These include medications such as methadone, amiodarone, citalopram, and fluconazole. Other medications may increase the risk for a low level of potassium in the blood, thereby indirectly increasing the risk for QT prolongation. For example, dexamethasone, hydrochlorothiazide, and theophylline can lower the level of potassium in the blood. CNS depression
Lofexidine can depress the central nervous system (CNS), which, in combination with other CNS depressants, may reduce a persons ability to perform tasks that require skills and attention. For example, clobazam, gabapentin, and levetiracetam all can depress the CNS. Hypotension
The risk of hypotension (low blood pressure) is increased when lofexidine is combined with other drugs that lower blood pressure. These may include losartan, metoprolol, and pramipexole. Pharmacology
Lofexidine is an agonist at the α-2A, 2B, and 2C adrenergic receptor subtypes, with the highest activity at the alpha-2A receptor. Ki represents the dissociation constant for lofexidines binding to a specific subtype of alpha-2 receptor. The smaller the Ki value, the stronger the drug binds to the receptor to exert its activity. Lofexidine inhibits the release of norepinephrine in the central and peripheral nervous system, thereby reducing some of the symptoms of opioid withdrawal, but it has no documented effect on drug craving and endogenous opioid levels. Pharmacokinetics
Lofexidines oral bioavailability is about 90%, with extensive oral absorption. Peak plasma concentrations occur at 3 hours after a single administration, with a half-life of 11 hours. Lofexidine is extensively metabolized by the liver, and primarily cleared by the kidney. It is 80-90% plasma protein bound.
Chemistry
Lofexidine exists as a solid at room temperature, with a melting point of 127 degrees C. The pair of ortho chlorine (Cl−) atoms on the phenyl ring are necessary for lofexidines agonism at the α2a adrenergic receptor subtype; removal of either chlorine atom results in antagonism at the receptor. Comparison to clonidine
Lofexidine is structurally analogous to clonidine, another α2 adrenergic receptor agonist used for treatment of opioid withdrawal symptoms. A comparison of the two structures is shown at right. Both contain an imidazoline 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 to people who abuse opioids 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. Society and culture
Britannia Pharmaceuticals has licensed lofexidine to be sold by US WorldMeds for sale in North America. In the United Kingdom, the hydrochloride form, lofexidine HCl, has been licensed and sold since 1992 for opioid withdrawal relief in tablet form as BritLofex by Britannia Pharmaceuticals.