Lofexidine
Lofexidine, sold as a generic by Indoco, MSN, Novitium, Ani Pharma, Regcon, etc; and under the brand name Lucemyra; is a medication historically used to treat high blood pressure; today, it is more commonly used to help with the physical symptoms of opioid withdrawal. It is taken by mouth. It is an α2A-adrenergic receptor agonist. It was initially approved for use by the Food and Drug Administration in the United States in 2018, considering it to be a first-in-class medication. Subsequent generic approvals by the FDA started August 21, 2024 with Indoco Remedies with Competitive Generic Therapy designation, which provided Indoco with a 180-day exclusivity period from the date of the product’s first commercial launch in the United States. Following this exclusivity period multiple generics were approved by other manufacturers: MSN February 24, 2025, NOVITIUM PHARMA October 22, 2025, Regcon Holdings. The FDA approval of multiple generic sources of Lofexidine has resulted in the widespread availability of FDA approved cheaper alternative to the branded medication with significant cost savings to patients. The normal out-of-pocket price of Lucemyra is $1,144.96 per 36, 0.18mg tablets. As of the 12th of December 2025 at one representative pharmacy, a branded Lucemyra 3 day supply costs $756, whereas the generic versions costs $142, an 81% discount. Due to widespread inter-generic competition the price/unit of generic lofexidine itself is under steady downward pressure and this is an example of the rapid erosion of the branded drug purchase and value in the face of generic competition; alongside the continued decreases in generic costs.
Medical uses
In the United States, lofexidine is approved for the "mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults," for a treatment duration of 14 days. In the United Kingdom, lofexidine is 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.Opioid withdrawal
The United Kingdom's National Institute for Health and Care Excellence guidelines recommend the use of methadone or buprenorphine as first-line agents in the management of opioid use disorder. However, lofexidine is considered an acceptable alternative for people with mild or uncertain opioid dependence in need of short-term detoxification.Lofexidine is not an opioid. It does not eliminate the symptoms of opioid withdrawal but reduces them. 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
Lofexidine's 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:In addition, people may experience a sudden jump in blood pressure after stopping lofexidine.
Overdose
The 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 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
CNS depression
Lofexidine can depress the central nervous system, which, in combination with other CNS depressants, may reduce a person's 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 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 alpha-2A, 2B, and 2C adrenergic receptor subtypes, with the highest activity at the α2A-adrengergic receptor.Ki represents the dissociation constant for lofexidine's binding to a specific subtype of α2 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.