Lofexidine, sold as a generic by Indoco, MSN, Novitium, Ani Pharma, Regcon, etc; and under the brand name Lucemyra[1]; 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.[2] It is taken by mouth.[3] It is an α2A-adrenergic receptor agonist.[3] It was initially approved for use by the Food and Drug Administration in the United States in 2018,[3] considering it to be a first-in-class medication.[4] Subsequent generic approvals by the FDA started August 21, 2024 with Indoco Remedies with Competitive Generic Therapy (CGT[5]) designation (ANDA #218613)[6], which provided Indoco with a 180-day exclusivity period from the date of the product’s first commercial launch in the United States[7]. Following this exclusivity period multiple generics were approved by other manufacturers: MSN February 24, 2025 (ANDA #218699)[8], NOVITIUM PHARMA October 22, 2025 (ANDA #219917)[9], Regcon Holdings (ANDA #218613)[10]. 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[11]. The normal out-of-pocket price of Lucemyra is $1,144.96 per 36, 0.18mg tablets[12]. 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[13], 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 (Lucemyra) purchase and value in the face of generic competition; alongside the continued decreases in generic costs[14][15].
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.[1] 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.[citation needed]
Lofexidine is not an opioid.[3] It does not eliminate the symptoms of opioid withdrawal but reduces them.[3] 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.[3]
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.[17] It is also used in treatment of cases with postmenopausal hot flashes.
The LD50 of lofexidine is above 77mg/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.[19]
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:[20]
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.[20]
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.[20]
Pharmacology
Lofexidine is an agonist at the alpha-2A, 2B, and 2C adrenergic receptor subtypes, with the highest activity at the α2A-adrengergic receptor.[21]
Ki represents the dissociation constant[22] 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.[2]
Pharmacokinetics
Lofexidine's 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.[19]
Chemistry
Lofexidine exists as a solid at room temperature, with a melting point of 127 degrees C.[19] The pair of orthochlorine (Cl−) atoms on the phenyl ring are necessary for lofexidine's agonism at the α2A adrenergic receptor subtype; removal of either chlorine atom results in antagonism at the receptor.[21]
Comparison to clonidine
Structure of clonidine and lofexidine
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.[23] 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.[citation needed]
Society and culture
Britannia Pharmaceuticals has licensed lofexidine to be sold by US WorldMeds for sale in North America.[24] 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.[2] BritLofex is only available by prescription. Before the approval of widespread generic versions since 2024[7][8][9][10][11], lofexidine was first approved by the US FDA on May 16, 2018, under the brand name Lucemyra, produced by US WorldMeds.[25] The Lucemyra official prescription drug promotion website currently (December 2025) advertises that "LUCEMYRA is the only FDA-approved, non-opioid medicine proven to help with symptoms of opioid withdrawal"[26]. However, this prescription drug promotion is obsolete, and thus potentially inaccurate and misleading[27] because of the FDA approval of multiple generic versions of lofexidine since August 2024 that provide significant cost savings to patients[7][8][9][10][11].
↑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.
123Fulton B (2014). Drug Discovery for the Treatment of Addiction: Medicinal Chemistry Strategies. John Wiley & Sons. p.151. ISBN978-0470614167.
↑Neubig RR, Spedding M, Kenakin T, Christopoulos A (December 2003). "International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology". Pharmacological Reviews. 55 (4): 597–606. doi:10.1124/pr.55.4.4. PMID14657418. S2CID1729572.
↑Gerra G, Zaimovic A, Giusti F, Di Gennaro C, Zambelli U, Gardini S, Delsignore R (July 2001). "Lofexidine versus clonidine in rapid opiate detoxification". Journal of Substance Abuse Treatment. 21 (1): 11–7. doi:10.1016/s0740-5472(01)00178-7. PMID11516922.
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