Lofexidine
Encyclopedia
Lofexidine is an alpha2-adrenergic receptor agonist, historically used as a short-acting anti-hypertensive, but more commonly used to alleviate physical symptoms of heroin and opiate
withdrawal.
, the hydrochloride
form, lofexidine HCl, has been licensed and sold since 1992 for opiate withdrawal relief in tablet form as BritLofex by Britannia Pharmacuetical. BritLofex is only available by prescription
. Lofexidine is also 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.
As the withdrawal symptoms subside, lofexidine works to restore natural levels of norepinephrine and endorphins to pre-opiate addiction levels.
, although the standard duration of detoxification using lofexidine is 10 days. The of lofexidine is 77 mg/kg.
Lofexidine is not currently available in the United States
. Britannia Pharmaceuticals has licensed lofexidine to be sold by US World Meds for sale in North America , and clinical trials are currently underway to secure approval for sale in the United States by the U.S. Food and Drug Administration (FDA).
An additional benefit of lofexidine treatment is that it is given as part of an outpatient, or ambulatory regimen, and can be completed without a hospital stay. This reduces costs for both healthcare provider and patient, and keeps specialist hospital beds free for particularly difficult withdrawal cases.
Lofexidine is structurally analogous to clonidine
, another alpha2-adrenergic receptor agonist used for treatment of opioid withdrawal symptoms. A comparison of the two structures is shown at right. Both contain an imidazole
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 in heroin addicts 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
.
Additionally, the possibility of lofexidine to treat ADHD symptoms in children has been investigated. Although this subject has only a small body of research, when a small dose of lofexidine is given (0.4 mg, 3x daily), ADHD severity significantly decreased. Similar studies have shown reduction of tics in children with the small dosage.
Opiate
In medicine, the term opiate describes any of the narcotic opioid alkaloids found as natural products in the opium poppy plant.-Overview:Opiates are so named because they are constituents or derivatives of constituents found in opium, which is processed from the latex sap of the opium poppy,...
withdrawal.
Indication
In the United KingdomUnited Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, the hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
form, lofexidine HCl, has been licensed and sold since 1992 for opiate withdrawal relief in tablet form as BritLofex by Britannia Pharmacuetical. BritLofex is only available by prescription
Medical prescription
A prescription is a health-care program implemented by a physician or other medical practitioner in the form of instructions that govern the plan of care for an individual patient. Prescriptions may include orders to be performed by a patient, caretaker, nurse, pharmacist or other therapist....
. Lofexidine is also commonly used in conjunction with the opioid receptor antagonist naltrexone
Naltrexone
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade...
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.
As the withdrawal symptoms subside, lofexidine works to restore natural levels of norepinephrine and endorphins to pre-opiate addiction levels.
Use in opioid detoxification
Lofexidine is not an opioid, whereas methadone is. Some opioid detox programs use methadone in decreasing amounts in their detox protocol, whereas other detox programs use lofexidine. The drugs are completely chemically unrelated, and their physiological effects are completely unrelated, although both are used as part of an opioid detoxification protocol. Whereas lofexidine cannot stop opioid withdrawal and merely eases some symptoms of withdrawal, methadone—being an opioid itself—will completely ameliorate all withdrawal symptoms in a sufficient dose. Indeed, one suggested use for lofexidine is to ease withdrawal symptoms of methadone dependence. While abstaining from opiates and taking lofexidine, effective detoxification can succeed in as little as 3 days, although the standard duration of detoxification using lofexidine is 10 days. The of lofexidine is 77 mg/kg.
Lofexidine is not currently available in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. Britannia Pharmaceuticals has licensed lofexidine to be sold by US World Meds for sale in North America , and clinical trials are currently underway to secure approval for sale in the United States by the U.S. Food and Drug Administration (FDA).
An additional benefit of lofexidine treatment is that it is given as part of an outpatient, or ambulatory regimen, and can be completed without a hospital stay. This reduces costs for both healthcare provider and patient, and keeps specialist hospital beds free for particularly difficult withdrawal cases.
Structural similarities to clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
, another alpha2-adrenergic receptor agonist used for treatment of opioid withdrawal symptoms. A comparison of the two structures is shown at right. Both contain an imidazole
Imidazole
Imidazole is an organic compound with the formula C3H4N2. This aromatic heterocyclic is a diazole and is classified as an alkaloid. Imidazole refers to the parent compound, whereas imidazoles are a class of heterocycles with similar ring structure, but varying substituents...
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 in heroin addicts 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
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
.
Other clinical uses
The possibility of using lofexidine to treat alcohol addiction withdrawal symptoms has been investigated, and has not yet been shown to be an effective treatment.Additionally, the possibility of lofexidine to treat ADHD symptoms in children has been investigated. Although this subject has only a small body of research, when a small dose of lofexidine is given (0.4 mg, 3x daily), ADHD severity significantly decreased. Similar studies have shown reduction of tics in children with the small dosage.