This document discusses sodium valproate and valproic acid, which are used to treat epilepsy, bipolar disorder, and migraine headaches. Sodium valproate is converted to valproic acid in the body. Valproic acid increases GABA levels in the brain through inhibiting GABA-degrading enzymes. It may also affect potassium channels. Common side effects include weight gain, tremors, and liver injury. Therapeutic drug monitoring is important due to its narrow therapeutic window. It is generally dosed at 10-15 mg/kg/day for epilepsy, 250 mg twice daily for migraines, and up to 750 mg/day for bipolar mania.

3. • Each film-coated controlled release tablet
contains: Sodium Valproate 333 mg and
Valproic Acid 145 mg (equivalent to Sodium
Valproate 500 mg).

4. Valpoic Acid Sodium Valproate

6. • Valproate Sodium is the sodium salt form of valproic
acid with anti-epileptic activity. Valproate sodium is
converted into its active form, valproate ion, in blood.
Although the mechanism of action remains to be
elucidated, valproate sodium increases concentrations
of gamma-aminobutyric acid (GABA) in the brain,
probably due to inhibition of the enzymes responsible
for the catabolism of GABA. This potentiates the
synaptic actions of GABA. Valproate sodium may also
affect potassium channels, thereby creating a direct
membrane-stabilizing effect.

7. • Valproate or valproic acid is a branched chain
organic acid that is used as therapy of
epilepsy, bipolar disorders and migraine
headaches and is a well known cause of
several distinctive forms of acute and chronic
liver injury

8. • Because VPA has a narrow therapeutic window,
therapeutic drug monitoring (TDM) of VPA is a
crucial part of drug therapy. The recommended
VPA therapeutic range for the treatment of
epilepsy is 50–100 mg l−1. A slightly higher range
of 50–125 mg l−1 is proposed for bipolar disorder
therapy 4, 14, 15. VPA levels greater than the
recommended range may result in
gastrointestinal side effects including nausea,
vomiting and diarrhoea 4. Tremor and
thrombocytopenia can occur at higher
concentrations.

9. • Prospective studies suggest that 5% to 10% of
persons develop ALT elevations during long
term valproate therapy, but these
abnormalities are usually asymptomatic and
can resolve even with continuation of drug.

10. • Valproic acid (VPA) is an organic weak acid
• VPA looses proton H+ and form
• The conjugate base is valproate
• The sodium salt of the acid is sodium
valproate

11. • Valproic acid (VA) is hygroscopic
• Sustained-release formulation of the combination
between VA and VAS reduces the fluctuation in
plasma drug concentrations, thus minimizing or
preventing plasma peak-related adverse events,
and allows prolongation of the dosing interval
enabling a once or twice daily administration
with inherent benefits in terms of patient
compliance

12. • Common side effects of Sodium Valproate +
Valproic Acid
• Weight gain, Sleepiness, Tremors, Liver injury,
Dizziness, Paresthesia (tingling or pricking
sensation), Hypersensitivity, Anemia (low
number of red blood cells), Deafness, Urinary
incontinence, Decreased sodium level in
blood, Pain during periods

13. • Sodium Valproate
• Discovered in 1881
• For 80 years valporic acid is used as solvent
• After 80 years, in 1960- marketed as
anitepileptic
• First clinical trial in 1964( sodium valproate
and valporic acid)
• It was launched in france in 1967 as DEPAKINE
• Britain-1973
• USFDA approval-1978

14. • In the United States, AbbVie Inc. (formerly Abbott
Laboratories) manufactures Depakote, Depakine,
and Depacon. In Europe, however, the drug is
called Depakine and is manufactured by Sanofi.
• Depakote is used to treat seizures and bipolar
disorder. When used by pregnant women, it has
the potential to harm their unborn children by
causing still births, slowed neurological
development, and congenital birth defects.

15. Why sodium valproate and valporic
acid
• sodium valproate has a short biological half-
life, and it is necessary to administer it three
times a day in order to maintain an effective
blood concentration. However, since such
frequent administration is troublesome for
patients, efforts have been made to develop
sustained-release sodium valproate
preparations, and several preparations have
already been marketed. .

16. • However, sodium valproate has a relatively
large daily dose of 1200 mg, and is relatively
water-soluble and has a high hygroscopic
property. This is not always satisfactory
because the amount added is large and the
weight per tablet is large.

17. MOA
• There is no single mechanism of action that can
explain valproate’s broad effects on neuronal
tissue. Its pharmacological effects include:
• increased gamma-aminobutyric acid transmission
• (GABA Trasaminase inhibitor, stimulates GABA
secretion)
• reduced release of excitatory amino acids
• blockade of voltage-gated sodium channels
• modulation of dopaminergic and serotonergic
transmission

18. • GABA

19. Indications
• VPA is a widely used AED since it possesses efficacy in
the treatment of various seizure types such as
absences, myoclonic, and generalized tonic-clonic
seizures (13,15,53). The drug has shown efficacy in the
treatment of partial seizures with or without secondary
generalization (85,104). VPA is also effective in the
acute treatment of status epilepticus (103).
Consequently, VPA is a drug with a broad antiepileptic
spectrum. In addition, VPA is extensively used in the
treatment of bipolar disorders (17) and in other
neurological conditions such as migraine and
neuropathic pain

20. • All types of epilepsy
• Bipolar disorder
• Neuropathic pain
• Migraine prophylaxis

21. • The most commonly reported adverse effects of valproate include
gastrointestinal disturbances, tremor and bodyweight gain. Other
notable adverse effects include encephalopathy symptoms (at
times associated with hyperammonaemia), platelet disorders,
pancreatitis, liver toxicity (with an overall incidence of 1 in 20,000,
but a frequency as high as 1 in 600 or 1 in 800 in high-risk groups
such as infants below 2 years of age receiving anticonvulsant
polytherapy) and teratogenicity, including a 1 to 3% risk of neural
tube defects. Some studies have also suggested that menstrual
disorders and certain clinical, ultrasound or endocrine
manifestations of reproductive system disorders, including
polycystic ovary syndrome, may be more common in women
treated with valproate than in those treated with other AEDs.

22. CI
• Pregnancy
• Lactating mothers
• Hepatic renal

23. • Acute mania or hypomania
• Step 1: Antipsychotic or valproate or lithium
• Step 2: add benzodiazepine
• Valproate stabilize patient in 5-7 days
• Prophylaxis bipolar
• First line : lithium
• Second line: valproate , antipsychotic

24. • lderly[edit]
• Valproate in elderly people with dementia
caused increased sleepiness. More people
stopped the medication for this reason.
Additional side effects of weight loss and
decreased food intake were also associated
with one-half of people who become sleepy

26. • VPA has been shown to reduce the number of
migraine attacks, as well as their duration and
intensity in 50 to 70% of patients for periods
of three months, up to one year or longer
(43,84,93,110,111). In the treatment of
migraine VPA was used at doses of 200 to
1500 mg a day (84

27. • VPA can cause direct bone marrow
suppression leading to aplastic anemia
• Hepatotoxicity: Regarding possible
hepatotoxicity of VPA, transient elevations of
hepatic enzymes without clinical symptoms
are seen in 15 to 30% of patients

28. • Polycystic ovary syndrome Polycystic ovary
syndrome is regarded as a controversial issue
in women with epilepsy. The syndrome is
characterized by endocrine dysfunction such
as irregular menstruation or amenorrhoea,
hirsutism and infertility, but its pathogenesis
and clinical symptoms are heterogeneous, and
the syndrome is also related to obesity,
regardless of drug treatment

29. • polycystic ovary syndrome appear to be more
common with VPA as compared to other AEDs

30. Epilepsy
• 10-15 mg /kg/day BID starting dose
• Upto 600 mg/kg/day

31. Migraine
• 250 mg PO q12hr; adjust dose based on
clinical response, not to exceed 1000 mg/day

32. Bipolar Mania
• 750 mg/day PO in divided doses; adjust dose
as rapidly as possible to desired therapeutic
effect; not to exceed 60 mg/kg/day