Zonisamide

Skin rashes

With drug therapy Zonegran^® The development of severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, has been reported.

The abolition of the drug Zonegran is recommended.^® in patients who have skin rashes and which cannot be explained by other causes. All patients with the appearance of lesions on the skin while taking the drug Zonegran^® must be carefully monitored, especially patients with the simultaneous administration of other antiepileptic drugs that themselves can cause skin rashes.

Cancellation syndrome

The abolition of the drug Zonegran^® produced by gradually reducing the dose in order to avoid the occurrence of epileptic seizures. Not enough data on the abolition of concurrently used antiepileptic drugs after achieving seizure control when using the drug Zonegran^® in the framework of adjuvant therapy for the transition to monotherapy with the drug Zonegran^®. Therefore, the abolition of concomitant antiepileptic treatment should be carried out with caution.

Reactions associated with the presence of sulfonamide group

Zoneran^® contains a sulfonamide group. Serious adverse reactions of the immune system associated with taking drugs that contain the sulfonamide group include the appearance of a skin rash and other allergic reactions, as well as the development of severe hematological disorders, including aplastic anemia, in very rare cases, leading to death.

The development of cases of agranulocytosis, thrombocytopenia, leukopenia, aplastic pancytopenia anemia and leukocytosis has been reported.Information to assess the possible relationship of these phenomena with the magnitude of the dose of the drug Zonegran^® and the duration of treatment is not enough.

Suicidal thinking and behavior

The development of suicidal thinking and behavior is possible in patients taking antiepileptic drugs for a number of indications. A meta-analysis of randomized, placebo-controlled studies of antiepileptic drugs also showed an increased risk of suicidal thoughts and behavior.

The mechanism of this phenomenon is unknown, the available data do not exclude the possibility of an increased risk of the formation of suicidal behavior even while taking the drug Zonegran^®.

Patients should be monitored for suicidal thoughts and behaviors, and appropriate treatment should be provided. Patients (and those caring for them) should be advised to seek medical help if suicidal thoughts and behaviors appear.

Nephrolithiasis

Some patients, especially those with a predisposition to nephrolithiasis, may have an increased risk of kidney stones and the appearance of signs and symptoms such as renal colic, kidney pain or side pain.

Nephrolithiasis can lead to chronic kidney damage. Risk factors for nephrolithiasis include previous kidney stone formation, as well as a family history of nephrolithiasis and hypercalciuria. None of these risk factors is a reliable sign that predicts the formation of kidney stones during treatment with zonisamide. In addition, the risk may be increased in patients taking other drugs that provoke the development of urolithiasis. Increased fluid intake and forced diuresis helps reduce the risk of stone formation, incl. and in patients with a predisposition for this.

Metabolic acidosis

The formation of hyperchloremic metabolic acidosis without anionic rupture (reduction of bicarbonate levels in the absence of chronic gas alkalosis) is associated with therapy with the drug Zonegran^®. The development of metabolic acidosis is due to the loss of bicarbonates in the kidneys due to the inhibitory effect of zonisamide on carbonic anhydrase, and possibly at any stage of treatment, although it is more often noted in the early stages of treatment. Similar irregularities were noted both during the placebo-controlled clinical trials and in the post-marketing period. A decrease in the level of bicarbonates is usually expressed only slightly (the average value is about 3.5 mEq / L with a daily dose of 300 mg in adults); in rare cases, patients may experience a more significant decrease. Conditions or treatments that predispose to the development of acidosis (for example, kidney disease, severe respiratory disorders, status epilepticus, diarrhea, surgical interventions, a diet that promotes the formation of ketone bodies, a number of drugs) can enhance the effect of zonisamide on bicarbonate levels.

The risk and severity of metabolic acidosis increase in young patients. In the event of signs or symptoms of metabolic acidosis, it is recommended to evaluate the content of bicarbonate in serum. If the developed metabolic acidosis does not pass, the possibility of reducing the dose or completely discontinuing the use of the drug Zonegran should be considered.^® (with a gradual decrease in dose), because possible development of osteopenia. If it is decided to continue therapy in the presence of persistent acidosis, the possibility of using alkaloids should be considered.

It is necessary to exercise caution when prescribing simultaneously with carbonic anhydrase inhibitors (for example, topiramate and acetazolamide), since insufficient data to exclude pharmacodynamic interaction (see. "Interaction").

Heatstroke

Cases of decreased sweating and fever have been recorded mainly in patients under 18 years of age. In some cases, heat stroke occurred, requiring inpatient treatment. Most cases occurred under conditions of high ambient temperature. Patients and / or their caregivers should be warned about the need to maintain adequate hydration of the body and avoid exposure to elevated temperatures. Care must be taken when prescribing the drug Zonegran^® simultaneously with drugs that promote overheating of the body, including carbonic anhydrase inhibitors and holinoblokatory.

Pancreatitis

With the development of patients with signs of pancreatitis while taking the drug Zonegran^®monitoring of pancreatic lipase and amylase levels is necessary. In the case of confirmed pancreatitis in the absence of other obvious reasons, the abolition of the drug Zonegran is recommended.^® and the appointment of appropriate treatment.

Rhabdomyolysis

With the development of patients taking Zonegran^®, severe muscle pain and / or weakness, especially with fever, requires an assessment of the content of muscle damage markers, including the level of CPK and aldolase. If they are elevated, in the absence of other obvious causes, such as an injury or a major epileptic seizure, it is recommended that the drug be canceled.^® and the appointment of appropriate treatment.

Women with preserved childbearing potential

Women with preserved childbearing potential should use reliable methods of contraception during treatment with the drug Zonegran^® and for 1 month after its cancellation (see. "Use during pregnancy and lactation").

Weight loss

Zoneran^® can cause weight loss, so during the treatment of patients with low body weight or while reducing it, you must assign nutritional supplements and enhanced nutrition. With a marked decrease in body weight, the possibility of drug withdrawal should be considered.^®. Reduced body weight in children may be more pronounced.

Pediatric patients

The above precautions apply to children and adolescents. The following are safety precautions for which special attention should be paid.

Heatstroke and dehydration

Prevention of overheating and dehydration in children. Zoneran^® may cause a decrease in sweating and lead to overheating, and in the absence of appropriate assistance, the child may experience brain damage and death. Children are at high risk, especially in hot weather.

If the child is taking the drug Zonerag^®: overheating should be avoided, especially in hot weather; considerable physical exertion should be avoided, especially in hot weather; should increase water consumption; The following drugs should not be used: carbonic anhydrase inhibitors (such as topiramate and acetazolamide) and anticholinergics (such as clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin).

If any of the following symptoms occur, you should immediately seek medical help: feeling a strong heat from the skin with little sweating or in the absence of it, or when a child becomes confused, have muscle spasms, or if the heart rate increases or the child is breathing. It is necessary to place the child in a cool shaded place; wet the baby’s skin with water to cool it; Give your child a drink of cool water.

Reported cases of decreased sweating and fever, mainly in children. In some cases, there was a heat stroke that required hospitalization. In some cases, a heat stroke with a fatal outcome has been reported. In most cases, the phenomenon occurred during warm weather.The patient and caregivers should be warned about the possible severity of heat stroke, situations where it may occur, as well as measures to be taken if any signs or symptoms appear. Patients or caregivers should be warned about the need to consume a sufficient amount of fluid and avoid excessive physical exertion, depending on the patient's condition. In case of signs and symptoms of dehydration, oligohydrosis or fever, you should consider withdrawing the drug Zonegran^®.

Drug Zonegran^® should not be used in children who receive other drugs at the same time, in which patients are prone to the occurrence of disorders associated with exposure to excessive heat; these include carbonic anhydrase inhibitors and anticholinergic drugs.

Weight loss

Cases of weight loss that have led to a deterioration of the general condition and the cessation of the use of an anti-epileptic drug, which are fatal, have been described. Use of the drug Zoneran^® not recommended in children with underweight or in children with poor appetite.

The frequency of weight loss is the same in different age groups, however, given the possible seriousness of weight loss in children, in this group of patients it is necessary to control body weight. When delaying weight gain in a patient, on the basis of physical development cards, it is recommended to review the diet or increase the amount of food intake, otherwise you should stop using the drug Zonegran^®.

In clinical studies, limited data were obtained from patients with a body weight less than 20 kg. In this regard, the treatment of children aged 6 years and older with a body weight less than 20 kg should be careful. The effect of prolonged low body weight on growth and development in children is unknown.

Metabolic acidosis

The risk of acidosis associated with the use of zonisamide in children and adolescents may be higher and more severe. In this group of patients, appropriate monitoring and control of serum bicarbonate levels should be carried out. The long-term effect of low bicarbonate levels on growth and development is unknown.

Drug Zonegran^® It should not be used in children with other carbonic anhydrase inhibitors, such as topiramate or acetazolamide.

Nephrolithiasis

Children have reported kidney stones. Some patients, especially those with a predisposition to nephrolithiasis, may have an increased risk of kidney stones and associated signs and symptoms, such as renal colic, kidney pain or side pain. Urolithiasis can lead to chronic kidney damage. Risk factors for urolithiasis include previous kidney stones and a hereditary predisposition to nephrolithiasis and hypercalciuria. None of these risk factors is a reliable sign that predicts the formation of kidney stones during treatment with zonisamide.

Increased fluid intake and forced diuresis can reduce the risk of kidney stones, especially in people with risk factors. At the discretion of the doctor can be carried out ultrasound of the kidneys. In case of detection of kidney stones, the drug Zonegran^®should cancel.

Liver dysfunction

In children and adolescents, an increase in liver function and biliary tract, such as ALT, AST, GGT and bilirubin, was observed, but no obvious patterns for values ​​exceeding VGN were found.

However, in case of suspected occurrence of adverse events on the part of the liver, it is necessary to evaluate liver function and decide on the abolition of the drug Zonegran^®.

Cognitive function

Impaired cognitive function in patients with epilepsy is associated with the underlying disease and / or with the use of AED.

In a placebo-controlled study using zonisamide in children and adolescents, the proportion of patients with impaired cognitive function was quantitatively higher in the zonisamide group compared with the placebo group.

Excipients

The composition of the drug Zoneran^® At a dosage of 100 mg, the dusts “Sunset Yellow” (E110) and “Red Charming” (E129), which can cause allergic reactions, are included.

Influence on the ability to drive and work with mechanisms. Special studies of the effect of the drug on the ability to drive and work with mechanisms were not conducted. Zoneran^® may cause (especially at the beginning of therapy or with an increase in dose) drowsiness and difficulty concentrating, and therefore, during the period of treatment, care must be taken when engaging in activities that require increased concentration and psychomotor reactions.

Symptoms: there were cases of deliberate and unintentional overdose of the drug Zonegran^® in adults and children. In some cases, overdose was asymptomatic, especially with immediate gastric lavage. In other cases, overdose was accompanied by the following symptoms: drowsiness, nausea, gastritis symptoms, nystagmus, myoclonus, coma, bradycardia, impaired renal function, hypotension and respiratory depression. A very high plasma concentration of zonisamide (100.1 μg / ml) was observed approximately 31 hours after an overdose of the drug Zonegran^® and clonazepam. A patient with an overdose of these drugs developed coma and respiratory depression. However, after 5 days he regained consciousness, and he did not have any complications.

Treatment: specific antidote for the treatment of overdose with the drug Zonegran^® does not exist. After a presumptive overdose, immediate gastric lavage is indicated against the background of conventional measures aimed at maintaining airway patency. Conduct supportive therapy, including regular monitoring of key indicators of the state of the body, and careful observation. Zonisamide has a long T_1/2In this connection, the symptoms of his overdose may be persistent. Studies of overdose treatment have not been conducted, however, it is known that hemodialysis reduces the concentration of zonisamide in the blood plasma of patients with renal insufficiency and can be considered as a treatment for overdose.