Antiepileptic Drugs and their side effects

S.No. Molecules ADR

1 Phenobarbitone Cognitive impairment, Drowsiness,

2 Phenytoin
3 Carbamazepine
4 Valproic Acid
birth defects, addictive
Narrow Therapeutic Index, Cardiac
S/E
worsen absence and
Myoclonic seizures
PCOS

5. Leveteracetam Irritability, Anxiety , Depression

09/08/2023 3
• Each film-coated controlled release tablet
contains: Sodium Valproate 333 mg and
Valproic Acid 145 mg (equivalent to Sodium
Valproate 500 mg).
Valpoic Acid Sodium Valproate
 Valproic acid (VPA) isban organic weak acid

VPA looses proton H+ and form

The conjugate base is valproate

The sodium salt of the acid is sodium valproate

Separated(Burton) from juice of Valeriana-1882
80
• For 80 years valporic acid is used as solvent

• After 80 years
First clinical trial in 1964( sodium valproate and
valporic acid)
It was launched in france in 1967 as DEPAKINE
Britain-1973
USFDA approval-1978
• In the United States, AbbVie Inc. (formerly Abbott
Laboratories) manufactures Depakine, and
Depacon.

•  In Europe, however, the drug is called Depakine

and is manufactured by Sanofi.
 Indications
 All types of epilepsy

 VPA is extensively used in the treatment of bipolar

disorders

 Other neurological conditions such as migraine and

neuropathic pain
10-15 mg /kg/day
BID starting dose

Upto 600
mg/kg/day
 250 mg PO q12hr;

adjust dose based

on clinical response,

not to exceed 1000

mg/day
• 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
750 mg/day PO in divided doses; adjust dose as rapidly as possible to desired therapeutic
effect; not to exceed 60 mg/kg/day
Acute mania or hypomania
• Step 1: Antipsychotic or valproate or lithium
• Step 2: add benzodiazepine

Prophylaxis bipolar
• First line : lithium
• Second line: valproate , antipsychotic
MOA
 GABA
Barbiturates
Benzodiazepines
Gabapentin
Levetiracetam
Tiagabine
Topiramate
Valproate
Vigabatrin

Na+ Ca2+
Carbamazepine
Ethosuximide
Lamotrigine
Levetiracetam
Oxcarbazepine
Pregabalin
Phenytoin
Valproate
Topiramate
Valproate
 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)
 blockade of voltage-gated sodium channels
 modulation of dopaminergic and serotonergic transmission
 modulation of dopaminergic and serotonergic transmission
 S/E
• 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
 S/E
• 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
 C/I

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.
 C/I
• Pregnancy
• Lactating mothers
• Hepatic Disease
 Elderly
• 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
Polycystic ovary syndrome (PCOS) is a condition in
which the ovaries produce an abnormal amount of
androgens, male sex hormones that are usually
present in women in small amounts.
 PCOS
• PCOS 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
• polycystic ovary syndrome appear to be
more common with VPA as compared to
other AEDs
 Target Customer
Psychiatrist

Neurologist

Who are prescribing Sodium Valprate

 Strategy

• Identification of customer

• List preparation

• Launching

• Conversion from other brand to Valrot

 Weakness/ Strength
• Brand Name

• Strong compititors

• Leveteracetam / Mind set

 strength
• Bioequivalence study

• Strong recognition from psychiatrit / Strong bonding

 High Volume Product after long time
• IN

• SOLAR
•Thank you