Means for the treatment of alcohol addiction.
Nalmefen is a modulator of the opioid system with a clear profile of action on receptors , and . An in vitro study showed that nalmefene is a selective ligand of opioid receptors with antagonistic activity against receptors and and partial agonistic activity against receptors An in vivo study showed that nalmefen reduces alcohol consumption by modulating corticomesolimbic functions.
Data from preclinical, clinical trials, and the medical literature do not indicate any form of dependence or potential abuse of Selinkro.
Selincro’s efficacy in reducing alcohol consumption in alcohol-dependent patients (DSM-IV) was evaluated in two studies. Most (80%) patients had a high or very high risk associated with harmful alcohol consumption (> 60 g / day for men and> 40 g / day for women, according to WHO risk levels). Selincro’s effectiveness was measured by a decrease in the monthly number of days of heavy drinking (RTA) and total alcohol consumption. An accident is defined as a day with consumption of 60 g of pure alcohol for men and 40 g for women.
Nalmefen is rapidly absorbed after taking a single dose of 18.06 mg, the maximum concentration (CMax) is 16.5 ng / ml after about 1.5 hours. Bioavailability is 41%. Eating high-fat foods increases total exposure (AUC) by 30% and maximum concentration (C Max) by 50%, the time to peak concentration (T Max) is delayed by 30 minutes (T Max is 1.5 hours), but such a change is not clinically significant.
The average proportion of nalmefene associated with plasma proteins is approximately 30%. These PET studies show receptor occupancy from 94% to 100% within 3 hours after taking the drug, which indicates that nalmefene easily penetrates the blood-brain barrier.
After taking nalmefen, it is actively and rapidly metabolized to the main metabolite of nalmefen-3-O-glucuronide with the enzymes UGT2B7, UGT1A3 and UGT1A8. A small fraction of nalmefene is converted to nalmefene-3-O-sulfate by sulfation and to nornalmefene, the enzyme CYP3A4 / 5. Metabolites are considered to be significantly pharmacologically active with respect to opioid receptors in the human body, with the exception of nalmefen-3-O-sulfate, which has a potential comparable to nalmefen.
Metabolism by conjugation with glucuronide is the main mechanism of clearance of nalmefene, and renal excretion is the main route of excretion of nalmefene and its metabolites. The final half-life is estimated at 12.5 hours.
Distribution, metabolism, and excretion data show that nalmefene has a high liver extraction rate.
Linearity / nonlinearity.
Nalmefen exhibits a dose-independent linear pharmacokinetic profile in a dose range of 18.06 mg-72.24 mg.
Nalmefen does not show any significant pharmacokinetic differences depending on gender, age, as well as ethnic groups of patients. Body size affects nalmefene clearance slightly (clearance increases with increasing body size).
No oral data available for patients with renal impairment. The use of 1 mg nalmefene intravenously in patients with severe renal failure led to an increase in exposure by 1.6 times and lower than in healthy individuals CMax. The elimination half-life (26 hours) was longer than in healthy individuals.
The use of a single dose of nalmefene 18.06 mg in patients with mild or moderate liver failure was accompanied by increased exposure. No clinically significant changes in TMax or elimination half-life were noted for any of the groups. There are no pharmacokinetic data on the oral administration of nalmefen in patients with severe hepatic impairment.
Patients aged 65 and over.
Special studies of oral administration in patients over 65 years of age have not been conducted. According to research studies, pharmacokinetic changes in the elderly are not contemplated.
Selinkro is indicated for reducing alcohol consumption in adult alcohol-dependent patients who have a high level of risk associated with harmful alcohol consumption (see the section “Pharmacological properties”), bwithout physical withdrawal symptoms and which do not require immediate detoxification.
Selinkro should be prescribed only in combination with ongoing psychological support aimed at adhering to the treatment regimen and reducing alcohol consumption.
Selinkro treatment should be prescribed only to patients who, two weeks after the initial assessment of their clinical condition, remain at high risk associated with harmful consumption of alcohol.
– Hypersensitivity to any components of the Selinkro drug.
– Concurrent use of opioid analgesics.
– Opiate addiction, including a history of it.
– The presence of acute symptoms of opioid withdrawal.
– Suspected recent opioid use.
– Severe hepatic impairment (Child-Pugh classification).
– Severe renal failure (approximate glomerular filtration rate (GFR) – Recent acute alcohol withdrawal syndrome (including hallucinations, convulsions and delirium).
Use in children (under 18 years of age) is not recommended. Safety and efficacy data for Selinkro for this age category is not.
Use during pregnancy and lactation
Data on the use of nalmefen in pregnant women is limited.
Animal studies have not shown reproductive toxicity.
Selinkro is not recommended for use during pregnancy.
Available pharmacodynamic / toxicological data in animals show that nalmefene and its metabolites pass into breast milk. It is unknown whether nalmefene is excreted in human milk.
Risk for newborns / infants is not excluded.
The decision to stop breastfeeding or to stop / refrain from Selinkro treatment should be made taking into account the benefits of breastfeeding for the baby and the benefits of therapy for the woman.
In animal studies, no effects of nalmefene on fertility, mating, pregnancy, or sperm parameters were detected.
Selinkro is not intended for patients for whom the goal of treatment is immediate withdrawal. Reducing alcohol consumption is an interim goal towards ending alcohol consumption.
Use of opioids: In an emergency when opioids are to be administered to a patient, takes Selinkro, the amount of opioids necessary to obtain the desired effect may be greater than usual. The patient should be carefully examined for symptoms of respiratory failure as a result of the use of opioids and other adverse reactions.
If opioids are necessary in an emergency, the dose should always be selected individually. Careful observation is necessary if large doses are used.
Reception of Selinkro should be temporarily discontinued 1 week before the intended use of opioids, for example, if opioid analgesics can be used during elective surgery.
Patients need to inform their doctor about the use of Selinkro if there is a need to use opioids.
Caution should be exercised when using medications, containing opioids (e.g. cough medicine, opioid analgesics).
Mental Disorders: Psychiatric effects have been reported in clinical studies. If the patient develops psychic symptoms that are not related to the initiation of Selinkro treatment and / or which are not transient, alternative causes of symptoms should be considered and the need for continued Selinkro treatment should be assessed.
The use of Selinkro has not been studied in patients with unstable psychiatric illness. Caution should be exercised if Selinkro is prescribed to patients with concomitant mental disorder, such as major depressive disorder.
Convulsive Disorders: There is limited experience with the drug in patients with a history of convulsive disorders, including alcohol withdrawal. Caution is advised in the treatment of such patients.
Renal or hepatic insufficiency: Selincro is metabolized by the liver and excreted primarily in urine. Therefore, caution should be exercised when prescribing Selinkro to patients with mild or moderate hepatic or mild or moderate renal failure.
Caution should be exercised when prescribing Selinkro to patients with more than three-fold excess of ALT or AST, since such patients have been excluded from the clinical research program.
Elderly patients ( 65 years of age): Clinical data on the use of Selinkro in patients over 65 years of age with alcohol dependence are limited. Caution should be exercised when prescribing Selinkro to such patients.
Others: Caution is advised if Selinkro is prescribed in conjunction with a potent inhibitor of UGT2B7.
Excipients: Patients with rare inherited problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medication.
The ability to influence the reaction rate when driving or working with other mechanisms:
The effect of nalmefen on the ability to drive a car and work with mechanisms has not been studied.
Selinkro caused adverse reactions such as nausea, dizziness, insomnia, and headaches. Most of these reactions were mild or moderate, associated with the initiation of treatment and short-lived.
– Nalmefen 18 mg
crospovidone type A,
magnesium stearate, srdlkrdrom, srdlkrdlp, mrdldprdrp, mrdlpdrdrp
White, oval, biconvex, film-coated tablets marked вЂњSвЂќ.
Dosage and administration of
During the first visit, the patient’s clinical condition, alcohol dependence and alcohol consumption (according to the patient) should be evaluated. After this, the patient should be asked to record data on his alcohol consumption for approximately two weeks.
Selinkro can be prescribed to patients who have a high risk associated with harmful consumption of alcohol, during this two-week period has not decreased, combining drug therapy with psychosocial support to adhere to the treatment regimen and reduce alcohol consumption.
In baseline studies, the greatest improvement was observed during the first 4 weeks. The patient’s response to treatment and the need for continued pharmacotherapy should be evaluated regularly (for example, monthly). The physician should evaluate progress in reducing patient alcohol consumption, general condition, adherence to treatment regimen, and any possible side effects.
There are clinical data on the use of Selinkro in randomized controlled conditions for a period of 6 to 12 months. Caution is recommended if Selinkro is prescribed for more than 1 year.
Selinkro should be used as needed: every day, if there is a risk of alcohol consumption, the patient should take one tablet, mainly 1-2 hours before the expected time, alcohol consumption. If the patient began to consume alcohol without taking the Selinkro tablet, it is necessary to take one tablet as soon as possible.
The maximum dose of Selinkro is 1 tablet per day. Selinkro can be taken with or without food.
Patients older than 65 years: Dose adjustment is not recommended.
Renal failure: Dosage adjustment is not recommended for patients with mild or moderate renal failure.
Hepatic Insufficiency: Dose adjustment is not recommended for patients with mild or moderate hepatic impairment.
Method of use: Selinkro inside.
The tablet should be swallowed whole.
A film-coated tablet should not be divided or crushed, as direct contact with the skin may cause nalmefene to cause skin irritation.
Side Effects of
The most common adverse reactions in clinical trials have been nausea, dizziness, insomnia, and headaches. Most of these reactions were mild or moderate, associated with the start of treatment, and short-lived.
Confusion and, less commonly, hallucinations and dissociations have been reported in clinical studies. Most of these reactions were mild or moderate, associated with the start of treatment, and short-term (from several hours to several days).
Most adverse reactions occur with continued treatment and do not recur with repeated use. Alcoholic psychoses, alcohol withdrawal syndrome or concomitant mental illness were also observed, as a rule, were short-term.
Frequency is defined as: very often (? 1/10), often (? 1/100 to
– From the side of nutrition and metabolism
Often: Decreased appetite. Weight loss.
– From the psyche
Very often: Insomnia.
Often: Sleep disturbance, confusion, restlessness, decreased libido (including loss of libido).
Frequency unknown: Hallucinations (including auditory, tactile, visual and somatic hallucinations), dissociation.
– From the nervous system
Very often: Dizziness, headache.
Often: Drowsiness, tremors, impaired attention, paresthesia, hypesthesia.
– From the cardiovascular system
Often: Tachycardia, palpitations.
– From the digestive system
Very common: Nausea.
Often: Vomiting, dry mouth.
– From the skin and subcutaneous tissue
– From the musculoskeletal system
Often: Muscle cramps.
– Common disorders
Often: Fatigue, asthenia, malaise, unusual sensations.
In vivo drug interaction studies have not been conducted.
Based on in vitro studies, no clinically significant interactions between nalmefene or its metabolites and concomitantly prescribed drugs that are metabolized primarily by CYP450 and UGT enzymes or membrane transporters.
Concomitant use with drugs that are potent inhibitors of the UGT2B7 enzyme (e.g., diclofenac, fluconazole, medroxyprogesterone acetate, meclofenamic acid) can significantly increase the effect of nalmefene. This is unlikely to cause a problem with episodic use, but if simultaneous long-term treatment is started with a potent UGT2B7 inhibitor, the potential for increased effects of nalmefene cannot be ruled out.
On the other hand, the simultaneous administration of an UGT inducer (eg, dexamethasone, phenobarbital, rifampicin, omeprazole) can lead to a subtherapeutic plasma concentration of nalmefene.
If Selinkro is used concomitantly with opioid agonists (for example, some cough and cold medicines, some antidiarrheal drugs, and opioid analgesics), the patient may not benefit from the use of opioid agonists.
There are no clinically significant pharmacokinetic interactions between nalmefen and alcohol. There may be a slight deterioration in cognitive and psychomotor functions after administration of nalmefen. However, the effect of nalmefen and alcohol in combination does not exceed the sum of the effects of each substance taken separately.
Concomitant use of alcohol and Selinkro does not prevent alcohol intoxication.
A single dose of 450 mg nalmefene has been reported without changing blood pressure, heart rate, respiratory rate, or body temperature.
No unusual adverse reactions were observed under such conditions, but experience is limited.
Overdose treatment should be symptomatic and should include observation.
Terms and conditions
tablet dosage form of tablets
H. Lundbeck A / O, Denmark