Trobult - instructions for use, dose, side effects, contraindications

Active substanceRetigabeenRetigabeen

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Dosage form: & nbspFilm coated tablets.

Composition:

Each tablet contains:

Name of components	Amount, mg
	50 mg	100 mg	200 mg	300 mg	400 mg
The core of the tablet
Active substance
Retigabeen	50,0	100,0	200,0	300,0	400,0
Excipients
Cellulose microcrystalline	22,8	45,6	91,2	136,8	182,4
Hypromellose-2910	2,4	4,8	9,6	14,4	19,2
Croscarmellose sodium	4,0	8,0	16,0	24,0	32,0
Magnesium stearate	0,8	1,6	3,2	4,8	6,4
Film sheath¹
Opadrai® II Purple	3,2	-	-	-	25,6
Opadrai® II Green	-	6,4	-	19,2	-
Opadrai® II Yellow	-	-	12,8	-	-

¹ The amount of film coating applied is given by 4 % excess. Acceptable is the deviation of the mass of the film coating of the tablet into 3-4 %.

Composition of the film shell:

Colour	Code Opadrai®	Name of components	Quantity,% (w / w)
Purple	Opadrai® II	Polyvinyl alcohol	40,00
		Titanium dioxide	17,64
		Macrogol-3350	20,20
		Talc	14,80
		Indigocarmine aluminum varnish (dosage of dye: 11-14 %)	3,70
		Indigocarmine aluminum varnish (dosage of dye: 30-36 %)	1,79
		Carmine red dye	1,87
Green	Opadrai® II	Polyvinyl alcohol	40,00
		Titanium dioxide	22,61
		Macrogol-3350	20,20
		Talc	14,80
		Indigocarmine Aluminum Lacquer (dosage of dye: 11-14 %)	0,93
		Dye iron oxide yellow	1,46
Yellow	Opadrai® II	Polyvinyl alcohol	40,00
		Titanium dioxide	22,52
		Macrogol-3350	20,20
		Talc	14,80
		Dye iron oxide yellow	2,48

Description:Dosage 50 mg: round, biconvex tablets, covered with a film shell of violet color, with engraving "RTG 50" on one side.
Dosage of 100 mg: round, biconvex tablets, covered with a film shell of green color with a grayish shade, with engraving "RTG 100" on one side.
Dosage of 200 mg: oval, biconvex tablets, covered with a film coating of brownish-yellow color, with engraving "RTG-200" on one side.
Dosage of 300 mg: oval, biconvex tablets, covered with a film shell of green color with a grayish shade, with engraving "RTG-300" on one side.
Dosage of 400 mg: oval, biconcave tablets covered with a film shell of violet color, with engraving "RTG-400" on one side.

Pharmacotherapeutic group:Antiepileptic agent.

ATX: & nbsp

N.03.A.X Other antiepileptic drugs

N.03.A.X.21 Retigabeen

Pharmacodynamics:Mechanism of action
Potassium channels are a type of potential-dependent ion channels of nerve cells and important determinants of neuron activity. In vitro studies have shown that retigabine operates mainly through the discovery of neural potassium channels (KCNQ2 [Kv7.2] and KCNQ3 [Kv7.3]). This results in the stabilization of the membrane resting potential and allows controlling the subthreshold electrical excitability of neurons, preventing the development of epileptiform jumps in the action potential. Mutations in the structure of KCNQ channels underlie a number of hereditary disorders, including epilepsy (KCNQ2 and 3). The mechanism of action of retigabine in relation to potassium channels is described in detail, but other mechanisms, through which retigabine has antiepileptic effect, remain insufficiently studied.
In a number of models of seizures retigabine increased the threshold of seizures caused by maximum electric shock,
pentylenetetrazole, picrotoxin and N-methyl-D-aspartate. Retigabeen also showed inhibitory properties in various models of kindling, both in development and in a neglected state. Besides, retigabine was effective in the prevention of epileptic status in rodents with cobalt-induced epileptogenic foci and inhibited tonic extensor cramps in susceptible mice.The significance of these models for human epilepsy, however, is unknown.
Pharmacodynamic effects
In rats retigabine increased the duration of sleep caused by sodium thiopental from about 4 minutes to 53 minutes, and sleep time caused by propofol, from about 8 minutes to 12 minutes. The drug had no effect on sleep time caused by halothane or methohexital sodium. Retigabeen can increase the duration of anesthesia caused by a series of anesthetics (eg, sodium thiopentone).

Pharmacokinetics:Suction
After a single and multiple oral administration retigabine is rapidly absorbed with the mean time to reach the maximum plasma concentration (Tmax) of 0.5 to 2 hours. Absolute bioavailability when taking retigabine inside compared with its intravenous administration is about 60%.
Although taking retigabine with high-fat food can lead to a Tmax delay (about 45 minutes) and an increase in the maximum plasma concentration Cmax (by 38%), no changes in the total absorption of retigabine were observed. In this way, retigabine can be taken with or without food.
Distribution
Retigabine approximately 80% binds to plasma proteins in the concentration range from 0.1 μg / ml to 2 μg / ml. The volume of distribution of retigabine in the equilibrium state after intravenous administration is from 2 l / kg to 3 l / kg.
Metabolism
Retigabine in the human body is subject to intensive metabolism. A significant proportion of retigabina
is metabolized to inactive Ν-glucuronides. Retigabeen is also metabolized to Ν-acetylmetabolites, which are subsequently also subjected to glucuronidation. Ν-acetylmetabolite retigabina (NAMR) has antiepileptic activity, but in studies in animals was less effective than retigabine.
Data on the oxidative metabolism of retigabine or its Ν-acetylmetabolite with cytochrome P450 isoenzymes in the liver are absent. Thus, it is unlikely that the combined use of the drug with inhibitors or inducers of cytochrome P450 isoenzymes will affect the pharmacokinetics of retigabine or its N-acetylmetabolite.
Re-administration of retigabine in doses of 600 mg to 1200 mg in healthy volunteers resulted in a slight, non-dependent increase in systemic exposure to digoxin (AUC in the range of 8% to 18%).
Research in vitro with the use of human liver microsomes showed the absence or weak manifestation of inhibitory potential of retigabine against the main isoenzymes of cytochrome P450 (including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 / 5). Besides, retigabine and its Ν-acetylmetabolite did not induce induction of CYP1A2 or CYP3A4 / 5 isoenzymes in primary human hepatocytes. Thus, the effect of retigabine on the pharmacokinetics of substrates of the main isoenzymes of cytochrome P450 due to the mechanism of induction or inhibition is unlikely.
Excretion
Retigabine is excreted mainly by the kidneys. About 84% of the administered dose is excreted through the kidneys, including N-acetylmetabolite (18%), Ν-glucuronides of the starting material and Ν-acetylmetabolite (24%), and the starting material (36%). Only 14% of retigabine is excreted through the intestine. The plasma half-life of retigabine is from 6 hours to 10 hours. The total clearance of retigabine from plasma with intravenous administration is usually from 0.4 l / h / kg to 0.6 l / h / kg.
Linearity
With a single intake of 25-600 mg by healthy volunteers or when patients with epilepsy are taken in a daily dose of up to 1200 mg, pharmacokinetics of retigabine are predominantly linear in nature, retigabine accumulation after repeated administration is not expected.
Special patient groups
Children and teens
The pharmacokinetics of retigabine in children and adolescents have not been studied.
Patients of advanced age (65 years and older)
In a single-dose study, retigabine excretion in healthy elderly volunteers (age 66 to 82 years) was slower than in healthy young (over 18 years) volunteers, leading to an increase in the area under the AUC concentration-time pharmacokinetic curve 40-50%) and the terminal half-life (by 30%).
Patients with impaired renal function
In a single-dose AUC study, retigabine was increased by approximately 30% in volunteers with mild renal impairment (creatinine clearance 50-80 ml / min) and approximately 100% in volunteers with moderate or severe renal impairment (creatinine clearance less than 50 ml / min) compared to healthy volunteers. The effect of mild renal dysfunction on retigabine AUC is not considered clinically significant, so correction of the dose of retigabine is not required. However, correction of the dose of retigabine is recommended in patients with moderate or severe renal dysfunction.
In a study with a single dose of the drug in volunteers with terminal stage of kidney disease, AUC retigabine increased by approximately 100% compared with healthy volunteers.
In another study with a single dose of the drug in patients with end-stage renal disease receiving chronic hemodialysis (n = 8), the onset of dialysis approximately 4 hours after a single dose of retigabine (100 mg) resulted in an average decrease in retigabine plasma concentration by 52% from the beginning to the end of dialysis. The percentage decrease in plasma concentration during dialysis fluctuated from 34% to 60%, with the exception of one patient whose decrease was 17%.
Patients with impaired hepatic function
In a study with a single application of retigabine, clinically significant effects of retigabine in volunteers with mild violations of liver function (5-6 points on the Child-Pugh scale) were not identified. The AUC of retigabine was increased by approximately 50% in volunteers with moderate hepatic impairment (7-9 on the Child-Pugh scale) and approximately 100% in volunteers with severe liver dysfunction (more than 9 on the Child-Pugh scale) compared to healthy volunteers.Correction of the dose of retigabine is recommended in patients with moderate or severe violations of the liver.
Body mass
When carrying out a pharmacokinetic analysis of the population, it was found that the clearance of retigabine increases with an increase in body surface area. However, this increase is not considered to be clinically significant, and, as retigabine dose titrated based on individual patient response and tolerability, the dose correction value of body weight is not required.
Floor
single dose study results showed that in young adult volunteers, the value Cmax retigabine was approximately 65% higher in females than in males, and in elderly volunteers (66 to 82 years), Cmax value of retigabine for women exceeded that of men about by 75%. When Cmax was normalized for body weight, the values were about 30% higher in young women than in men, and in older women it was approximately 40% higher than in men. However, obvious differences between genders for clearance normalized for body weight, is not available, and since retigabine dose titrated based on individual patient response and tolerability, dose adjustments depending on the floor is required.
Race
After a posteriori analysis, a 20% decrease in the clearance of retigabine in healthy volunteers of the black race was demonstrated in a study involving a number of healthy volunteers compared to healthy volunteers of the white race. However, this effect is not considered clinically significant, thus, correction of the dose of the drug is not recommended.

Indications:Epilepsy: as an additional therapy in adults with partial seizures, accompanied or not accompanied by secondary generalization.

Contraindications:- Hypersensitivity to retigabine or any component of the drug;
- Children and adolescents under 18 years (due to insufficient data).

Carefully:Retigabeen should be used with caution in patients at risk of urinary retention, in patients with congenital prolongation of the QT interval, congestive heart failure, ventricular hypertrophy, hypokalemia, or hypomagnesemia.

Pregnancy and lactation:Fertility
The use of retigabine had no effect on fertility in studies in animals.Nevertheless, the concentrations of retigabine in blood plasma, achieved in these studies, were less than the values obtained with the application of therapeutic doses.
The effect of retigabine on fertility has not been established.
Pregnancy
Retigabine and / or its metabolites penetrate the placental barrier in rats, resulting in practically identical concentrations of the drug in the tissues of the maternal body and fetus.
Retigabine had no teratogenic effect when used in pregnant animals.
Appropriate and controlled studies of retigabine in pregnant women have not been conducted. In a developmental study in rats whose mothers received retigabine in pregnancy, the offspring had a delay in the acoustic response of flinch. The clinical significance of this fact is unknown.
It is not recommended to apply retigabine at pregnancy except for cases when the expected benefit from treatment exceeds possible risk for a fetus.
The risk associated with antiepileptic drugs in general
Women who are capable of childbearing, you need to get a recommendation of specialists.In case a woman plans a pregnancy, the need for treatment with antiepileptic drugs should be reviewed.
Women who are treated with epilepsy should avoid sudden discontinuation of antiepileptic therapy, as this may lead to the resumption of seizures, which can have serious consequences for the woman and the unborn child. In the offspring of mothers who received antiepileptic drugs, the risk of congenital malformations increases by 2-3 times in comparison with the expected incidence of the general population, which is about 3%. The most frequently detected defects are hare lip, cardiovascular anomalies and neural tube developmental defects. Multiple therapy with antiepileptic drugs is associated with a higher risk of congenital malformations than monotherapy, and monotherapy should be used whenever possible.
The risk associated with the drug Trobult
Appropriate and controlled studies of retigabine in pregnant women are not available. Animal studies are not sufficient to determine reproductive toxicity, as plasma levels of the drug,the results obtained in these studies were less than in humans when receiving the drug at recommended doses.
Lactation
There is no data on the isolation of retigabine with breast milk.
But, retigabine and / or its metabolites were present in the milk of lactating rats.
There is insufficient data to recommend the drug Trobult during lactation.

Dosing and Administration:The drug Trobbal is taken inside daily, the daily dose is divided into three doses. The drug can be taken with or without food. Tablets should be swallowed whole, not chewing, not breaking and not dividing them.
For adults (from 18 to 64 years) the initial daily dose is 300 mg (100 mg 3 times a day). After this, the daily dose rises by no more than 150 mg per week, depending on the individual response and the patient's tolerability. The standard maintenance dose for achieving the optimal therapeutic effect is from 600 to 1200 mg / day.
The maximum maintenance dose is 1200 mg / day. Safety and efficacy of doses above 1200 mg / day are not established.
To prevent the development of unwanted reactions, the dose of retigabine should be increased gradually until an effective maintenance dose is reached.
If a patient misses one or more doses, it is recommended to immediately take a single dose of the drug.
After taking the missed dose, the interval before the next dose should be at least three hours, after which the standard reception scheme resumes.
If you cancel the drug, tbroalt dose should be reduced gradually.
Special patient groups
Children and teenagers (under the age of 18)
The safety and efficacy of the drug Trobalt in patients under the age of 18 years is not established, so the use of the drug in this age group is not recommended.
Patients of advanced age (65 years and older)
Data on the safety and efficacy of Trobalt in patients 65 years of age or older are limited. It is recommended to reduce the initial and maintenance dose of the drug. The initial daily dose is 150 mg, during the dose selection it is recommended to increase the daily dose to a maximum of 150 mg weekly depending on the individual response and the patient's tolerability. A dose above 900 mg / day is not recommended for use.
Patients with impaired renal function
Retigabine and its metabolites are excreted mainly by the kidneys.
In patients with mild renal impairment (creatinine clearance 50-80 ml / min), dose adjustment is not required.
In patients with moderate or severe impairment of renal function (creatinine clearance less than 50 ml / min), a reduction in the initial and maintenance dose by 50% is recommended. The initial daily dose is 150 mg, during the dose selection it is recommended to increase the daily dose by 50 mg weekly to the maximum daily dose of 600 mg / day.
Patients with impaired hepatic function
Dose reduction in patients with mild violations of liver function (5-6 points on the Child-Pugh scale) is not required.
In patients with moderate or severe liver function disorders (more than 7 on the Child-Pugh scale), an initial and maintenance dose reduction of 50% is recommended. The initial daily dose is 150 mg, during the dose selection it is recommended to increase the daily dose by 50 mg weekly to the maximum daily dose of 600 mg / day.

Side effects:Combined safety data from three multicenter, randomized, double-blind, placebo-controlled studies have information on adverse reactions, usually from
mild to moderate intensity, developing most frequently in the first 8 weeks of treatment.
There was a clear dependence on the dose for such reactions as dizziness, drowsiness, confusion, aphasia, impaired coordination, tremor, imbalance, memory impairment, gait disturbance, impaired vision and constipation.
The most frequent adverse reactions leading to withdrawal of the drug were dizziness,
drowsiness, fatigue and confusion.
The undesirable reactions presented below are listed in accordance with the damage to organ systems and frequency of occurrence. The frequency of occurrence is determined as follows: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10000 and <1/1000). Frequency Categories
were formed on the basis of clinical studies of the drug.
Frequency of occurrence of undesirable reactions
Disorders of the psyche
Often: confusion, psychotic disorders, hallucinations, disorientation, anxiety.
Disturbances on the part of the organ of sight
Very often: a change in the pigmentation (color change) of the eye tissues, including the retina (mainly after prolonged treatment). Some of these reactions may be accompanied by a visual impairment.
Often: diplopia, blurred vision.
Disorders from the metabolism and nutrition
Often: weight gain, increased appetite.
Disturbances from the nervous system
Very often: dizziness, drowsiness.
Often: amnesia, aphasia, impaired coordination, vertigo, paresthesia, tremor, imbalance, memory impairment, dysphasia, dysarthria, attention disturbance, gait disturbance, myoclonus.
Infrequently: hypokinesia.
Disorders from the gastrointestinal tract
Often: nausea, constipation, indigestion, dry mouth.
Infrequently: dysphagia (or difficulty swallowing).
Disturbances from the liver and bile ducts
Often: increased hepatic samples.
Disturbances from the skin and subcutaneous tissues
Often: the change in pigmentation to the gray-blue tinge of nails, lips and / or skin (observed, as a rule,
at higher doses and after several years of treatment).
Infrequent: hyperhidrosis, skin rash.
Disorders from the kidneys and urinary tract
Often: dysuria, difficulty in the beginning of urination, hematuria, chromaturia.
Infrequent: retention of urine, nephrolithiasis.
General disorders and disorders at the site of administration
Very often: fatigue.
Often: asthenia, discomfort, peripheral edema.
Description of individual undesirable
In 5% of patients from the combined safety data set who received retigabine, undesirable reactions associated with impaired urination, including urinary retention, have been reported. Most of the reactions developed during the first 8 weeks of treatment, with no apparent dependence on the dose observed.
According to generalized data, among patients who received retigabine, confusion was recorded in 9% of patients, hallucinations in 2% of patients and psychotic disorders in 1% of patients. Most of the unwanted reactions developed during the first 8 weeks of treatment, a clear dependence on the dose was observed only in cases of confusion.

Overdose:Symptoms
Data on the overdose of retigabine are limited.
When conducting clinical trials, cases of overdose of retigabine with excess daily dose of up to 2500 mg / day were reported. In addition to the undesirable reactions observed in therapeutic doses, the symptoms of regestabine overdose included agitation, aggressive behavior and irritability.The effects of an overdose were not reported. In studies of volunteers, cardiac arrhythmia (asystole or ventricular tachycardia) was noted in two subjects within 3 hours after a single dose of retigabine 900 mg. The arrhythmia resolved spontaneously, and two subjects showed recovery without consequences.
Treatment
When an overdose is recommended, symptomatic therapy, including monitoring the electrocardiogram (ECG). Further treatment is conducted in accordance with the recommendations of national toxicology centers. Hemodialysis is indicated in order to reduce the concentrations of retigabine and NAMR in plasma by about 50%.

Interaction:Other antiepileptic drugs
The results of aggregate clinical trial data show that retigabine did not cause a clinically significant effect on plasma concentrations immediately before taking the following antiepileptic drugs: carbamazepine, clobazam, clonazepam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate, valproic acid preparations, zonisamide.
The results of the combined clinical trials show that the following drugs did not have a clinically significant effect on the pharmacokinetics of retigabine: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, preparations of valproic acid.
However, the equilibrium data obtained from a limited number of patients in small Phase II studies indicate that:
- phenytoin can reduce the systemic exposure of retigobin by 35%;
- carbamazepine can reduce the systemic exposure of retigobin by 33%.
Oral contraceptives
At doses of retigabine up to 750 mg / day, there was no clinically significant effect of retigabine on the pharmacokinetics of estrogen (ethinyl estradiol) and progestogen (norgestrel, norethindrone) components of oral contraceptives. In addition, given the lack of influence of retigabine on human cytochrome P450 in vitro, the development of drug interactions for retigabine in doses exceeding 750 mg / day is not expected. In addition, there was no clinically significant effect of low-dose combined oral contraceptives on the pharmacokinetics of retigabine.
Interaction with digoxin
Data in vitro are convincing evidence of the effect of NAMR on the P-glycoprotein-dependent drug transport. NAMR suppresses the transport of digoxin with the direct participation of P-glycoprotein, and the degree of inhibition depends on the concentration. Based on a study conducted on healthy volunteers, dose adjustment is not required.
Interaction with anesthetics
The drug Trobbal may prolong the duration of anesthesia induced by certain anesthetics (for example, sodium thiopental).
Interaction with alcohol
The combined use of alcohol (1.0 g / kg) and retigabine (200 mg) in healthy volunteers resulted in blurred vision. It is recommended that patients be warned about possible visual effects when taking retigabine with alcohol.
Lab tests
It was shown that retigabine can affect the laboratory performance of both serum bilirubin and urinary bilirubin, leading to a false increase in indices.

Special instructions:Disturbances on the part of the organ of sight
In the long-term clinical trials of the drug Trobult, a change in the pigmentation (change in color) of the eye tissues, including the retina,but not always in combination with changes in the pigmentation of the skin, lips or nails. Comprehensive ophthalmologic examination (including visual acuity assessment, eye examination with a slit lamp and eye fundus examination) should be performed in all patients at the beginning of treatment and at least every six months during treatment.
If a change in retinal pigmentation or visual impairment is detected, the Trobalt preparation is necessary
Cancel if no other suitable treatment options are available.
When continuing treatment patients should be under close medical supervision. The doctor should discuss with the patient possible risks compared to the benefits associated with maintenance treatment with the drug Trobult.
Retention of urine
In controlled clinical trials of the drug, there was a delay in urine, dysuria and
difficulty in starting urination, especially in the first 8 weeks of therapy.
The drug Trobult should be used with caution in patients with a risk of retention of urine, it is recommended
warn patients about the risk of such an effect.
QT Interval
The study of intracardiac conduction in healthy volunteers showed that retigabine, the dose of which is titrated up to 1200 mg / day, causes the effect of prolongation of the QT interval. On the average, lengthening of the corrected interval QT¹ by 6.7 ms (the upper limit of 95% of the one-way confidence interval of 12.6 ms) within three hours after taking the dose of the drug. It should be observed
caution with the use of the drug Trobalt in combination with drugs that can prolong the QT interval, and in patients with the syndrome of congenital prolongation of the QT interval, congestive heart failure, ventricular hypertrophy, hypokalemia or hypomagnesemia,
who started taking the drug Trobult at the age of over 65 years. Such patients are recommended
ECG before the start of the drug. Patients who have a corrected QT interval
more than 440 ms was detected before the start of the drug, an ECG should be performed after dose selection.
Note:
1. Corrected interval QT - value of QT interval adjusted with respect to frequency
heart rate (HR) patient.
Mental disorders
In controlled clinical trials of the drug Trobult, the following undesirable
reactions: confusion, psychotic disorders and hallucinations. These reactions developed mainly in the first 8 weeks of therapy and often led to withdrawal of the drug in such patients. It is recommended to warn patients about the risk of these possible reactions.
The risk of suicide
Patients with epilepsy may develop symptoms of depression and / or bipolar disorder, and there is evidence of an increased risk of suicide in these patients.
Suicidal ideation and behavior were noted in patients receiving antiepileptic drugs for several indications. A meta-analysis of randomized placebo-controlled trials of antiepileptic drugs also showed a moderate increase in the risk of suicidal ideation and behavior. The mechanism of such a risk is unknown, and the available data do not exclude the possibility of increasing this risk with the use of the drug Trobult.
Therefore, patients should be monitored to identify signs of suicidal ideation or behavior. Patients (and caregivers) should be warned about the need to seek medical help when suicidalideas or behavior.
Patients older than 65 years
Elderly patients may be at increased risk of developing central nervous system diseases, urinary retention and atrial fibrillation. The drug Trobult should be used with caution in this age group, it is recommended to lower the initial and maintenance doses.
Convulsions with withdrawal of the drug
Like other antiepileptic drugs, the drug Trobalt should be canceled gradually to avoid cramping when canceled. It is recommended to reduce the dose of retigabine for at least three weeks, unless the drug is discontinued for safety reasons.

Effect on the ability to drive transp. cf. and fur:In controlled clinical trials, especially when choosing a dose, unwanted reactions were noted, such as dizziness, drowsiness, diplopia, and blurred vision. It is recommended that patients be warned of the risk of developing such unwanted reactions at the beginning of therapy and after each dose change, and recommend not to drive the car or mechanisms until it is clearly established how the patients' retigabine.

Form release / dosage:Film-coated tablets, 50 mg, 100 mg, 200 mg, 300 mg and 400 mg.

Packaging:Dosage of 50 mg and 100 mg: 21 tablets in a PVDC / A1 blister. For 1 or 4 blisters with instructions for use in a cardboard pack;
Dosage of 200 mg, 300 mg and 400 mg: 12 tablets in a blister of PVDC / A1. For 7 blisters with instructions for use in a cardboard bundle

Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:18 months.
Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001680

Date of registration:02.05.2012

Date of cancellation:2016-07-27

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GLAXO WELLCOME, S.A. Spain

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp27.07.2016

Illustrated instructions

Instructions

Trough (Trobalt)