Celinkro (Selincro)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceNalmefenNalmefen
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  • Celinkro
    pills inwards 
    H. Lundbeck A / S     Denmark
    • Dosage form: & nbspfilm coated tablets
    Composition:

    One tablet contains:

    Active substance - nalmefene hydrochloride dihydrate 21.917 mg in terms of nalmefene hydrochloride 20.0 mg, calculated as nalmefene 18.06 mg;

    Excipients - microcrystalline cellulose 61.4 mg, lactose anhydrous 60.683 mg, crospovidone (type A) 4.5 mg, magnesium stearate 1.5 mg;

    Film sheath - Fall Down OY-S-28849 white 4.5 mg (hypromellose (5 mPa.s), macrogol 400, titanium dioxide (E171)).

    Description:

    Oval, biconcave, white tablets, covered with a film sheath, embossed "S" on one side.

    Pharmacotherapeutic group:The drugs used to treat alcohol dependence
    ATX: & nbsp

    N.07.B.B.05   Nalmefen

    Pharmacodynamics:

    Mechanism of action

    Nalmefene is a modulator of the opioid system with pronounced affinity for the μ-, δ- and κ-receptors.

    - Research in vitro showed that nalmefene is a selective opioid receptor ligand, exhibiting properties of an antagonist for the μ and δ receptors and a partial agonist for κ receptors.

    - Research in vivo showed that nalmefene reduces the consumption of alcohol, apparently, modulating cortico-mesolimbic functions. Data obtained from preclinical studies, clinical studies and literature,Do not assume that nalmefene has the ability to cause addiction or abuse.

    Clinical efficacy and safety

    The effectiveness of nalmefene in reducing alcohol consumption in patients with alcohol dependence was evaluated in two studies. From the study excluded patients with alcohol delirium in history, hallucinations, convulsive seizures, serious mental disorders, patients with significant impairment of liver function. Also excluded were patients who, at the time of screening or randomization, showed significant physical symptoms of alcohol withdrawal. The majority of patients (80%) included in the study had a high or very high level of risk of developing harmful effects of alcohol use at the time of screening (DRL) (according to WHO definition, intake> 60 g of pure alcohol per day for men and> 40 g of pure alcohol per day for women), of whom 65% retained a high or very high risk until randomization.

    Both studies were randomized, double-blind, placebo-controlled studies in parallel groups, and after 6 months of treatment, patients who received nalmefenewere re-randomized to receive either nalmefene, or a placebo for 1 month of so-called run-out period. The efficacy of nalmefene was also studied in a 1-year, randomized, double-blind, placebo-controlled study in parallel groups. In total, 1941 patients were treated in these studies, of which 1144 patients received nalmefene in a dose of 18 mg as needed.

    During the first visit, the clinical status of the patient, the social situation and the nature of alcohol consumption were assessed (from the patient's words). At randomization, which was carried out after 1 to 2 weeks, the risk level of development of harmful consequences of alcohol consumption was reassessed and nalmefene therapy was administered in combination with psychosocial intervention (BRENDA), aimed at maintaining adherence to treatment and reducing alcohol consumption. Nalmefen was taken as necessary, which was an average of half the days of study.

    The effectiveness of nalmefene was evaluated by two main criteria: the change in the number of days of heavy drunkenness (RTA) per month for the period between the baseline survey and the 6th month and the change in the daily dose of alcohol (SDA) for the period between the baseline survey and the 6th month.The accident was defined as the day that consumed ≥60 g of pure alcohol by men and ≥40 g by women.

    In the period between the initial visit (screening) and randomization, a significant reduction in the number of road accidents and SDA caused by non-pharmacological effects was noted in some patients. In Studies 1 (n = 579) and 2 (n = 655) 18% and 33% of the total number of patients participating in the study, respectively, significantly reduced alcohol consumption between screening and randomization. As for patients with an initially high and very high risk of developing harmful effects of alcohol use, 35% of them improved because of non-pharmacological causes between screening and randomization. In these patients, by the time of randomization, the amount of alcohol consumed was so small that the possibilities for further improvement were very limited (the baseline was almost at a minimum level). Patients who maintained a high and very high risk of developing harmful effects of alcohol use between screening and randomization, retrospectively composed the target population.In this group, the effect of treatment was more significant than in the population as a whole.

    The clinical efficacy of nalmefene and the reliability of the data were analyzed in patients with a high and very high risk of developing harmful effects of alcohol use in screening and randomisation. Initially, these patients had an average of 23 accidents per month (11% of patients - less than 14 accidents per month) with a daily intake of 106 grams of pure alcohol. In most patients, the level of alcohol dependence, as measured by the Alcohol Dependence Scale, was low (0-13 points in 55% of patients) or intermediate (14-21 points in 36% of patients).

    Retrospective analysis of efficacy in patients with a high and very high risk of developing harmful effects of alcohol use at the time of randomization

    In Study 1, the proportion of patients dropping out of the study was higher in the nalmefene group than in the placebo group (50% and 32%, respectively). The number of road accidents at the initial examination was 23 days per month as in the nalmefene group (n = 171), and in the placebo group (n = 167). Among patients who continued to participate in the study and who received performance data at 6 months, the number of road accidents was 9 days per month in the nalmefene group (n = 85) and 14 days per month in the placebo group (n = 114). At the initial examination, SDA was 102 g in the nalmefene group and 99 g in the placebo group. Among patients who continued to participate in the study and who received performance data at 6 months, the SDA was 40 g in the nalmefene group and 57 g in the placebo group.

    In Study 2, the proportion of patients dropping out of the study was higher in the nalmefene group than in the placebo group (30% and 28%, respectively). At the initial examination, the number of road accidents was 23 days per month in the nalmefene group (n = 148) and 22 days per month in the placebo group (n = 155). Among patients who continued to participate in the study and who received performance data at 6 months, the number of road accidents was 10 days per month in the nalmefene group (n = 103) and 12 days per month in the placebo group (n = 111). At the initial examination, SDA was 1 13 g in the nalmefene group and 108 g in the placebo group. Among patients who continued to participate in the study and who received efficacy data at 6 months, the SDA was 44 g in the nalmefene group and 52 g in the placebo group.

    An analysis of the generalized data on patients who participated in two studies responding to therapy is given in the table below.

    A summary of the analysis of patients with a high and very high risk of developing harmful effects of alcohol use at the time of screening and randomization responding to therapy

    Answera

    Placebo

    Nalmefen

    The inequality coefficient (95% CI)

    p-value

    SDA R70b

    19,9%

    25,4%

    1,44 (0,97; 2,13)

    0,067

    0-4 Road accidentfrom

    16,8%

    22,3%

    1,54 (1,02; 2,35)

    0,040

    a In the analysis, patients who left the study were classified as not responding to therapy.

    b Reduction by ≥70% of the initial level of SOM by 6 months (28-day period)

    from from 0 to 4 accidents per month to 6 months (28-day period)

    For the nalmefene group, only limited efficacy data are available for the 1-month run-out period.

    Annual research

    The study included 665 patients. 52% of them had a high or very high risk of developing harmful effects of alcohol use at the time of screening; in turn, 52% of these patients (27% of the total population) retained a high or very high risk by the time of randomization. In this target population, among patients who stopped treatment prematurely, more patients were in the nalmefene group (45%) compared with patients who discontinued treatment in the placebo group (31%). At the initial examination, the number of road accidents was 19 days per month, both in the nalmefene group (n = 141), and in the placebo group (n = 42). Among patients who continued to participate in the study and who received performance data at 1 year, the number of road accidents was 5 days per month in the nalmefene group (n = 78) and 10 days per month in the placebo group (n = 29). At the initial examination, SDA was 100 g in the nalmefen group and 101 g in the placebo group. Among patients who continued to participate in the study and who received efficacy data at 1 year, SDA was 24 g in the nalmefen group and 47 g in the placebo group.

    Pharmacokinetics:

    Suction

    After the administration of a single oral dose of 18.06 mg nalmefene quickly absorbed. The maximum concentration in the blood plasma (CmOh) - 16.5 ng / ml - is achieved in approximately 1.5 hours. Exposure (AUC) is 131 ng * h / ml.

    Absolute bioavailability of nalmefene after oral administration is 41%. Simultaneous reception with food with a high fat content increases the total exposure (AUC) by 30% and CmOh by 50%, while the time to reach the maximum concentration in the blood plasma (TmOh) is increased by 30 min, which is not considered clinically significant.

    Distribution

    Binding to plasma proteins is about 30%. Apparent volume of distribution (Vd/F) about 3200 liters.

    According to the data obtained during the study by positron emission tomography (PET), after single and repeated administration of nalmefene in a daily dose of 18.06 mg, binding of 94-100% of the receptors is achieved already after 3 hours, which suggests that nalmefene easily penetrates the blood-brain barrier.

    Biotransformation

    Ingestion nalmefene is extensively metabolized to the main metabolite of nalmefene-3-O-glucuronide mainly under the action of an isoenzyme UGT2B7 and, to a lesser extent, through isoenzymes UGT1A3 and UGT1A8. A relatively small amount of nalmefene is metabolized to nornalmefene by isoenzyme CYP3A4/5 and nalmefene-3-O-sulfate by sulfonation. Nornalmefen in turn turns into nornalmefen-3-O-glucuronide and nornalmefen-3-O-sulfate. Metabolites do not make a significant contribution to the pharmacodynamic effects associated with exposure to opioid receptors in humans, with the exception of nalmefene-3-O-sulfate, which has a comparable activity to nalmefene. However, the concentration of nalmefene-3-O-sulfate is less than 10% of the concentration of nalmefene. For this reason, it is unlikely that this metabolite makes a significant contribution to the development of pharmacological effects of nalmefene.

    Excretion

    Binding to glucuronides is the main mechanism determining the clearance of nalmefene. Renal excretion is the main way of removing nalmefene and its metabolites. 54% is excreted in the urine in the form of nalmefene-3-O-glucuronide, itself nalmefene and its other metabolites are determined in urine in an amount not exceeding 3% each.

    Nalmefene clearance when administered orally (CL/F) is 169 l / h. The final half-life (T1 / 2) is 12.5 hours. The data on the distribution, metabolism and excretion of nalmefene indicate its high hepatic clearance.

    Linearity / nonlinearity

    The pharmacokinetics of nalmefene is dose-independent linear in the dose range from 18.06 mg to 72.24 mg. In the equilibrium state, compared with a single administration of nalmefene, an increase in Cmax in 4.4 times and the total exposure of the drug (AUC0-tou) in 4,3 times. There were no significant differences in the pharmacokinetics of nalmefene, depending on sex, age or ethnicity. It has been found that the body size has a minimal effect on the pharmacokinetic parameters of nalmefene (with increasing body size, the clearance increases), but probably this difference is not clinically significant.

    Impaired renal function

    At present, there is no data on the pharmacokinetics of nalmefene in oral administration in patients with renal insufficiency. Administration of 1 mg of nalmefene intravenously to patients with severe renal insufficiency resulted in an increase in nalmefene exposure (dose-adjusted AUCinf) in 1,6 times in comparison with healthy subjects. The half-life increased to 26 hours compared with healthy subjects.

    Violation function liver

    When taking a single dose of nalmefene, 18.06 mg in patients with mild and moderate hepatic insufficiency, an increase in nalmefene exposure was observed compared with healthy subjects. In patients with mild hepatic insufficiency, an increase in the exposure of the drug was observed 1.5 times and a decrease in clearance by approximately 35%. In patients with moderate hepatic impairment, the exposure increased by 2.9 times, CmOh in 1,7 times, and the ground clearance decreased approximately by 60%. Changes in TmOh and T1 / 2 had no clinical significance in any group of patients. At present, there is no data on the pharmacokinetics of nalmefene after oral administration in patients with severe hepatic insufficiency.

    Elderly patients

    Special studies of the pharmacokinetics of nalmefene after oral administration in patients aged 65 years and older have not been conducted. In a study with intravenous administration of nalmefene, no significant differences in pharmacokinetics between age groups were found.

    Indications:

    Reduction of alcohol consumption in adult patients with alcohol dependence who have a high risk of alcohol abuse (see section "Pharmacodynamics"), in the absence of physical manifestations of withdrawal syndrome or the need for immediate detoxification.

    Selincro is recommended to be used in combination with long-term psychosocial support aimed at maintaining adherence to treatment and reducing alcohol consumption.

    Celinkro is administered after two weeks of monitoring a patient with a continuing high risk of alcohol abuse.

    Contraindications:

    Hypersensitivity to nalmefene or any of the components of the drug; hereditary intolerance to galactose, deficiency of lactase or glucose-galactose malabsorption.

    Use in patients currently taking opioid analgesics.

    Current or recent opioid dependence.

    Acute withdrawal symptoms of opioids.

    Suspicion of the recent use of opioids.

    Severe hepatic insufficiency (Child-Pugh classification).

    Severe renal failure (calculated glomerular filtration rate (rSKF) <30 ml / min at 1.73 m2).

    The state of alcohol withdrawal (including hallucinations, seizures and alcohol delirium) in the recent past.

    Children and adolescence (up to 18 years of age) (efficacy and safety of use not confirmed).

    Pregnancy, the period of breastfeeding.

    Carefully:

    Concomitant mental disorders in the phase of decompensation (due to the lack of clinical data); convulsive disorders in the anamnesis, including convulsions developing with the abolition of alcohol; mild to moderate renal or hepatic insufficiency, elevated ALT levels and ACT (more than 3 times the upper limit of the norm); simultaneous application of powerful inhibitors of isoenzyme UGT2B7 During a long time; elderly patients (≥65 years).

    Pregnancy and lactation:

    Data on the use of nalmefene in pregnant women are limited (less than 300 cases of pregnancy outcomes).Studies in animals have revealed the reproductive toxicity of nalmefene.

    Studies in animals have not revealed a direct adverse effect of nalmefene on fertility, pregnancy, embryo-fetal development, childbirth and postnatal development. In the study of embryo-fetal toxicity in rabbits, a decrease in fetal mass and delay in ossification (bone formation process) was observed, no other serious disturbances were detected. Exposition (AUC) when taking a higher non-toxic dose (NOAEL/ VLNTD) with these undesirable effects was lower than the exposure at reception therapeutic dose recommended for humans. An increase in the incidence of stillbirths and a decrease in their postnatal survival was observed in studies of pre- and postnatal toxicity in rats. This effect was considered indirect and associated with toxicity in females. Preclinical data did not reveal a particular hazard of nalmefene for humans on the basis of standard pharmacological safety studies, oxicity at multiple use, genotoxicity and carcinogenic potential.

    Selincro is not recommended for use during pregnancy.

    Available pharmacodynamic and toxicological data in animals have shown the ability of nalmefene and metabolites to penetrate into breast milk. It is not known whether the nalmefene in human milk.

    At this time, the potential risk for newborns / infants can not be excluded, so Celincro is not recommended for use during breastfeeding.

    Fertility

    Studies in rats have not revealed the influence of nalmefene on fertility, the mating process, pregnancy, or the process of spermatogenesis.

    Dosing and Administration:

    Dosing regimen

    During the initial visit, before Selincro is appointed, the doctor needs to assess the patient's clinical condition and the level of alcohol consumption (these words). In cases where additional information is required, the patient is asked to register the level of alcohol consumption approximately for the next two weeks. For those patients who have remained comparable to the initial level of alcohol consumption during these two weeks, Selinkro can be appointed on a second visit.

    Selincro is recommended to be used in conjunction with psychosocial support aimed at maintaining adherence to treatment and reducing alcohol consumption.

    Celinkro is not intended to achieve immediate abstinence from alcohol. Reducing alcohol consumption is an intermediate goal on the road to complete abstinence.

    Selinkro is applied as needed. The decision to take the drug is taken by the patient himself: on those days when, in his opinion, there is a high probability of drinking alcohol, 1 tablet of Selinkro in a dose of 18 mg is taken 1-2 hours before the expected moment of taking. If the patient began taking alcohol without taking Selincro's pill first, he needs to do it as quickly as possible.

    The maximum daily dose of Selincro is 1 tablet. Selincro can be taken regardless of the meal.

    In clinical trials, the maximum improvement was observed during the first 4 weeks of therapy. The patient's response to treatment and the appropriateness of continuing pharmacotherapy should be assessed regularly (for example, monthly). The doctor must constantly determine the progress of the patient in reducing alcohol consumption, his general condition, adherence to therapy and the occurrence of side effects.The duration of clinical studies of Selinkro did not exceed 12 months, so its appointment for a period of more than one year should be carried out with caution.

    Mode of application

    Tablets, covered with a film shell, should be taken whole. Tablets should not be divided or otherwise violated their integrity, since nalmefene may cause irritation in case of direct contact with the skin.

    Special patient groups

    Elderly (≥65 years)

    This group of patients does not require dose adjustment.

    Renal impairment

    In patients with mild and moderate renal failure, dose adjustment is not required.

    Dysfunction of the liver

    In patients with mild and moderate hepatic insufficiency, dose adjustment is not required.

    Children and adolescents (under 18 years of age)

    Safety and efficacy of Selincro in patients younger than 18 years of age have not been established. There is no data for this age group.

    Side effects:

    In clinical trials, more than 3,000 patients received nalmefene treatment. Overall, the safety profile looked similar in all studies conducted.

    The most common adverse reactions were nausea, dizziness, insomnia and headache.Most of these reactions had mild and moderate severity and were noted only at the beginning of treatment.

    Confusion and, less commonly, hallucinations and dissociative disorders have also been observed in clinical trials. Most of these reactions had mild and moderate severity and were noted only at the beginning of treatment (the first hours or days). Most of these unwanted reactions were resolved with continued therapy and did not resume with repeated use of the drug. These disorders, generally short-term, may be symptoms of alcoholic psychosis, alcoholic hangover syndrome or comorbid psychiatric disorders.

    The frequency of unwanted adverse reactions was calculated on the basis of the results of three randomized, double-blind, placebo-controlled trials in patients with alcohol dependence (1144 patients received Celincro in "as needed" and 797 received placebo in "as needed" mode).

    The frequency is defined as follows: very often (≥1 / 10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥1 / 10000 to <1/1000), very rarely (<1/10000), is unknown (it is not possible to estimate based on available data).

    Organs and organ systems

    Frequency

    Unwanted reaction

    Disorders from the metabolism and nutrition

    Often

    Decreased appetite

    Disorders of the psyche

    Often

    Insomnia

    Often

    Sleep disorders

    Confusion of consciousness

    Anxiety

    Reduction of libido (including absence)

    Unknown

    Hallucinations (including auditory, tactile, visual and somatic)

    Dissociative disorders

    Disturbances from the nervous system

    Often

    Dizziness

    Headache

    Often

    Drowsiness

    Tremor

    Attention disorders

    Paresthesia

    Hypesesia

    Heart Disease

    Often

    Tachycardia

    Heart palpitations
    Disorders from the gastrointestinal tract

    Often

    Nausea

    Often

    Vomiting

    Dry mouth

    Disturbances from the skin and subcutaneous tissues

    Often

    Increased sweating

    Disturbances from musculoskeletal and connective tissue

    Often

    Muscle spasms

    General disorders and disorders at the site of administration

    Often

    Fatigability

    Asthenia

    Malaise

    Feeling of an altered state (including a fog in the head, numbness)
    Laboratory and instrumental data

    Often

    Weight loss
    Overdose:

    In a study in patients with a diagnosis of pathological predilection for gambling nalmefene was used in doses up to 90 mg / day for 16 weeks. In a study in patients with interstitial cystitis, 20 patients nalmefene in a dose of 108 mg / day for more than 2 years. A case of single administration of nalmefene in a dose of 450 mg was reported, which was not accompanied by changes in blood pressure, heart rate, respiratory rate, or body temperature.

    In these cases, the safety profile of nalmefene was as described in the "Side effect" section above, however, the observation experience is limited.

    Treatment

    In case of overdose, symptomatic therapy and monitoring of the patient's condition is recommended.

    Interaction:

    Investigations of interaction with other medicinal products in vivo not carried out.

    According to the research data in vitro there is no reason to assume a clinically significant interaction between nalmefene or its metabolites and drugs that undergo metabolism involving most isoenzymes CYP450 and UGT or membrane vectors.Simultaneous use with drugs that are potent inhibitors of isoenzyme UGT2B7 (eg, diclofenac, fluconazole, medroxyprogesterone acetate, meclofenamic acid), can significantly increase the exposure of nalmefene. Rare use of these drugs simultaneously with nalmefen can hardly lead to clinically significant consequences. At the same time, in the case of prolonged simultaneous application of potent inhibitors of isoenzyme UGT2B7, it is impossible to exclude the potentially possible increase in exposure to nalmefene (see section "Special instructions and precautions"). Accordingly, simultaneous use with inducers UGT (eg, dexamethasone, phenobarbital, rifampicin, omeprazole) can potentially lead to a decrease in the concentration of nalmefene in the plasma below the therapeutic level.

    If nalmefene is used simultaneously with opioid agonists (eg, some antitussive, anti-cold, anti-diarrheal and opioid analgesics), their therapeutic effect may decrease (see section "Special instructions and precautions").

    There is no clinically significant pharmacokinetic interaction between nalmefene and alcohol.

    After applying nalmefene, there may be a slight deterioration in cognitive and psychomotor functions. However, the result of simultaneous administration of nalmefene and alcohol did not exceed the sum of the effects of each substance used separately.

    Simultaneous use of alcohol and Selincro does not prevent the development of alcohol intoxication.

    Special instructions:

    Celinkro is not intended to achieve immediate abstinence from alcohol. Reducing alcohol consumption is an intermediate goal on the road to complete abstinence.

    Use of opioids

    In an emergency situation, when a patient taking Selincro needs opioid administration, the doses of the latter required to achieve the desired effect may exceed the standard. In this case, it is necessary to closely monitor the symptoms of respiratory depression resulting from the introduction of opioids, and other unwanted reactions.

    If the introduction of opioids is necessary to help the patient in an emergency situation, their doses should be selected individually.In cases where too high doses of opioids are required, care should be taken to monitor the patient's condition.

    Selincro should be temporarily discontinued 1 week before the proposed use of opioids, for example, during routine surgical intervention.

    The doctor appointing Selincro should recommend to the patient to inform the medical staff about the time of the last intake of the drug in cases where the use of opioids becomes necessary.

    Caution should be exercised when medications containing opioids (for example, antitussives and opioid analgesics) are used in patients already receiving Selincro therapy.

    Nalmefene is contraindicated in patients taking opioid ananalgesics.

    Accompanying illnesses

    Mental disorders

    In the course of clinical trials reported on adverse reactions from the psyche (see section "Side effect"). If a patient develops psychiatric disorders that are not associated with the onset of Selincro and / or are not temporary, the physician should consider the alternative causes of these symptoms and assess the need for continuation of Selincro treatment.

    Celincro has not been studied in patients with unstable course of mental illness. Care should be taken to place Selincro with patients with concomitant mental illness during the decompensation phase, including patients diagnosed with "major depressive disorder."

    Convulsive disorder

    The experience of using the drug in patients with convulsive disorders in the anamnesis, including convulsions developing with the abolition of alcohol, is limited. It is advisable to use caution if Selincro is used to reduce alcohol consumption in this group of patients.

    Impaired kidney or liver function

    Selincro is actively metabolized in the liver and excreted mainly in the urine. For this reason, caution should be exercised in prescribing Celincro to patients with mild to moderate renal or hepatic insufficiency. Caution should be exercised in appointing Selincro to patients with elevated ALT levels and ACT (more than 3 times the upper limit of the norm), since this category of patients was excluded during clinical trials.

    Elderly patients (≥65 years of age)

    Clinical data on the use of Celincro in patients with alcohol dependence at the age of 65 years and older are limited. It should be observed caution in appointing Celinecro to patients aged 65 years and over.

    DOther

    Caution should be exercised while simultaneously using CelinCroc with potent inhibitors of isoenzyme UGT2B7.

    Lactose

    Patients with such rare hereditary problems as galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not use this drug.

    Effect on the ability to drive transp. cf. and fur:

    The influence of nalmefene on the ability to drive vehicles and work with mechanisms has not been studied.

    Celincro can cause unwanted reactions, such as nausea, dizziness, insomnia and headache. Most of these reactions had mild and moderate severity and were noted only at the beginning of treatment.

    Patients who take Selincro are advised not to drive vehicles and work with the mechanisms until an individual response to the drug is elucidated.

    Form release / dosage:

    Tablets, film-coated, 18 mg.

    Packaging:

    Packing:

    7 pcs., 14 pcs. and 28 pcs.

    For 7 or 14 tablets in a contour squeeze box (blister) made of PVC / PVDC and aluminum foil. 1 blister for 7 tablets or 1 or 2 blisters

    14 tablets with instructions for use in a cardboard box.

    Storage conditions:

    At a temperature of no higher than 30 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003001
    Date of registration:22.05.2015
    Expiration Date:22.05.2020
    The owner of the registration certificate:H. Lundbeck A / SH. Lundbeck A / S Denmark
    Manufacturer: & nbsp
    Representation: & nbspLUNDBEK EXPORT A / C LUNDBEK EXPORT A / C Denmark
    Information update date: & nbsp09.10.2017
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