Starting daily dose for adults testosterone suspension results and children weighing more than 25 kg. It is usually 10-15 mg / kg, followed by doses gradually raised to 5-10mg. / kg. in Week. The maximum dose is 30 mg / kg / day (the dose may be increased under the control of the concentration in the blood plasma to 60mg / kg / day). Adults – initial dose of 300 mg 2 times a day with a gradual increase to 200 mg / day with a 3-day intervals until clinical effect (usually 1000-1600mg / day, sometimes up to 2600mg / day). Children with body weight less than 25 kg, the mean daily dose of 20-30mg / kg, the maximum daily dose of 50 mg / kg. Older patients the dose should be determined by clinical
drug Depakine enteric, can be administered twice a day.
- Individual intolerance of testosterone suspension results
- Acute hepatitis
- Chronic hepatitis
- Cases of severe hepatitis in a patient or his family, particularly those caused by medications.
- Disorders pancreatic functions
- Thrombocytopenia, bleeding diathesis
- Hepatic porphyria
- Children up to 3 years.
- Rare cases of hepatic dysfunction (see. “Warnings”)
- The teratogenic risk (see. “Pregnancy”)
- Neurological disorders: confusion, ataxia, tremors, drowsiness, lethargy, coma. Most often, these cases are described in the complex treatment (in particular with phenobarbital) or after a sharp increase in the dose of valproate.
We describe the very rare cases of dementia.
- Some patients in the early treatment often develop gastrointestinal symptoms (nausea, vomiting, diarrhea, anorexia, stomach) which typically tested independently without drug withdrawal for several days.
- There are quite frequent reports of temporary and / or dose-dependent side effects: hair loss, drowsiness.
- Hematologic side effects are described some cases lowering fibrinogen level or increase bleeding time, usually without associated clinical symptoms, and particularly at high doses (testosterone suspension results has an inhibitory effect on platelet aggregation second step) (see “Pregnancy”.).
- often – thrombocytopenia, rare cases of anemia, leukopenia, pancytopenia, or.
- Described rare cases of pancreatitis, sometimes leading to fatal.
- We describe the occurrence of vasculitis.
- Can meet frequently isolated and moderate hyperammonemia without change in liver function assays, it does not require discontinuation of therapy.
- There are also reports of increasing the weight of the patients, amenorrhoea and violating the regularity of the menstrual cycle.
- Described rare cases of hearing loss, both reversible and irreversible, but its causes and dependence on the drug have not been established.
- When using valproate may experience allergic skin reactions such as exanthematous rash, urticaria, angioedema. In extremely rare cases, described the occurrence of toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema poliformnoy.
There are some reports of a reversible Fanconi syndrome associated with valproate therapy.
Pregnancy and lactation
overall risk of malformations with valproate during the first trimester of pregnancy has not been higher than when taking other anti-epileptic drugs. There are cases of facial dysmorphia. There were rare cases of multiple malformations, especially the limbs. The frequency of these effects is still uncertain. Along with this, mainly testosterone suspension results causes a disturbance of the embryonic neural tube: myelomeningocele, spina bifida … The frequency of such complications 1-2%.
In light of these data:
If a woman planning a pregnancy should be reviewed evidence antiepileptic treatment; it is recommended to consider the introduction of additional folate.
The appointment of the drug during pregnancy is possible when the expected benefit to the mother outweighs risk to the fetus.
During pregnancy should not interrupt an effective antiepileptic treatment with valproate if it is effective. In such cases monotherapy.
The risk to the newborn
are described only rare cases of haemorrhagic syndrome in newborns whose mothers took during pregnancy, testosterone suspension results. This haemorrhagic syndrome is associated with hypofibrinogenemia;afibrinogenemia has also been described, which can be fatal. This gipofibrinogenemia may be associated with a decrease of coagulation factors. However, this syndrome should be distinguished from reduce vitamin K-dependent factors induced by phenobarbital and other inducers of microsomal enzymes.
Therefore, y should be examined infants coagulation, to evaluate the number of platelets in the plasma fibrinogen level, bleeding time and clotting time.
Excretion valproate milk low and ranges from 1 to 10% of that in maternal serum. Until now, were under the supervision of children are breastfed, who did not develop any marked adverse clinical symptoms.However, breast-feeding is not recommended.
Interaction with other drugs
Actions valproate on other drugs
- Antipsychotics, MAO inhibitors, antidepressants and benzodiazepines
- Depakine may potentiate the effects of other psychotropic drugs, such as antipsychotics, MAO inhibitors, antidepressants and benzodiazepines, therefore proposed clinical monitoring and, if necessary, dose adjustment.
- Depakinum increases phenobarbital concentration in blood plasma.
- Depakinum primidone concentration increases in blood plasma.
- Depakine increases the concentration of phenytoin in plasma. Moreover, increasing the amount of free Depakinum phenytoin forms with the possible appearance of signs of overdose (phenytoin volproevaya acid replaces its binding to plasma proteins and reduces its catabolism in the liver).
- valproate may potentiate toxic effects of carbamazepine.
- Valproate may slow the metabolism of lamotrigine and increase its half-life period
- Valproate may increase the concentration of AZT in the plasma, which leads to increased toxicity of the latter.
Effect of other drugs on valproate
Antiepileptic drugs having enzyme-inducing action (phenytoin, phenobarbital, carbamazepine) reducing the concentration of valproate in serum.
On the other hand, the combination of felbamate and valproate may increase serum concentrations of valproate. It is necessary to control the dose of valproate.
Mefloquine increases the metabolism of valproic acid and can cause seizures. Therefore, the combination therapy may occur epileptic seizures.
In the case of concurrent use of valproate and agents strongly binding to proteins (acetylsalicylic acid), the concentration of free valproate in serum may increase.
In the case of joint use with a vitamin K-dependent anticoagulant should be carried out strict control . prothrombin index
level in serum valproate can increase (as a result of reduced hepatic metabolism) in case of simultaneous use with cimetidine or erythromycin.
Panipenem / meropenem: decrease of valproic acid levels in the blood was observed with the drug combination with panipenemom or meropenem.
Valproate usually has no enzyme-inducing action; as a consequence, valproate does not reduce the effectiveness of drugs estroprogestagennyh for women using oral hormonal contraceptives.
Special warnings and precautions
When no correlation between the established daily dose of valproate in serum concentration and therapeutic effect, the optimal dose should be determined according to the clinical results. Determination of valproic acid concentration in blood plasma can be regarded as an additional criterion when only clinical criteria do not achieve adequate control or when side effects are manifested. Effective level Depakin according to the literature, is usually 40-100 mg / liter (300-700 mk.mol / liter).
Home treatment Depakine (ingestion)
- For patients who are not taking other antiepileptic drugs, the dose should be increased sequentially within 2-3 days, in order to achieve the optimal dose for about one week.
- For patients previously treated with anti-epileptics, replaceable Depakine, to achieve the optimal dose should be gradual, for about 2 weeks. This reduces the previous dose of the drug, and then it stops receiving.
- Administration of other anti-epileptic drugs, if necessary, should be gradual. (See. “Drug Interactions”)
Liver dysfunction :
- Terms of occurrence:
- Risk group consists of patients receiving anticonvulsant therapy complex, high-risk infants and children up to 3 years. At the age of 3 years, the frequency of such complications is significantly reduced and gradually decreases with age.
In most cases, the reaction expressed by the liver was observed during the first 6 months of treatment.
- Possible symptoms:
- Early diagnosis is based mainly on clinical examination.In particular, it should be taken into account the following symptoms which may precede jaundice, particularly for patients at-risk (see “condition occurs.”):
- nonspecific symptoms usually appear suddenly, such as fatigue, anorexia, extreme fatigue, drowsiness, sometimes accompanied by repeated vomiting and abdominal pain.
- recurrent seizures
It is recommended to inform the patient, and if it is a child, his family, that the development of clinical symptoms should be cause for immediate consultation, which, in addition to clinical studies, should include an immediate measurement of liver function.
- At the beginning and during the first 6 months of treatment, it is necessary to periodically check liver function. Among the classical tests are the most important tests which reflect protein-synthetic function of the liver, and especially prothrombin index. In the case of confirmation of an abnormally low prothrombin, especially accompanied by other changes in laboratory data (significant decrease in fibrinogen and coagulation factors, increased bilirubin and transaminases) Depakine treatment should be suspended. As a precautionary measure to interrupt treatment with salicylates, if they were included in the treatment regimen, because they use the same metabolic pathway.
- To carry out certain functions of the liver before starting treatment (see. “Contraindications”) and periodically during the first 6 months of treatment, especially in patients at risk (see. “Warnings”).
In the treatment of Depakine as other antiepileptic drugs, there may be isolated and temporary increase of liver enzymes in serum, especially at the beginning of treatment.
- Before therapy or surgery, in case of spontaneous bruising or bleeding, it is recommended to carry out a blood test (to determine blood count, including platelet count, bleeding time and coagulation tests) (see. “Side effects”).
- Patients with renal failure can be necessary to reduce the dose. The dosage should be adjusted according to clinical response (see. “Pharmacokinetic properties”)
- Although the treatment Depakine were marked only exceptionally rare disorders of the immune system, it is necessary to weigh the possible benefits of the appointment of the drug to patients suffering from systemic lupus erythematosus, as compared to the potential risk.
- In acute abdominal pain syndrome it is recommended prior to surgery to investigate the levels of pancreatic enzymes, as there are reports of rare cases of pancreatitis.
If there is a suspicion of deficiency of enzymes urea cycle, pre-treatment should be carried out metabolic tests, because of the risk of hyperammonemia in the treatment of valproate .
Effects on ability to drive vehicles and perform work requiring special attention
The patient should be made aware of the risk of drowsiness, especially in the case of multiple anticonvulsant therapy (see. “Interactions with other medications”)
Use caution when performing work that requires quickness of psychomotor reactions.
Clinical manifestations of acute massive overdoses are typically carried out in a coma, hypotension muscle hyporeflexia, miosis and respiratory depression.
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However, there may be a variety of symptoms, and at very high concentrations in the blood product described seizures. Also described cases of increased intracranial pressure due to brain swelling.
Emergency care in a hospital should include gastric lavage, which is effective within 10-12 hours after ingestion of tablets, activated charcoal method, the constant surveillance of the cardiovascular and respiratory systems.
There are several individual reports of successful use of naloxone.
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