UNIVERSITY COLLEGE OF PHARMACY
DRUG PROFILE
Drug Name (Generic) PHENYTOIN
1. PRODUCT DESCRIPTION
Sr. Manufacturer’s Dosage Form Amount of Storage
No. Proprietary Name active Conditions
Ingredients
1 Dilantin® Capsules, USP 30 mg or 100 mg Store at
(extended phenytoin phenytoin controlled room
temperature.
sodium) sodium, USP. Preserve in tight,
light-resistant
Pfizer
containers.
Protect from
moisture.
Di-hydan Tablets 100mg Store at
2 French controlled room
temperature.
Preserve in tight,
light-resistant
containers.
Protect from
moisture.
Epilantin Suspension 300mg/5ml Store in the
3 Pharmedic Tablets 30mg original package
in order to protect
from light. Do
not store above
25°C.
4 Epitoin Capsules 100mg Store in the
Adamjee original package
in order to protect
from light. Do
not store above
25°C.
5 Epanutin™ parenteral 250mg/5ml Do not store
Pfizer above 25°C Once
opened, use
immediately and
discard any
unused contents.
2. CHEMISTRY OF PRODUCT
Chemical Structure Nature Physical Properties
Class
Hydantoin salt White crystalline powder or
granule. Non taste. non smell
Hydantoin • Solubility
Derivative o Acetone,
Ethanol :
slightly
sodium 5,5-diphenyl-2, 4- soluble
imidazolidinedione o Chloroform,
Ether : hardly
soluble
o Water : almost
insoluble
3. BIO-PHARMACEUTICS
i. ABSORPTION
Dosage Form Route of Administration Site of Absorption
Tablets Completely absorbed from
Oral GIT
ii. DISTRIBUTION
Bio %Protein Placenta Blood Volume of Therapeutic
Time for
-availability l Barrier Brain Distribution peak blood
Barrier levels
70-100% oral, 90% Crosses Crosses 0.52 and 1.19 1.5-3hrs for 10-20
24.4% for protein litres/kg prompt release mcg/mL
rectal and binding in & 4 to 12 hrs
intravenous adults for extended
administration release
administration.
iii. ELIMINATION
Elimination Half Site of Metabolite(s) Route of Excretion
Life Metabolism
22hours Oxidized in liver Parahydroxyphenyl Primarily through the
derivative; Inactive bile, urinary
metabolites
4. CLINICAL PHARMACOLOGY
Therapeutic Pharmacological Mechanism of Action Activity of
Class Class Metabolite(s) (if
any)
Anticonvulsants Anti-epileptics The mechanism by which No
phenytoin exerts its
anticonvulsant action has
not been fully elucidated
however, possible
contributory effects
include:
1. Non-synaptic effects to
reduce sodium
conductance, enhance
active sodium extrusion,
block repetitive firing and
reduce post-tetanic
potentiation
2. Post-synaptic action to
enhance gaba-mediated
inhibition and reduce
excitatory synaptic
transmission
3. Pre-synaptic actions to
reduce calcium entry and
block release of
neurotransmitter.
Effects on Organ Systems Therapeutic Uses Spectrum (if antibiotic)
used in generalized epilepsy,
partial epilepsy, preventing or
treating seizures caused by
brain surgery or a head injury
and trigeminal neuralgia
Monitoring of Blood levels (if required / for narrow therapeutic index drugs)
Measurement of serum phenytoin levels is recommended when using phenytoin in the
management of status epilepticus and in establishing a maintenance dose. The usually accepted
therapeutic level is 10-20 mg/litre, although some patients with tonic-clonic seizures can be
controlled with lower serum levels
Adverse Effects Contraindications / Precautions
• Phenytoin may cause a febrile
reaction, hypotension (during
intravenous infusion), or bradycardia.
• Mouth - Gingival hyperplasia Phenytoin is contraindicated in those patients
• Neurologic : Hyperreflexia or who are hypersensitive to phenytoin or other
hyporeflexia, Abnormal gait hydantoins
(bradykinesia, truncal ataxia) , Phenytoin should be administered caution in
Respiratory distress, patients with renal, hepatic impairments &
Encephalopathy , Meningeal irritation diabetics.
with pleocytosis , Tremor (intention) ,
Irritability or agitation, Confusion ,
Hallucinations , Mental status varies
from completely normal to the
extremes of stupor and coma,
particularly if co-ingestants are
present , Peripheral neuropathy
(chronic use) , Priapism ,Urinary
incontinence, Choreoathetoid
movements,, Dysarthria ,
Dysphagia ,Seizures (rare) ,Death
(rare)
• Eyes : Nystagmus (horizontal,
vertical) , Ophthalmoplegia , Diplopia
,Miosis or mydriasis
• Hypersensitivity reactions: Fever,
rash, and lymphadenopathy,
commonly observed together ,
Systemic lupus erythematosus (SLE),
Polyarteritis , Polymyositis ,
Eosinophilia , Megaloblastic anemia,
Pseudolymphoma, Lymphadenopathy
• Vascular - Phlebitis
• Skin :Hirsutism ,Acne ,Rashes, can
be mild, morbilliform, scarlatinoid or
as severe as Stevens-Johnson
syndrome ,Jaundice ,Facial or
periorbital edema ,Erythema
multiforme (EM) , Toxic epidermal
necrolysis (TEN)
• GI/abdomen : Hepatitis
5 DOSAGE:
S Indication Dosage Form Recommended Dosage ranges
r s & Route of
. Administration
N
o
.
Neonates/Infant Child Adult *
s mg/kg/day mg/kg/day mg/kg/day O
Frequency Frequency Frequency t
h
e
r
s
1 Loading Dose 5 mg/kg/day in two 5 mg/kg/day in one gram of
or three equally two or three phenytoin
(IV):
divided doses equally divided capsules is
doses divided into
three doses
(400 mg, 300
mg, 300 mg)
and
administered
at two-hour
intervals
2 Maintenance recommended daily recommended 200 to 500mg
Oral maintenance daily maintainence
dosage is usually 4- maintenance dose daily in
8mg/kg dosage is usually single or
4-8mg/kg divided doses
d by
3 Loading Dose 10 - 20 mg/kg
(IV):
IV injection
* Others: Pregnancy, Cardiac Patients, Renal / Liver impairment.
6. ADMINISTRATION GUIDELINES
FOR ORAL ROUTE
Type Could be crushed Directions for reconstitution (in
Y/N case of granules for susp. or
syp.)
Tablet Yes
extended-release capsule No
Suspension Shake well before use. Take the exact
measured dose of suspension with
Measuring spoon.
Interaction Significance Effects Mechanism Recomme
Level / onset ndations /
Managem
ent
2 Phenytoin decreases Increased Monitor
Phenytoin↔ Delayed serum CBZ levels. metabolism of CBZ serum
Moderate resulting from levels of
Carbamazepine enzyme both drugs
induction.CBZ may & adjust
reduce the dose to
bioavailability of avoid
phenytoin toxicity
4 Serum phenytoin Unknown Monitor
Phenytoin↔ Delayed conc. May be serum
Moderate elevated increasing phenytoin
Gabapentin risk of toxicity conc.Adjust
the dose
Phenytoin↔ 3 Phenytoin may Reduced oral Increased
furosemide Delayed decrease the diuretic absorption of furosemide
Major effect of furosemide furosemide doses may
be needed
1 Cyclosporin conc. Possibly decreased Tailor
Delayed May be decreased by cyclosporine cyclosporin
Phenytoin↔ Major phentoin resulting in absorption or e dose to
decreased metabolism maintain
Cyclosporin immunosuppressive therapeutic
activity range
FOR I/V ROUTE
Dilution Compatible Compatibl Incompatibilitie Storage time Stability
for Dose I/V Fluids e Drugs s & after
temperature dilution
after
reconstitution
parenteral 5% glucose or Phenytoin Parenteral Do not store The diluted
phenytoin 0.9% sodium should not be mixed above 25˚C form is
should be chloride solution with other drugs suitable for
Diluted in because of use as long
50-100 ml precipitation of as it
of normal phenytoin acid. remains
saline,final clear and
conc. Not free of
exceeding precipitate
10mg/ml
DIRECTIONS FOR USE
Route Directions
Oral
Shake the bottle well before each dose. Take this medication by mouth as
directed, with a full glass (8 oz or 240 ml) of water, or as directed by your
doctor. Patient may take it with food if stomach upset occurs. Take the
medicine at the right time
Injection This drug must be administered slowly, at a rate not exceeding 50 mg/minute in adults. In
neonates, the drug should be administered at a rate not exceeding 1-3 mg/kg/min. The
response to phenytoin may be significantly altered by the concomitant use of other drugs
7. DRUG – DRUG INTERACTIONS
8. DRUG – LAB INTERACTIONS
Lab Test Nature of Interference
Phenytoin may interfere with Metyrapone & Phenytoin produce lower than normal values for
1mg Dexamethasone tests dexamethasone or metapyrone tests
Phenytoin may cause raised serum levels of glucose,
Blood sugar metabolism tests.
9. DRUG-FOOD INTERACTION
Type of food Mechanism Management
Folic acid, Their absorption decreased serum folate concentrations be
calcium & by phenytoin measured at least once every 6
Vitamin D months, and folic acid
supplements given if necessary
Enteral They decrease phenytoin phenytoin should not be
nutrition absorption administered concomitantly
Supplements with an enteral feeding
preparation. Do not take
enteral feeds or other
nutritional supplements two
hours before, or two hours
after, taking medicine.If
administered then monitor the
serum phenytoin level and
increase the dose of phenytoin
10. TOXICOLOGY
Toxic Dose Sign & Lethal Dose Management/Treatment
Symptoms (including antidote)
There are The initial The lethal dose Treatment is non-
marked symptoms are in children is specific since there is
variations among nystagmus, not known, in no known antidote. If
individuals with ataxia, and adults 2 to 5 ingested within the
respect to dysarthria. Other grams previous 4 hours the
phenytoin serum signs are tremor, stomach should be
levels where hyperreflexia, emptied. If the gag
toxicity may lethargy, slurred reflex is absent, the
occur. speech, nausea, airway should be
Nystagmus on vomiting. The supported. Oxygen, and
lateral gaze patient may assisted ventilation may
usually appears become be necessary for central
at 20mg/l, and comatose and nervous system,
ataxia at 30mg/l, hypotensive. respiratory and
dysarthria and Death is due to cardiovascular
lethargy appear respiratory and depression.
when the serum circulatory Haemodialysis can be
concentration is depression considered since
greater than phenytoin is not
40mg/l completely bound to
plasma proteins. Total
exchange transfusion
has been utilised in the
treatment of severe
intoxication in children
REFERENCES
http://emc.medicines.org.uk/emc/assets/c/html/DisplayDoc.asp?
DocumentID=13289#CLINICAL_PARTS
http://www.rxlist.com/dilantin-drug.htm#
http://www.drugs.com/phenytoin.html
http://en.wikipedia.org/wiki/Phenytoin
http://chrom.tutms.tut.ac.jp/JINNO/DRUGDATA/21phenytoin.html#Property
http://www.globalrph.com/anticonvulsants.htm
Pakistan Drug Manual
Drug Interaction Facts
