|Systematic (IUPAC) name|
|Mol. mass||259.131 g/mol|
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Lofexidine (sold under the brand names: Britlofex and Kai Er Ding) is an α2A-adrenergic receptor agonist, historically used as an anti-hypertensive, but more commonly used to alleviate the physical symptoms of heroin and other types of opioid withdrawal.
In the United Kingdom, the hydrochloride form, lofexidine HCl, has been licensed and sold since 1992 for opiate withdrawal relief in tablet form as Britlofex by Britannia Pharmaceuticals. Britlofex is only available by prescription. Lofexidine is also commonly used in conjunction with the opioid receptor antagonist naltrexone in rapid detoxification cases. When these two drugs are paired, naltrexone is administered to induce an opioid-receptor blockade sending the subject into immediate withdrawal and accelerating the detoxification process, while lofexidine is given to relieve the symptoms associated with the withdrawal including chills, sweating, stomach cramps, muscle pain, and runny nose.
Lofexidine inhibits the release of norepinephrine in the central and peripheral nervous system, thereby reducing some of the withdrawal symptoms, but it has no documented effect on drug craving and endogenous opioid levels.
Use in opioid detoxification
Lofexidine is not an opioid, whereas methadone is. Some opioid detox programs use methadone in decreasing amounts in their detox protocol, whereas other detox programs use lofexidine. The drugs are completely chemically unrelated, and their physiological effects are completely unrelated, although both are used as part of an opioid detoxification protocol. Whereas lofexidine cannot stop opioid withdrawal and merely eases some symptoms of withdrawal, methadone—being an opioid itself—will completely ameliorate all withdrawal symptoms in a sufficient dose. Indeed, one suggested use for lofexidine is to ease withdrawal symptoms of methadone dependence. While abstaining from opiates and taking lofexidine, effective detoxification can succeed in as little as 3 days , although the standard duration of detoxification using lofexidine is 10 days. The LD50 of lofexidine is 77 mg/kg. Lofexidine is not currently available in the United States. Britannia Pharmaceuticals has licensed lofexidine to be sold by US World Meds for sale in North America, and clinical trials are currently underway to secure approval for sale in the United States by the U.S. Food and Drug Administration (FDA).
An additional benefit of lofexidine treatment is that it is given as part of an outpatient, or ambulatory regimen, and can be completed without a hospital stay. This reduces costs for both healthcare provider and patient, and keeps specialist hospital beds free for particularly difficult withdrawal cases.
Structural similarities to clonidine
Lofexidine is structurally analogous to clonidine, another alpha2-adrenergic receptor agonist used for treatment of opioid withdrawal symptoms. A comparison of the two structures is shown at right. Both contain an imidazole ring and a 2,6-dichlorinated phenyl ring. The differences in structure are shown in red, while the similarities are in black. In addition to the structural differences, administration of lofexidine in heroin addicts has been shown to be more effective for a longer duration, with fewer withdrawal symptoms than clonidine even after one day. However, Clonidine is often preferred as it is substantially cheaper than Lofexidine when purchased with a private (non-NHS) prescription. This factor is exacerbated by the considerable number of and quantities of medications prescribed to alleviate the constellation of withdrawal signs and symptoms. Additionally, clonidine has been shown to significantly lower blood pressure. Therefore, although similar to lofexidine, clonidine is most frequently prescribed to treat high-blood pressure.
Other clinical uses
The possibility of using lofexidine to treat alcohol addiction withdrawal symptoms has been investigated, and has not yet been shown to be an effective treatment.
Adverse side effects
- Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. p. 330. ISBN 978-0-85711-084-8.
- G. Gerra, et al., Lofexidine versus clonidine in rapid opiate detoxification, Journal of Substance Abuse TreatmentVolume 21, Issue 1, , July 2001, Pages 11-17.
- J. Bearn, M. Gossop, J. Strang, Drug Alcohol Depend. 43, 87 (1996)
- Britannia Pharmaceuticals Limited
- US WorldMeds | +1 502 893 3235
- Keaney F, Strang J, Gossop M, Marshall EJ, Farrell M, Welch S, Hahn B, Gonzalez A. A double-blind randomized placebo-controlled trial of lofexidine in alcohol withdrawal: lofexidine is not a useful adjunct to chlordiazepoxide. Alcohol Alcohol (2001) 36:426–30.