Tallat Sultana, M.D., Steven Lippmann, M.D. 

Lofexidine

Lofexidine is a newly released drug indicated for attenuating opioid withdrawal in the United States (1). A clonidine analogue and alpha 2-agonist, it has been prescribed in United Kingdom for this indication for decades (2). It reduces the signs and symptoms of withdrawal in animals and humans.

With central alpha 2 activity, it attenuates the adverse clinical manifestations of acute opioid discontinuance (3). There is the implication that it is the first pharmaceutical to treat opioid withdrawal (4). However, methadone (5), buprenorphine, and a number of other symptomatic pharmacotherapies, like clonidine (6) well-preceded at this indication. 

Opioid Withdrawal

The fatality rate of opioid overdose toxicity is a major concern (7). Lofexidine reduces the discomfort of opioid withdrawal, but it does not attenuate its toxicity.

Acute opioid discontinuance induces autonomic, gastrointestinal, musculoskeletal, and mental distress. By diminishing the discomfort of withdrawal, lofexidine has a role in treating people with addiction by making it more likely that they will complete chemical dependence therapies. It can be prescribed in place of clonidine because of a lower potential for hypotension (8). Lofexidine, methadone, and clonidine reportedly have somewhat similar efficacy in treating opioid withdrawal (9).

Pharmacotherapy

Prescribing lofexidine may induce hypotension, bradycardia, arrhythmias, fainting, and/or somnolence (10). Hypertension may occur upon discontinuation (10).

The brand name of lofexidine is Lucemyra (10). It is marketed in 0.18mg oral tablets for the purpose of diminishing opioid abstinence manifestations. Lofexidine is conventionally started at an oral dose of three, 0.18mg, tablets, four times daily during the time of withdrawal.  Dosing is directed by clinical observation of withdrawal severity and/or possible hypotension. Usually several hours are recommended to elapse between recurrent dosing, with no single quantity of over 0.72mg and the daily maximum of 2.88mg (10). Lofexidine is gradually discontinued once withdrawal has subsided.

Advantage

Lofexidine provides a non-opioid means to minimize opioid withdrawal signs and symptoms. Thus, it should help people better attend to sobriety interventions.

References

1. FDA approves the first non-opioid treatment for management of opioid withdrawal symptoms in adults (accessed July 2, 2018) https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm607884.htm
2. Akhurst JS. The use of lofexidine by drug dependency units in the United Kingdom. Eur Addict Res, 1999;5:(1): 43–49
3. Washton AM,  Resnick  RB,  Geyer  Opiate  with-drawal  using lofexidine—a  clonidine  analoguewith  fewer  side  effects.  J  Clin  Psych. 1983;44: 335–337
4. Jarrott B, Louis WJ, Summers RJ. Characterization of central alpha adrenoceptors using 3H-clonidine and its derivatives. Chest. 1983; 83(2):S339–S340
5. Howells C, Allen S, Gupta J, et al. Prison-based detoxification for opioid dependence: A randomized double-blind controlled trial of lofexidine and methadone. Drug Alcoh Depend. 2002;67:169–176
6. CarnwathT, Hardman J. Randomised double-blind comparison of lofexidine and clonidine in the out-patien treatment of opiate withdrawal Drug Alco Depend. 1998; 50(3): 251–254
7. Gonzalez G, Oliveto A, Kosten TR. Combating opiate dependence: a comparison among the available pharmacological options. Exp. Opin. Pharmacother 2004;5(4): 713–725
8. Washton AM, Resnick RB, Perzel JF, Garwood J. Opiate detoxification using lofexidine. NIDA Res Monogr. 1982;41: 261–263
9. Kleber H. Opioids: detoxification. In: Galanter M, Kleber HD. eds. Textbook of Substance Abuse Treatment 2nd ed. Washington, DC: American Psychiatric Press; 1999:251–269
10. Highlights of prescribing information Lucemyra (accessed July 2, 2018) https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf