Valproic Acid

Mechanism of Action:
Increased -aminobutyricacid (GABA)-ergic transmission, reduced release and/or effects of excitatory amino acids, blockade of voltage-
gated sodium channels and modulation of dopaminergic and serotoninergic transmission.
Pharmacokinetics
Well absorbed after an oral dose, bioavailability is greater than 80%
Peak blood levels observed within 2hours. If enteric-coated, 3-4 hours.
Valproic acid is 90% bound to plasma proteins.
Vast majority of valproate (95%) undergoes hepatic metabolism, with less than 5% excreted unchanged in the urine
Clearance is low, and dose-dependent; half-life varie from 9-18 hours.
Approximately 20% of the drug is excreted as a direct conjugate of valproate.
Therapeutic level
Therapeutic levels of valproate range from 50 to 100 mcg/mL (Katzung); 30-100 (Goodman and Gilman). However, there is a poor correlation
between the plasma concentration and efficacy.
Dosage and administration
In adults, the starting dosage is usually 250mg twice daily, which is then increased at intervals of 2- days according to clinical response. The usual
effective dosage is 500-2500 mg/day in two or three divided doses with conventional formulation or two divided daily doses with sustained
release formulations. Enteric coating ensures an improved gastric tolerability, whereas use of sustained-release formulations reduces the
fluctuation in plasma drug concentrations and allows a prolongation of the dosing interval, with inherent benefits in terms of compliance.
Therapeutic Use
Valproate is a broad-spectrum anti-seizure drug effective in the treatment of absence, myoclonic, partial, and tonic-clonic seizures. The initial
daily dose usually is 15 mg/kg, increased at weekly intervals by 5-10 mg/kg per day to a maximum daily dose of 60 mg/kg. Divided doses should
be given when the total daily dose exceeds 250 mg.

Side-Effects

GASTROINTESTINAL: nausea, vomiting, weight gain, increased appetite, indigestion, pancreatitis
HEPATIC: hepatotoxicity, hyperamylasemia, hyperammonemia
NERVOUS: hand tremors, headache, depression, ataxia, suicidal thoughts, slowed thinking
HEMATOLOGIC: reversible thrombocytopenia, bone marrow suppression
DERMATOLOGIC: hair loss, stomatitis, cutaneous leukoclastic vasculitis, psoriasiform eruption, Stevens-Johnson syndrome, toxic
epidermal necrolysis
CARDIOVASCULAR: peripheral edema
RENAL: Fanconis syndrome
ENDOCRINE: polycystic ovaries, elevated serum testosterone concentrations, menstrual disturbances, hyperandrogenism.
RESPIRATORY: eosinophilic pleural effusion
MUSCULOSKELETAL: decreased bone mass, increased bone turnover
GENERAL: hypothermia


Brand Indication Dosage Form Cost/ Packing
Depacon
(Valproic Acid)
Monotherapy &
adjunctive therapy in
the treatment of
patients w/ complex
partial seizures that
occur in isolation or
in association w/
other types of
seizures. Sole &
adjunctive therapy in
the treatment of
patients w/ simple &
complex absence
seizures &
adjunctively in
patients w/ multiple
seizure types that
include absence
seizures.
Complex partial
seizure Adult & childn 10
yr
Initially 10-15 mg/kg/day,
increased by 5-10
mg/kg/wk.

Simple/Complex absence
seizure Initially 15
mg/kg/day, increasing at 1-
wk interval by 5-10
mg/kg/day. Max: 60
mg/kg/day.
Depacon should be
administered
intravenously as a
60 minute infusion
(but not more than
20 mg/min) with the
same frequency as
the oral products, as
noted above. It
should be diluted
with at least 50 mL
of a compatible
diluent. Any unused
portion of the vial
contents should be
discarded.
Depacon inj
500 mg/5 mL
5 mL x 10 1's
(P23628.23/box)

Php 1, 724,860.79
Depakene Monotherapy & Complex partial seizure PO (Depakene,
Stavzor): 15
Depakene syr 120 mL x 1's
(Valproic Acid) adjunctive therapy in
the treatment of
patients w/ complex
partial seizures. Sole
& adjunctive therapy
in the treatment of
patients w/ simple &
complex absence
seizures &
adjunctively in
patients w/ multiple
seizure types that
include absence
seizures.
Adult & childn 10 yr
Initially 10-15 mg/kg daily.
Dosage should be
increased by 5-10
mg/kg/wk. Max: 60 mg/kg
daily.
Simple/complex absence
seizure
Initially 15 mg/kg/day,
increasing at 1-wk intervals
by 5-10
mg/kg/day. Elderly Should
be determined by seizure
control. Monitor patients
when receiving daily doses
>50 mg/kg.
mg/kg/day PO
initially, divided q6-
12hr; increase by 5-
10 mg/kg/day at
weekly intervals; may
increase dose up to
60 mg/kg/day
250 mg/5 mL (P567.25/bottle)
Depakote 125 mg
Sprinkle Capsule
Divalproex Na
Monotherapy &
adjunctive therapy in
the treatment of
patients w/ complex
partial seizures that
occur in isolation or
in association w/
other types of
seizures. Sole &
adjunctive therapy in
the treatment of
patients w/ simple &
complex absence
seizures & adjunctive
therapy in patients
w/ multiple seizure
types that include
absence seizures.
Complex partial
seizure Adult & childn 10
yr Initially 10-15
mg/kg/day, increased by 5-
10
mg/kg/wk.Simple/complex
absence seizure Childn 10
yr Initially 15 mg/kg/day,
increasing at 1-wk interval
by 5-10 mg/kg/wk. Max: 60
mg/kg/day.
Depakote Sprinkle
Capsules may be
swallowed whole or
the contents may be
sprinkled on soft food.
10-15 mg/kg/day PO
initially; may increase
by 5-10 mg/kg/week
to achieve optimal
clinical response; not
to exceed 60
mg/kg/day
Depakote: If daily
dose >250 mg, give
as divided dose

Depakote 125
mg Sprinkle
Capsule cap
125 mg
100's (P1518.09/pack)
Depakote ER
Divalproex Na
Treatment of acute
manic or mixed
episodes associated
w/ bipolar disorder.
Monotheraphy &
adjunctive in the
treatment of simple
& complex partial
seizures in adults &
childn 10 yr.
Prophylaxis of
migraine headaches
in adults.
Complex partial
seizure Adult & childn 10
yr Initially 10-15
mg/kg/day, increased by 5-
10
mg/kg/wk.Simple/complex
absence seizure Adult &
childn 10 yr Initially 15
mg/kg/day, increasing at 1-
wk interval by 5-10
mg/kg/wk. Max: 60
mg/kg/day
Depakote ER is
intended for once-a-
day oral
administration.
10-15 mg/kg/day PO
initially; may increase
by 5-10 mg/kg/week
to achieve optimal
clinical response; not
to exceed 60
mg/kg/day
Depakote: If daily
dose >250 mg, give
as divided dose

Depakote ER
XR tab 250 mg

Depakote ER
XR tab 500 mg
100's
(P3050.00/bottle)


100's
(P5425.00/bottle)
Epival
(Divalproex Na)
Monotheraphy &
adjunctive therapy in
the treatment of
complex partial
seizures; simple &
complex absence
seizures & adjunctive
w/ multiple seizure
types including
absence seizure.
Epilepsy Initially 10-15
mg/kg, increased by 5-10
mg/kg/wk.
Maintenance: Adult 20-30
mg/kg/day.
Patients should
initiate therapy at
10 to 15
mg/kg/day. The
dosage should be
increased by 5 to
10 mg/kg/week to
achieve optimal
clinical response.
Ordinarily, optimal
clinical response is
achieved at daily
doses below 60
mg/kg/day.
Epival tab 250
mg
100's (P3100.00/pack)
Valparin XR
(Na valproate 333
mg, valproic acid
145 mg)
Treatment of
generalized epilepsy
particularly w/
absence, myoclonic,
tonic-clonic, atonic &
Initially 10-15 mg/kg. Usual
dose: Adult 20-30
mg/kg/day. Childn 30
mg/kg/day. Monitor
patients receiving daily
Initial daily dosage is
usually 10-15 mg/kg,
then doses are
titrated up to the
optimum dose. This
Valparin XR
500 CR tab
100's (P3360.00/pack)
mixed patterns of
seizures, & partial
epilepsy particularly
w/ simple or
complex, secondary
generalized, specific
syndromes (Lennox
Gastaut).
doses >50 mg/kg. is generally within
the range 20-
30mg/kg/day.

The use of sustained
release form follows
to give the drug once
daily.
Valpros
(Na valproate 333
mg, valproic acid
145 mg)
Treatment of
generalized, partial
or other epilepsy.
Treatment &
prevention of mania
associated w/ bipolar
disorders.
Epilepsy 1,000-2,000
mg/day, may be further
increased to 2,500
mg/day.
Combined therapy w/
anticonvulsants which
induce liver enzyme
activity (eg phenytoin,
phenobarb &
carbamazepine)Increase
dose by 5-10 mg/kg/day,
target dose reached after 2
wk.
The starting dose is
600mg daily. Your
doctor will gradually
increase
this dose by 200mg
every 3 days
depending on your
condition
The usual dose is
generally between
1000mg and 2000mg
(20-30mg
per kilogram of body
weight) each day
This may be
increased to 2500mg
each day depending
on your
illness
Valpros 500
mg controlled-
release tab
30's (P538.88/box)