Therapeutic Switch to Buprenorphine/Naloxone from Buprenorphine Alone

Abstract

Pharmacological therapy has an important place in the management of opioid dependence. Methadone has been the mainstay of therapy but has a number of limitations. Buprenorphine monotherapy is another option, but misuse and diversion can have negative consequences. The opioid receptor antagonist, naloxone, has been added to buprenorphine to create a combination product with a reduced potential for misuse and diversion. This study evaluated the use of buprenorphine/naloxone for 24 weeks as a pharmacological management of opioid-dependent patients after therapeutic switch from buprenorphine alone. Patients (n = 43) received sublingual tablets of buprenorphine/naloxone. The buprenorphine dose was 2-24 mg (mean 16). Patients saw a physician, including an interview using a structured data sheet, and had counselling each week. Assessments were performed at week 2 (period 1), week 6 (period 2), week 16 (period 3) and week 24 (period 4). Laboratory immunoenzymatic testing was performed weekly to detect drugs in the urine. The management of withdrawal symptoms was rated as 'satisfactory' by 67% of patients during period 1 and 91% during period 4. The majority of patients was highly satisfied with therapy and considered that buprenorphine/naloxone provided good control of cravings. Two patients dropped out of therapy, but all others continued to receive buprenorphine throughout the study. Approximately 50% of patients stated that they disliked the sensory properties (taste, colour, odour and feel) of buprenorphine/naloxone. Adverse effects were as would be expected on the basis of the mechanism of action of buprenorphine (i.e. opioid-induced constipation) and for patients undergoing drug withdrawal. Only 2% of patients attempted the intravenous misuse of buprenorphine/naloxone, none of whom experienced any gratifying effects. Opioid-dependent patients maintained on buprenorphine monotherapy can be safely switched to a sublingual buprenorphine/naloxone tablet without any loss of treatment effectiveness. Buprenorphine/naloxone can be administered in an outpatient or primary care setting, and effectively controls cravings and withdrawal symptoms. Patient satisfaction was high, making retention in treatment more likely.

Efficacy of Buprenorphine/Naloxone Rapidly Dissolving Sublingual Tablets (BNX-RDT) After Switching From BNX Sublingual Film

“…Previously reported preference data on sublingual buprenorphine-containing products have been mixed. Although patients reported preferring the first approved BNX tablet formulation (Suboxone) over buprenorphine alone in terms of taste, size, and sublingual dissolution time ( Daulouede et al, 2010 ), the palatability of the first BNX tablet formulation received less favorable ratings in a separate study ( Montesano et al, 2010 ). In that study of patients who switched from a buprenorphine tablet to a BNX tablet formulation, approximately 50% of participants reported disliking the sensory properties (taste, color, odor, and mouthfeel) of the BNX tablet.…”

“…Individualized treatment plans should address factors that influence recovery, including past treatment history, living conditions, social and cultural factors, and patient acceptance and satisfaction with treatment ( World Health Organization, 2009 ). Of these factors, patient satisfaction with opioid-substitution treatment may be affected by patient perception of the convenience of treatment and sensory properties (eg, taste, mouthfeel) of medication ( Osterberg and Blaschke, 2005 ; Montesano et al, 2010 ; Fischer et al, 2015 ). Assessing patient satisfaction with treatment is a potential target to improve adherence and maximize the clinical and societal benefits of therapy ( Montesano et al, 2010 ; Tkacz et al, 2012 , 2014 ).…”

“…Of these factors, patient satisfaction with opioid-substitution treatment may be affected by patient perception of the convenience of treatment and sensory properties (eg, taste, mouthfeel) of medication ( Osterberg and Blaschke, 2005 ; Montesano et al, 2010 ; Fischer et al, 2015 ). Assessing patient satisfaction with treatment is a potential target to improve adherence and maximize the clinical and societal benefits of therapy ( Montesano et al, 2010 ; Tkacz et al, 2012 , 2014 ). Although improved clinical outcomes are understandably the primary goal for mental health treatment interventions, specific patient-focused outcomes may have fundamental value as well, including the importance of patient preference when selecting treatment and patient engagement in clinical decision-making ( Kroenke, 2015 ).…”

“…Whereas data from healthy volunteers may suggest preferable characteristics of BNX-RDT ( Fischer et al, 2015 ), clinical data with opioid-dependent patients are needed for further validation. Although several studies assessed the efficacy and safety of switching from generic buprenorphine to BNX formulations ( Daulouede et al, 2010 ; Montesano et al, 2010 ; Stimolo et al, 2010 ), clinical evidence is lacking with regard to switching between different BNX formulations, including BNX-RDT, which has a 5.7/1.4 mg buprenorphine/naloxone ratio as determined by a pharmacokinetic bioequivalence trial rather than clinical outcome data ( Fischer et al, 2015 ). Hence, comparative data between BNX products are needed to evaluate patient preference and also clinical efficacy.…”

Buprenorphine Use and Risk of Abuse and Diversion

“…Significantly more buprenorphine patients (35.5%) than methadone-maintained patients (17.8%) admitted intravenous misuse; the main reason given was self-treatment. Also in Italy, a cross-sectional survey by Montesano et al [128] studied the effect in 43 opioid-dependent patients of 24 weeks' treatment with buprenorphine/naloxone after the patients had switched from buprenorphine alone. Only 2% of patients attempted to misuse buprenorphine/naloxone intravenously, and none of them experienced any gratifying effects.…”