Wellbutrin (Wellbutrin)

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Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceBupropionBupropion
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  • Wellbutrin
    pills inwards 
    Bayouville Corporation     Canada
    • Dosage form: & nbsptablets of prolonged action, coated
    Composition:

    Component

    Quantity (mg in one tablet)

    150 mg | 300 mg

    Active substance

    Bupropion

    hydrochloride

    150 mg

    300 mg

    Excipients

    Polyvinyl chloride

    alcohol

    5,3

    10,6

    Glyceryl

    tribehenate

    4,7

    9,4

    Ethyl cellulose-

    100

    12,0

    13,05

    Povidone

    9,0

    12,4

    Macrogol-1450

    3,46

    4,24

    Methacrylic acid and ethyl acrylate copolymer [1: 1] (containing 0.7% sodium

    lauryl sulfate, 2.3%

    polysorbate-80)

    4,59

    6,86

    Silicon

    dioxide

    1,72

    2,57

    Triethyl citrate

    0,23

    0,35

    Purified water

    how

    necessary

    how

    necessary

    Ink black

    footprints

    footprints
    Composition of black ink

    Component

    Quantity (% w / in)

    Glaze

    pharmaceutical

    44,467

    Isopropanol

    26,882

    Iron oxide black

    23,409

    Butanol

    2,242

    Propylene glycol

    2,000
    Description:Tablets with a dosage of 150 mg - round tablets from creamy white to pale yellow color with the marking "GS5FV" black on one side and with no inscriptions on the other side.
    Tablets with a dosage of 300 mg - round tablets from cream white to pale yellow color with the marking "GS5YZ" black on one side and with no inscriptions on the other side. . .
    Pharmacotherapeutic group:Antidepressant
    ATX: & nbsp

    N.06.A   Antidepressants

    Pharmacodynamics:

    Mechanism of action

    Bupropion is a selective inhibitor of the reuptake of catecholamines (noradrenaline and dopamine) with little effect on the capture of indolamines (serotonin), does not inhibit monoamine oxidase.

    Despite the fact that the mechanism of action of bupropion, like other antidepressants, is not currently known, it is suggested that its antidepressant effect is effected by influencing the noradrenergic and / or dopaminergic mediator system.

    Pharmacokinetics:

    Suction

    After ingestion of bupropion in prolonged-action tablets in healthy volunteers, the time to reach the maximum plasma concentration was approximately 5 hours.

    Eating does not have a significant effect on the absorption of bupropion when taking prolonged-action tablets.

    The kinetics of bupropion and its metabolites is linear in chronic therapy at doses of 150 to 300 mg / day.

    Distribution

    Bupropion well penetrates into the tissues, its apparent volume of distribution is approximately equal to 2000 liters.

    Bupropion and hydroxybupropion moderately bind to plasma proteins (84% and 77%, respectively). The degree of binding to proteins of the metabolite of threo-hydrobupropion is approximately 50% of the bupropion values.

    Metabolism

    Bupropion is subject to intensive metabolism. In the plasma three active metabolites are determined: hydroxybupropion and isomers of amino alcohols - threo-hydrobupion and erythro-hydrobupion. This fact can be of clinical importance, since the concentrations of metabolites in the plasma are high or even higher than the concentration of bupropion in the plasma. Erythro-hydrobupropion is not quantitatively determined in the plasma after a single dose of the drug. Active metabolites are further metabolized to inactive and excreted by the kidneys.

    In in vitro studies, it was shown that bupropion metabolized to its main metabolite hydroxybupropion, mainly through the isoenzyme CYP2B6, while the cytochrome P450 isoenzyme system does not participate in the formation of threo-hydrobupropion.

    In vitro bupropion and hydroxybupion are comparatively weak competitive inhibitors of the CYP2D6 isoenzyme system (Ki - the inhibition constant is 21 and 13.3 μmol, respectively).In volunteers, for whom a high metabolic rate was observed with the participation of the CYP2D6 isoenzyme, simultaneous administration of bupropion and desipramine resulted in a two- and five-fold increase in the maximum concentration (FROMmOh) and the area under the pharmacokinetic concentration-time curve (AUC) of desipramine. This effect persisted for no less than 7 days after the last dose of bupropion.

    Because the bupropion is not metabolized by the CYP2D6 isoenzyme, do not expect that desipramine will influence the pharmacokinetics of bupropion. It is advisable to use caution when prescribing bupropion simultaneously with substrate preparations for the enzyme system of the CYP2D6 isoenzyme.

    In studies involving volunteers or patients who received recommended doses of bupropine for 10-45 days, no induction of enzyme systems was detected under the influence of bupropion or hydroxybupropion.

    The maximum concentration of hydroxybupropion in the plasma is approximately 10 times higher than the maximum concentration of the starting material in the equilibrium state.

    The time to reach the maximum concentration for erythro-hydrobupropion and threo-hydrobupropion is approximately the same as for hydroxybupropion.

    In a study in healthy volunteers, simultaneous administration of ritonavir at a dose of 100 mg twice daily led to a decrease in the area under the pharmacokinetic curve of concentration-time (AUC) and maximum concentration (FROMmOh) of bupropion by 22% and 21%, respectively. AUC and FROMmOh metabolites of bupropion decreased from 0 to 44%. In another study, conducted in healthy volunteers, ritonavir in a dose of 600 mg 2 times a day reduced AUC and FROMmOh bupropion by 66% and 62%, respectively. AUC and FROMmOh metabolites of bupropion decreased by 42% and 78%, respectively.

    In a study in healthy volunteers, a combined dose of lopinavir 400 mg / ritonavir 100 mg twice a day was associated with a decrease in AUC and Bupropion Stach by 57%. AUC and FROMmOh hydroxybupropion were reduced by 50% and 31%, respectively.

    The maximum concentration of hydroxybupropion in the plasma is achieved 7 hours after taking bupropion in prolonged-release tablets.

    Excretion

    After ingesting 200 mg of carbon-labeled C-bupropion, 87% and 10% of the radioactive dose were detected in urine and feces, respectively. The dose fraction of bupropion, outputting in unchanged form, was only 0.5%which is associated with active metabolism of bupropion. Less than 10% isotope-labeled dose was detected in the urine as an active metabolite.

    The clearance of bupropion on intake is approximately 200 l / h, the half-life is 20 h.

    The half-life of hydroxybupropion is approximately 20 hours, the AUC in the equilibrium state is approximately 17 times greater than that of bupropion. The half-life of threo-hydrobupropion and erythro-hydropropion is longer (37 and 33h, respectively), AUC is 8 and 1.6 times higher than that of bupropion. Time to reach the equilibrium state of bupropion and its metabolites - for 8 days.

    Special patient groups:

    Elderly patients

    Pharmacokinetic studies in elderly patients showed different results. A single-dose, dose-based study showed that the pharmacokinetics of bupropion and its metabolites in elderly patients did not differ from that in young adult patients. In another pharmacokinetic study of single doses and repeated use, it was shown that bupropion and its metabolites are accumulated more in elderly patients. Clinical experience has not revealed differences in the tolerability of the drug among elderly and young patients,but we can not exclude hypersensitivity to the drug in elderly patients. Patients with impaired renal function

    The excretion of bupropion and its major metabolites may decrease in patients with impaired renal function. Exposure of bupropion and / or its metabolites is increased in patients with a terminal stage of renal failure or impaired renal function of moderate to severe severity.

    Patients with hepatic impairment

    The pharmacokinetics of bupropion and its active metabolites did not have statistically significant differences in patients with cirrhosis of mild to moderate degree compared to healthy volunteers, despite the high individual variability. In patients with severe hepatic cirrhosis FROMmOh and AUC bupropion are significantly reduced (approximately 70% and 3 times, respectively) and have greater variability compared to similar values ​​in healthy volunteers, the elimination half-life also increases (by approximately 40%). For metabolites, the mean FROMmOh decreases (by about 30-70%), the average AUC increases (by about 30-50%), the average TmOh increases (about 20 hours), the mean value of the half-life period also increases (approximately 2-4 times) compared with the values ​​of those in healthy volunteers.

    Clinical efficacy

    The efficacy and tolerability of bupropion in sustained-release tablets was investigated in 7 double-blind studies; of these 7 studies, 3 were conducted in Europe in the range of interest (up to 300 mg / day). The following 4 studies were conducted in the USA with a flexible dose range up to 450 mg / day. Evidence of long-term support for the effect is provided by a 1-year study of the prevention of exacerbations with bupropion; 816 patients received bupropion in the phase of a one-sided blind reception of this study, of which 423 were randomized into a subsequent double-blind phase (bupropion - 210, placebo - 213).

    Bupropion was effective in patients with severity of depression from mild to moderate, as well as for patients with severe depression. In pooled comparative European studies, similar degrees of drug excellence over placebo were observed in patients with mild and moderate depression (-1.8, p = 0.032) and in patients with severe depression (-2.3, p = 0.041) .

    Indications:Treatment of depression.When an adequate response is achieved, continuation of bupropion therapy To prevent exacerbations and relapses of depressive episodes.
    Contraindications:

    - Hypersensitivity to bupropion or any other component of the drug

    - Convulsive disorder

    - Severe withdrawal of alcohol or sedatives (including benzodiazepines)

    - Concomitant use of other bupropion-containing drugs (the onset of seizures is a dose-dependent effect)

    - Bulimia or anorexia nervosa in the anamnesis (there may be seizures)

    - Concomitant use with monoamine oxidase inhibitors (MAO). Do not start therapy with bupropion at least 2 weeks after the cancellation of irreversible MAO inhibitors.

    - Age to 18 years.

    Carefully:It should be used with caution in patients with impaired liver function, impaired renal function, cardiovascular disease and reduced threshold convulsive readiness.
    Pregnancy and lactation:

    Pregnancy

    The safety of bupropion in pregnant women is not established.

    Bupropion can be administered during pregnancy to patients, only when the expected benefit from its use exceeds the possible risk.

    In a retrospective study (n = 7005 infants), there was no increase in the occurrence of congenital malformations (2.3%) or cardiovascular malformations (1.1%) associated with bupropion use by the mother in the first trimester of pregnancy (n = 1213 infants ), compared with the use of other antidepressants in the first trimester of pregnancy (n = 4743 babies - 2.3% and 1.1% respectively); when using bupropion not in the first trimester (n = 1049 babies, 2.2% and 1.0%, respectively).

    Lactation

    Because the bupropion and its metabolites penetrate into breast milk, it is recommended to stop breastfeeding during bupropion therapy.

    Dosing and Administration:Tablets of bupropion prolonged action should be swallowed whole, without chewing, not breaking or chopping, as this can lead to an increased risk of adverse reactions, including convulsive disorders.

    Treatment of depression

    The clinical effect appears 14 days after the initiation of therapy. As with all antidepressants, the antidepressant effect may occur after a few weeks of treatment.

    The maximum single dose of sustained-release bupropion should be no more than 450 mg. The interval between bupropion should be at least 24 hours after the last dose. Increase the dose should not be more than 100 mg per day for three days.

    - Adults

    Start treatment

    The initial dose of bupropion is 150 mg once a day, in the morning.

    If an adequate therapeutic response is not achieved, it is recommended to increase the dose to the usual target dose for adults 300 mg / day 1 time per day.

    Increase in dose above 300 mg / day

    Increasing the dose to a maximum of 450 ~ mg / day 1 times in the bluest is possible for patients who do not experience clinical improvement after several weeks of therapy at a dose of 300 mg / day.

    Supportive therapy

    Acute episodes of depression require continuous treatment lasting from 6 months after reaching the initial therapeutic response. The efficacy of bupropion (300 mg / day) is proven with long-term therapy (up to 1 year).

    - Children and teenagers

    The safety and effectiveness of bupropion in patients under the age of 18 years is not established.

    Treatment of depression in special patient groups

    Elderly patients

    In elderly patients, the development of a hypersensitivity reaction is more likely, therefore, the dose or frequency of administration of the drug should be reduced.

    Patients with impaired renal function

    Treatment of such patients should be initiated with a lower dose of the drug, since buprotion and its metabolites may accumulate in these patients more than usual. The dose of bupropion in prolonged-release tablets, for such patients, should not exceed 150 mg once a day.

    Patients with hepatic impairment

    Due to the fact that the difference in pharmacokinetics is increased in patients with impaired liver function of mild or moderate degree, they may need to increase the interval between doses of the drug.

    The dose of bupropion in prolonged-release tablets in patients with severe hepatic cirrhosis should not exceed 150 mg once every 2 days.

    Side effects:

    Below is a list of adverse events identified in clinical trials grouped by organ systems. Criteria for the frequency of unwanted reactions: very often (≥1 / 10), often (≥1 / 100, <1/10) sometimes (≥1 / 1000, <1/100), rarely (≥1 / 10,000, <1 / 1000), very rarely (<1/10 000).

    From the immune system:

    Often

    hypersensitivity reactions such as urticaria

    Rarely

    more severe hypersensitivity reactions, including angioedema, dyspnea / bronchospasm and anaphylactic shock, arthralgia, myalgia and fever, accompanied by a rash, and other symptoms of a delayed-type hypersensitivity reaction. These symptoms may resemble serum sickness.

    From the side of metabolism

    Often:

    anorexia

    Sometimes:

    weight loss

    Rarely:

    change in blood glucose

    From the side of the psyche and behavior

    Often

    insomnia

    Often:

    agitation, anxiety

    Sometimes

    depression, confusion

    Rarely:

    aggression, hostility, irritability, anxiety, hallucinations, unusual dreams, depersonalization, illusions, delusions.

    From the nervous system

    Often:

    headache

    Often:

    tremor, dizziness, dysuria

    Sometimes:

    impaired ability to concentrate.

    Rarely:

    convulsive disorders.

    Rarely:

    dystonia, ataxia, parkinsonism, movement coordination disorders, memory impairment, paresthesia, fainting.

    From the side of the organ of vision

    Often

    visual disturbances

    From the side of the hearing organ

    Often

    tinnitus

    From the side of the cardiovascular system

    Often:

    increased blood pressure (sometimes severe), "hot flashes"

    Sometimes:

    tachycardia

    Rarely:

    heart beat, vasodilation, orthostatic hypotension

    From the gastrointestinal tract

    Often

    dry mouth, gastrointestinal disorders, including nausea and vomiting

    Often

    abdominal pain, constipation

    Rarely:

    increased activity of hepatic enzymes, jaundice, hepatitis

    From the skin and subcutaneous tissues

    Often:

    rash, itchy skin, sweating

    Rarely:

    muliform erythema, Stevens-Johnson syndrome

    From the musculoskeletal system and connective tissue

    Rarely:

    twitching of the limbsth

    From the side of the urinary system

    Rarely:

    frequency of urination

    From the body as a whole

    Often

    fever, chest pain, asthenia

    Insomnia is a very common side reaction of a transient nature, if necessary, reduce the dose or frequency of taking the drug. Do not take the drug before bedtime, observing a 24-hour interval between taking the drug.

    Overdose:

    Symptoms

    In case of an overdose of bupropion, in addition to the symptoms described in the "Side effect" section, drowsiness, loss of consciousness and changes in the ECG are observed, such as conduction disorders (including QRS prolongation) or arrhythmia. It was reported about a case of simultaneous ingestion of bupropion in doses 10 times higher than the maximum therapeutic dose.

    Treatment

    The specific antidote of bupropion is not known.

    In case of an overdose, hospitalization is recommended. It is necessary to monitor the ECG and indicators of vital functions. It is required to provide airway patency, oxygenation and pulmonary ventilation. Once the bupropion is taken orally, the use of activated carbon is indicated. Further tactics of treatment should be based on the clinical picture and recommendations of the toxicological center.

    Interaction:

    Bupropion undergoes metabolism with the formation of its main active metabolite - hydroxybupropion, mainly with the participation of the isoenzyme P450 IIB6 (CYP2B6). Therefore, care should be taken when concurrently administering bupropion with drugs that affect the activity of the isoenzyme CYP2B6 (eg, orfenadrine, cyclophosphamide, ifosfamide, ticlopidine, clopidogrel).

    In an in vitro study of the P450 enzyme system, it was shown that bupropion and hydroxybupion are inhibitors of the metabolism of the isoenzyme CYP2D6. The simultaneous use of bupropion with preparations that are predominantly metabolized by the CYP2D6 isoenzyme (such as β-adrenoblockers (eg, metoprolol), antiarrhythmics, selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics) should be initiated when the lower dose range of the concomitant drug is reached. If bupropion therapy is associated with an already administered regimen of a drug that is metabolized by the CYP2D6 isoenzyme, consideration should be given to reducing the dose of the concomitant drug, which is especially important for drugs with a narrow therapeutic index. Although citalopram is not subjected to preferential metabolism by means of the CYP2D6 isoenzyme, one study found that when bupropion was used, the maximum concentration (Сmах) and the area under the pharmacokinetic concentration-time curve (AUC) of citalopram by 30% and 40%, respectively.

    Because the bupropion is subject to active metabolism, the simultaneous administration of inducers (eg, carbamazepine, phenobarbital, phenytoin, ritonavir, efavirenz) or inhibitors of cytochrome P450 isoenzymes may influence the therapeutic effect of bupropion.

    In studies involving healthy volunteers, taking ritonavir (in doses of 100 mg twice daily or 600 mg twice daily) or a combination of ritonavir (100 mg) and lopinavir (400 mg) 2 times a day reduced the exposure of bupropion and its metabolites in dependence from a dose of approximately 20-80%. Efavirenz (in a dose of 600 mg once a day) for two weeks reduced the exposure of bupropion by approximately 55%. This influence, presumably, is mediated by the induction of bupropion metabolism.

    As a consequence, patients receiving these drugs may require a higher dose of bupropion, however, the dose should not exceed the maximum dose.

    Limited clinical data revealed an increase in frequency

    the occurrence of psychoneurological adverse reactions in patients receiving bupropion simultaneously with levodopa or amantadine.Caution should be exercised with the concomitant administration of bupropion to patients receiving levodopa or amantadine.

    The administration of repeated doses of bupropion did not have a statistically significant effect on the pharmacokinetics of lamotrigine taken once: in 12 patients and only slightly increased the AUC of glucuronide lamotrigine.

    The simultaneous use of bupropion and a transdermal nicotine system can cause an increase in blood pressure. Drugs that require metabolic activation via the CYP2D6 isoenzyme (eg, tamoxifen), may be less effective when administered with CYP2D6 inhibitors, such as bupropion.

    Special instructions:

    Convulsive disorder

    Do not exceed the recommended dose of bupropion. the risk of seizures as a result of taking bupropion is dose-dependent. In general, the incidence of seizures when taking long-acting bupropion tablets at a dose of 450 mg / day in clinical trials was approximately 0.1%.

    The occurrence of seizures that occur with the use of bupropion is associated with the presence of risk factors. Consequently, bupropion should be administered with extreme caution to patients who have one or more conditions leading to a reduction in the threshold of convulsive readiness, including:

    - craniocerebral traumas in the anamnesis;

    - CNS tumors;

    - convulsive disorders in the anamnesis;

    - concomitant therapy with other drugs that reduce the threshold of convulsive readiness.

    In addition, caution must be observed in clinical situations associated with an increased risk of seizures, including alcohol and sedation, the use of hypoglycemic drugs or insulin, and the use of stimulants or drugs to reduce appetite (sibutramine).

    If there are seizures during treatment bupropion should be canceled, the resumption of therapy with bupropion is not recommended.

    Hypersensitivity reactions

    When developing hypersensitivity reactions bupropion should be canceled immediately. The physician should be aware that the symptoms may persist after the withdrawal of bupropion and appropriate medical intervention may be required.

    Dysfunction of the liver

    Bupropion is largely exposed to active metabolism in the liver with the formation of active metabolites, which are further metabolized. Bupropion should be used with caution in patients with impaired liver function, it is necessary to solve the problem of increasing the intervals between admission in patients with impaired liver function of mild to moderate degree.

    Bupropion should be used with extreme caution in patients with severe cirrhosis. In such patients, a reduction in the frequency of receptions is required. the maximum concentrations of bupropion are greatly increased, and the incidence of cumulation in these patients is more frequent than usual.

    All patients with impaired liver function should be closely monitored for the development of adverse reactions (eg, insomnia, dry mouth, seizures), which may be a sign of high concentrations of bupropion or its metabolites.

    Patients with impaired renal function and elderly patients

    Bupropion undergoes intensive metabolism in the liver with the formation of active metabolites, which are subsequently excreted by the kidneys.Therefore, treatment of patients with impaired renal function should be initiated with lower doses, since bupropion and its metabolites can be cumulated in such patients more often than usual. Such patients should be carefully monitored for the development of adverse reactions (eg, insomnia, dry mouth, seizures), which may be a sign of high concentrations of bupropion or its metabolites.

    Clinical studies have not revealed differences in the tolerability of bupropion in elderly patients and younger patients. However, the possibility of hypersensitivity in some elderly patients can not be ruled out, so a dose or frequency reduction may be required.

    Use in children and adolescents under the age of 18 years

    Treatment with antidepressants is associated with an increased risk of suicidal thoughts and behavior in children and adolescents with major depressive disorder and other mental disorders.

    Clinical deterioration and suicidal risk associated with mental disorders in adults

    In patients with depression, exacerbation of the symptoms of the disease and / or the appearance of suicidal thoughts and suicidal behavior can be observed regardless of whether they receive antidepressants.Because the improvement may not occur within the first few weeks of treatment and for longer, patients should be closely monitored for clinical deterioration (including development of new symptoms) and suicidal behavior / thoughts, especially at the beginning of the course of treatment and during dose changes (increase or decrease ). This risk persists until a pronounced remission is achieved. Clinical experience with the use of all antidepressants shows that suicidal risk may increase in the early stages of recovery.

    The greatest suicidal risk is experienced by patients with a history of suicidal behavior or suicidal ideation, young patients, and patients with suicidal thoughts prior to treatment. Such patients should be carefully monitored during treatment.

    In addition, a meta-analysis of placebo-controlled clinical trials of the use of antidepressants in adult patients with major depression or other mental disorders demonstrated an increased risk of suicidal ideation and behavior associated with taking antidepressants compared with placebo in patients younger than 25 years of age.

    Patients and caregivers should be warned about the need for close monitoring of the condition of patients (including the appearance of new symptoms), and in case of worsening of their condition and / or appearance of suicidal thoughts / behavior or autoaggression, and if they arise, for medical assistance.

    These symptoms can be associated with both the underlying disease and the ongoing drug therapy.

    In case of clinical deterioration (including when new symptoms appear) and / or suicidal thoughts / behavior, especially if the symptoms are severe, characterized by a sudden onset and not manifested before the start of treatment, it is necessary to decide on changing the treatment regimen, including possible cancellation of the drug.

    Mental disorders, including mania and bipolar disorder

    Psychotic disturbances and mania were observed, mainly in patients with mental illnesses in the anamnesis. In addition, a major depressive episode can be an initial manifestation of bipolar disorder. It is generally accepted (although it is not proven by controlled clinical trials),that treating such an episode with only antidepressants may increase the likelihood of an accelerated development of a mixed / manic episode in patients at risk of bipolar disorder.

    Limited clinical data on the use of bupropion in combination with normotimics in patients with bipolar disorder in the anamnesis show a low frequency of transition to the manic phase.

    Before starting treatment, a thorough screening should be performed to assess the risk of bipolar disorder (including suicide, bipolar disorder and family history of depression).

    Cardiovascular diseases

    There are limited clinical data on the use of bupropion for the treatment of depression in patients with cardiovascular disease. Care must be taken when using bupropion in such patients. But, bupropion, in general, was well tolerated in studies with smoking cessation in patients with ischemic heart disease.

    In studies in patients who are not depressed (including both smokers and non-smokers) with untreated grade 1 hypertension, bupropion did not have a statistically significant effect on blood pressure. However, in the course of routine monitoring, cases of increased blood pressure (sometimes severe) have been reported. The concomitant use of bupropion and the transdermal nicotine system can cause an increase in blood pressure.

    Before the appointment of a combination of bupropion and transdermal nicotine system for the treatment of nicotine dependence, information on the use of the appropriate transdermal system should be taken into account, blood pressure monitoring should be provided.

    There have been reports of rare cases of neurological and mental disorders, as well as a decrease in alcohol tolerance in patients receiving bupropion therapy. During treatment, bupropion should minimize or avoid alcohol.

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

    Like other drugs that affect the central nervous system, bupropion can adversely affect the ability to perform tasks that require clarity of consciousness, as well as motor activity and cognitive skills.

    Patients should be careful when driving and / or other mechanisms.

    Form release / dosage:Tablets of prolonged action, coated with a coating of 150 mg, 300 mg.
    Packaging:For 7, 30 or 90 tablets of 150 mg or 7 or 30 tablets of 300 mg each in white opaque high-density polyethylene bottles containing a separate container with an activated charcoal and silica gel desiccant covered with a polypropylene cover protected from children. The opening of the neck of the bottle is sealed with a membrane of Al / polyester / polyethylene. One bottle together with the instruction is placed in a cardboard box.
    Storage conditions:At a temperature not higher than 25 ° C, out of the reach of children.
    Shelf life:

    1,5 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-008003/10
    Date of registration:12.08.2010
    Expiration Date:Unlimited
    Date of cancellation:2016-08-22
    The owner of the registration certificate:Bayouville CorporationBayouville Corporation Canada
    Manufacturer: & nbsp
    Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO
    Information update date: & nbsp24.01.2017
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