SINGLE-DOSE ORAL

PHENYTOIN IN GTC STATUS

EPILEPTICUS
Suryani Gunadharma, Dede Gunawan,
Yustiani Dikot

DEFINITION

Generalized tonic-clonic status epilepticus is

define as either continuous (>30) min tonic
clonic convulsions
or
Convulsions that are so frequent that each
attack begins before the postictal period of
the preceding one ends

BACKGROUND

The outcome following an episode of SE

depends on the underlying disease and the
duration of the seizures plus metabolic
abnormalities.
Local biochemical tissue changes may occur
after 20-30 minutes of SE, and within 60
minutes irreversible neuronal damage may
be seen

BACKGROUND

Phenytoin is a very effective AED with very

little effect on the patients level of
consciousness and EEG
Phenytoin is theorized to act by blocking
sodium channels in neuronal tissue, causing
in prolongation of their rate of recovery and
reduction in the frequency of sustained
repetitive firing of action potentials

BACKGROUND

If the patient has had several seizures and

cannot be hospitalised for some reason, one
might wish to administer 18 mg/kg oral
phenytoin in the first 24 hours, perhaps
divided into 3 doses
The entire loading dose can be given at once
if even more rapid dilantinization is desired,
this method would result in therapeutic levels
in 5-6 hours.

BACKGROUND

Predose or trough samples are the most

appropriate samples to use when monitoring
orally dosed antiepileptic drugs
Postdose or peak sampling can be done after
intravenous administration of a loading dose,
obtain samples after intravenous dosing of
phenytoin at 14 h postdose or at 2 h
postintravenous

PURPOSE

In our neurology inpatient ward most SE

patient cannot afford to buy phenytoin iv
In this cases we used to use oral phenytoin
loading dose300 mg q8h for 3 doses;
followed by 300 mg/d PO
With the dosage of 1,000 mg stat; followed by
300 mg/d of penytoin PO, the therapeutic
range will be reached faster (in 4-6 hr ) than if
divided in 3 doses

METHODS

Specimens and timing

Specimens can be chosen between serum, plasma, or whole

blood as the sample for analysis of total drug, according to the
requirements of the analytical method chosen
Serum is always an appropriate sample for monitoring
antiepileptic drugs
Generally, use of plasma for total drug measurement, plasma is
not an appropriate specimen for the measurement of free drugs
The most appropriate sample for free drug analysis is serum

METHODS

Specimens and timing

In general, before using plasma, it is necessary to verify that a

particular anticoagulant does not interfere with the analysis
Avoid citrate and oxalate in samples obtained for phenytoin and
analysis.
The effect of EDTA is not established; results of studies are
discrepant
Draw samples after oral dosing of anticonvulsants immediately
before the next dose for drugs with short half-lives; for drugs with
long half-lives (24 h), the draw time during the dosing interval is
less critical. Always ascertain and report the time of sample draw

METHODS

METHODS

METHODS

Therapeutic serum levels of 5-20g/ml correlate well

with the anticonvulsant properties of phenytoin.
The therapeutic ranges in wide use: phenytoin, 40
80 mol/L (1020 g/mL)
When given at 5 mg/kg/day (about 300mg/day in
average adult), it takes 5-15 days to reach
therapeutic range.
If a loading dose at 18 mg/kg ( 15 to 20 mg/kg;
maximum 1 g) is given PO, the therapeutic range
can be reached within few hours.
If the drug is given IV, the therapeutic range can be
reached in minutes.

METHODS

Measuring a serum concentration of an

antiepileptic drug is most appropriate when
the blood sample is drawn after steady-state
conditions have been reached, i.e., after 45
half-lives on an unchanged dose regimen.

METHODS

Non-steady-state concentrations may be

indicated in emergency treatment of serial
seizures or status epilepticus.
Measuring a serum concentration is usually
appropriate within 6 h after a seizure
recurrence in a controlled patient
With the dosage of 1,000 mg stat; followed by
300 mg/d of penytoin PO, the therapeutic
range will be reached in 4-6 hr

METHODS

Draws 5cc venous blood

Centrifuge at 3000-3500 rpm for 10 minutes
Put in a tube for 10 minutes
Separate the serum to another tube
Store serum (sample) in 2-8 C
If the sample will be store for > 24 hours, keep in
temperature < -10 C
Send the sample to prodia the next day with ice
cubes or ask people from prodia to pick up the
sample

Various methods of Dilantinization

Administration of 15-20 mg/kg, maximum 1 g over 20 min of
phenytoin IV, the therapeutic range will be reached in 10-20 min
after initial dose
With the dosage of 1,000 mg stat; followed by 300 mg/d of
penytoin PO, the therapeutic range will be reached in 4-6 hr
( local gastric upset is common; give with meals or milk)
300 mg q8h for 3 doses; followed by 300 mg/d PO, the
therapeutic range will be reached in 24-30 hr (mild ataxia is
common initially)
300mg/d phenytoin PO, the therapeutic range will be reached in
5-15

REFERENCES

RESULTS

CONCLUSIONS

Oral loading dose of phenytoin is safe,

effective and can be considered in patient
who need prompt control of seizures within
few hours