Capsules size 4, with a lid and a white body, with the company logo and the name of the drug with the digital dosage indication "ZONEGRAN 25", the contents of the capsules are white and white with a yellowish tinge powder, free from visible inclusions.
1 caps.
zonisamide 25 mg
Excipients: vegetable hydrogenated oil - 0.75 mg, microcrystalline cellulose - 49.06 mg, sodium lauryl sulfate - 0.19 mg.
The composition of the capsule shell: gelatin is 36.895 mg, titanium dioxide (E171) is 1.105 mg, 1014 Tekprint SW-9008 * ink (shellac is 36.0-40.5 Ојg, propylene glycol is 4.5-10.5 Ојg, potassium hydrochloride is 0.075-0.150 Ојg), dye iron oxide black (E172) - 36.0-42.0 Ојg).
14 pcs. - blisters (1) - packs of cardboard.
Capsules size 3, with a gray lid and a white body, with the company logo and the name of the drug with the digital dosage indication "ZONEGRAN 50", the contents of the capsules are white and white with a yellowish tinge powder, free from visible inclusions.
1 caps.
zonisamide 50 mg
Excipients: vegetable hydrogenated water - 1.5 mg, microcrystalline cellulose - 98.12 mg, sodium lauryl sulfate - 0.38 mg.
The composition of the capsule shell: gelatin - 46.575 mg, titanium dioxide (E171) - 1.353 mg, iron dye oxide black (E172) - 0.072 mg, 1014 ink Tekprint SW-9008 * (shellac - 36.0-40.5 Ојg, propylene glycol 4.5-10 Ојg , potassium hydrochloride - 0.075-0.150 Ојg), ferric oxide black oxide (E172) - 36.0-42.0 Ојg).
14 pcs. - blisters (2) - packs of cardboard.
Capsules of size 1, with a red lid and white body, with a black company logo and the name of the drug with the digital dosage indication "ZONEGRAN 100", the contents of the capsules are white and white with a yellowish tinge powder, free from visible inclusions.
1 caps.
zonisamide 100 mg
Excipients: vegetable hydrogenated oil - 3 mg, microcrystalline cellulose - 196.25 mg, sodium lauryl sulfate - 0.75 mg.
The composition of the capsule shell: gelatin - 74.239 mg, titanium dioxide (E171) - 1.613 mg, red dye (E129) - 0.147 mg, dye sunset yellow (E110) 0.002 mg, 1014 ink Tekprint SW-9008 * (shellac - 36.0 -40.5 Ојg, propylene glycol 4.5-10.5 Ојg, potassium hydrochloride 0.075-0.150 Ојg), ferric iron oxide black (E172) 36.0-42.0 Ојg).
14 pcs. - blisters (4) - packs of cardboard.
14 pcs. - blisters (7) - packs of cardboard.
* Theoretical quantities, based on the total amount of 0.15 mg.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Zonisamide is an antiepileptic drug, a derivative of benzisoxazole, in vitro weakly inhibits carbonic anhydrase. Chemically, its structure is different from other antiepileptic drugs.
Mechanism of action
The mechanism of action of zonisamide is not fully studied, it probably blocks potential potent sodium and calcium channels, reduces the intensity of synchronized neuronal excitation, inhibits the development of seizures and prevents the further spread of epileptic activity. Zonisamide also reduces the convulsive activity of neurons by enhancing the inhibitory effect of gamma-aminobutyric acid (GABA).
Pharmacodynamic effects
Anticonvulsant activity of zonisamide has been studied in various models of epilepsy, in groups with induced or congenital seizures, while zonisamide has proved to be an antiepileptic broad-spectrum agent. Zonisamide prevents the development of maximum electroconvulsive attacks, limits the development of convulsions, including the spread of the focus of excitation from the cortex to the subcortical structures, and also inhibits the activity of the epileptogenic focus. Unlike phenytoin and carbamazepine, zonisamide has a selective effect on seizures that occur in the cerebral cortex.
Clinical efficacy and safety
Monotherapy of partial seizures with secondary generalization or without
The effectiveness of zonisamide in the monotherapy regimen in patients with newly diagnosed partial epileptic seizures with or without secondary generalization, with generalized tonic-clonic seizures without a clear foci was shown in a double-blind, parallel-group study involving 583 adult patients to establish no less efficacy of therapy Zonegran В® preparation before prolonged-action carbamazepine therapy, which lasted up to 24 months depending on the response to treatment. The dose was raised to the target value of 600 mg of carbamazepine or 300 mg of zonisamide. When patients had seizures, they increased to the next dose, i.e. 800 mg of carbamazepine or 400 mg of zonisamide. If the seizures persisted, the dose was increased to a maximum of 1200 mg for carbamazepine and up to 500 mg for zonisamide. Patients who did not have seizures for 26 weeks, while taking the target dose, continued to receive the same dose for another 26 weeks.
Additional therapy of partial seizures with secondary generalization or without in adults
The efficacy of additional zonisamide therapy was shown in 4 double-blind, placebo-controlled studies lasting up to 24 weeks. These studies showed a decrease in the median incidence of partial epileptic seizures when zonisamide was administered at daily doses of 300-500 mg once or twice daily.
Additional therapy of partial seizures with secondary generalization or demotion of adolescents and children from 6 years of age
In children (age 6 years and older), the efficacy of zonisamide was demonstrated in a double-blind, placebo-controlled study of 24 weeks with the participation of 207 patients. With a 12-week application of the target dose, the frequency of seizures decreased by 50% or more in 50% of patients receiving zonisamide and in 31% of patients receiving placebo.
Special safety problems that arose in the conduct of research in children included: impaired appetite and weight loss, lower bicarbonate levels, increased risk of urolithiasis, and dehydration. All these phenomena and especially weight loss can adversely affect the growth and development of the child, and can also lead to a deterioration in overall health. In general, a limited amount of data has been obtained on the long-term effects of the drug on the growth and development of the child.
PHARMACOKINETICS
Suction
Zonisamide is almost completely absorbed after oral administration, the maximum concentration (C max ) in plasma is reached within 2-5 hours after administration.The expression of primary metabolism is insignificant - absolute bioavailability is estimated at 100%. Bioavailability of zonisamide during ingestion does not depend on food intake, although the time to reach C max in blood plasma can be slowed down.
The value of AUC (area under the concentration-time curve) and C max of zonisamide practically linearly increases after single dose administration (in the dose range of 100-800 mg) and after repeated administration (in the dose range of 100-400 mg once a day). The increase in these values ​​when the equilibrium state was reached was somewhat higher than assumed, based on the accepted dose, possibly in connection with the saturation of the binding of zonisamide with erythrocytes. The equilibrium state is reached within 13 days. There is a somewhat greater accumulation than was expected, compared with a single dose of the drug.
Distribution
Zonisamide binds to plasma proteins by 40-50%, according to the results of in vitro studies, various anticonvulsants (phenytoin, phenobarbital, carbamazepine and sodium valproate) have no significant effect on the degree of its binding to plasma proteins. The apparent volume of distribution in adults is 1.1-1.7 l / kg, indicating a significant distribution of zonisamide in tissues. The ratio of zonisamide concentrations in erythrocytes and plasma is about 15 at low concentrations and about 3 at high concentrations.
Metabolism
Zonisamide is metabolized with the participation of the CYP3A4 isoenzyme, the main pathway of metabolism is the cleavage of the benzisoxazole ring to form 2-sulfamoylacetylphenol (SMAP), as well as N-acetylation. The starting material and SMAP can bind to glucuronic acid. Metabolites, which are not detected in the blood plasma, are deprived of anticonvulsant activity. Data that zonisamide is able to induce its own metabolism is absent.
Excretion
The clearance of zonisamide after reaching C ss reaches 0.70 l / h, the final half-life (T 1/2 ) is about 60 h (provided there is no simultaneous reception of inducers of the activity of the isoenzyme CYP3A4). T 1/2 does not depend on the magnitude of the dose taken, nor on the duration of treatment. Variations in the concentration of zonisamide in plasma are insignificant (<30%). Metabolites and unchanged zonisamide are excreted mainly through the kidneys. The renal clearance of unchanged zonisamide is relatively low (about 3.5 ml / min); about 15-30% of the accepted dose is excreted unchanged.
Linearity / nonlinearity
The concentration of zonisamide increases until equilibrium is reached, which usually occurs after about 8 weeks. When comparing the same dose level, patients with a higher body weight tend to have lower equilibrium concentrations in the serum, but these differences are insignificant. Age (? 12 years) and gender, corrected for body weight, do not affect the concentration of zonisamide in patients with epilepsy when equilibrium concentrations of the drug are reached. The need to reduce the dose when using any PEP, incl. inducers of the isoenzyme CYP3A4, is absent.
Ratio of pharmacodynamics and pharmacokinetics
Zonisamide reduces the average frequency of seizures during the 28-day period and this decrease is proportional (log-linear dependence) of the average concentration of zonisamide.
Use in special patient groups
Patients with renal insufficiency. In patients with renal failure, the renal clearance of single doses of zonisamide is directly proportional to the creatinine clearance (CK). AUC of zonisamide is increased by 35% in patients with severe renal insufficiency (CC <20 ml / min) (see section "Dosage regimen").
Patients with hepatic insufficiency. The pharmacokinetics of zonisamide in patients with hepatic insufficiency has not been adequately studied.
Patients of advanced age. There are no clinically significant differences in the pharmacokinetics of zonisamide in young (21-40 years) and elderly (65-75 years) patients.
Patients of childhood (5-18 years). Limited data indicate that the pharmacokinetic parameters of zonisamide at a daily dose of 1 mg / kg, 7 mg / kg or 12 mg / kg in children and adolescents are similar to those in adult patients (adjusted for body weight).
INDICATIONS
- monotherapy in adult patients with partial epileptic seizures with secondary generalization or without, with newly diagnosed epilepsy;
- as part of complementary therapy in adults, adolescents and children from age 6 with partial epileptic seizures with secondary generalization or without.
DOSING MODE
Inside, washing down with water, regardless of food intake.
Adult patients
Zonegran В® can be given to adults in the form of monotherapy and as an adjunct to already prescribed treatment. The dose of the drug is selected taking into account the clinical effect. The recommended dose regimen and the amount of maintenance doses are shown in Table 1. Some patients, in particular those who do not take CYP3A4 isoenzyme inducing drugs, can respond to lower doses.
Table 1. Recommended regimen for increasing the dose and the amount of maintenance doses in adults
Treatment regimen Dose selection Supportive dose
Monotherapy Adults with newly diagnosed epilepsy Week 1-2 Week 3-4 Week 5-6 300 mg per day (single dose). If higher doses are required: an increase of 100 mg at a two-week interval to a maximum recommended dose of 500 mg
100 mg per day (single dose) 200 mg per day (single dose) 300 mg per day (single administration)
Additional therapy: - patients taking drugs that induce the isoenzyme CYP3A4 Week 1 Week 2 Week 3-5 300 to 500 mg per day (once or in 2 divided doses)
50 mg per day (in 2 divided doses) 100 mg per day (in 2 divided doses) an increase of 100 mg at weekly intervals
- Patients who do not take drugs that induce the isoenzyme CYP3A4 or patients with renal or hepatic insufficiency Week 1-2 Week 3-4 Week 5-10 300 to 500 mg per day (once or in 2 divided doses). Some patients may respond to lower doses.
50 mg per day (in 2 divided doses) 100 mg per day (in 2 divided doses) an increase of 100 mg with two-week intervals
Cancel
Zonegran В® is canceled gradually by reducing the dose by 100 mg per week while simultaneously correcting the dose of other co-administered antiepileptic drugs (if necessary).
Teens and children from 6 years old
Zonegran В® can be given to children from 6 years old as an adjunct to already prescribed treatment. The dose of the drug is selected taking into account the clinical effect. The recommended dose-increasing regimen and the amount of maintenance doses are given in Table 2. Some patients, in particular those who do not take CYP3A4 isoenzyme-inducing drugs, can respond to lower doses.
Children and their parents or caregivers should be alerted to special instructions for the patient on measures to prevent heat stroke (see section "Special instructions").
Table 2. Recommended mode of dose increase and the value of maintenance doses in children from 6 years of age
Treatment regimen Dose selection Supportive dose
Additional therapy: - Patients taking drugs inducing the isoenzyme CYP3A4 Week 1 Week 2-8 Patients weighing between 20 and 55 kg * Patients weighing more than 55 kg
1 mg / kg / day (single dose) increase by 1 mg / kg at weekly intervals from 6 to 8 mg / kg per day (once) 300 to 500 mg per day (single dose)
- Patients not taking drugs inducing the isoenzyme CYP3A4 Week 1-2 Week 3 and further from 6 to 8 mg / kg per day (once) 300 to 500 mg per day (once)
1 mg / kg / day (single dose) increase by 1 mg / kg at two-week intervals
* To ensure maintenance of a maintenance dose, it is necessary to monitor the weight of the child's body and change the dose as the body weight changes to 55 kg.The dosage regimen is 6-8 mg / kg per day up to a maximum daily dose of 500 mg.
The safety and efficacy of Zonegran В® in children younger than 6 years of age or in children weighing less than 20 kg have not been established.
In clinical studies, limited data were obtained in patients with a body weight of less than 20 kg. In this regard, in children aged 6 years and older with a body weight of less than 20 kg in treatment should be careful
Cancel
The discontinuation of Zonegran В® is effected gradually by reducing the dose by 2 mg / kg per week (in accordance with the recommendations in Table 3)
Table 3. Recommended dose reduction scheme for children from 6 years of age
Body weight Dose reduction with weekly intervals at *:
20-28 kg from 25 to 50 mg per day
29-41 kg from 50 to 75 mg per day
42-55 kg 100 mg per day
More than 55 kg of 100 mg per day
* for a single admission
Use in elderly patients
Care should be taken when prescribing the drug because of limited experience. It is necessary to take into account the safety profile of the drug (see the "Side effect" section).
Use in patients with renal insufficiency
Care must be taken when treating patients with renal insufficiency due to limited clinical experience - a slower selection of the dose of the drug may be required.Because zonisamide and its metabolites are excreted by the kidneys, it should be discarded in patients who developed acute renal failure, or clinically significant hypercreatininaemia is observed.
In patients with renal failure, the renal clearance of single doses of zonisamide is directly proportional to the creatinine clearance (CK). AUC of zonisamide is increased by 35% in patients with severe renal insufficiency (CC <20 ml / min)
Use in patients with hepatic impairment
The use of the drug in patients with hepatic insufficiency has not been studied. Use in patients with severe hepatic insufficiency is not recommended. Care should be taken when treating patients with mild to moderate hepatic insufficiency - a slower dose selection may be required.
SIDE EFFECT
The experience with ZonegranВ® includes clinical studies for more than 1200 patients, 400 of whom received ZonegranВ® for at least 1 year, and extensive post-marketing use (in Japan since 1989, in the US since 2000).
Zonisamide contains a sulfonamide group. Serious adverse reactions from the immune system associated with taking drugs that contain a sulfonamide group include the appearance of skin rashes and other allergic reactions, as well as the development of severe hematologic disorders, including aplastic anemia, in very rare cases leading to lethal outcome (see section "Special instructions").
The most common adverse reactions in controlled trials, combination therapy were somnolence, dizziness and anorexia. The most common adverse reactions in a randomized controlled trial zonisamide monotherapy in comparison with a sustained release carbamazepine in patients treated with zonisamide were reducing bicarbonates, loss of appetite and weight loss. Frequency of significant reduction in serum bicarbonate level (reduction to less than 17 mEq / l, and 5 mEq / l) was 3.8%. Frequency of significant reduction in body weight by 20% or more was 0.7%.
The frequency of occurrence was defined as: very common (1/10?), Common (1/100 <1/10?), Rare (1/1000 <1/100?) And very rare (<1/10 000).
Table 4: Adverse reactions identified in clinical trials, combination therapy, and post-marketing observational
organ systems Very often Often Not often Very seldom
Infectious and parasitic diseases Pneumonia Urogenital infections
Violations of the blood and lymphatic system Ecchymosis Agranulocytosis Aplastic anemia Leukocytosis Leukopenia Lymphadenopathy Pancytopenia Thrombocytopenia
Violations by immune hypersensitivity reactions to the drug hypersensitivity syndrome drug constant prices rash with eosinophilia and systemic symptoms
Metabolism and nutritionAnorexia Hypokalaemia Metabolic acidosis tubular renal acidosis
mental disorders Excitation Irritability Confusion Depression Affective lability Anxiety Insomnia Psychotic disorder Anger Aggression Suicidal thoughts Suicide attempts Hallucinations
disorders of the nervous system Ataxia Dizziness Reduced memory Drowsiness Bradifreniya Violation attention Nystagmus Paresthesias speech disorders Tremor Seizures Amnesia Coma grand mal attacks with myasthenic Indra Neuroleptic malignant syndrome Status epilepticus
Violations of the organ of vision diplopia
Disorders of the respiratory system, organs, thoracic and mediastinal disordersShortness of breath Report Aspiration pneumonia hypersensitivity pneumonitis
Disorders of the gastrointestinal tract Abdominal pain Constipation Dyspepsia Diarrhea Nausea Vomiting Pancreatitis
Disorders of the liver and biliary tract cholecystitis Cholelithiasis Hepatocellular damage
Disorders of the skin and subcutaneous tissue disorders Rash Pruritus Alopecia anhidrosis erythema multiforme syndrome Stevens- Johnson Toxic epidermal necrolysis
Violations of the musculoskeletal and connective tissue disorders Rhabdomyolysis
disorders with of the kidneys and urinary tract Nephrolithiasis Hydronephrosis Renal failure Urolithiasis Violation urinalysis
General disorders and injection siteFatigue Flu state Fervescence peripheral edema
Laboratory and instrumental data Snizhenieurovnyabikarbonatov Weight loss Increased CK Increased creatinine Increased urea Report biochemical liver function
Injury, poisoning and complications manipulation Thermal shock
described isolated cases of sudden unexplained deaths in patients with epilepsy taking Zonegran В® (SUDEP).
Table 5. Adverse reactions identified in RCT zonisamide monotherapy in comparison with carbamazepine sustained release
organ systems very often Frequently Infrequently
Infectious and parasitic diseases Urogenital infections Pneumonia
Violations of the blood and lymphatic system Leukopenia Thrombocytopenia
Metabolic and nutritional Decreased appetite Hypokalaemia
mental disorders Stimulation Depression Insomnia Emotional lability Anxiety Confusion Acute psychosis Aggression Suicidal thoughts Hallucinations
disorders of the nervous system Ataxia Dizziness Memory Reduction Drowsiness Bradifreniya Violation attention Nystagmus Paresthesias On ushenie speech Tremor Seizures
Disorders part of the vision diplopia
Disorders of the respiratory system, organs, thoracic and mediastinal disordersRespiratory disorder
Disorders of the gastrointestinal tract Constipation Diarrhea Dyspepsia Nausea Vomiting Abdominal Pain
Disorders of the liver and biliary tract acute cholecystitis
Disorders of the skin and subcutaneous tissue disorders Rash Itching ecchymosis
General disorders and injection site Fatigue body temperature irritability
Laboratory and instrumental data Reducing the level of bicarbonate weight loss Increased CPK increased ALT levels Increased AST urinalysis Violation
D additionally safety information in special patient groups
Elderly patients
Overall safety data analysis in 95 elderly patients showed a relatively high incidence of peripheral edema and itching compared with younger patients.
Review of post-marketing data on the tolerability of therapy with Zonegran В® in elderly patients (over 65 years) suggests that in these patients the development of Stevens-Johnson syndrome and drug hypersensitivity reactions are detected more frequently than in the general population.
Child patients
The safety profile of zonisamide in children who participated in placebo-controlled clinical trials (ages 6 to 17 years), complies with the safety profile of the drug in adults. Of the 465 patients included in the safety database in children (including 67 patients who continued to participate in the open during the continuation phase of controlled clinical studies) death occurred in 7 children (1.5%; 14.6 / 1000 patient-years): 2 cases as a result of status epilepticus, one of which was associated with significant weight loss (10% for 3 months) in a patient with low body weight, followed by withdrawal of the drug;in one case, as a result of traumatic brain injury / hematoma and 4 cases of deaths occurred in patients with previous functional neurological deficit various genesis (2 cases of sepsis associated with pneumonia / organ failure, 1 case SUDEP and 1 case of traumatic brain injury) . A total of 70.4% of patients in the controlled study, which in the open phase or the continuation of this study was obtained zonisamide, during therapy at least once determined level less bicarbonatesduring therapy at least once determined level less bicarbonatesduring therapy at least once determined level less bicarbonates
22 mmol / l. Low levels of bicarbonate was maintained for a long period of time (median 188 days).
In the pooled analysis, the safety data obtained from 420 children (183 aged 6 to 11 years and 237 from 12 to 16, in which the average length of the drug was approximately 12 months), it has been relatively more frequent messages delivery of occurrence of pneumonia, dehydration, reduction of perspiration, impaired liver function, otitis media, pharyngitis, sinusitis, and upper respiratory tract infections, cough, rhinitis and nasal bleeding, abdominal pain, vomiting, rash and eczema, and ihoradki compared with older patients (especially those under 12 years of age). With a lower incidence of reports of amnesia occurs, increased creatinine, lymphadenopathy, and thrombocytopenia. The frequency of weight loss for 10% or more was 10.7% (see. "special instructions" section).In some cases, reduce the delay of body weight was observed at the transition to the next stage of Tanner and maturation of bone tissue.
Notification of adverse reactions
is extremely important to notify about adverse reactions that occurred during post-marketing use of medicinal sredstva.Eto allows you to control the ratio of benefits and risks of the drug. Please inform health professionals about the occurrence of any adverse reactions.
CONTRAINDICATIONS
- hypersensitivity to the active substance, any of the excipients or to sulfonamides;
- Children under 6 years of age (safety and efficacy have not been established for this category of patients);
- with severe liver failure patients (use in these patients has not been studied);
- Pregnancy and lactation (for drug safety data for this category of patients is not enough (see "Pregnancy and Lactation" section).);
- simultaneous application in children with carbonic anhydrase inhibitors such as acetazolamide and topiramate.
Carefully
- Elderly patients (existing application experience is limited);
- Patients with renal failure (due to the limited clinical experience, may require a slow titration of the drug (see "Dosing and dose" section).);
- Patients with mild to moderate hepatic severity deficiency (due to the limited clinical experience, may require a slow titration of the drug (see "Dosing and dose" section).);
- simultaneous application in adults with carbonic anhydrase inhibitors such as acetazolamide and topiramate (insufficient data to exclude pharmacodynamic interaction);
- simultaneous application in adults with pyrogenic drugs, including carbonic anhydrase inhibitors and drugs with an anticholinergic action;
- the beginning of treatment, its abolition or modification of zonisamide dose while the use of substrates of P-glycoprotein (e.g., digoxin, quinidine);
- Patients weighing less than 20 kg (clinical experience is limited).
PREGNANCY AND LACTATION
Women with childbearing potential stored
Women with childbearing potential must be saved to use reliable methods of contraception during treatment with Zonegran В® and for 1 month after its cancellation.
Pregnancy
There is insufficient data on the use of the drug Zonegran В® in pregnant women. Animal studies have shown that zonisamide has the potential reproductive toxicity, the risk of which is unknown in humans.
Zonegran В® should not be used during pregnancy except in cases where the potential benefits, according to the doctor, take precedence over the possible risk to the fetus. If a woman is planning to become pregnant, you should analyze the need for anticonvulsant therapy. In the case of drug destination Zonegran В® recommended careful observation.
The risk of congenital malformations in infants whose mothers are taking antiepileptic drugs, increases by 2-3 times. The following defects are detected more often: the splitting of the upper lip, malformations of the cardiovascular system and neural tube defects. Combination therapy with anticonvulsants is accompanied by an increased risk of birth defects compared to monotherapy.
Unacceptable abrupt withdrawal of anticonvulsant therapy due to the risk of an epileptic seizure, which can lead to serious consequences for both mother and child.
Breast-feeding
The drug is excreted in breast milk in concentrations similar to those in plasma, so you should decide to discontinue breast-feeding or to remove the drug in nursing mothers. Because of the long half-life, breastfeeding can not be resumed earlier than one month after discontinuation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Care should be taken when treating patients with renal failure due to limited data from clinical studies. It may be necessary to adjust the dose. Should stop taking the drug to patients who develop acute renal failure or who have observed clinically indicated a continuous increase in serum creatinine.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with liver failure - is not known. It is not recommended to take the drug in patients with severe hepatic impairment, caution is advised to take the drug for mild to moderate hepatic insufficiency. It may be necessary to adjust the dose.
APPLICATION FOR CHILDREN
There are limited data from clinical studies in pediatric and adolescent patients.
APPLICATION IN ELDERLY PATIENTS
There are limited data on clinical trials in elderly patients. It is necessary to be careful at the start of the drug.
SPECIAL INSTRUCTIONS
Skin rashes
When therapy with Zonegran В® reported on the development of severe skin reactions including Stevens-Johnson syndrome .
Recommended the abolition of the drug Zonegran В® in patients who develop skin rashes and which can not be explained by other causes. All patients with the appearance of skin rash while taking Zonegran drug В® should be carefully monitored, especially patients with concurrent administration of other antiepileptic drugs, which themselves can cause skin rashes.
Withdrawal
Remove the drug Zonegran В®produced by gradually reducing the dose to avoid occurrence of epileptic seizures. Insufficient data on cancellation simultaneously used antiepileptic drugs after achieving seizure control with the use of the drug Zonegran В® under adjunctive therapy to access monotherapy Zonegran В® . So the abolition of concomitant antiepileptic treatment should be done with caution.
Responses associated with the presence of the sulfonamide group
Zonegran В®It contains a sulfonamide group. Serious adverse reactions of immune system related to reception of preparations that contain a sulfonamide group include the appearance of skin rash and other allergic reactions and the development of pronounced hematological disorders, r. H. Aplastic anemia, in rare cases, leading to lethal outcome.
It has been reported about the development of cases of agranulocytosis, thrombocytopenia, leukopenia, aplastic anemia, pancytopenia and leucocytosis. Information for assessing the possible relationship of these phenomena with the received value of the drug dose Zonegran В® and duration of treatment is insufficient.
Suicidal thinking and behavior
Development of suicidal thinking and behavior is possible in patients taking antiepileptic drugs for a variety of indications. A meta-analysis of randomized placebo-controlled trials of antiepileptic drugs has also shown an increased risk of suicidal thoughts and behavior.
The mechanism of this phenomenon is unknown, available evidence does not exclude the possibility of an increased risk of suicidal behavior and formation in patients receiving the drug Zonegran В® .
We need to monitor patients for the emergence of suicidal ideation and behaviors and appropriate treatment provided. Patients (and caregivers
The information is provided for your information, do not self-medicate, it is dangerous for your health.
