Briviac pills 25mg, 56pcs

Composition

Active ingredient:  

brivaracetam 25.00 mg;

Auxiliary substances:

croscarmellose sodium 5.00 mg,

lactose monohydrate 48.50 mg,

Betadex 6.75 mg,

lactose anhydrous 48.25 mg,

magnesium stearate 1.50 mg,

Opadray II film coating 85F275014 grey 6.75 mg (polyvinyl alcohol, talc, polyethylene glycol 3350 / macrogol 3350, titanium dioxide, iron oxide yellow dye, iron oxide black dye).

Pharmacological action

PHARMACOTHERAPY GROUP: Antiepileptic drug Code ATX: N03AX23 PHARMACOLOGICAL Propertiespharmacodynamicabrivaracetam has a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, a transmembrane glycoprotein found in neurons and endocrine cells at the presynaptic level. Although the exact role of this protein is currently unknown, it has been shown to modulate neurotransmitter exocytosis. Binding of synaptic vesicles 2A (SV2A) to glycoprotein appears to be the main mechanism of the anticonvulsant effect of brivaracetam. Efficacy and safety of clinical application The efficacy of brivaracetam as an adjunctive therapy for partial seizures (PSP) was established in three randomized, double-blind, placebo-controlled, multicenter studies of the drug in a fixed dose in patients aged 16 years and older. 1558 patients received the study drug, of which 1099 patients received brivaracetam at a dose of 5 to 200 mg / day. In all studies, there was an initial 8-week period, followed by a 12-week period of treatment without increasing the dose. The study included patients with uncontrolled PSP while taking 1 or 2 concomitant antiepileptic drugs (AEDs). The treatment period included patients who had at least 8 PSPs during the initial period. The primary endpoints in the phase 3 trials were the percentage of reduction in PSP compared to placebo and the proportion of patients who achieved a reduction in PSP of at least 50% relative to baseline. When included in the study, patients most often took such AEDs as carbamazepine (40.6%). lamotrigine(25.2%), valproate (20.5%), oxcarbazepine (16.0%), topiramate (13.5%). phenytoin (10.2%) and levetiracetam (9.8%). When included in all three studies, the median seizure frequency over 28 days was 9. The average duration of epilepsy was about 23 years. Brivaracetam has been shown to be effective as an adjunctive therapy for PSP in patients aged 16 years and older at doses ranging from 50 mg / day to 200 mg / day. In clinical studies, the reduction in the frequency of seizures compared to the placebo group was more pronounced when using brivaracetam at a dose of 100 mg / day than 50 mg / day. With the exception of a small dose-dependent increase in drowsiness and fatigue, the use of brivaracetam at doses of 50 mg / day and 100 mg / day was characterized by comparable safety, including in relation to adverse events from the central nervous system and against the background of long-term therapy. According to the pooled analysis, the percentage of patients whose PSP rate decreased by at least 50% relative to baseline while taking brivaracetam at 50 mg / day,100 mg / day, and 200 mg/day was 34.2%,39.5%, and 37.8%, respectively, compared to 20.3% in the placebo group (this analysis did not include patients taking levetiracetam). A combined analysis of the data from the three baseline studies did not reveal any differences in the effectiveness (defined as a 50% reduction in the frequency of PSP relative to baseline) of brivaracetam doses ranging from 50 mg/day to 200 mg/day in combination with inducing or non-inducing AEDs. During the treatment period, which was 12 weeks, freedom from seizures was achieved in 2,5% (4/161),5,1% (17/332) patients who received brivaracetam at 50 mg/day,100 mg/day, and 200 mg/day, respectively, compared to the placebo group, where the figure was 0.5% (2/418). A decrease in the frequency of seizures over 28 days was observed in patients who initially suffered from type 1 seizures (secondary generalized tonic-clonic seizures), taking brivaracetam at doses of 50 mg / day,100 mg / day and 200 mg / day, by 66.6% (n=62),61.2% (n=100) and 82.1% (n=75), respectively, compared with placebo – by 33.3% (n=115). The efficacy of brivaracetam as monotherapy has not been confirmed. Brivaracetam is not recommended as monotherapy. Levetiracetam therapy In two randomized, placebo-controlled clinical trials, levetiracetam was concomitant with PE in approximately 20% of patients. Although the number of such patients is limited, it was noted that the benefits of brivaracetam compared to placebo were not observed in them, which could be due to competitive binding to the SV2A glycoprotein. There were no additional problems with the safety and tolerability of this therapy. A third study showed the benefit of brivaracetam at 100 mg / day and 200 mg / day compared to placebo in patients previously treated with levetiracetam. In this subgroup of patients, the lower efficacy of brivaracetam compared to patients not previously treated with levetiracetam could be due to the use of a larger number of AEDs in the anamnesis and a higher initial frequency of seizures. Use in elderly patients (aged 65 years and older)A total of 38 patients aged 65 to 80 years were enrolled in three baseline, double-blind, placebo-controlled trials. The efficacy of brivaracetam in elderly patients was comparable to that in younger patients, although data are limited. Use in children The efficacy and tolerability of brivaracetam in children under 16 years of age have not been established (see section “Pharmacokinetics”). Open-label extended-release studiesafter the completion of randomized trials,81.7% of patients were included in the long-term open-label phase of brivaracetam use. After 6 months of randomized trial inclusion,5.3% (n=1500) of patients had no seizures,12 months later – 4.6% (n=1188) of patients, and 24 months later – 3.7% (n=847) of patients receiving brivaracetam. However, given the fact that a significant proportion of patients (26%) prematurely stopped participating in extended studies due to lack of effectiveness, it cannot be excluded that an unrepresentative sample was included in the data analysis, since the remaining patients responded better to therapy than those who left early. Preclinical safety data Pharmacological safety studies revealed a predominant effect on the central nervous system (mainly transient CNS depression and a decrease in spontaneous motor activity), which was observed when the drug was administered at doses significantly (more than 50 times) higher than the pharmacologically active dose of brivaracetam 2 mg/kg. Brivaracetam had no effect on learning and memory. There were no pathological changes in the liver of rats and monkeys with chronic use of brivaracetam in doses much (from 5 to 42 times) higher than the therapeutic dose of 200 mg / day. Signs of CNS damage were reported that weakened over time (depression, loss of balance, discoordination), in monkeys when using brivaracetam at doses 64 times higher than the clinical Cmax In dogs, the use of brivaracetam led to the development of changes in the liver, mainly porphyria, at doses that provide an exposure (determined by the area under the concentration-time curve, AUC) close to the average exposure in humans at a dose of 200 mg/day. However, toxicological data on brivaracetam and structurally similar components show that the development of changes in the liver of dogs occurs by mechanisms that are not characteristic of humans. No mutagenic or clastogenic activity was detected in genotoxicity studies. Studies of carcinogenicity in rats did not reveal oncogenic potential, while the increased incidence of hepatocellular tumors in male mice was considered to be due to a non-genotoxic mechanism of action related to phenobarbital-like induction of liver enzymes, which is a well-known phenomenon specific to rodents. Brivaracetam did not affect the fertility of males and females, and no teratogenic potential was found in experiments on rats and rabbits. Embryotoxicity was observed when brivaracetam was used in pregnant female rabbits at a dose toxic to the female, at which the exposure is 8 times higher than the clinical exposure at the maximum recommended dose. In rats, brivaracetam rapidly passed through the placenta and was excreted in the milk of lactating rats at a concentration close to the concentration in the mother’s plasma. Studies in rats have not revealed the potential for drug addiction. Studies in immature animals and immature rats with brivaracetam exposure 6-15 times higher than the clinical exposure at the maximum recommended dose, there was an adverse effect on developmental processes (mortality, clinical signs, weight loss and brain mass reduction). There were no negative effects on CNS function, as well as neuropathological and histopathological changes in the brain. In immature dogs, when brivaracetam was administered at a dose providing exposures 6 times higher than the therapeutic level, the changes were similar to those in adult animals. No side effects were observed, taking into account the standard criteria for assessing the processes of development and maturation.Pharmacokinetics Vivaracetam is characterized by linear and duration-independent pharmacokinetics, low intra-and interindividual variability, as well as complete absorption, a very low degree of binding to plasma proteins, renal excretion after extensive biotransformation, and the presence of pharmacologically inactive metabolites. Absorption Vivaracetam is rapidly and completely absorbed after oral use, and its absolute bioavailability is approximately 100%. The median time to reach the maximum concentration (Tmax) when taking tablets on an empty stomach is 1 hour (the range of Tmax values is from 0.25 to 3 hours). Concomitant use of brivaracetam with a high-fat diet slows the rate of absorption (median Tmax 3 h) and reduces the maximum concentration of the drug in plasma by 37%, while the degree of absorption remains unchanged. Distribution Vivaracetam binds little to plasma proteins ( The volume of distribution is 0.5 l / kg, which is close to the total volume of fluid in the body. Due to its lipophilicity (Log P), brivaracetam penetrates well through cell membranes. Metabolism Brivaracetam is primarily metabolized by hydrolysis of the amide component to form the corresponding carboxylic acid (approximately 60% of the dose), and secondarily by hydroxylation of the propyl side chain (approximately 30% of the dose). Hydrolysis of the amide component to form carboxylic acid (34% of the dose excreted by the kidneys) is mediated by hepatic and extrahepatic amidase. In vitro hydroxylation of brivaracetam is mediated primarily by the cytochrome P450 isoenzyme CYP2C19. Both metabolites are further converted to hydroxylated acid. In vivo, in people with an inactive CYP2C19 isoenzyme due to a mutation, the formation of the hydroxy metabolite is reduced by 10 times, while the concentration of brivaracetam increases by 22% or 42% in subjects with one or both mutated alleles. These three metabolites have no pharmacological activity. Excretion Brivaracetam is primarily metabolized and excreted by the kidneys. More than 95% of the dose, including metabolites, is eliminated by the kidneys within 72 hours after use. Less than 1% of the dose is excreted by the intestine and less than 10% of the dose is excreted unchanged by the kidneys. The terminal half-life of brivaracetam (T 1/2) is approximately 9 hours. The total plasma clearance of brivaracetam in patients is 3.6 l / hrlinearyfarmacokinetics are proportional to the dose in the range from 10 to at least 600 mg. Drug Interactionstrivaracetam is excreted through several pathways, including renal excretion, non-cytochrome P450 isoenzyme-mediated hydrolysis, and cytochrome P450 isoenzyme-mediated oxidation. In vitro studies have shown that brivaracetam is not a substrate of human glycoprotein (P-gp), human proteins responsible for multiple drug resistance (MRP1 and MRP2), and probably polypeptides that carry organic anions 1 In 1 (OATP 1 In 1) and (OATP 1 IN 1). In vitro experiments have shown that the biotransformation of brivaracetam does not significantly depend on inhibitors of CYP isoenzymes (for example, CYP1A,2C8,2C9,2D6 and ZA4). In vitro studies have shown that brivaracetam is not an inhibitor of CYP1A2,2A6,2B6,2C8,2C9,2D6, ZA4 isoenzymes or transporters P-gp, BCRP, BSEP MRP2, MATE-K, MATE-1, OATP 1V1, OATP 1VZ, OATP 1 and OSP at concentrations comparable to those used in the clinic. Also, in vitro studies, brivaracetam did not induce the CYP1A2 isoenzyme. Pharmacokinetics in special groups of elderly patients (65 years and older)In a study in elderly patients (aged 65-79 years, with a creatinine clearance of 53-98 ml / min/1.73 m) who received brivaracetam at a dose of 400 mg / day in two doses, the drug’s half-life was 7.9 hours and 9.3 hours in the groups 65-75 years and older than 75 years, respectively. At steady state, the clearance of brivaracetam in elderly patients was close (0.76 ml / min / kg) to that in healthy young men (0.83 ml/min/kg). In patients with impaired renal function in patients with severe renal insufficiency (creatinine clearance At the same time, the concentrations of acid, hydroxyl, and hydroxyacid metabolites increased 3,4, and 21 times, respectively. The renal clearance of these inactive metabolites decreased 10-fold. According to the results of preclinical studies, the safety of hydroxyacid metabolites did not raise concerns. Brivaracetam has not been studied in patients undergoing hemodialysis. In patients with impaired liver function, a pharmacokinetic study in patients with cirrhosis (A, B, C according to Child-Pugh) revealed a comparable increase in exposure to brivaracetam, regardless of the severity of the disease (50%,57% and 59%), compared with a control group of healthy volunteers. In a pharmacokinetic study in 99 children aged 1 month to 16 years who received brivaracetam solution orally, the concentration of brivaracetam in plasma was proportional to the dose taken in all age groups. Data from population pharmacokinetic modeling showed that a dose of 2.0 mg / kg twice daily leads to the same average steady-state plasma concentration as a dose of 100 mg twice daily in adults. Effect of Weightthe steady-state plasma concentration of brivaracetam decreased by 40% in patients with a body weight in the range from 46 to 115 kg. However, this difference in the pharmacokinetics of brivaracetam is considered clinically insignificant. The effect of semi-clinically significant differences in the pharmacokinetics of brivaracetam in patients of different sexes was not revealed. The effect of Rasyras (Caucasian, Mongoloid) did not significantly affect the pharmacokinetic parameters of brivaracetam, according to the results of population pharmacokinetic modeling in patients with epilepsy. The number of patients of other ethnic origin was limited. Pharmacokinetic/pharmacodynamic relationship The value of the plasma concentration of brivaracetam, which is 50% of the maximum effective concentration (EC 50) corresponds to 0.57 mg/l. This plasma concentration slightly exceeds the median exposure value of brivaracetam after taking a dose of 50 mg / day. A further decrease in the frequency of seizures was observed with an increase in the dose to 100 mg / day, the effectiveness reaches a plateau when taking the drug at a dose of 200 mg / day.

Indications

Briviac is indicated as an adjunct therapy in the treatment of partial seizures with or without secondary generalization in adults and adolescents with epilepsy from the age of 16.

Use during pregnancy and lactation

Pregnancy risk due to epilepsy and taking antiepileptic drugs Among children born to women who received antiepileptic drugs, the number of congenital malformations is 2-3 times higher than the value of about 3% typical for the general population. Concomitant treatment with multiple antiepileptic drugs is associated with a higher risk of congenital malformations, but the contribution of each drug and/or the disease itself was not evaluated separately. Discontinuation of antiepileptic therapy can lead to an exacerbation of the disease, which may be dangerous for the mother and fetus. Risk due to Brivaracetam Studies of brivaracetam in animals have not revealed a teratogenic potential. Data on the use of brivaracetam in pregnant women are limited. In clinical studies, when using brivaracetam as an adjunct therapy in combination with carbamazepine, a dose — dependent increase in the concentration of the active metabolite of carbamazepine, carbamazepine epoxide, was noted (see the section “Interaction with other drugs”). There are insufficient data to determine the clinical significance of this effect in pregnant women. There are no data on the penetration of brivaracetam through the placental barrier in humans. In rats, brivaracetam easily passes through the placenta. The potential risk to humans is unknown. Brivaracetam should not be used during pregnancy unless clinically necessary, when the benefits to the mother clearly outweigh the potential risk to the fetus. Stopping taking brivaracetam can cause an exacerbation of the disease, which can be dangerous for the mother and fetus. Breast-feeding It is not known whether brivaracetam is excreted in human breast milk. In lactating rats, brivaracetam is excreted in milk. The decision to stop breastfeeding or taking brivaracetam is made based on an assessment of the need for therapy for the mother. When taking brivaracetam and carbamazepine simultaneously, the amount of carbamazepine epoxide may increase. excreted in breast milk. There is insufficient data to assess clinical significance. Fertility There is no data on the effect of brivaracetam on human fertility. In rats, taking brivaracetam did not affect fertility. Women with preserved childbearing potencybefore prescribing brivaracetam, the doctor should discuss family planning and contraception measures with women who have preserved childbearing function. When a woman is planning pregnancy, the question of continuing to take brivaracetam should be reviewed.

Contraindications

• Hypersensitivity to the Active ingredient or other pyrrolidone derivatives, as well as any of the auxiliary components listed in the “Composition” section.
• Children under 16 years of age (due to lack of clinical data).
• Rare hereditary problems of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.
• End-stage renal failure requiring hemodialysis (due to lack of clinical data).

PRECAUTIONS FOR USE

In patients with the presence of:

• suicidal thoughts and suicide attempts
• liver function disorders (see sections “Dosage and use” and “Special instructions”).

Side effects

Safety profile summary The safety of Briviac was evaluated in 2,388 patients, of whom 1,740 received brivaracetam for > 6 months,1,363 patients for > 12 months,923 for> 24 months, and 569 for> 60 months (5 years). Drowsiness (14.3%) and dizziness (11.0%) were most common (>10%) during treatment with brivaracetam. These adverse drug reactions (NLRs) were usually mild to moderate in severity. The incidence of drowsiness and fatigue (8.2%) increased with increasing dose of the drug. The types of adverse reactions observed during the first 7 days of therapy were similar to those recorded during the entire treatment period. The rate of early termination of therapy due to the development of NLR was 3.5%,3.4% and 4.0% in patients randomized to receive brivaracetam at doses of 50 mg / day,100 mg / day and 200 mg / day, respectively; the same indicator in the placebo group was 1.7%. The most common NLRs that led to early withdrawal of brivaracetam were dizziness (0.8%) and seizures (0.8%). NLRs are presented according to organ and organ system involvement (MedDRA) and classification by frequency: very common (> 1/10); common (>1/100, but > > < 1/10) and infrequent (> 1/1000, but < 1/10) and infrequent (>Infectious and parasitic diseases Often: Flu Blood and lymphatic system disorders Often: Neutropenia Metabolic and nutritional disorders Often: Decreased appetites Mental disorders Often: Depression, anxiety, insomnia, irritability Infrequently: Suicidal thoughts, psychotic disorder, aggressiveness, agitation Nervous system disorders Very often: dizziness, drowsiness Often: convulsions, Vertigo disorders of the respiratory system, chest and mediastinal organs Often: upper respiratory tract infections, cough disorders of the gastrointestinal tract Often: nausea, vomiting, constipation and injection site disorders Often: Fatigue Description of individual NLRNeutropenia was observed in 0.5% (6 out of 1099) of patients treated with brivaracetam, and in 0% (0 out of 459) of patients treated with placebo. In 4 of these patients, the number of neutrophils was reduced at baseline, and there was a further decrease in the indicator against the background of treatment with brivaracetam. None of the 6 cases of neutropenia was serious, did not require special treatment, did not lead to discontinuation of brivaracetam, and was not accompanied by infectious complications. Suicidal intentions were reported in 0.3% (3 out of 1099) of patients treated with brivaracetam and 0.7% (3 out of 459) of patients treated with placebo. In short-term clinical trials of brivaracetam use in patients with epilepsy, no cases of suicide or suicide attempts were reported, but both of these events were registered in the open-label extended study phase. Open-label extended-release studiesthe safety profile of brivaracetam in short-term placebo-controlled trials was comparable to its safety profile in patients who continued to use the drug in long-term open-label phases for up to 8 years. Use in children Safety data on the use of brivaracetam in open-label studies in children aged 1 month to A total of 152 children (from 1 month to According to the limited data available, the most common adverse events identified by the investigator as drug-related were drowsiness (10%), decreased appetite (8%), fatigue (5%), and weight loss (5%). The safety profile in children was comparable to that of brivaracetam in adults. There are no data on the effect on the development of the nervous system. Currently, there is no information on the results of clinical use of the drug in newborns. Use in elderly patients 130 elderly patients included in clinical trials of brivaracetam phase 2-3 (44 with epilepsy),100 patients were aged 65-74 years and 30 patients were aged 75-84 years. The safety profile of brivaracetam was similar in elderly patients and in younger adult patients.

Interaction

Studies of drug-drug interactions were conducted only in adults. Pharmacodynamic interactions Concomitant use with levetiracetam In a limited number of clinical trials, no benefit of brivaracetam compared to placebo was observed in patients taking levetiracetam concomitantly. There was also no additional effect on safety or tolerability (see section “Pharmacodynamics”). Interaction with ethanol In the study of pharmacokinetic and pharmacodynamic interaction between brivaracetam (with a single dose of 200 mg) and ethanol (with its prolonged infusion at a concentration of 0.6 g / l) in healthy volunteers, no pharmacokinetic interaction was observed. However, the effect of alcohol on psychomotor function, attention, and memory was doubled when co-administered with brivaracetam. It is not recommended to drink alcohol during brivaracetam therapy. Pharmacokinetic interactionsthe effect of other drugs on the pharmacokinetics of brivaracetama Brivaracetam is characterized by a low potential for participation in drug-drug interactions in vitro. The main biotransformation pathway of brivaracetam is CYP-independent hydrolysis. The second biotransformation pathway involves hydroxylation mediated by the CYP2C19 isoenzyme (see section “Pharmacokinetics”). It is possible to increase the concentration of brivaracetam when it is combined with powerful inhibitors of the CYP2C19 isoenzyme (fluconazole, fluvoxamine), but the risk of clinically significant interaction mediated by the CYP2C19 isoenzyme is considered low. Simultaneous use of rifampicin to healthy volunteers with the potent enzyme inducer rifampicin (600 mg / day for 5 days) was associated with a 45% reduction in brivaracetam exposure. The dose of brivaracetam should be adjusted in patients starting or completing rifampicin therapy. The concentration of brivaracetam in blood plasma decreases when it is co-administered with AEDs that are powerful inducers of enzymes (carbamazepine, phenobarbital, phenytoin), but no dose adjustment is required in this situation. Other enzyme Inducersother potent enzyme inducers (such as St. John’s wort) may also reduce systemic exposure to brivaracetam. Therefore, caution should be exercised at the beginning and at the end of taking St. John’s Wort holed against the background of treatment with brivaracetam. Effect of brivaracetam on other medicinal productsbrivaracetam at doses from 50 to 150 mg / day did not affect the AUC of midazolam (metabolized by the CYP3A4 isoenzyme). The risk of developing clinically significant interactions mediated by the CYP3A4 isoenzyme is considered low. In vitro studies have shown that brivaracetam inhibits CYP450 isoenzymes to a small extent, or does not inhibit them at all, with the exception of CYP2C19. Brivaracetam may increase the plasma concentration of drugs metabolized with the participation of the CYP2C19 isoenzyme (for example, lanzoprazole, omeprazole, diazepam). In vitro experiments, brivaracetam did not induce the CYP1A1 / 2 isoenzyme, but it did induce the CYP3A4 and CYP2B6 isoenzymes. There was no induction of the CYP3A4 isoenzyme in vivo (see midazolam above). The effect on the CYP2B6 isoenzyme has not been studied in vivo, brivaracetam can reduce the plasma concentration of drugs metabolized with the participation of the CYP2B6 isoenzyme (for example, efavirenz). In vitro drug-drug interaction studies to assess the potential inhibitory effect of the drug on transporters concluded that there were no clinically significant effects, except for the effect on the organic anion transporter 3 (OATP). The concentration of brivaracetam in vitro, which provides 50% of the maximum OATP inhibitory effect, was 42 times higher than the Ctax at the maximum therapeutic dose. Brivaracetam at a dose of 200 mg / day may increase the plasma concentration of drugs tolerated by OATD. Potential interactions between brivaracetam (at doses from 50 to 200 mg / day) and other AEDs were evaluated as part of a combined analysis of the drug’s plasma concentrations obtained in all phase 2 and 3 studies (including population pharmacokinetic analysis of placebo-controlled phase 2 and 3 studies), and in special drug interaction studies for the following AEDs: carbamazemine, lamotrigine. phenytoin and topiramate. Carbamazepine Brivaracetam is a moderate reversible epoxide hydrolase inhibitor that increases the concentration of carbamazepine epoxide (the active metabolite of carbamazepine) in the blood. In controlled studies, plasma concentrations of carbamazepine epoxide increased by an average of 37%,62%, and 98% (with low variability) when brivaracetam was co-administered at doses of 50 mg/day,100 mg/day, or 200 mg/day, respectively. The security profile was not changed. No additional effect of brivaracetam and valproate on the AUC of carbamazepine epoxide was found. Combined use of brivaracetam (at a dose of 100 mg / day) with an oral contraceptive containing ethinyl estradiol (0.03 mg) and levonorgestrel (0.15 mg) did not affect the pharmacokinetic parameters of any of the components of this combination.Concomitant use of brivaracetam at a dose of 400 mg / day (at a dose exceeding the maximum recommended daily dose by 2 times) with an oral contraceptive containing ethinyl estradiol (0.03 mg) and levonorgestrel (0.15 mg) showed a decrease in the AUC values of estrogen and progestin by 27% and 23%, respectively, which did not affect the degree of ovulation suppression. There were no changes in the time-dependent concentration profiles for endogenous markers of estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin.

How to take, course of use and dosage

Inside, without chewing, with water, regardless of food intake (see the section “Pharmacological properties”).

The recommended starting dose is 50 mg / day or UOmg/day, as decided by the attending physician, based on the desired anticonvulsant effect and potential and side effects. The daily dose is divided equally into two doses, in the morning and in the evening. Depending on the individual patient response and tolerability, the dose may vary from 50 mg/day to 200 mg/day, in which brivaracetam is effective as a concomitant therapy for PSP. Initial titration of the dose to an effective dose does not require taking into account the tolerability of brivaracetam therapy.

In case of missing one or more doses, it is recommended to take the missed dose of the drug as soon as possible; the next dose is taken at the usual time in the morning or evening. Making up for the missed dose will avoid lowering the concentration of brivaracetam in plasma below the effective level and prevent the recurrence of seizures.

Drug withdrawal

If it is necessary to stop treatment with brivaracetam, it is recommended to cancel the drug gradually, reducing the dose by 50 mg / day per week. After one week of taking a dose of 50 mg/day, it is recommended to take brivaracetam at a dose of 20 mg/day for the last week.

Features of use in certain groups of patients

Elderly (65 years and older)

No dose adjustment is required in elderly patients (see section “Pharmacokinetics”). There is limited experience in patients aged 65 years and older.

Impaired renal function

No dose adjustment is required in patients with impaired renal function (see section “Pharmacokinetics”). Brivaracetam is not recommended in patients with end-stage renal failure requiring hemodialysis due to a lack of clinical data.

Impaired liver function

In patients with chronic liver disease, exposure to brivaracetam is increased. You should start with a dose of 50 mg / day. The recommended maximum daily dose for all stages of hepatic insufficiency is 150 mg, divided into two doses (see section ” Pharmacokinetics)”.

Children

The safety and efficacy of brivaracetam in newborns and children under 16 years of age have not been established. The data obtained so far are listed in the sections “Side effects” and “Pharmacological properties”.

Overdose

Clinical experience with brivaracetam overdose in humans is limited. Healthy volunteers who took a single brivaracetam dose of 1400 mg experienced drowsiness and dizziness. There is no specific antidote for brivaracetam. In case of overdose, general maintenance therapy is performed. Since less than 10% of brivaracetam is excreted in the urine, it is unlikely that hemodialysis will significantly increase the clearance of brivaracetam (see section “Pharmacological properties”).

Special instructions

Discontinuation of the drug If it is necessary to stop treatment with brivaracetam, it is recommended to discontinue the drug gradually, reducing the dose by 50 mg / day per week. After one week of taking a dose of 50 mg/day, it is recommended to take brivaracetam at a dose of 20 mg/day for the last week. Suicidal intentions and suicide attempts Suicidal intentions and suicide attempts have been reported in patients treated with AEDs, including brivaracetam, for various indications. A meta-analysis of the results of randomized placebo-controlled studies of PEP also showed a small increase in the risk of suicidal intentions and attempts. The mechanism of occurrence of the risk of suicide is unknown, and the possibility of an increased risk with the use of brivaracetam is not excluded. It is necessary to monitor signs of suicidal intentions and attempts in patients, and to start appropriate treatment in a timely manner. Patients (and caregivers) should be informed to seek immediate medical attention if suicidal intentions or attempts occur. Hepatic impairment Clinical data on the use of brivaracetam in patients with hepatic insufficiency are limited. It is recommended to adjust the dose of the drug in patients with impaired liver function (see the section “Dosage and use”). EFFECT ON THE ABILITY TO DRIVE VEHICLES AND OTHER MECHANISMSIBrivaracetam has a slight or moderate effect on the ability to drive vehicles and other mechanisms. Due to differences in individual sensitivity to the drug, a number of patients may develop drowsiness, dizziness, and other effects from the central nervous system. Patients are advised not to drive a car or operate other potentially dangerous machinery until they understand the effects of brivaracetam on their ability to perform such activities.

Storage conditions

Store at a temperature not exceeding 30 °C. Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

Brivaracetam

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Epilepsy