Before and during therapy with Konvulsofin®, especially during the first 6 months of treatment, particularly at-risk patients, it is recommended thorough clinical and laboratory investigation, including the liver, pancreas, blood coagulation, metabolic rate (the study hemogram, including the determination of the number of platelets, the concentration of bilirubin,activity of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, lipase, alpha-amylase activity in blood plasma glucose, total protein concentration in blood plasma indicator SWIR, partial thromboplastin time, fibrinogen, Factor VIII, other coagulation factors).
During the first 6 months of treatment, the patient, people close to the patient and the attending physician should regularly contact in order to prevent the development of unwanted effects.
It is necessary to warn people close to the patient about the possibility of liver function abnormalities and involve them in monitoring the patient's condition.
Increased risk of developing severe hepatitis, including fatalities, infants and children up to 3 years with severe epilepsy, especially epilepsy, linked with brain damage, mental retardation and / or congenital metabolic or degenerative diseases. At the age of more than 3 years the frequency of such complications decreases significantly and gradually decreases.
In most cases, liver function abnormalities were observed during the first 6 months of treatment, usually between 2 and 12 weeks, and most often at CPET.
Of particular importance for the early detection of liver disease are, first, the clinical manifestation of nonspecific symptoms (severe asthenia, intolerance to conventional food, intolerance to valproic acid, anorexia, fatigue, drowsiness, vomiting and abdominal pain, hemorrhages, epistaxis, edema of the eyelids and lower extremities that occur even before the change in laboratory parameters), secondly, relapse or increased frequency and / or change in the severity of epileptic seizures against the background of antiepileptic therapy. It is recommended to inform the patient, if it is a child, then his parents, that if such symptoms appear, you should immediately consult a doctor.
When detecting an abnormally low prothrombin content, a significant decrease in fibrinogen and clotting factors, an increase in bilirubin concentration and activity of "hepatic" aminotransferases, treatment with valproic acid should be immediately stopped.
It should be remembered that treatment with Convulsofin ®, like other PEPs, may be accompanied by a small transient increase in the activity of "hepatic" aminotransferases, especially at the beginning of treatment, in the absence of any clinical symptoms.In this case it is recommended to conduct a complete laboratory examination, including the determination of a prothrombin index, and to adjust the dose of the drug.
In the event that a patient with liver damage takes salicylates, stop taking them; the metabolism of salicylates goes along the same path as the metabolism of valproic acid.
Children are at increased risk of developing pancreatitis with valproic acid. With age, the risk of developing pancreatitis is reduced. Pancreatitis in combination with liver failure increases the risk of death.
If severe abdominal pain, nausea, vomiting and / or anorexia occur, the patient should be examined immediately. In case of confirmation of the diagnosis of pancreatitis, in particular when the activity of pancreatic enzymes in the blood plasma increases, the use of Convulsofin® should be stopped and appropriate treatment initiated.
When used in women of reproductive age, before using the drug Convulsofin®, make sure that the patient is not pregnant, and recommend an effective method of contraception for her.
In children, valproic acid dosage forms should be used, allowing dosing of the drug.
In the treatment of patients with renal insufficiency and hypoproteinemia, the concentration of valproic acid in the blood plasma increases. Correction of the dose of Convulsofin® is necessary.
When taking PEP for various indications, there were reports of cases of suicidal thoughts and suicidal behavior. A meta-analysis of randomized placebo-controlled studies of PEP also revealed a moderately increased risk of suicidal ideation and suicidal behavior. The mechanism of development of this effect is not known and the available data do not allow to exclude the risk of its occurrence with the use of the preparation Convulsofin®.
Patients should be checked for signs of suicidal thoughts or suicidal behavior. If necessary, appropriate treatment is provided. Patients and people caring for patients should be warned about the need to seek medical help when there are signs of suicidal thoughts or suicidal behavior.
Drugs containing valproic acid, in rare cases, can cause a reaction of the body's immune system. Nevertheless, in patients with systemic lupus erythematosus, the use of Convulsofin ® is only possible if the expected use benefit exceeds the possible risk.
The use of Convulsofin® in patients with deficient enzymes of the ornithine urea cycle is not recommended. There have been reports of cases of encephalopathy developing against a background of hyperammonemia with a lethal outcome. In case of symptoms of apathy, drowsiness, vomiting, arterial hypotension and an increase in the number of antiepileptic seizures, the concentration of ammonium and valproic acid in the blood plasma should be determined and, if necessary, the dose of the drug should be reduced. If there is a suspicion of an already existing enzymatic breakdown in the urea cycle, the concentration of ammonia in the blood serum should be determined before using Convulsofin®.
It should be borne in mind that the initiation of treatment with Convulsofin® may be accompanied by transient symptoms of nausea, vomiting, anorexia, which disappear when the dose is reduced.Before the surgical intervention, it is necessary to conduct a study of the blood coagulation system.
If there is a symptomatology of the "acute" abdomen before the beginning of surgical intervention, it is recommended to determine the activity of amylase in the blood to exclude acute pancreatitis.
Patients with oppression of bone marrow function should be under the supervision of a doctor.
Before taking the drug Convulsofin®, it is necessary to warn the patient about a possible increase or decrease in body weight during treatment and the need to monitor this indicator, including diet.
Despite the fact that there is no reliable data on the occurrence of a relapse of epileptic seizures after the sudden withdrawal of Convulsofin®, cancellation should be done gradually and only under the supervision of a doctor.
Patients who receive other antiepileptic drugs should be transferred to receive Convulsofin ® gradually, reaching a clinically effective dose within 2 weeks. After this, a gradual cancellation of other antiepileptic drugs is carried out.
In patients who do not receive other antiepileptic drugs, a clinically effective dose should be achieved within 1 week.
At simultaneous application of preparations-antagonists of vitamin A recommend to supervise changes of parameter Kvika. It is necessary to warn patients that they do not use acidic drinks and refrigerated foods at the same time with the use of the drug Convulsofin®.
Do not drink beverages that contain ethanol.
During treatment of patients with diabetes should be aware of the possible distortion of the results of urine tests (ketone bodies in the urine).
Dyspeptic disorders develop less frequently when taking antispasmodics and enveloping agents.