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Lofexidine: An option for treating withdrawal

Tallat Sultana, MD, Tejaswini Doifode, MD, and Steven Lippmann, MD

Dr. Sultana is a Research Scholar, Department of Internal , pioid use disorder (OUD) and Adverse effects. ’s efficacy and University of Louisville School of deaths by opioid overdose are a safety were evaluated in 3 randomized, Medicine, Louisville, Kentucky. major public health concern, espe- double-blind, placebo-controlled trials that Dr. Doifode is an Observer Physician, O Department of Psychiatry, cially with the advent of synthetic included 935 participants dependent on University of Louisville School of such as .1 Enrolling patients with short-acting opioids who were experienc- Medicine, Louisville. Dr. Lippmann is Emeritus Professor, Department OUD into substance abuse treatment pro- ing abrupt and received of Psychiatry, University of Louisville grams can be a difficult hurdle to cross lofexidine, 2.16 or 2.88 mg/d, or placebo.3 School of Medicine, Louisville. because patients do not want to experience The most common adverse effects of lofexi- Disclosures The authors report no financial withdrawal. The of withdrawal leads dine were , orthostatic hypoten- relationships with any companies many individuals to refuse appropriate sion, , , dizziness, whose products are mentioned in 3 this article, or with manufacturers interventions. For these patients, consider , sedation, and dry mouth. In of competing products. the alpha-2 lofexidine, which was the 3 trials, these effects were reported by FDA-approved in 2018 to help diminish ≥10% of patients receiving lofexidine, and the signs and symptoms of opioid with- occurred more frequently compared with drawal.1-3 Use of lofexidine might encour- placebo (Table,3 page 31). age more patients with OUD to accept Take precautions when prescribing lofex- substance abuse treatment.1,4,5 idine because it can cause QT prolongation and CNS depression, especially when co- How to prescribe lofexidine administered with agents.3 It also For decades, clinicians in Britain have pre- can result in rebound once scribed lofexidine to attenuate opioid with- discontinued. This may be minimized by 1 3 drawal. An analog of , lofexidine gradually reducing the dosage. is reportedly less likely than clonidine to induce hypotension.1,4 While this agent A pathway to OUD treatment does not diminish drug toxicity, it can pro- Lofexidine can help relieve symptoms vide symptomatic relief for patients under- of opioid withdrawal, such as stomach going opioid withdrawal, and is efficacious cramps, muscle spasms or twitching, feel- as a supplement to and/or replacement for ing cold, muscular tension, and aches and , , clonidine, or pains.1-5 This new option might help clini- other symptomatic pharmacotherapies.1,4,5 Lofexidine is available in 0.18-mg tablets. Every issue of Current Psychiatry For patients experiencing overt symptoms ‘ ’ Discuss this article at of opioid withdrawal, initially prescribe 3 has its Pearls www.facebook.com/ 0.18-mg tablets, 4 times a day.3 The recom- Yours could be found here. MDedgePsychiatry mended maximum dosage is 2.88 mg/d, Read the ‘Pearls’ guidelines for and each dose generally should not exceed manuscript submission at MDedge.com/ 0.72 mg/d. Lofexidine may be continued for CurrentPsychiatry/page/pearls. up to 14 days, with dosing guided by symp- Then, share with your peers a ‘Pearl’ toms. Initiate a taper once the patient no lon- Current Psychiatry of wisdom from your practice. 30 January 2020 ger experiences withdrawal symptoms.3 Pearls

Table Lofexidine-induced adverse effects Treatment Lofexidine, 2.88 mg/d Lofexidine, 2.16 mg/d Placebo Adverse effect (n = 222) (n = 229) (n = 151) Insomnia 55% 51% 48% Orthostasis 42% 29% 5% Bradycardia 32% 24% 5% Use of lofexidine Hypotension 30% 30% 1% might help more Dizziness 23% 19% 3% Somnolence 13% 11% 5% patients with Sedation 12% 13% 5% OUD engage in 11% 10% 0% substance abuse Source: Reference 3 treatment

cians encourage more patients with OUD to newsevents/newsroom/pressannouncements/ucm607884. htm. Published May 16, 2018. Accessed December 13, 2019. fully engage in substance abuse treatment. 3. Lucemyra [package insert]. Louisville, KY: US WorldMeds, LLC; 2018. References 4. Carnwath T, Hardman J. Randomized double-blind 1. Rehman SU, Maqsood MH, Bajwa H, et al. Clinical efficacy comparison of lofexidine and clonidine in the out-patient and safety profile of lofexidine hydrochloride in treating treatment of withdrawal. Drug Depend. opioid withdrawal symptoms: a review of literature. 1998;50(3):251-254. Cureus. 2019;11(6):e4827. doi: 10.7759/cureus.4827. 5. Gonzalez G, Oliveto A, Kosten TR. Combating opiate 2. FDA approves the first non-opioid treatment for dependence: a comparison among the available management of opioid withdrawal symptoms in adults. pharmacological options. Exp Opin Pharmacother. 2004; US Food & Drug Administration. https://www.fda.gov/ 5(4):713-725.

Current Psychiatry Vol. 19, No. 1 31