in women.8

Compared to treatment with oral naltrexone, treatment with XR-NTX has shown increased rates of adherence, which may result in XR-NTX being effective as a smoking cessation aid.15,16 In addition, XR-NTX achieves greater cumulative plasma concentrations than oral naltrexone – the AUC of XR-NTX after multiple dose administration is 160 ngxh/mL, while that of oral naltrexone is only 35 ngxh/mL.17

As a result, oral naltrexone may not provide high enough plasma levels or enough exposure to naltrexone for the drug to be effective as a smoking cessation aid. It is therefore possible that the increase in the AUC of naltrexone when administered as XR-NTX may result in XR-NTX being more effective for smoking cessation.18

Case studies have shown that patients who were chronic cigarette smokers had decreased cravings for nicotine following initiation of XR-NTX therapy. In addition, some patients stopped smoking entirely when treated with XR-NTX combined with nicotine replacement therapy and smoking cessation classes.19 Increased exposure to naltrexone and increased compliance to the naltrexone regimen may support the use of XR-NTX for smoking cessation.18, 21 XR-NTX has not yet been studied for the treatment of nicotine dependence, which may be a possible use for this medication.

 

SOURCES:

  1. Comer SD, Sullivan MA, Hulse GK. Sustained-release naltrexone: novel treatment for opioid dependence. Informa. Expert Opinion on Investigational Drugs. 2007;16(8):1285-94.
  2. King AC, Cao D, O’Malley SS, et al. Effects of naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and women. J Clin Psychopharmacol. 2012; 32(5):630-6.
  3. O’Malley SS, Cooney JL, Krishnan-Sarin S, et al. A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation. Arch Intern Med. 2006;166(6):667-74.
  4. Toll BA, White M, Wu R, et al. Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: A randomized trial. Drug and Alcohol Dependence. 2010;111(3):200-6.
  5. Wong GY, Wolter TD. A randomized trial of naltrexone for smoking cessation. Addiction. 1999; 94(8):1229-37.
  6. King A, de Wit H, Riley RC, et al. Efficacy of naltrexone in smoking cessation: A preliminary study and an examination of sex differences. Nicotine & Tobacco Research. 2006; 8(5):671-82.
  7. Ahmadi J, Ashkani H, Ahmadi M, et al. Twenty-four week maintenance treatment of cigarette smoking with nicotine gum, clonidine and naltrexone. Journal of Substance Abuse Treatment. 2003; 24(3):251-5.
  8. Covey LS, Glassman AH, Stetner F. Naltrexone effects on short-term and long-term smoking cessation. J Addict Dis. 1999; 18(1):31-40.
  9. King AC. Role of naltrexone in initial smoking cessation: preliminary findings. Alcoholism: Clinical and Experimental Research. 2002; 26(12):1942-4.
  10. Byars JA, Frost-Pineda K, Jacobs WS, et al. Naltrexone augments the effects of nicotine replacement therapy in female smokers. J Addict Dis. 2005; 24(2):49-60.
  11. Krishnan-Sarin S. Naloxone challenge in smokers: preliminary evidence of an opioid component in nicotine dependence. Archives of General Psychiatry. 1999; 56(7):663-8.
  12. Nemeth-Coslett R, Griffiths RR. Naloxone does not affect cigarette smoking. Psychopharmacology (Berl). 1986; 89(3):261-4.
  13. Sutherland G, Stapleton J, Russell M, Feyerabend C. Naltrexone, smoking behaviour and cigarette withdrawal. Psychopharmacology. 1995; 120(4):418-25.
  14. Rohsenow DJ, Monti PM, Colby SM, Gulliver SB, Swift RM, Abrams DB. Naltrexone treatment for alcoholics: Effect on cigarette smoking rates. Nicotine & Tobacco Research. 2003; 5(2):231-6.
  15. Gastfriend DR. Intramuscular extended-release naltrexone: current evidence. Annals of the New York Academy of Sciences. 2011; 1216(1):144-66.
  16. Harris KM, DeVries A, Dimidjian K. Datapoints: Trends in naltrexone use among members of a large private health plan. Psychiatr Serv. 2004; 55(3):221.
  17. Dunbar JL, Turncliff RZ, Dong Q, et al. Single- and multiple-dose pharmacokinetics of long-acting injectable naltrexone. Alcoholism: Clinical and Experimental Research. 2006; 30(3):480-90.
  18. Almeida LE, Pereira EF, Camara AL, et al. Sensitivity of neuronal nicotinic acetylcholine receptors to the opiate antagonists naltrexone and naloxone: receptor blockade and up-regulation. Bioorg Med Chem Lett. 2004; 14(8):1879-87.
  19. Byars JA, Frost-Pineda K, Jacobs WS, et al. Naltrexone augments the effects of nicotine replacement therapy in female smokers. PubMed. J Addict Dis. 2005; 24(2):49-60
  20. Krupitsky EM, Blokhina EA. Long-acting depot formulations of naltrexone for heroin dependence: a review. Wolters Kluwer Health. Current Opinion in Psychiatry. 2010; 23:210-214
  21. Almeida LEF, Pereira EFR, Alkondon M, et al. The opioid antagonist naltrexone inhibits activity and alters expression of α7 and α4β2 nicotinic receptors in hippocampal neurons: implications for smoking cessation programs. Neuropharmacology. 2000; 39(13):2740-55.

[pubmed_related keyword1=”naloxone” keyword2=”smoking” keyword3=”cessation”]

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