DANDII BORU COLLEGE DESSIE CAMPUS

DEPARTEMENT OF PHARMACY
DRUG INFORMATICS

Drug Monograph on"Phenytoin"

Prepared by group Four(4) students

Submitted to: Mieraf G

Student Name. I'd number

1.Anwar shikur.............................................................................052

2.Mohammedjuhar Ali.................................................................053

3.Girma Tesfaye ..........................................................................054

4.Mohammed Adem....................................................................055

5.Mohammedjuhar Kassaw .......................................................056

6.Betelhem Birhanu ..............................................................058

7.Almaz Tadesse .........................................................................059

8.Hiwot Mengesha........................................................................060

9.Meaza Tesfahun .................................................................136

10.Abubeker Jemal.......................................................................138

11.Wubshet Akllo .....................................................................139

12.Hayat Yimam ........................................................................140

13.Yitages Techan......................................................................141
 14.Genet Haftu............................................................................144

15.Mahlet Tadesse.......................................................................145

16.Sadam Seid..............................................................................146

17.Semira Awol.............................................................................147

18.Eman Ebrahim..........................................................................148

19.Tigist Mengste.........................................................................149

Submitted Date............

Table of Contents
1.Generic name:...............................................................................................1

2.Brand names:................................................................................................1

3. Pharmacologic Category:.............................................................................1

4. Indications and Usage..................................................................................1

5.Dosage:.........................................................................................................1

6.DosageForms and Strengths:........................................................................2

7.Administration..............................................................................................3

8.Pricing...........................................................................................................3

9.Adverse Drug Reactions:...............................................................................3

10.Contraindication:.........................................................................................4

11.Warning/Precautions...................................................................................4

12.Drug Interactions:........................................................................................5

13. Pregnancy and Lactation ............................................................................6

14.Clinical Pharmacology..................................................................................6

14.1. Mechanism of action............................................................................... 6

14.2.Pharmacodynamics:...................................................................................6

14.3.Pharmacokinetics.......................................................................................7

15.Overdosage:..................................................................................................7

16.Patient education.........................................................................................7

References.........................................................................................................83

Phenytoin Monograph
1. Generic name: Phenytoin
2.Brand names: Dilantin, Phenytek, Dilantin 125

3.Pharmacologic Category: Anticonvulsants, Hydantoins, Group I antiarrhythmics

4.Indications and Usage:

Phenytoin is primarily used to control and prevent various types of seizures, including:

⦁ Grand mal seizures (tonic-clonic seizures)

⦁ Complex partial seizures(Psychomotor seizures)

⦁ Status epilepticus ,particularly in emergency settings

⦁ Trigeminal neuralgia

⦁ Prevention and treatment of seizures during or following neurosurgery

⦁ It may also be used for certain types of irregular heartbeats.

5.Dosage:

The dosage of phenytoin varies based on the condition being treated, patient age, and individual
response. Here are the general guidelines:

 For Seizures:
 i. Adults:

⦁ Initial Dose: 100 mg orally three times a day.

⦁ Maintenance Dose: Adjusted as needed, typically ranging from 300 mg to 600 mg per day, divided
into multiple doses.

ii.Children (Aged 12 to 17 years):

⦁ Initial Dose: 300 mg to 400 mg per day, taken in two doses.

⦁ Children (Under 11 years):

⦁ Dosage is weight-dependent and should be calculated based on the child's weight.

 For Trigeminal Neuralgia:

⦁ The usual dose is between 300 mg to 500 mg daily, taken in one or two doses.

 Loading Doses:

In cases requiring rapid control of seizures:

⦁ A loading dose of 1 g can be administered orally, divided into three doses (400 mg, 300 mg, and 300
mg) given at two-hour intervals. Maintenance dosing should begin 24 hours after the loading dose.

 Intravenous Administration:

For patients unable to take oral medication:

⦁ An intravenous loading dose of 10 to 15 mg/kg may be given at a rate not exceeding 50 mg per
minute, followed by maintenance doses of 100 mg IV every 6 to 8 hours as needed.

 Monitoring:

Therapeutic drug monitoring is essential due to phenytoin's narrow therapeutic index. Serum levels
should typically be maintained between 10 to 20 mcg/mL to ensure efficacy while minimizing toxicity.

6.Dosage Forms and Strengths:

Phenytoin is available in various forms and strengths:

⦁ Capsules (immediate-release): 30 mg, 100 mg

⦁ Capsules (extended-release): 100 mg, 200 mg, 300 mg

⦁ Chewable tablets: 50 mg
⦁ Oral suspension: 125 mg/5 mL

⦁ Injectable solution: 50 mg/mL

 Seizures
 Status epilepticus Load 10-15 mg/kg or 15-20 mg/kg at 25-50 mg/min, THEN Maintenance:
100 mg IV/PO q6-8hr PRN,Administer IV slowly; not to exceed 50 mg/min.

 Anticonvulsant
 Tablet 100 mg PO TID ,Maintenance: 300-400 mg/day; increase to 600 mg/day if necessary,May
adjust dose no sooner than 7-10 day intervals when indicated.
 Suspension 125 mg PO TID, initially Increase to 625 mg/day if necessary May adjust dose no
sooner than 7-10 day intervals when indicated
 Extended release
 Loading dose: 1 g divided into 3 doses (400, 300, 300 mg) administered at 2 hr intervals; initiate
dosage 24 hr after loading dose.
 Loading dose not for administration to patients with a history of renal or hepatic disease;
reserve for patients who require rapid steady serum levels, when IV administration not
desirable, and for patients in a clinic or hospital setting where phenytoin levels can be closely
monitored
 Treatment (naive): 100 mg PO TID initially
 May adjust dose no sooner than 7-10 day intervals
 Therapeutic range: 10-20 mcg/mL (total) or 1-2 mcg/mL free drug

7.Administration:

 Phenytoin can be administered orally or intravenously.

 When given IV, it should not exceed an infusion rate of 50 mg/min to avoid complications.
 For oral administration, the extended-release formulation may be taken once daily if seizure
control is established.

8.Pricing:

 Oral Suspension (25 mg/mL):

⦁ Approximately $41 for a 237 mL supply.

⦁ Price per unit ranges from $0.17 to $0.22.

 Chewable Tablets (50 mg):

⦁ Cost is around $19.85 for a supply of 30 tablets.

⦁ Price per tablet is about $0.66.

  Injectable Solution (50 mg/mL):

⦁ The price is approximately $26 for a 50 mL supply.

⦁ Price per unit ranges from $0.52 to $0.90 depending on the quantity purchased.

9.Adverse Drug Reactions:

⦁Phenytoin is associated with a range of adverse drug reactions, which can vary in severity and are often
concentration-dependent. The primary ADRs include:

⦁ Neurotoxicity: Symptoms can range from mild nystagmus at serum levels of 10-20 mg/L to severe
effects like ataxia, slurred speech, and even coma at levels exceeding 50 mg/L.

⦁ Cardiovascular Effects: Intravenous administration can lead to bradycardia, hypotension, and asystole
due to its propylene glycol content. Rapid infusion rates should not exceed 50 mg/min.

⦁ Hypersensitivity Reactions: Chronic use may lead to conditions such as Drug Reaction with Eosinophilia
and Systemic Symptoms (DRESS) syndrome, which can manifest as fever, rash, and multi-organ
involvement.

⦁ Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are severe skin reactions
that can be life-threatening.

. ⦁ Blood disorders such as agranulocytosis, leukopenia, and thrombocytopenia.

⦁ Liver damage, indicated by symptoms like loss of appetite, jaundice, or dark urine.

⦁ Cardiovascular issues including hypotension and arrhythmias, particularly with rapid intravenous
administration.

⦁ Drowsiness,Confusion,Slurred speech, Abnormal eye movements,Problems with balance and

coordination.

⦁ Other Effects: Long-term use may result in folate deficiency and peripheral neuropathy, while acute
overdose can lead to seizures in rare cases.

10.Contraindications:

Phenytoin is contraindicated in the following situations:

⦁ Hypersensitivity: Known allergy to phenytoin or other hydantoins.

⦁ Pregnancy: The use of phenytoin during pregnancy is generally avoided unless the benefits outweigh
the risks due to potential teratogenic effects, including fetal hydantoin syndrome and other congenital
malformations.

11.Warnings/Precautions:

Important warnings and precautions include:

⦁ Suicidal thoughts: Phenytoin may increase the risk of suicidal thoughts or actions, particularly in
individuals with a history of mood disorders.

⦁ Skin reactions: Patients should be monitored for signs of severe skin reactions like SJS or TEN,
especially within the first few weeks of treatment.

⦁ Vitamin D deficiency: Chronic use may lead to decreased vitamin D levels, increasing the risk of bone
health issues.

⦁ Cardiovascular risks: Rapid intravenous administration can lead to hypotension and arrhythmias;
infusion rates should not exceed recommended limits.

12.Drug Interactions:

Phenytoin has significant interactions with various medications due to its enzyme-inducing properties.
Important interactions include:

⦁ Reduced efficacy of oral contraceptives and anticoagulants like warfarin due to increased metabolism.

⦁ Increased toxicity when combined with other drugs that inhibit its metabolism (e.g., amiodarone,
fluconazole).

⦁ Altered serum concentrations when taken with drugs that affect liver enzymes or plasma protein
binding.

13.Pregnancy and Lactation

Phenytoin, a commonly prescribed anticonvulsant for managing epilepsy, poses several risks during
pregnancy and lactation. Understanding these risks is crucial for women of childbearing age who are on
this medication.

 Pregnancy Considerations

Phenytoin should be used during pregnancy only if absolutely necessary due to risks of major congenital
malformations. Women of childbearing age should be counseled on effective contraception as
phenytoin can reduce the effectiveness of hormonal contraceptives.Phenytoin is associated with
significant risks when taken during pregnancy, particularly in the first trimester. The primary concerns
include:
⦁ Fetal Hydantoin Syndrome: Babies born to mothers who take phenytoin during pregnancy have a risk
of developing fetal hydantoin syndrome, which can manifest as a range of birth defects.

⦁ Congenital Malformations: Studies indicate that prenatal exposure to phenytoin increases the risk of
major congenital malformations.

⦁ Vitamin K Deficiency: Infants exposed to phenytoin in utero may be at risk for vitamin K deficiency,
which can lead to bleeding disorders.

⦁ Folic Acid Supplementation: Women taking phenytoin are advised to take high doses of folic acid (5
mg daily) before conception and during the first trimester to help reduce the risk of neural tube defects
and other malformations.

⦁ Monitoring and Adjustment: Pregnancy alters the metabolism of phenytoin, often leading to lower
serum drug levels.

 Lactation Considerations

During lactation, phenytoin is excreted in breast milk; however, breastfeeding is generally considered
safe when the mother is on monotherapy. Close monitoring of the infant for any adverse reactions is
advised.When it comes to breastfeeding while on phenytoin:

⦁ Drug Transfer to Breast Milk: Phenytoin does pass into breast milk but in relatively low
concentrations.

⦁ Infant Side Effects: Most infants do not exhibit adverse effects from breastfeeding while their mothers
are on phenytoin.

⦁ Long-term Development: Longitudinal studies suggest that breastfeeding during maternal phenytoin
therapy does not adversely affect infant cognitive development.

In fact, some studies have indicated that breastfed infants may perform better on cognitive assessments
than those who are not breastfed.

⦁ Consultation with Healthcare Providers: It is crucial for breastfeeding mothers on phenytoin to

maintain communication with their healthcare providers regarding any concerns about their infant's.
14.Clinical Pharmacology

14.1 Mechanism of Action

 Phenytoin is primarily a voltage-gated sodium channel blocker. It stabilizes the inactive state of
these channels, which prolongs the neuronal refractory period and decreases neuronal
excitability. This action is particularly effective in preventing the propagation of high-frequency
action potentials associated with seizures, especially in the motor cortex. Additionally,
phenytoin affects cardiac tissue by shortening action potentials and prolonging the refractory
period, which can also influence cardiac rhythm during its use.

14.2 Pharmacodynamics

 Phenytoin's pharmacodynamics are characterized by its interaction with voltage-gated sodium

channels in both the central nervous system and cardiac tissues. By inhibiting sustained
repetitive firing of neurons, phenytoin effectively reduces seizure activity.The drug's effects can
lead to various clinical outcomes, including its antiepileptic properties and potential side effects
such as ataxia, nystagmus, and gingival hyperplasia with chronic use.

14.3 Pharmacokinetics

Phenytoin exhibits nonlinear pharmacokinetics due to saturation of metabolic pathways at therapeutic

concentrations.

Key pharmacokinetic parameters include:

⦁ Absorption: Phenytoin is completely absorbed from the gastrointestinal tract, with peak plasma
concentrations typically reached within 1.5 to 3 hours after oral administration.

⦁ Volume of Distribution (Vd): Approximately 0.75 L/kg, indicating extensive distribution into body
tissues.

⦁ Protein Binding: About 90% bound to plasma proteins, primarily albumin; only the unbound fraction is
pharmacologically active.

⦁ Metabolism: Primarily metabolized by the hepatic cytochrome P450 enzyme system (CYP2C9 and
CYP2C19) to inactive metabolites. This metabolism can be affected by various factors including liver
function and concurrent medications.
⦁ Elimination Half-Life: The half-life ranges from 7 to 42 hours but averages around 22 hours under
normal conditions. It can be significantly prolonged in cases of overdose or metabolic impairment.

15. Overdosage

 Overdose of phenytoin can lead to severe neurological symptoms such as ataxia, nystagmus,
and even coma. Management typically involves supportive care and monitoring of vital signs. In
cases of significant toxicity, activated charcoal may be administered if ingestion was recent,
along with careful monitoring of serum levels to guide further treatment interventions.

16. Patient Education

 Patients should be educated on the importance of adherence to prescribed dosing regimens and
the need for regular monitoring of serum phenytoin levels due to its narrow therapeutic index.
They should be informed about potential side effects, including dental hygiene practices to
mitig.
 References
1. DrugBank Online

2. Drugs.com

3. FDA Labeling Information

4. StatPearls - NCBI Bookshelf