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Components:
Valproic Acid
Method of action:
Anticonvulsant, Antiepileptic, Muscle Relaxant
Medically reviewed by Fedorchenko Olga Valeryevna, Pharmacy-Provisor. Last updated on 2020.01.25

Pharmacodynamic properties

The information provided in Pharmacodynamic properties of Depakine Chrono is based on data of another medicine with exactly the same composition as the Depakine Chrono of the medicine (Valproic Acid). Be careful and be sure to specify the information on the section Pharmacodynamic properties in the instructions to the drug Depakine Chrono directly from the package or from the pharmacist at the pharmacy.
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Pharmacotherapeutic Group: Fatty acid derivatives

ATC code: N03AG01

The mode of action of valproic acid is not fully understood but may involve an elevation of gamma-amino butyric acid levels in the brain.

In certain in-vitro studies, it was reported that sodium valproate could stimulate HIV replication, but studies on peripheral blood mononuclear cells from HIV-infected subjects show that sodium valproate does not have a mitogen-like effect on inducing HIV replication. Indeed, the effect of sodium valproate on HIV replication ex-vivo is highly variable, modest in quantity, appears to be unrelated to the dose and has not been documented in man.

The increased expression of drug efflux transporters at the blood-brain barrier can results in lower concentrations of their respective substrate, i. e. the active substance, in the brain compared to its free concentration in plasma, and thereby reduce the concentration of antiepileptics at the site of action. This can lead to pharmacoresistance and thus to the development of a treatment-resistant status epilepticus or treatment-resistant epilepsy. However, in vitro data suggest that sodium valproate is not a substrate for transporters such as ATP-binding cassette (ABC) transporters (e. g. P-glycoprotein (Pgp)) or multidrug resistance-associated proteins (MRP1, MRP2 and MRP5). The development of pharmacoresistance against valproate by these transporters is therefore considered unlikely.

Pharmacokinetic properties

The information provided in Pharmacokinetic properties of Depakine Chrono is based on data of another medicine with exactly the same composition as the Depakine Chrono of the medicine (Valproic Acid). Be careful and be sure to specify the information on the section Pharmacokinetic properties in the instructions to the drug Depakine Chrono directly from the package or from the pharmacist at the pharmacy.
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With peroral administration 90-100 % of the dose is rapidly absorbed.

Maximal plasma concentration is achieved with Depakine Chrono® within 6.5 ± 3.3 hours. The half-life is 12-16 h in most patients but can in exceptional cases be considerably lower. Impaired renal function prolongs the half-life. In infants under 2 months the half-life can be prolonged up to 60 hours but in older children it is the same as in adults.

Steady-state concentration is normally achieved after treatment in 3-5 days. A satisfactory effect is most often achieved at 50-100 µg/mL, but the patient's overall situation must be considered.

The relation between the dose and effect, and between plasma concentrations and effect, has not been fully clarified.

The cerebrospinal fluid concentration is up to 10 % of the plasma concentration. About 90 % of sodium valproate is bound to plasma protein (mainly to albumin), which may entail a risk of clinically significant interactions with other antiepileptics, primarily phenytoin. Protein binding decreases at higher dosages. Plasma protein binding is lower in elderly patients and in patients with kidney or liver dysfunction. In one study, elevated levels of the free drug (8.5 % up to more than 20 %) were observed in patients with significantly reduced renal function.

However, if hypoproteinaemia is present, the total concentration of valproic acid (free and protein-bound substance) can be essentially unchanged, although it may also be reduced due to the increased metabolism of the free portion.

Sodium valproate is metabolised to a great extent and is excreted in the urine as conjugated metabolites. Sodium valproate crosses the placental barrier and concentrations of foetal plasma are comparable to those in the mother.

Valproic acid passes into breast milk but is not likely to influence the child when therapeutic doses are used.

Pharmacotherapeutic group

The information provided in Pharmacotherapeutic group of Depakine Chrono is based on data of another medicine with exactly the same composition as the Depakine Chrono of the medicine (Valproic Acid). Be careful and be sure to specify the information on the section Pharmacotherapeutic group in the instructions to the drug Depakine Chrono directly from the package or from the pharmacist at the pharmacy.
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Fatty acid derivatives

Preclinical safety data

The information provided in Preclinical safety data of Depakine Chrono is based on data of another medicine with exactly the same composition as the Depakine Chrono of the medicine (Valproic Acid). Be careful and be sure to specify the information on the section Preclinical safety data in the instructions to the drug Depakine Chrono directly from the package or from the pharmacist at the pharmacy.
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Testicular atrophy, degeneration of the vas deferens and inadequate spermatogenesis as well as changes to the lungs and prostate gland have been observed in chronic toxicity studies with high oral dosages (250 mg/kg in rats and 90 mg/kg in the dog).

Mutagenicity tests in bacteria, rats and mice yielded no evidence of mutagenic potential.

Long-term studies have been conducted in rats and mice. At very high doses, the rate of subcutaneous fibrosarcomas was increased in male rats. Animal studies have shown valproic acid to be teratogenic.

Incompatibilities

The information provided in Incompatibilities of Depakine Chrono is based on data of another medicine with exactly the same composition as the Depakine Chrono of the medicine (Valproic Acid). Be careful and be sure to specify the information on the section Incompatibilities in the instructions to the drug Depakine Chrono directly from the package or from the pharmacist at the pharmacy.
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None known

Special precautions for disposal and other handling

The information provided in Special precautions for disposal and other handling of Depakine Chrono is based on data of another medicine with exactly the same composition as the Depakine Chrono of the medicine (Valproic Acid). Be careful and be sure to specify the information on the section Special precautions for disposal and other handling in the instructions to the drug Depakine Chrono directly from the package or from the pharmacist at the pharmacy.
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