Nalmefene
Nalmefene Uses, Dosage, Side Effects, Food Interaction and all others data.
Nalmefene is a 6-methylene analogue of naltrexone and opioid system modulator but with no opioid activity . It mediates a partial agonist effect on kappa receptors . It is primarily used in the management of alcohol dependence in adult patients in conjunction with continuous psychosocial support focused on treatment adherence and reducing alcohol consumption when it is exists as the hydrochloride dihydrate form under the trade name Selincro. Selincro is orally administered as tablets. Nalmefene works to reduce alcohol consumption in individuals by positive reward effect of alcohol which involves the opioid system, as well as the sedative and dysphoric properties of alcohol .
It is also indicated to prevent or reverse the effects of opioids, including respiratory depression, sedation, and hypotension by acting on the opioid receptor as an antagonist under the trade name Revex for intramuscular, intravenous and subcutaneous injection, where nalmefene hydrochloride is an active ingredient.
Nalmefene has not been shown to produce tolerance, physical dependence, or abuse potential .
| Trade Name | Nalmefene |
| Availability | Discontinued |
| Generic | Nalmefene |
| Nalmefene Other Names | Nalmefene, Nalmefeno |
| Related Drugs | naloxone, Narcan Nasal Spray, Evzio, Kloxxado, Zimhi, Revex |
| Type | |
| Formula | C21H25NO3 |
| Weight | Average: 339.435 Monoisotopic: 339.183443669 |
| Protein binding | The average protein-bound fraction of nalmefene in plasma is approximately 30-45% . |
| Groups | Approved, Investigational, Withdrawn |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Nalmefene is an opioid antagonist used in conjunction with psychosocial support to help adults with alcohol dependence reduce alcohol consumption.
Indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level (DRL), without physical withdrawal symptoms and who do not require immediate detoxification .
Indicated for the complete or partial reversal of opioid drug effects, including respiratory depression - induced by either natural or synthetic opioids - or in the management of known or suspected opioid overdose .
Nalmefene is also used to associated treatment for these conditions: Alcohol Dependency, Opioid Intoxication, Opioid Overdose
How Nalmefene works
Nalmefene is an opioid system modulator with a distinct μ, δ, and κ receptor profile. It acts as a selective opioid receptor ligand with antagonist activity at the μ and δ receptors and partial agonist activity at the κ receptor . Animal studies suggest that the kappa receptor signalling responses lead to antagonism of acute reward and positive reinforcement effects of drugs by decreasing dopamine in the nucleus accumbens . Thus it is suggested that nalmefene may be more effective treatment for alcohol dependence than Naltrexone, which is a pure mu and delta receptor antagonist . In vivo studies and rat studies have demonstrated that nalmefene reduces self-administration of alcohol, possibly by modulating cortico-mesolimbic functions .
Nalmefene, a 6-methylene analogue of naltrexone, is a competitive opioid antagonist which binds with high affinity to the mu opioid receptor. Nalmefene itself does not induce any opioid activity, but prevents or reverses the effects of opioids such as respiratory depression and sedation when injected. Some pharmacodynamic studies showed that nalmefene has a longer duration of action than naloxone at fully reversing doses however the relative potency of these two antagonists are reported to be similar .
Toxicity
Studies in animals do not indicate direct effect in the reproductive system. In a rabbit embryo-foetal developmental toxicity study, reduced fetal weight and delayed ossification were observed in the fetus but did not result in abnormalities. Studies in rats have shown excretion of nalmefene or its metabolites in milk. The nonclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity, or carcinogenic potential .
Food Interaction
No interactions found.Nalmefene Disease Interaction
Volume of Distribution
The volume of distribution (Vd/F) of oral nalmefene is estimated to be approximately 3200 L . According to a PET study after single and repeated daily dosing with 18.06 mg nalmefene, the drug displayed 94% to 100% receptor occupancy within 3 hours after dosing, indicating that nalmefene readily crosses the blood-brain barrier .
Nalmefene is reported to be rapidly distributed following a 1mg parenteral dose. Parenteral nalmefene also crosses the blood-brain barrier effectively, where the study of brain receptor occupancy demonstrated the blockage of over 80% of brain opioid receptors within 5 minutes after administration. The apparent volumes of distribution centrally (Vc) and at steady-state (Vdss) are 3.9 ± 1.1 L/kg and 8.6 ± 1.7 L/kg, respectively. In vitro study suggest that 67% of the drug is distributed into red blood cells and 39% of the drug distributed into plasma .
Elimination Route
Following a single oral administration of 18.06 mg, nalmefene is rapidly absorbed with a peak plasma concentration (Cmax) of 16.5 ng/ml with the time to reach the peak concentration (Tmax) of approxmately 1.5 hours and the exposure (AUC) of 131 ng x h/ml. Although there is little association to clinical relevance, the AUC and Cmax values are expected to increase by 30 to 50%, respectively, and the Tmax is delayed by 30 minutes after consumption of high-fat food. The absolute oral bioavailability of nalmefene is 41% .
Nalmefene exhibits dose-proportional pharmacokinetics following intravenous injection. The Tmax following intramuscular or subcutaneous injection is approximately 1.5-2.3 hours. In an emergency setting, however, therapeutic plasma concentrations are likely to be reached within 5-15 minutes after a 1 mg dose given intravenously where the plasma concentration is approximately 3.7 ng/mL at 5 minutes in young adult males .
Half Life
The terminal half-life is approximately 12.5 hours following oral administration . After intravenous administration of 1 mg in adult males, the terminal half life was 10.8 ± 5.2 hours .
Clearance
The oral clearance of nalmefene (CL/F) was estimated as 169 L/h . After intravenous administration of 1 mg in adult males, the systemic clearance of was 0.8 ± 0.2 L/hr/kg and the renal clearance was 0.08 ± 0.04 L/hr/kg .
Elimination Route
Renal excretion is the main route of elimination for nalmefene and its metabolites. 54% of the total dose is excreted in the urine as nalmefene 3-O-glucuronide. Less than 3% of the dose is excreted as nalmefene or other metabolites . Approximatly 17% of the total dose is reported to be excreted in the feces .
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