Indeed, one suggested use for lofexidine is to ease withdrawal symptoms of methadone dependence. Its use is approved in the United States for up to 14 days. Other clinical uses
The possibility of using lofexidine to treat alcohol withdrawal symptoms has been investigated, and has not yet been shown to be an effective treatment. It is also used in treatment of cases with postmenopausal hot flashes. Special populations
Lofexidines safety in pregnancy or in the setting of breastfeeding are unknown. Caution is warranted if chronic kidney impairment is present. Adverse effects
Adverse effects that have occurred after taking lofexidine include the following:
Slow heart rate
Dizziness
Sleepiness
Mouth dryness
Low blood pressure
QT prolongationIn addition, people may experience a sudden jump in blood pressure after stopping lofexidine. Overdose
The LD50 of lofexidine is above 77 mg/kg in animals. Studies of high-dose, single administrations of lofexidine proved tolerable for animals, but repeat administration induced symptoms consistent with toxicity. In studies on mice, rats, and dogs, these included ataxia, somnolence, and tremors. It is expected that an overdose of lofexidine would result in symptoms akin to its pharmacological side effects in humans, such as bradycardia and hypotension. Interactions
Many drug-drug interactions with lofexidine are possible. QT prolongation
Lofexidine prolongs the QT interval, which can result in a severe interaction (torsade de pointes) when combined with other drugs that also prolong the QT interval. Patient-specific characteristics that increase the risk for a clinically significant drug-drug interaction include:
increasing age
female sex
cardiac disease
electrolyte disturbances (low blood potassium)As a result, there are many QT-prolonging drugs that may interact with lofexidine.
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.