Topsaver - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate 23,000 mg, pregelatinized starch 7,200 mg, partially pregelatinized starch 0,800 mg, microcrystalline cellulose 20,800 mg, sodium carboxymethyl starch 2,400 mg, magnesium stearate 0,800 mg;

shell: hypromellose 1,272 mg, polysorbate 80 0.060 mg, talc 0.780 mg, titanium dioxide (E171) 0.288 mg.

In 1 tablet, 50 mg contains:

active substance: topiramate 50.0 mg;

Excipients: lactose monohydrate 46,000 mg, pregelatinized starch 14,400 mg, starch partially pregelatinized 1,600 mg, microcrystalline cellulose 41,600 mg, sodium carboxymethyl starch 4,800 mg, magnesium stearate 1,600 mg;

sheath: hypromellose 2.544 mg, polysorbate 80 0.120 mg, talc 1.560 mg, titanium dioxide (E171) 0.547 mg, iron oxide yellow (E172) 0.029 mg.

In 1 tablet, 100 mg contains:

active substance: topiramate 100.0 mg;

Excipients: lactose monohydrate 92,000 mg, pregelatinized starch 28,800 mg, partially pregelatinised starch 3,200 mg, microcrystalline cellulose 83,200 mg, sodium carboxymethyl starch 9,600 mg, magnesium stearate 3,200 mg;

shell: hypromellose 5.088 mg, polysorbate-80 0.240 mg, talc 3.120 mg, titanium dioxide (E171) 0.922 mg, iron oxide yellow (E172) 0.230 mg.

In 1 tablet 200 mg contains:

active substance: topiramate 200.0 mg;

Excipients: lactose monohydrate 184,000 mg, pregelatinized starch 57,600 mg, starch partially pregelatinized 6,400 mg, microcrystalline cellulose 166,400 mg, sodium carboxymethyl starch 19,200 mg, magnesium stearate 6,400 mg;

shell: hypromellose 10,176 mg, polysorbate-80 0,480 mg, talc 6,240 mg, titanium dioxide (E171) 2,035 mg, iron oxide red (E172) 0.269 mg.

Description:

Tablets 25 mg: white, round, biconvex tablets, covered with a film sheath, marked "TO" on one side and "25" on the other.

Tablets 50 mg: light yellow, round, biconvex tablets, covered film shell, labeled "TO" - on one side and "50" - on the other.

Tablets 100 mg: yellow, round, biconvex tablets, film-coated, marked "TO" on one side and "100" on the other.

Tablets 200 mg: grayish pink, round, biconvex tablets, film-coated with "TO" on one side and "200" on the other.

Pharmacotherapeutic group:antiepileptic agent

ATX: & nbsp

N.03.A.X Other antiepileptic drugs

N.03.A.X.11 Topiramate

Pharmacodynamics:

Topiramate refers to sulfate-substituted monosaccharides. It blocks sodium channels and suppresses occurrence of repeated potentials of action against the background of prolonged depolarization of the neuron membrane. Increases the activity of gamma-aminobutyric acid (GABA) with respect to some subtypes of GABA receptors. Prevents activation of kainate sensitivity of the kainate / AMPK subtype (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) -receptors to glutamate, without affecting activity N-methyl-D-aspartate (NMDA) in a relationship NMDAreceptors. These effects are dose-dependent. Besides, topiramate inhibits the activity of certain isoenzymes of carbonic anhydrase. This effect is much weaker than that of the acetoazolamide carbonic anhydride inhibitor and is not the main component of the antiepileptic activity of topiramate.

Pharmacokinetics:

Topiramate is quickly and well absorbed. Eating does not have a clinically significant effect on its bioavailability, which is about 80%. The connection with plasma proteins is 13-17%.The average volume of distribution is 0.55-0.8 l / kg for a single dose up to 1200 mg. This indicator depends from the floor: in women, these values are 50% of the values observed in men, which is associated with a higher content of adipose tissue in women.

About 20% of the topiramate is metabolized. Up to 50% of topiramate is metabolized in patients taking other antiepileptic drugs (PEP) simultaneously, inducing metabolic enzymes. Of the plasma, urine and human feces, six practically inactive metabolites of topiramate were isolated. Unchanged topiramate and its metabolites are mainly excreted through the kidneys. Plasma clearance is about 20-30 ml / min. After a single dose, the pharmacokinetics is linear, the plasma clearance is constant, and the area under the concentration / time curve in the dosage range of 100 to 400 mg increases in proportion to the dose. With normal function, patients may need 4-8 days to achieve an equilibrium plasma concentration. The average value of the maximum concentration after repeated intake of 100 mg of topiramate twice a day is 6.76 μg / ml.The half-life after repeated administration of 50 and 100 mg twice a day is 21 hours.

In patients with impaired renal function (creatinine clearance <60 ml / min) reduces plasma and renal clearance of topiramate; in patients with terminal stage of renal failure, the plasma clearance of topiramate decreases.

The plasma clearance of topiramate does not changeI am in elderly patients in the absence of violations of the kidney function.

Plasma clearance of topiramate decreases in patients with moderate and severe liver function disorders.

Pharmacokinetics of topiramate in children, as well as in adults is linear. The clearance of the drug does not depend on the dose, the equilibrium concentration in the blood plasma increases in proportion to the dose. However, children are characterized by higher clearance values and a shorter half-life. Consequently, the concentration of topiramate in blood plasma when taking the same doses per kg of body weight may be lower in children than in adults.

Topiramate is effectively excreted from the blood plasma during hemodialysis.

Presumably penetrates into breast milk.

Indications:

- Mepilepsy epilepsy in children from the age of 7 and adults (including patients with newly diagnosed epilepsy);

- auxiliary therapy in children from 3 years old and adults with insufficient efficiency of the first-choice PEP with partial or generalized tonic-clonic seizures, as well as seizures with Lennox-Gastaut syndrome.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- children up to 3 years;

- pregnancy and lactation.

Carefully:Pkidney or liver failure, nephrourolythiasis (including past or family history), hypercalciuria.

Dosing and Administration:

Are common

Inside, swallowing the pill entirely without chewing, regardless of food intake.

For optimal control of seizures, it is recommended to begin treatment with low doses with subsequent increase to an effective dose.

As part of complex therapy

Adultse: minimum effective dose of 200 mg / day. The usual daily dose of 200-400 mg (for 2 admission). The maximum daily dose is 1600 mg. Treatment begins with 25-50 mg daily for the night for 1 week. Then the dose is increased by 25-50 mg per day for 1-2 weeks, with a frequency of reception 2 times a day.If this dosage regimen is intolerant, the dose is increased by a smaller amount or at large intervals. The dose and the frequency of reception are selected depending on the clinical effect.

Children over 3 years old: the recommended daily dose is 5-9 mg / kg body weight, divided into 2 doses. Treatment begins with a dose of 25 mg per night for 1 week.

Then the dose is increased by 1 -3 mg / kg / day for 1 -2 weeks, with a frequency of 2 times a day, until the optimal clinical effect is achieved.

Monotherapy

Adults: treatment is started with 25 mg at night for 1 week. Then the dose is increased by 25-50 mg per day for 1-2 weeks, with a frequency of reception 2 times a day. If this dosage regimen is intolerant, the dose is increased by a smaller amount or at large intervals. The dose and the frequency of reception are selected depending on the clinical effect. The recommended initial dose of topiramate for monotherapy in adults with newly diagnosed epilepsy is 100 mg / day, the maximum recommended dose is 500 mg / day. These doses are recommended for all adults, including the elderly with normal kidney function.

Children from 7 years old: treatment is started with a dose of 0.5-1 mg / kg of body weight at night for 1 week.Then the dose is increased by 0.5-1 mg / kg / day for 1-2 weeks, the frequency of reception is 2 times a day. If this dosage regimen is intolerant, the dose is increased by a smaller amount or at large intervals. The dose and the frequency of reception are selected depending on the clinical effect. The recommended dose range is 3-6 mg / kg body weight.

Children with newly established partial seizures can be prescribed up to 500 mg per day.

Side effects:

Side effects were distributed in frequency as follows: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000), including isolated cases.

Infections: very rarely - nasopharyngitis.

On the part of the blood and lymphatic system: often - anemia, infrequently - leukopenia, thrombocytopenia, lymphadenopathy, in children - eosinophilia; very rarely - neutropenia.

From the nervous system: very often - drowsiness, dizziness, paresthesia, in children - apathy, attention violation; disorder of coordination, nystagmus, lethargy, memory impairment, impaired concentration, tremor, amnesia, hypoesthesia, taste distortion, impaired thinking, speech impairment, cognitive disorders, apathy, mental disorders, psychomotor disorders, seizures,intentional tremor, sedation; infrequently - loss of taste sensitivity, loss of smell, aphasia, burning sensation (mostly on the face and extremities), cerebellar syndrome, clumsiness, postural dizziness, increased salivation, dysesthesia, dysgraphia, dyskinesia, dysphasia, "chills" the body, gipogevziya, hypokinesia, peripheral neuropathy, parosmiya, lightheadedness, repetitive speech, impaired sense of touch, stupor, syncope in children - psychomotor hyperactivity; rarely - apraxia, hyperaesthesia, hyposphresia, anosmia, essential tremor, akinesia, unresponsive to stimuli in children - a circadian rhythm sleep disorder.

Mental disorders: Very often - depression often - slow thinking, confusion, insomnia, agitation, irritability, confusion, emotional lability, anger, erectile dysfunction in children - abnormal behavior, aggressive reactions; infrequently - sexual dysfunction, impaired sexual arousal, disfemiya, early awakening in the morning, euphoria, auditory and visual hallucinations, hypomania, decreased libido, panic attack,paranoid states, perseveration of thinking, violation of reading skills, anxiety, sleep disorders, suicidal thoughts, suicidal attempts, tearfulness; rare mania, anorgasmia, a feeling of despair, a decrease in sensations during orgasm, in children - apathy, crying.

From the side of the organ of vision: often - blurred vision, diplopia, impaired vision; infrequently - a violation of accommodation, amblyopia, blepharospasm, myopia, photopsy, presbyopia, scotoma, incl. ciliary, decreased visual acuity; rarely - one-sided blindness, transient blindness, dry eye mucosa, increased lacrimation, mydriasis, night blindness; very rarely - closed-angle glaucoma, violation of eyeballs, maculopathy, edema of the eyelids, conjunctival edema.

From the side of the hearing organ: often - pain in the ears, ringing in the ears, children - vertigo; infrequently - deafness, incl. sensory and one-sided, discomfort in the ears, hearing loss.

From the side of the cardiovascular system: infrequently - bradycardia, palpitations, "hot flashes" of blood, orthostatic hypotension; rarely - the phenomenon of Raynaud.

From the respiratory system: often - shortness of breath, nasal congestion, epistaxis; in children - rhinorrhea; infrequently - hoarseness, dyspnea with exercise, hypersecretion in the paranasal sinuses.

From the gastrointestinal tract: very often - nausea, diarrhea; often - loss of appetite, anorexia, constipation, pain in the upper abdomen, dryness of the oral mucosa, dyspepsia, abdominal discomfort, paresthesias in the oral cavity, gastritis, children - vomiting; infrequently - Pancreatitis, flatulence, gastroesophageal reflux disease, pain in the lower abdomen, hypoesthesia in the oral cavity, bleeding gums, halitosis, flatulence, glossodiniya, pain in the oral cavity, polydipsia, increased appetite, hypersecretion salivary glands, discomfort in the epigastrium .

From the musculoskeletal system and connective tissue: Often - myalgia, muscle cramps, muscle spasms, muscle weakness, arthralgia, musculoskeletal pain in the chest area; infrequently - musculoskeletal stiffness, pain in the side, muscle weakness, muscle fatigue; rarely - swelling of the joints, discomfort in the limbs, discomfort in the lumbar region.

Overdose:

Symptoms: convulsions, drowsiness, speech disorders, impaired vision, diplopia, thinking disorders, coordination disorders, lethargy, stupor, lowering of blood pressure, abdominal pain, dizziness, agitation and depression. In most cases, the clinical consequences were not severe, but there were deaths after an overdose with a combination of several drugs, including topiramate.

Overdose of topiramate can cause severe metabolic acidosis (see "Special instructions").

Treatment for acute overdose: if a short while before the patient took food, immediately wash the stomach or induce vomiting. In studies in vitro it was shown that Activated carbon adsorbs topiramate. If necessary, symptomatic therapy should be given.

An effective way to remove topiramate from the body is hemodialysis.

Patients are advised to adequately increase the amount of fluid consumed.

Interaction:

Influence of topiramate on other PEPs

Simultaneous reception of topiramate with other PEPs phenytoin, carbamazepine, valproic acid, phenobarbital, primidon) does not affect their plasma concentration, except for individual patients in whom the addition of topiramate to phenytoin may cause an increase in plasma phenytoin concentration. This may be due to the fact that topiramate inhibits the specific polymorphic isoenzyme CYP2C19 of the cytochrome P450 system. Therefore, every patient who takes phenytoin and in which clinical signs or symptoms of toxicity develop, it is necessary to monitor the concentration of phenytoin in the plasma.

In the study of pharmacokinetics in patients with epilepsy, the addition of topiramate to lamotrigine did not affect the equilibrium concentration (Css) of the latter at doses of topiramate 100-400 mg per day. During treatment and after lamotrigine withdrawal (average dose of 327 mg per day), Css topiramate did not change.

The influence of other PEPs on topiramate

Phenytoin and carbamazepine reduce the concentration of topiramate in plasma. Addition or cancellation of phenytoin or carbamazepine against the background of treatment of topiramate may require a change in the dose of the latter. Dose should be selected, focusing on achieving the desired clinical effect.

The addition or withdrawal of valproic acid does not cause clinically significant changes in the plasma topiramate concentration and, therefore, does not require a dose change. results These interactions are presented in Table 1.

Table №1. The effect of other PEP on the concentration of topiramate

PEP	Concentrations of PEP	Concentration topiramate
Phenytoin	↔/↓	↓
Carbamazepine	↔	↓
Valproic acid	↔	↔
Phenobarbital	↔	nor
Primidone	↔	nor

↔ - no effect;

↑ - increased concentration in individual patients;

↓ - decrease in plasma concentration;

NO - not investigated.

Other interactions

Area under the curve "concentration-time" (AUC) single dose digoxin Decreased by 12% with simultaneous reception with topiramate. The clinical significance of this observation is not clear.

There is no data on simultaneous application of topiramate and admission alcohol or application other drugs that depress the central the nervous system (CNS). A combination of topiramate and drugs depressing the central nervous system is not recommended.

In the study of the drug interaction of topiramate with oral contraceptives, in which a combined preparation containing norethisterone (1 mg) and ethinyl estradiol (35 μg), topiramate in doses of 50-800 mg per day did not have a significant effect on the effectiveness of norethisterone and in doses of 50-200 mg per day - the effectiveness of ethinylestradiol. Significant dose-dependent reduction in the efficacy of ethinylestradiol was observed with doses of topiramate 200-800 mg per day. The clinical significance of the described changes is not clear. Possible decrease in the effectiveness of oral contraceptives and an increased risk of development of breakthrough uterine bleeding should be considered in patients taking topiramate. Patients receiving estrogen-containing contraceptives, it is necessary to warn about the need to inform the doctor about any changes in the timing and nature of menstruation.

In healthy volunteers, there was a decrease AUC lithium by 18% with the simultaneous administration of topiramate at a dose of 200 mg per day. In patients with bipolar affective disorder, the use of topiramate in doses up to 200 mg per day did not affect the pharmacokinetics of lithium, but at higher doses (up to 600 mg per day) AUC lithium was increased by 26%. With the simultaneous use of topiramate and lithium, concentration of the latter in blood plasma.

With simultaneous application risperidone with a single and repeated administration of topiramate to healthy volunteers and patients with bipolar affective disorder, gave the same results. With the simultaneous use of topiramate in doses of 250 or 400 mg per day AUC risperidone, taken in doses of 1-6 mg per day, decreases by 16 and 33%, respectively. In this case, the pharmacokinetics of 9-hydroxyrisperidone did not change, and the total pharmacokinetics of the active substances (risperidone and 9-hydroxyrisperidone) changed slightly. The change in the systemic effect of risperidone / 9-hydroxyrisperidone and topiramate was not clinically significant, and this interaction has no significant clinical effect.

Drug Interactions hydrochlorothiazide (25 mg) and topiramate (96 mg) was evaluated in healthy volunteers. The results of the studies showed that in this case the maximum concentration (C_max) of topiramate is increased by 27% and AUC of topiramate by 29%. The clinical significance of these studies has not been revealed.

Pharmacokinetic parameters hydrochlorothiazide did not undergo significant change with concomitant therapy with topiramate.

With the simultaneous administration of topiramate and metformin there is an increase in C_m_Oh and AUC metformin at 18 and 25%, respectively, whereas the clearance of metformin decreased by 20%. Topiramate did not affect the time to reach C_m_Ohmetformin in the blood plasma. The clearance of topiramate when used concomitantly with metformin is reduced. The degree of revealed changes in clearance is not studied. Clinical significance of the effects of metformin on the pharmacokinetics of topiramate is not clear.

With simultaneous application pioglitazone and topiramate was found to decrease AUC pioglitazone by 15%, without change in C_m_Oh pioglitazone. These changes are not were statistically significant. Also for the active hydroxy metabolite of pioglitazone, a decrease in C_m_Oh and AUC at 13 and 16%, respectively, and for active ketometabolite, a decrease in C_m_Oh and AUC by 60%. The clinical significance of these data is not clear.

When applying glibenclamide (5 mg per day) in isolation or simultaneously with topiramate (150 mg per day) in patients with type 2 diabetes mellitus AUC Glibenclamide decreased by 25%.The systemic exposure of 4-trans-hydroxyglybeneclamide and 3-cis-hydroxyglybene clamamide was also reduced by 13 and 15%, respectively. Glibenclamide did not affect the pharmacokinetics of topiramate in equilibrium state.

Simultaneous application of topiramate with other drugs, predisposing to nephrolithiasis, may increase the risk of kidney stones.

Simultaneous application of topiramate and valproic acid patients who tolerate each drug well, is accompanied by hyperammonia with or without encephalopathy. In most cases, symptoms and symptoms disappear after the withdrawal of one of the drugs. This adverse event is not caused by pharmacokinetic interaction. Connection between hyperamonia and Topiramate alone or in combination with other drugs is not established.

Additional studies of drug interactions are presented in Table 2.

Table number 2. The results of additional studies of the interaction between topiramate and various drugs (LP).

LP	Concentration LP^a	Concentration topiramate^a
Amitriptyline	increase in C_max and AUC metabolite of nortriptyline by 20%	NO
Dihydroergotamine (oral and oral administration)	↔	↔
Haloperidol	enlargement AUC metabolite by 31%	NO
Propranolol	increase for 4-OH propranolol on 17% (topiramate 50 mg)	increase in C_maxby 9%, an increase AUC by 16% (propranolol 80 mg)
Sumatriptan (oral and s / c)	↔	NO
Pisotifen	↔	↔
Diltiazem	decrease in AUC diltiazem by 25%; and deacetylldithiasem by 18% and 1 - for N-demethylidithiasem	increase in AUC by 20%
Venlafaxine	↔	↔
Flunarizine	an increase in AUC by 16% (50 mg every 12 hours)^b	↔

^a - expressed in% of the values of the maximum concentration in the blood plasma and AUC with monotherapy;

↔ - no change in C_mOh in blood plasma and AUC (up to 15% of the initial data);

^{b -} with repeated administration of a single flunarizine, an increase AUC by 14%, which may be due to its accumulation in the process of achieving the equilibrium state;

NO - not investigated.

Special instructions:

PEP, including Topsaver, should be withdrawn gradually to minimize the possibility of an increase in seizure frequency. In clinical trials, the dose of topiramate was reduced by 50-100 mg at weekly intervals for adults with epilepsy, in children topiramate gradually canceled within 2-8 weeks.If, according to medical indications, a quick cancellation of Topsaver is necessary, it is recommended that it be carried out under the supervision of a doctor.

Patients with mild to severe renal impairment may need 10-15 days to achieve an equilibrium plasma concentration, in contrast to 4-8 days for patients with normal renal function. As with all patients, a gradual increase in dose should be made according to clinical outcomes (such as seizure control, the incidence of side effects), given that patients with moderate or severe renal failure may need more time to reach a stable state after each dose.

When Topsaver is treated with drugs, it is very important to adequately increase the amount of fluid consumed to reduce the risk of developing nephrolithiasis, as well as the side effects that can occur under the influence of physical exertion or elevated temperatures. Risk factors for developing nephrolithiasis are nephrolithiasis in history (including family history), hypercalciuria, concomitant therapy with drugs that contribute to the development of nephrolithiasis.

Oligohydrosis and an increase in body temperature during Topsaver treatment can develop in children exposed to high ambient temperatures.

Topsaver treatment can be accompanied by mood changes and depression.

A meta-analysis of a randomized placebo-controlled study of topiramate showed a slight increase in the risk of suicidal ideation and suicidal behavior, the mechanism of development of which is not known. The available data do not allow excluding the connection with the use of topiramate.

In double-blind clinical trials using topiramate for approved and studied indications, suicidal attempts occurred in 0.5% of patients (46 of 8652 patients), which is almost 3 times higher than in patients receiving placebo (0.2% (8 of 4045 patients)). It is necessary to warn patients, as well as people caring for them, and caregivers to closely monitor the appearance of signs of suicidal thoughts and immediately inform the doctor about these conditions.

In patients with impaired liver function Topsover should be used with caution because of the possible decrease in the clearance of topiramate.

When Topsover is used, acute myopia can develop with concomitant secondary closed angle glaucoma. Symptoms may be accompanied by a decrease in visual acuity and / or pain in the eye. Ophthalmic examination can reveal myopia, flattening of the anterior chamber of the eye, hyperemia (reddening) of the eyeball, increased intraocular pressure, and may also be observed mydriasis. This simtomocomplex can be accompanied by the secretion of fluid, leading to a shift in the lens and iris forward with the development of secondary closed-angle glaucoma. Symptoms may occur 1 month after the start of treatment. Unlike the primary open angle glaucoma, which is rarely observed in patients under 40 years of age, secondary closed angle glaucoma is observed with topiramate in both adults and children. If a symptom complex develops involving myopia associated with occlusive glaucoma, the treating doctor, if possible, should stop taking topiramate and take appropriate measures to lower the intraocular pressure. Usually it is enough that the intraocular pressure is normalized.Increased intraocular pressure of any etiology in the absence of adequate treatment can lead to serious complications, including loss of vision.

When Topsover is used, hyperchloremic, not associated with an anion deficiency, metabolic acidosis (eg, a decrease in the concentration of hydrocarbonates in the plasma below the norm in the absence of respiratory alkalosis) may occur. Similar a decrease in the concentration of serum hydrogen bicarbonates is a consequence of the inhibitory effect of topiramate on renal carboanhydrase. In most cases, the decrease in the concentration of hydrocarbonates occurred at the beginning of treatment, although this effect can occur in any treatment period. When used in adult patients at a dose above 100 mg per day and in children at a dose of about 6 mg / kg / day, the decrease in the concentration of hydrocarbonates is usually weak or moderate (mean value is 4 mmol / l). In rare cases, patients have a concentration of hydrocarbonate less than 10 mmol / l. Some diseases or treatments that predispose to the development of acidosis (eg, kidney disease, severe respiratory disease, epileptic status, diarrhea, surgery,ketogenic diet, intake of certain medications) may be additional factors that enhance bicarbonate-reducing effect of topiramate.

In children, chronic metabolic acidosis can lead to slower growth. The effect of topiramate on growth and possible complications associated with the bone system has not been systematically studied in children and adults.

When treating Topsaver, it is recommended that a serum concentration of hydrogen bicarbonate be tested. If signs of metabolic acidosis, such as Kussmaul's respiration, shortness of breath, loss of appetite, nausea, vomiting, rapid fatigue, tachycardia or arrhythmia, consider lowering the dose or stopping treatment with topiramate.

Topsover should be used with caution in patients who have risk factors for metabolic acidosis.

If the patient loses weight with Topsaver treatment, then it is necessary to consider the expediency of prescribing supplementary food.

The cause of violations of cognitive functions in epilepsy can be both the disease itself, and the ongoing therapy of PEP.Cases of impairment of cognitive functions in adults were described, in which a dose reduction or discontinuation of treatment with topiramate was required. Influence of topiramate on cognitive functions in children is not well understood.

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

Care should be taken when driving vehicles and other activities that require a high concentration of attention and speed of psychomotor functions, due to the fact that the Topsaver drug affects the central nervous system and can cause drowsiness, dizziness, and can also cause visual impairment.

Form release / dosage:

Pills, coated with a film sheath, 25 mg, 50 mg, 100 mg and 200 mg.

Packaging:

Tablets 25 mg, 50 mg, 100 mg:

For 14 tablets in blister of orientated and polyamide / aluminum foil / PVC / aluminum foil. 2 blisters together with instructions for use in a cardboard box.

Tablets 200 mg:

7 tablets per blister of orientated polyamide / aluminum foil / PVC / aluminum foil. For 4 blisters together with instructions for use in a cardboard box.

Tablets 25 mg, 50 mg, 100 mg (when packaged on the territory of the Russian Federation):

For 14 tablets in blister of oriented polyamide / aluminum foil / PVC / aluminum foil.

2 blisters together with instructions for use in a cardboard box.

In-bulk packaging (tablets 25 mg, 50 mg, 100 mg):

For 15 kg of tablets are placed in a double plastic bag with a desiccant located between the packages. The package is tightly closed with a clamp-tie.

1 packet is placed in a cardboard drum.

Storage conditions:Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001352/08

Date of registration:29.02.2008 / 07.09.2015

Expiration Date:Unlimited

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

Representation: & nbspTeva Teva Israel

Information update date: & nbsp04.01.2017

Illustrated instructions

Instructions

Topsaver (Topsaver)