Convulex Chrono caps. 300 mg. 100caps
For the treatment of generalized and partial epilepsy, especially in these types of seizures:
Convulex Chrono caps. 300 mg. 100caps
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet Convulex chrono 300 mg contains 300 mg sodium valproate.
Each tablet Convulex chrono 500 mg contains 500 mg sodium valproate.
Prolonged-release tablets: White, oval dividing line engraved with "GCC", respectively. "SS5" on one side.
For the treatment of generalized and partial epilepsy, especially in these types of seizures:
as for partial epilepsy:
simple or complex seizures
secondarily generalized seizures
specific syndromes (West, Lennox-Gastaut)
Treatment and prevention of mania in bipolar disorder.
Dosage and method of administration
Convulex chrono tablets are intended for oral administration.
Convulex chrono is c prolonged release sodium valproate, which decreases the peak concentration and ensures equal plasma concentrations throughout the day.
Convulex chrono can be taken once or twice daily. Convulex chrono tablets can be broken in half, but should not be crushed or chewed. The tablets should be taken with plenty of liquid during or after a meal.
The daily dosage is determined by age and weight. It is advisable to take into account individual sensitivity to valproic acid. No association was found between daily dose, serum concentrations, and therapeutic effect, and therefore the optimal dose should be determined primarily by clinical response.
Usual requirements are as follows:
Treatment starts with 500-600 mg per day and the dose gradually increased to three-day intervals, to achieve control over attacks. This is most often achieved with doses between 1000 mg and 2000 mg per day ie 20-30 mg / kg body weight. When no adequate control of seizures in this dose, the dose may be increased to 2500 mg daily.
Children over 20 kg:
The initial dose should be 250-300 mg / day (regardless of weight) diluted with increasing intervals to obtain control of seizures, most often occurs in 20-30 mg / kg body weight per day. When no adequate control of seizures "at this dose, then the dose may be increased to 35 mg / kg body weight per day.
Children under 20 kg:
The usual starting dose is approximately 10-15 mg / kg body weight per day, followed by an increase in diluted intervals until the control seizures.
Although pharmacokinetics. valproate changes with age, it is of limited clinical significance and dosage is determined by seizure control. With increasing age, the volume of distribution and therefore reduced binding to serum albumin, the proportion of free drug increases. This should be considered in the clinical interpretation of plasma valproic acid.
Patients with renal insufficiency
It may be necessary to reduce the dosage. The dose should be tailored to the clinical manifestations, while monitoring of plasma concentrations may be false-orientation (see 5.2. Pharmacokinetic properties).
When initiating treatment with Convulex chrono patients already receiving other anticonvulsants, these should be stopped slowly and increasing 'dose Convulex chrono should be gradual, with the goal target dose is reached in about two weeks . In some cases, it appears necessary to increase the daily dosage of 5 to 10 mg / kg / day when administered together with anticonvulsants that induce hepatic enzyme activity, such as: phenytoin, phenobarbital, and carbamazepine.
After discontinuation of enzyme inducers is possible to achieve seizure control with lower doses Convulex chrono. When co-administered with barbiturates and noticed some sedation (especially in children), the dose of barbiturate should be reduced.
NB. In children, the condition of which requires dosage to be higher than 40 mg / kg / day should be monitored clinically-chemical and hematological parameters.
The optimum dosage is determined mainly by achieving control over the attacks and regular measurement of plasma levels is not necessary. Measurement of plasma levels, however, it is necessary and can be very useful when you are making good clinical control or suspected occurrence of side effects (see 5.2. Pharmacokinetic properties).
Affective psychoses (only for adults):
Recommended initial dose of 500 - 1000 mg per day, divided into one or two doses. Highly agitated patients may be treated with doses up to 1500 mg / day. Titration can be done in 2-4 days, it should be accompanied by monitoring of plasma levels (therapeutic range 50 to 125 mg / 1), ~ while achieving the desired clinical effect or side effects occur. Prophylactic treatment is individual and is conducted with the lowest effective dose.
Hypersensitivity to sodium valproate. Active liver disease, family history of severe hepatic dysfunction (particularly related to medication), porphyria, concomitant use of mefloquine, acute and chronic hepatitis.
Special warnings and precautions for use
Liver: routine measurement of liver function should be performed prior to initiation of treatment and periodically during the first six months, particularly in those patients who fall into risk group or have a history of liver disease. Such patients should be subjected to frequent clinical examination (see 4.8. Undesirable effects).
Hematologic: before treatment and before surgery, the clinician should be provided by conducting blood tests (blood count elements, bleeding time, coagulation tests) in order to avoid complications related to bleeding (see 4.8 . Undesirable effects).
Pancreatitis: Very rare cases of severe pancreatitis, which can be fatal. The risk of fatalities is higher in infants and decreased with increasing age. Severe seizures and severe neurological complications with use of a combination anticonvulsant therapy may be risk factor for severe pancreatitis. The combination of liver damage with pancreatitis increases the risk of death. Patients should be advised to consult their physician immediately at the symptoms of the digestive tract or pancreatitis (eg, abdominal pain, nausea and vomiting). Medical examination (including measurement of serum amylase) should be performed in patients with suspected pancreatitis and Convulex chrono therapy should be discontinued if a diagnosis of pancreatitis is confirmed.
Obesity: valproate often causes an increase in body weight, which can be significant and progressive. All patients should be warned of this risk at the start of treatment and appropriate steps are taken to prevent obesity.
Pregnancy: It is recommended that treatment with Convulex chrono in women of childbearing age should be performed only in severe cases or those resistant to other therapy because of potential teratogenic risk to the fetus. Women of childbearing age should be informed of the potential risks and benefits of continuing antiepileptic treatment during pregnancy (see 4.6., Pregnancy).
Systemic lupus erythematosus: Special attention is required when this drug is used in patients who have symptoms suggestive of systemic lupus erythematosus and rarely symptoms of other immune disorder. (See 4. 8. Undesirable effects).
When suspected enzyme deficiency in the urea cycle, before starting treatment with valproate should be made relevant metabolic studies, the risk of hyperammonaemia associated with the use of valproate.
Valproate is eliminated primarily by the kidneys, partly in the form of ketone bodies, which can give false positive results when testing urine and should be considered for possible diagnosis of diabetes.
Interactions with other medicaments and other forms of interaction
Effects of valproate on other drugs:
Neuroleptics, MAO inhibitors, antidepressants and benzodiazepines, valproate may potentiate the effects of other psychotropic drugs such as neuroleptics, MAO inhibitors, antidepressants and benzodiazepines, clinical monitoring is recommended and the dose should be adjusted if necessary.
Valproate increases the serum concentrations of phenobarbital (due to inhibition of hepatic catabolism) and can be obtained sedation, more common in children. Clinical monitoring is recommended during the first 15 days of combined treatment with immediate reduction of the dose of phenobarbital, if sedation occurs and determination of phenobarbital plasma levels when necessary.
Valproate increases primidone plasma levels with exacerbation of its adverse effects (such as sedation), and these traits are "occur in long-term treatment. Clinical monitoring is recommended, especially at the beginning of combined therapy with dosage adjustment when necessary.
Valproate decrease in total plasma concentrations of phenytoin. More often valproate increases phenytoin free form with possible overdosage symptoms (valproic acid displaces phenytoin from its prehensile sites on plasma proteins and reduces its hepatic metabolism). Clinical monitoring, when determining the plasma levels of phenytoin should be defined and free forms.
Reported clinical manifestations of toxicity with both valproate and carbamazepine as valproate may potentiate toxic effects of carbamazepine. Clinical monitoring is recommended especially at the beginning of combined therapy with dosage adjustment when necessary.
Valproate may reduce lamotrigine metabolism and increase its average life, therefore the dose should be adjusted (reduced dose of lamotrigine). Concomitant use can increase the risk of rash.
Valproate may increase the plasma concentrations of zidovudine, leading to increased toxicity of zidovudine.
Vitamin K - dependent anticoagulant
Anticoagulant effect of warfarin and other coumarin anticoagulants may be increased due to replacement by prehensile sites on plasma proteins valproic acid. Often you have to monitor the prothrombin time.
Co-administration of temozolomide and valproate may cause a slight decrease in the clearance of temozolomide, which has no significant clinical value.
Accelerates metabolism of valproic acid and a convulsive effect, and in case of combination therapy may experience seizures.
Effects of other drugs on valproate.
AEDs with enzyme inducing effect (phenytoin, phenobarbital, carbamazepine) decrease plasma concentrations of valproic acid. The dosage should be adjusted according to plasma levels in cases of combination therapy.
On the other hand, the combination of felbamate and valproate may increase plasma levels of valproic acid. The dosage of valproate should be monitored.
Mefloquine and chloroquine may reduce paroxysmal threshold. Mefloquine in addition can lower the level of valproate. Dose Convulex chrono should 'be adjusted accordingly.
In the case of concurrent use of valproate in substances with high afenitet binding to plasma proteins (eg, aspirin), plasma levels of free valproic acid may increase.
Plasma levels of valproic acid may increase (as a result of reduced hepatic metabolism) when co-administered with cimetidine or erythromycin.
Carbapenem antibiotics may reduce the plasma of valproic acid to sub-therapeutic levels. If you need to enforce such antibiotics is recommended frequent monitoring of plasma levels of valproic acid.
Cholestiramine may reduce the absorption of valproate.
Caution should be exercised with concomitant Convulex chrono with the newer AEDs, whose pharmacodynamics may not be fully established.
Convulex chrono does not induce significant liver enzymes, so the efficacy of oral contraceptives should not be affected.
Pregnancy and lactation
Increased incidence of congenital malformations (including facial dizmorfiya, neural tube defects and multiple defects, especially in the extremities) is observed in children born to mothers with epilepsy both untreated and treated, including treatment with sodium valproate.
The incidence of neural tube defects in the fetus of women receiving valproate during the first trimester of pregnancy is approximately 1-2%. It has been shown that the addition of folic acid reduces the incidence of neural tube defects in infants of women at high risk. There is no direct evidence for the occurrence of such effects in women receiving antiepileptic drugs, so there is no reason not to recommend adoption of folic acid such women. The accumulated evidence and experience necessary assumption that anticonvulsant monotherapy is preferred. Dosage should be revised before pregnancy and to use the lowest effective dose in divided doses throughout the day, as it tends pregnancies with an adverse outcome to be associated with: higher total daily doses. Women of childbearing age should be informed about the risks and benefits of continuing antiepileptic therapy during pregnancy. Pregnant women should be carefully monitored by ultrasound measurement of alpha-fetoprotein and other appropriate techniques. (See 4. 4. Special warnings and precautions for use).
There are rare reports of incidence of hemorrhagic syndrome in newborns whose mothers took sodium valproate during pregnancy. This haemorrhagic syndrome is caused by hipofibrinemiya. Also been reported afibrinemiya, which can be fatal. Hipofibrinemiyata is probably related to the reduction of coagulation factors. It should be noted that hemorrhagic syndrome may be caused by phenobarbital and other enzyme inducers. In newborns should be screened platelets, plasma levels of fibrinogen and coagulation.
The concentration of valproic acid secreted in breast milk is very low - between 1% and 10% of the total maternal plasma. Therefore this should not be a contraindication to breastfeeding by the patient taking valproate. The decision on whether to continue breastfeeding patient taking valproate should be taken after discuss all known observations.
Effects on ability to drive and use machines.
None known. Application of Convulex chrono can establish full control over the attacks, so the patient to hold a driver's license.
Patients should be cautioned about the risk of transient drowsiness, especially in cases of anticonvulsant polytherapy or combination with benzodiazepines.
By the liver: disorders in the function of the liver, liver failure, including fatal, may occur in patients whose treatment included valproic acid or sodium valproate. Patients at greatest risk are children - mostly under the age of three years and those with congenital metabolic or degenerative disorders, organic brain disease or severe seizures associated with mental retardation. Such incidents can happen especially during the first six months of treatment, the period of greatest risk is between the second and twelfth week and usually affects patients on anticonvulsant polytherapy. In this group of patients, monotherapy is preferred.
Clinical symptoms are more indicative signs than laboratory abnormalities in the early stages of liver failure. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms, usually with sudden onset, such as loss of treatment effect on seizures, malaise, weakness, lethargy, edema, anorexia, vomiting, abdominal pain, lethargy, jaundice. These signs are a signal for immediate cessation of treatment.