Lofexidine Hydrochloride

(BANM, USAN, rINNM)
Lofexidine Hydrochloride Chemical formula
Synonyms: Ba-168; Hidrocloruro de lofexidina; Lofeksidin Hidroklorür; Lofexidine, Chlorhydrate de; Lofexidini Hydrochloridum; MDL14042; MDL-14042A; RMI-14042A. 2-[1-(2,6-Dichlorophenoxy)ethyl]-2-imidazoline hydrochloride.
Cyrillic synonym: Лофексидина Гидрохлорид.

💊 Chemical information

Chemical formula: C11H12Cl2N2O,HCl = 295.6.
CAS — 31036-80-3 (lofexidine); 21498-08-8 (lofexidine hydrochloride).
ATC — N07BC04.
ATC Vet — QN07BC04.

Pharmacopoeias.

In Chin.

💊 Adverse Effects

Lofexidine has central alpha-adrenergic effects and may cause drowsiness, dryness of the mouth, throat, and nose, hypotension, and bradycardia; prolongation of the QT interval has also been reported. Sedation may occur following overdosage. Sudden withdrawal of lofexidine may produce rebound hypertension.

💊 Precautions

Lofexidine should be used with caution in patients with cerebrovascular disease, ischaemic heart disease including recent myocardial infarction, bradycardia, renal impairment, or a history of depression. It may cause drowsiness and if affected, patients should not drive or operate machinery. Withdrawal of lofexidine therapy should be gradual over 2 to 4 days or more to reduce the risk of rebound hypertension.

💊 Interactions

Lofexidine may enhance the central depressant effects of sedatives, including alcohol. It may also enhance the effects of antihypertensives. Tricyclic antidepressants may reduce the efficacy of lofexidine.

Methadone.

A 44-year-old opioid-dependent female receiving methadone had prolongation of the QT interval after a single 400-microgram dose of lofexidine.1 The patient had previously had a normal QT while receiving methadone and it was suggested the effect might have been caused by the combination of the 2 drugs.
1. Schmittner J, et al. QT interval increased after single dose of lofexidine. BMJ 2004; 329: 1075.

💊 Pharmacokinetics

Lofexidine is absorbed from the gastrointestinal tract with peak plasma concentrations occurring after about 3 hours. It is extensively metabolised in the liver and excreted mainly in the urine. The elimination half-life is 11 hours.

💊 Uses and Administration

Lofexidine is an alpha2-adrenoceptor agonist structurally related to clonidine. It has antihypertensive activity, but is used mainly in the control of opioid withdrawal symptoms. In opioid withdrawal, lofexidine is given as the hydrochloride in an initial oral dose of 800 micrograms daily in divided doses. The dose may be increased gradually by 400 to 800 micrograms daily to a maximum of 2.4 mg daily; the maximum single dose should not exceed 800 micrograms. After 7 to 10 days, or longer in some cases, treatment is withdrawn gradually over at least 2 to 4 days.

Opioid dependence.

A systematic review1 of the use of alpha2-adrenoceptor agonists in the management of opioid dependence concluded that they were as effective as methadone, although patients stayed in treatment for longer with methadone and there were fewer adverse effects with methadone than with clonidine. Lofexidine was associated with less hypotension than clonidine and may therefore be preferred, particularly for outpatient treatment.
1. Gowing L, et al. Alpha2 adrenergic agonists for the management of opioid withdrawal. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2004 (accessed 04/10/05).

💊 Preparations

Proprietary Preparations

UK: Britlofex.
Published November 20, 2018.