Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial

Fishman, Marc; Tirado, Carlos; Alam, Danesh; Gullo, Kristen; Clinch, Thomas E.; Gorodetzky, Charles W.; Team, Cleen-Slate

doi:10.1097/adm.0000000000000474

Cited by 41 publications

(52 citation statements)

References 20 publications

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“…The label analyses were less conservative and used a "missing at random" approach with no imputation of missing data. Nonetheless, SOWS-G efficacy results presented in the label analyses, using a "missing at random" approach, were very similar to the per-protocol "missing not at random" analyses previously reported 9,10 . This confirmation of SOWS-G results across two different statistical analyses corroborates the efficacy of lofexidine for treatment of OWS.…”

Section: Discussionsupporting

confidence: 81%

“…Pivotal study data analyses presented in the lofexidine prescribing information (label; LUCEMYRA, US WorldMeds LLC) differ from the previously published study reports 9,10 . Specifically, the main efficacy endpoint (Short Opioid Withdrawal Scale of Gossop [SOWS-G] 2 score change) and subject retention rates were analyzed and presented to standardize analyses across the two studies and improve ease of data interpretation.…”

Section: Introductionmentioning

confidence: 80%

See 1 more Smart Citation

Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials

Alam

Tirado²,

Pirner

et al. 2020

Journal of Drug Assessment

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166

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Objectives: Fear of opioid withdrawal syndrome (OWS) often dissuades opioid discontinuation. Lofexidine is an FDA-approved, alpha 2-adrenergic receptor agonist for treatment of OWS. Pivotal trial results from the per-protocol statistical analyses have been published. However, the FDA prescribing information presents these efficacy results using a different, standardized statistical approach that does not transform data or impute missing values. This analysis is easier to interpret and allows comparison across studies. This reanalysis is presented here. Methods: Studies were double-blind, placebo-controlled for 7 days in Study 1 and 5 days in Study 2. Opioid-dependent adults received placebo or lofexidine; efficacy was assessed using the Short Opioid Withdrawal Scale of Gossop (SOWS-G) daily. Results: Study 1 (N ¼ 602) mean SOWS-G scores were 6.1 (SE: 0.35), 6.5 (SE: 0.34), and 8.8 (SE: 0.47) over Days 1-7 for lofexidine 2.88 mg/day, 2.16 mg/day, and placebo, respectively (for 2.88, p < .0001; for 2.16 mg, p < .0001). Study 2 (N ¼ 264) mean SOWS-G scores were 7.0 (SE: 0.44) and 8.9 (SE: 0.48) over Days 1-5 for lofexidine 2.16 mg/day and placebo, respectively (p ¼ .0037). Median time to treatment discontinuation was approximately 2 days later with lofexidine treatment than with placebo and significantly more lofexidine-treated subjects completed the studies. Hypotension and bradycardia were more common with lofexidine. More placebo subjects withdrew prematurely for lack of efficacy. Conclusion: This simplified analysis confirmed previous per-protocol results, that lofexidine better reduces OWS severity and increases retention compared with placebo in opioid-dependent adults. These results are robust and comparable across studies using various methods of analysis.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 80%

Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials

Alam

Tirado²,

Pirner

et al. 2020

Journal of Drug Assessment

Self Cite

166

View full text Add to dashboard Cite

show abstract

“…The efficacy of lofexidine for the mitigation of OWS was established in 2 randomized, double‐blind, placebo‐controlled clinical trials of 866 inpatient adults using short‐acting opioids (eg heroin, hydrocodone, oxycodone) who met DSM‐IV criteria for opioid dependence and were undergoing abrupt opioid discontinuation (Study 1: NCT01863186 and Study 2: NCT00235729) . Patients were randomized to receive either lofexidine or placebo, and study endpoints were treatment benefit (evaluated using mean total Short Opiate Withdrawal Scale of Gossop [SOWS‐Gossop]) scores at baseline and each study day, as well as the proportion of patients who completed the study.…”

Section: Resultsmentioning

confidence: 99%

“…The SOWS‐Gossop is a patient‐reported outcome instrument that evaluates a number of OWS. Patients were asked to rate the severity of each symptom severity using four response options (‘none’, ‘mild’, ‘moderate’ and ‘severe’); the total potential score ranged from 0 to 30, with higher scores indicating greater withdrawal symptom severity . In both studies, patients in the lofexidine groups reported significantly lower mean SOWS‐Gossop total scores over the study periods compared with placebo.…”

Section: Resultsmentioning

confidence: 99%

Opioid withdrawal symptoms, a consequence of chronic opioid use and opioid use disorder: Current understanding and approaches to management

2020

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What is known and objective Opioid use in the United States has reached unprecedented—some would even say crisis—levels. Although many individuals use opioid drugs as part of legitimate pain management plans, a significant number misuse prescription or illicit opioids. With regular opioid use, individuals develop tolerance and physical dependence; both are predictable, physiologic responses to repeated opioid exposure. However, a substantial number of individuals who misuse opioids will develop opioid use disorder (OUD), a complex, primary, chronic, neurobiological disease rooted in genetic, environmental and psychosocial factors. This article discusses OUD, opioid receptor physiology, and opioid withdrawal symptomatology and pathophysiology, as well as current treatment options available to reduce opioid withdrawal symptoms in individuals with physical dependence and/or OUD. Methods The research articles regarding OUD and its management have been reviewed thoroughly based on a PubMed literature search using keywords related to opioid dependence, its pathophysiology and current treatment strategies. Results and discussion Tolerance/physical dependence and the behavioural characteristics associated with OUD reflect complex neurobiologic adaptations in several major systems of the brain, including the locus ceruleus and mesolimbic systems. Physical dependence is responsible for the distressing withdrawal symptoms individuals experience upon abrupt cessation or rapid dose reduction of exogenous opioids. Opioid withdrawal symptoms are a key driver behind continued opioid use, and a barrier to opioid discontinuation. Several opioid‐based medications are available to treat patients with OUD; these treatments can diminish opioid withdrawal symptoms and cravings as well as block opioid effects in the event of relapse. Additionally, non‐opioid drugs may be used during acute detoxification to help alleviate opioid withdrawal symptoms. What is new and conclusion The opioid crisis has produced many challenges for physicians, one being the need to determine which patients would benefit most from maintenance therapy and which may be candidates for opioid discontinuation. In addition to summarizing current understanding of OUD, we provide a new algorithm for determining the need for continued opioid use as well as examples of situations where management of opioid withdrawal symptoms is indicated.

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“…15 Approval was obtained on the basis of results of 2 randomized, double-blind, placebo-controlled trials comparing lofexidine with placebo in patients undergoing inpatient opioid withdrawal. 16,17 Both studies demonstrated a benefit with lofexidine in decreasing opioid withdrawal symptoms and improving treatment retention rates when compared with placebo. 16,17 Upon FDA approval of lofexidine in the United States, the FDA required 15 postmarketing studies to assess the safety of lofexidine continually.…”

Section: Lofexidine Approvalmentioning

confidence: 99%

Lofexidine versus clonidine for mitigation of opioid withdrawal symptoms: A systematic review

Kuszmaul¹,

Palmer²,

Frederick³

2020

Journal of the American Pharmacists Association

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Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial

Abstract: Supplemental Digital Content is available in the text

Cited by 41 publications

References 20 publications

Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials

Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials

Opioid withdrawal symptoms, a consequence of chronic opioid use and opioid use disorder: Current understanding and approaches to management

Lofexidine versus clonidine for mitigation of opioid withdrawal symptoms: A systematic review

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