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Phenytoin Sodium

Class: Hydantoins
VA Class: CN400
CAS Number: 57-41-0
Brands: Dilantin, Dilantin Infatabs, Phenytek

Medically reviewed by Drugs.com. Last updated on Oct 28, 2019.

Warning

    Cardiovascular Risk Associated with Rapid IV Administration
  • Must be administered IV slowly.194 (See Cardiovascular Toxicity under Cautions.)

  • Do not exceed rate of 50 mg/minute in adults.194

  • Do not exceed rate of 1–3 mg/kg per minute or 50 mg/minute, whichever is slower, in pediatric patients.194

  • Carefully monitor cardiac function during and after IV administration; reduction in infusion rate or drug discontinuance may be needed.194

Introduction

Hydantoin-derivative anticonvulsant.b

Uses for Phenytoin Sodium

Seizure Disorders

Management of generalized tonic-clonic (grand mal) seizures.195 196 197 240

Management of partial seizures with complex symptomatology (psychomotor and temporal lobe seizures).195 196 197 240 258

Not recommended for treatment of pure absence (petit mal) seizures since the drug may increase frequency of these seizures, but may be used in conjunction with other anticonvulsants when mixed seizure types are present.b

Seizures Associated with Neurosurgery

Prevention and treatment of seizures occurring during and following neurosurgery.194 195

Status Epilepticus

Used IV for treatment of status epilepticus; however, use may be limited by its slow onset of action and need for slow administration.184 186 194 233

Benzodiazepines (e.g., diazepam, lorazepam, midazolam) are considered drugs of choice for initial treatment of status epilepticus; IV phenytoin (or fosphenytoin) may be used as a second-line agent if seizures continue.186 187 188 189 191 192 233 235 236 262

Concurrent administration with an IV benzodiazepine or short-acting barbiturate will usually be necessary for rapid control of seizures.194

Fosphenytoin appears to be better tolerated than phenytoin, and some experts state that fosphenytoin is preferred when both drugs are available.233

Cardiac Arrhythmias

Has been used IV for treatment of cardiac arrhythmias, particularly ventricular arrhythmias, in patients who do not respond to conventional antiarrhythmic agents or cardioversion.b However, current use as an antiarrhythmic agent is limited by the drug's narrow therapeutic window, multiple drug interactions, and adverse effect profile.266

Cardiac Glycoside Intoxication

Has been used IV for treatment of arrhythmias caused by cardiac glycoside intoxication, especially in the presence of AV block, because the drug improves conduction through the AV node.b d

Phenytoin Sodium Dosage and Administration

General

Seizure Disorders

  • Carefully and slowly adjust dosage according to individual requirements and response.b Generally initiate with a low dosage and gradually titrate over several weeks.258

  • When a patient is transferred from phenytoin to another anticonvulsant, gradually reduce the phenytoin dosage over a period of about 1 week while at the same time therapy is instituted with a low dosage of the replacement drug.b

  • Withdraw phenytoin therapy slowly to avoid precipitating seizures or status epilepticus.195 (See Discontinuance of Therapy under Cautions.)

  • Closely monitor for notable changes in behavior that could indicate emergence or worsening of suicidal thoughts or behavior or depression.100 102 195 (See Suicidality Risk under Cautions.)

Oral Loading-Dose Regimens

  • Therapeutic serum phenytoin concentrations can be achieved more rapidly (in 2–24 hours) by the use of an oral loading-dose regimen.b Some clinicians have recommended use of oral loading doses to achieve rapid steady-state concentrations when IV administration is not desirable.195

  • Various regimens have been suggested, and clinicians should consult published protocols for information on specific regimens.b (See Pediatric Patients and also Adults under Dosage for suggested regimen.)

  • Reserve oral loading-dose regimens for patients in a clinic or hospital setting where serum phenytoin concentrations can be closely monitored.195 b

  • Patients with a history of renal or liver disease should not receive an oral loading-dose regimen.195 b

Therapeutic Drug Monitoring

  • Therapeutic drug monitoring of serum phenytoin concentrations usually recommended to guide dosing.194 195 258 268

  • Trough concentrations (obtained just prior to next scheduled dose) can be used to assess therapeutic effect and patient compliance, while peak concentrations (obtained at the time of expected peak concentration) can be used to assess toxicity.195

  • Usual therapeutic range is 10–20 mcg/mL (or 1–2 mcg/mL based on unbound [free] phenytoin concentrations); however, some patients may achieve adequate seizure control or experience toxicity with lower or higher concentrations.194 195 258 269

  • Obtain serum concentrations at least 5–7 half-lives after treatment initiation, change in dosage, or addition or discontinuance of another drug to the regimen, so that steady-state drug levels may be achieved.b

  • Patients with renal or hepatic impairment and those with hypoalbuminemia have an increased fraction of unbound (free) phenytoin; monitor free phenytoin concentrations rather than total serum concentrations in these patients.195 268

Administration

Usually administered orally for management of seizure disorders;195 196 197 198 may be administered parenterally if oral administration temporarily not possible.194

Administer by slow IV injection or IV infusion for treatment of status epilepticus.194

IM administration generally not recommended because of risk of necrosis, abscess formation, and erratic absorption.184 194 (See IM Administration under Dosage and Administration.)

Because parenteral administration of phenytoin is associated with more frequent and severe complications, oral route generally preferred for maintaining therapeutic concentrations of the drug during nonemergency situations; routinely assess feasibility of oral therapy in patients receiving the drug parenterally.184 194

Oral Administration

Administer orally as chewable tablets, oral suspension, or extended-release capsules.195 196 197 198

Only extended-release phenytoin sodium capsules should be used for once-daily dosing regimens.195 198 Other oral formulations (e.g., oral suspension, chewable tablets) have different dissolution characteristics and absorption rates that do not permit once-daily dosing.195 196 197 198 Carefully monitor serum phenytoin concentrations whenever there is a change in dosage form or preparation.195 198

Suspension

Administer using a calibrated measuring device; a household teaspoon or tablespoon is not adequate.197

Minimize loss of phenytoin oral suspension during oral administration via a nasogastric tube (secondary to adherence to PVC tubing) by diluting (e.g., threefold) the suspension with a compatible diluent (e.g., sterile water, 5% dextrose, 0.9% sodium chloride) prior to administration, combined with flushing the tube with at least 20 mL of diluent after administration.b

IV Administration

Administer by slow IV injection or IV infusion.194

To prevent local tissue irritation, administer directly into a large peripheral or central vein through a large-gauge IV catheter.194 (See Local Toxicity under Cautions.) Use a 0.22–0.55-µm inline filter during infusion.194 Must administer slowly to minimize cardiac toxicity.194 (See Rate of Administration.)

Prior to administration, flush IV catheter with sterile saline to check patency.194 Following administration, flush IV catheter again with saline to reduce local venous irritation from the alkaline solution.194

Monitor ECG, BP, and respiratory status during IV administration.194

Dilution

To prepare solution for IV infusion, dilute commercially available phenytoin sodium injection with 0.9% sodium chloride injection to a final concentration of no less than 5 mg/mL.194 Start infusion immediately after preparation of the solution and complete administration within 1–4 hours.194 (See Storage under Stability.)

Crystallization generally occurs in more acidic solutions (e.g., dilutions in 5% dextrose), which should not be used.194 HID (See Solution Compatibility under Stability.)

Rate of Administration

Manufacturer states that rate of IV administration should not exceed 50 mg/minute in adults and 1–3 mg/kg per minute (or 50 mg/minute, whichever is slower) in pediatric patients.194 Some clinicians recommend not exceeding a rate of 0.5 mg/kg per minute in neonates and a rate of 1 mg/kg per minute in infants, children, and adults.267

A slower rate of administration is recommended in nonemergent situations.194

IM Administration

IM administration generally not recommended because of unreliable absorption and local adverse effects (e.g., pain, necrosis, abscess formation).184 195 Some experts state that phenytoin should not be administered IM under any circumstance; if IM administration is needed (e.g., when IV access not possible), IM fosphenytoin is preferred.184 270

Do not administer IM for treatment of status epilepticus because of delay in reaching therapeutic drug concentrations.194

Patients transitioning from oral to an equal dosage of IM phenytoin may experience a 50–60% decrease in peak plasma phenytoin concentrations as a result of slower IM absorption.194 If IM administration is necessary, must increase dosage by 50% over previously established oral dosage to maintain therapeutic serum phenytoin concentrations; reduce dosage once oral therapy is resumed.194 (See Dosage under Dosage and Administration.)

Experience with IM administration for >1 week is lacking; monitor serum phenytoin concentrations.194

Dosage

Phenytoin formulations containing the free acid form of the drug (oral suspension and chewable tablets) have approximately 8% greater drug content than phenytoin sodium formulations (extended-release capsules and injection); consider the difference when switching from the free acid to sodium salt form or vice versa.194 195 196 197 198

Pediatric Patients

Seizure Disorders
Oral

Recommended initial dosage is 5 mg/kg daily in 2 or 3 equally divided doses (as chewable tablets, extended-release capsules, or oral suspension).195 196 197 198 267 Adjust dosage based on individual requirements up to a maximum of 300 mg daily in divided doses.195 196 197 198 258

A period of 7–10 days may be required to achieve steady-state concentrations; any change in dosage should not be made sooner than this interval.195

Usual maintenance dosage in pediatric patients is 4–8 mg/kg daily (administered in 2 or 3 equally divided doses); however, usual dosages may vary depending on whether phenytoin is used alone or as adjunctive therapy.195 196 197 198 258 Children >6 years of age and adolescents may require minimum adult dosage of 300 mg daily.195 196 197 198

Some clinicians state that usual daily maintenance dosage (administered in 2 or 3 divided doses) in pediatric patients is 8–10 mg/kg for those 6 months to 3 years of age, 7.5–9 mg/kg for those 4–6 years of age, 7–8 mg/kg for those 7–9 years of age, and 6–7 mg/kg for those 10–16 years of age.267

Therapeutic serum concentrations may be achieved more rapidly with an oral loading dose (e.g., 500- to 600-mg oral loading dose, in divided doses, followed by usual maintenance dosage 24 hours after initiating loading dose).b

IV

When oral therapy is not feasible, may temporarily administer IV at the same total daily dosage.194

Serum phenytoin concentrations may increase slightly when IV phenytoin is substituted for extended-release capsules since bioavailability of the capsules is about 90%.194

If IV phenytoin is used in a nonemergent situation (e.g., prevention of seizures during neurosurgery), manufacturer states IV loading dose of 15–20 mg/kg will usually produce serum concentrations within generally accepted therapeutic range of 10–20 mcg/mL.194 The rate of IV administration should not exceed 1–3 mg/kg per minute (or 50 mg/minute, whichever is slower); however, slower rates recommended to minimize risk of cardiovascular toxicity.194 Following loading dose, administer maintenance IV or oral doses every 6–8 hours.194

IM

Generally should not be administered IM; if IM administration required, dosage adjustment is necessary to maintain therapeutic serum concentrations.194

Increase IM dosage by 50% over previously established oral dosage.194 To avoid drug accumulation from eventual absorption from IM sites, reduce dosage to one-half the original oral dosage (one-third of the IM dosage) for the first week back on oral therapy.194

Monitoring of serum concentrations is recommended.194 Experience with IM therapy for periods >1 week is lacking.194

Status Epilepticus
IV followed by IV/Oral

Manufacturer states IV loading dose of 15–20 mg/kg will usually produce serum concentrations of phenytoin within the generally accepted therapeutic range of 10–20 mcg/mL; administer slowly at a rate not exceeding 1–3 mg/kg per minute (or 50 mg/minute, whichever is slower).194

Some clinicians recommend initial IV dose of 20 mg/kg (administered at a rate not exceeding 1 mg/kg per minute); an additional dose of 5–10 mg/kg may be given after 10 minutes if seizures continue.236 262 However, individual requirements may vary, and as much as 30 mg/kg may be required in some patients for adequate seizure control.233 262 271

Some clinicians recommend maximum total dose of 1.5 g in 24 hours for the loading dose.267

Following loading dose, administer IV or oral maintenance doses every 6–8 hours.194

Because of required slow rate of IV phenytoin administration, concurrent use of an IV benzodiazepine usually is necessary for rapid control of seizures.194

Monitor serum concentrations when IV phenytoin is used for status epilepticus; however, do not delay treatment to measure serum concentrations.194 262

Cardiac Glycoside Intoxication
IV followed by IV/Oral

For arrhythmias secondary to cardiac glycoside intoxication, some clinicians recommend IV loading doses of 1.25 mg/kg every 5 minutes up to a total of 15 mg/kg, and IV or oral maintenance doses of 5–10 mg/kg daily in divided doses every 8–12 hours.267

Adults

Seizure Disorders
Oral

Recommended initial dosage in patients who have not previously received the drug is 100 mg 3 times daily (as chewable tablets or extended-release capsules) or 125 mg (5 mL) 3 times daily (as the oral suspension).195 196 197 198 Adjust dosage based on individual requirements up to a maximum of 200 mg 3 times daily (for chewable tablets or extended-release capsules) or 625 mg (25 mL) daily (for oral suspension).195 196 197 198

May gradually increase daily dosage in increments of 100 mg every 2–4 weeks until desired response is obtained.b Some experts recommend that dosage adjustments above 300 mg daily be made in 25- or 30-mg increments.258

A period of 7–10 days may be required to achieve steady-state concentrations; any change in dosage should not be made sooner than this interval.195

For patients receiving extended-release phenytoin sodium capsules who are stabilized on a dosage of 100 mg 3 times daily, may consider once-daily dosing with 300 mg as extended-release phenytoin sodium capsules.195 198 Do not use oral suspension or chewable tablets for once-daily dosing.195 196 198

Optimum daily dosage varies considerably, but usually in the range of 300–400 mg daily for most adults.195 196 198 200 258

Therapeutic serum concentrations may be achieved more rapidly with a 1-g oral loading dose given as 400, 300, and 300 mg at 2-hour intervals, followed by usual maintenance dosage 24 hours after initiating loading dose.195 196 198 Reserve oral loading-dose regimens for patients in a clinic or hospital setting where serum phenytoin concentrations can be closely monitored.195 196 198

IV

When oral therapy is not feasible, may temporarily administer IV at same total daily dosage.194

Serum phenytoin concentrations may increase slightly when IV phenytoin is substituted for extended-release capsules since bioavailability of the capsules is about 90%.194

If IV phenytoin is used in a nonemergent situation (e.g., prevention of seizures during neurosurgery), manufacturer states that a loading dose of 10–15 mg/kg should be administered slowly.194 The rate of IV administration should not exceed 50 mg/minute; however, slower rates recommended to minimize risk of cardiovascular toxicity.194 Following loading dose, administer IV or oral maintenance doses every 6–8 hours.194

IM

Generally should not be administered IM; if IM administration required, dosage adjustment is necessary to maintain therapeutic serum concentrations.194

Increase IM dosage by 50% over previously established oral dosage.194 To avoid drug accumulation from eventual absorption from IM sites, reduce dosage to one-half the original oral dosage (one-third of the IM dosage) for the first week back on oral therapy.194

Monitoring of serum concentrations is recommended.194 Experience with IM therapy for periods >1 week is lacking.194

Status Epilepticus
IV followed by IV/Oral

Manufacturer recommends IV loading dose of 10–15 mg/kg, administered slowly at a rate not exceeding 50 mg/minute.194

Some clinicians recommend initial IV dose of 20 mg/kg (administered at a rate not exceeding 50 mg/minute); an additional dose of 5–10 mg/kg may be given after 10 minutes if seizures continue.236 262 However, individual requirements may vary, and as much as 30 mg/kg may be required in some patients for adequate seizure control.233 262 271

Some clinicians recommend maximum total dose of 1.5 g in 24 hours for the loading dose.267

Following loading dose, administer IV or oral maintenance doses every 6–8 hours.194

Because of required slow rate of IV phenytoin administration, concurrent use of an IV benzodiazepine usually is necessary for rapid control of seizures.194

Monitor serum concentrations when IV phenytoin is used for status epilepticus; however, do not delay treatment to measure serum concentrations.194 262

Cardiac Arrhythmias
Ventricular Tachycardia
Oral

100 mg 2–4 times daily has been given.b

IV

100 mg has been administered by direct IV injection at 5-minute intervals until the arrhythmia was abolished or undesirable effects appeared or until a total of 1 g was given.b

Cardiac Glycoside Intoxication
IV followed by PO

For arrhythmias secondary to cardiac glycoside intoxication, some clinicians recommend IV loading doses of 1.25 mg/kg every 5 minutes up to a total of 15 mg/kg, and an oral maintenance regimen consisting of 250 mg 4 times daily for 1 day, then 250 mg every 12 hours for 2 days, then 300–400 mg daily (in divided or once-daily doses).267

Prescribing Limits

Pediatric Patients

Seizure Disorders
Oral

Maximum 300 mg daily.195 196 197 198 258

Adults

Seizure Disorders
Oral

Chewable tablets and extended-release capsules: Manufacturers state maximum of 200 mg 3 times daily.195 196 198

Oral suspension: Manufacturers state maximum of 625 mg (25 mL) daily.197

Special Populations

Hepatic Impairment

Consider reduced maintenance dosage in patients with hepatic cirrhosis.200

Do not use oral loading-dose regimens.195

Renal Impairment

Do not use oral loading-dose regimens.195

End-stage renal impairment: Generally can receive usual loading and maintenance dosages initially, adjusting as necessary.200

Geriatric Patients

Lower doses or less frequent dosing may be required in geriatric patients.195

Obese Patients

Ideal or nonobese weight probably correlates best with maintenance dosages.200 Loading doses may require adjustment for increased volume of distribution.200

Pregnancy

Monitor serum phenytoin concentrations closely (concentrations may decline and protein binding may change) and adjust dosage as necessary.195 200 201 (See Pregnancy under Cautions.) Restoration of original dosage will probably be necessary postpartum.195 201

Cautions for Phenytoin Sodium

Contraindications

  • IV use contraindicated in patients with sinus bradycardia, SA block, second- or third-degree AV block, or Adams-Stokes syndrome.194

  • Concomitant use with delavirdine.194 195

  • History of prior acute hepatotoxicity with phenytoin.195

  • Known hypersensitivity to phenytoin, any ingredient in the formulation, or other hydantoins.194 195

Warnings/Precautions

Warnings

Cardiovascular Toxicity

Rapid IV administration has caused severe hypotension and cardiac arrhythmias, including bradycardia, heart block, ventricular tachycardia, and ventricular fibrillation; sometimes resulted in asystole, cardiac arrest, and death.194

Severe complications reported more commonly in critically ill patients, elderly patients, and those with hypotension and severe myocardial insufficiency.194

Administer IV with extreme caution in patients with respiratory depression, MI, frank or impending CHF, or otherwise damaged myocardium, and in patients in whom a sudden change in BP may lead to serious complications.b

Do not exceed recommended rates of administration.194 (See Boxed Warning.) Risk of toxicity increases with infusion rates above recommended rates; however, cardiac events also can occur at or below these rates.194

Carefully monitor cardiac and respiratory function during and after IV administration; reduce rate of administration or discontinue drug if necessary.194

IV use contraindicated in patients with cardiac conduction disorders because of the drug's effect on ventricular automaticity.194 (See Contraindications under Cautions.)

Sensitivity Reactions

Serious Dermatologic Reactions

Serious dermatologic reactions, including acute generalized exanthematous pustulosis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), reported.195 196 197

Discontinue phenytoin at the first sign of a rash unless it is clearly not drug related; do not resume if SJS/TEN is suspected.195 196 197

Pharmacogenomic Considerations in the Development of Cutaneous Reactions

Limited data suggest an increased risk of SJS/TEN in individuals of Asian ancestry who carry the human leukocyte antigen (HLA)-B*1502 allele.104 105 195 196 197 231 232 A strong association has been found between presence of HLA-B*1502 and risk of SJS/TEN in patients with Chinese ancestry receiving carbamazepine; although evidence more limited, HLA-B*1502 also associated with SJS/TEN in such patients receiving structurally similar anticonvulsants such as phenytoin.195 196 197 231 232

Phenytoin generally should not be used as an alternative to carbamazepine in HLA-B*1502-positive patients.195 196 197 231

Multi-organ Hypersensitivity

Multi-organ hypersensitivity (also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) reported; can be fatal or life-threatening.195 196 197 Clinical presentation is variable but typically includes fever, rash, lymphadenopathy, and/or facial swelling associated with other organ system involvement (e.g., eosinophilia, hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis).195 196 197

If manifestations of DRESS occur, evaluate patient immediately.195 196 197 If an alternative etiology cannot be identified, discontinue phenytoin.195 196 197

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and angioedema, reported.195 196 197 If manifestations (e.g., facial, perioral, or upper airway swelling) occur, discontinue drug immediately.195 196 197 (See Contraindications under Cautions.)

Consider alternatives to structurally similar compounds such as carboxamides, barbiturates, succinimides, and oxazolidinediones in patients who have experienced phenytoin hypersensitivity.195 196 197 Also consider alternatives to phenytoin if there is a history of hypersensitivity reactions to these structurally similar drugs in the patient or immediate family member.195 196 197

General Precautions

Suicidality Risk

Increased risk of suicidality (suicidal ideation or behavior) observed in an analysis of studies using various oral anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).100 102 195 196 Increased suicidality risk was observed as early as 1 week after initiation of anticonvulsant therapy and continued through 24 weeks.100 102 Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.100 102 195

Closely monitor all patients currently receiving or beginning oral anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behaviors or depression.100 102 195

Balance risk of suicidality with the risk of untreated illness.100 195 Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.195 196 If suicidal thoughts or behaviors emerge during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.195 196 (See Advice to Patients.)

Discontinuance of Therapy

Abrupt withdrawal can increase seizure frequency, including status epilepticus; reduce dosage, discontinue therapy, or substitute with another anticonvulsant gradually.195 In the event of an allergic or hypersensitivity reaction, may consider more rapid substitution with an alternative non-hydantoin anticonvulsant.195

Hepatotoxicity

Acute hepatotoxicity, including infrequent cases of acute hepatic failure, reported.195 May or may not occur in association with DRESS.195 (See Multi-organ Hypersensitivity under Cautions.)

If acute hepatotoxicity occurs, discontinue phenytoin immediately and do not resume.195

Hematologic Effects

Adverse hematologic effects (e.g., thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, pancytopenia with or without bone marrow suppression), sometimes fatal, reported.195 b

Local or generalized lymphadenopathy (e.g., benign lymph node hyperplasia, pseudolymphoma, lymphoma, Hodgkin's disease) also reported, although a causal relationship not established.195 Lymph node involvement may or may not occur in association with DRESS.195 (See Multi-organ Hypersensitivity under Cautions.) If lymphadenopathy develops, further evaluate to establish a differential diagnosis; switch to an alternative anticonvulsant if possible.195

May exacerbate porphyria; use with caution in patients with this condition.195

Local Toxicity

Local soft-tissue reactions (e.g., irritation, inflammation, pain, necrosis, sloughing) reported at site of injection following IV administration; amputation required rarely.172 173 174 175 176 177 178 179 180 181 182 184 May occur in presence or absence of extravasation.172 176

Purple glove syndrome (PGS), characterized by progressive pain, discoloration, and edema of the distal limb, reported in patients receiving peripheral IV injections of phenytoin; may occur with or without extravasation.173 174 175 176 177 178 179 180 181 182 184 194 Generally mild and self-limiting; however, tissue necrosis and limb ischemia requiring surgical intervention (e.g., fasciotomies, skin grafting, amputation) have occurred.173 174 175 176 177 178 179 180 181 182 Possible risk factors include young or advanced age, female gender, use of small-bore IV catheters, preexisting cardiovascular disease, multiple or large doses, and rapid rates of IV infusion.172 173 174 175 177 178 179 180 181 182 184

To minimize risk of PGS or other types of soft-tissue injury, follow appropriate IV administration procedures and precautions.172 175 194 (See Administration under Dosage and Administration.) Monitor injection sites frequently during and for 72 hours following administration.177 182 184 If PGS occurs, discontinue drug immediately, remove IV catheter, and institute appropriate supportive measures (e.g., elevate affected extremity, apply dry heat).175 176 177 178 180 184

Effect on Vitamin D and Bone Metabolism

Long-term use in patients with epilepsy associated with decreased bone mineral density (BMD) and related bone effects (e.g., osteopenia, osteoporosis, osteomalacia, fractures).195 259 Thought to be caused by phenytoin’s interference with vitamin D metabolism.195 259

Consider monitoring vitamin D concentrations and other measures of bone health in patients receiving long-term therapy with the drug.195 259

Hyperglycemia

In large doses, may increase blood glucose concentrations resulting in hyperglycemia and glycosuria.195 b

Average doses do not regularly elevate blood glucose or increase insulin requirements in diabetic patients, but a few patients have experienced fatal, hyperosmolar, nonketotic coma in which phenytoin may have played at least an accessory etiologic role.b

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.195 201

Evidence of substantial risk of congenital malformations, fetal hydantoin syndrome (e.g., craniofacial abnormalities, nail and digital hypoplasia, prenatal growth deficiency, microcephaly, cognitive deficiency), and other developmental toxicity.195 201

Life-threatening bleeding disorders secondary to decreased concentrations of vitamin K-dependent clotting factors may occur in neonates exposed to phenytoin in utero; administration of vitamin K to the mother prior to delivery and to the neonate after birth may prevent these complications.195

Slow Metabolizers

A small percentage of individuals have been shown to metabolize phenytoin slowly; this appears to be genetically determined and may be due to limited enzyme availability and lack of induction.195

CNS Toxicity

Serum phenytoin concentrations sustained above the therapeutic range may produce confusional states such as delirium, psychosis, or encephalopathy; rarely, irreversible cerebellar dysfunction may develop.195 b

Check serum phenytoin concentrations immediately at the first sign of toxicity.195 Reduce dosage if serum concentrations are excessive; if symptoms persist, discontinue therapy.195

Specific Populations

Pregnancy

May cause fetal harm if used during pregnancy.195 201 (See Fetal/Neonatal Morbidity and Mortality under Cautions.) However, risk-to-benefit ratio generally favors continued use during pregnancy in women whose seizure control depends on the drug.201 258

Malignancies, including neuroblastoma, reported rarely in children whose mothers received phenytoin during pregnancy.195

Because of altered pharmacokinetics of phenytoin during pregnancy, increased frequency of seizures may occur.195 Monitor serum phenytoin concentrations and adjust dosage accordingly; restoration of the patient’s usual dosage will probably be necessary postpartum.195 201 Because of altered protein binding, monitor free phenytoin fraction in pregnant women.195

North American Antiepileptic Drug (NAAED) pregnancy registry at 888-233-2334 or [Web].193 195

Lactation

Distributed into milk.195 201 However, use generally considered compatible with breast-feeding.201 Consider known benefits of breast-feeding along with the woman's clinical need for phenytoin and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.195

Geriatric Use

Clearance may be reduced in geriatric patients.195

Geriatric patients may show early signs of toxicity.195 Some adverse CNS effects (e.g., drowsiness, ataxia, diplopia) are more likely to occur at lower serum phenytoin concentrations in geriatric patients than in other patients.258 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Principally metabolized by the liver; patients with impaired liver function may show early signs of toxicity.195

Since fraction of free phenytoin may be increased in patients with hepatic impairment, monitor free phenytoin concentration rather than total serum concentration in such patients.195 268

Renal Impairment

In large doses, may increase blood glucose concentrations resulting in hyperglycemia and glycosuria; patients with impaired renal function may be most susceptible to this effect.b

Since fraction of free phenytoin may be increased in patients with renal impairment, monitor free phenytoin concentration rather than total serum concentration in such patients.195 268

Patients with Hypoalbuminemia

Since fraction of free phenytoin may be increased in patients with hypoalbuminemia, monitor free phenytoin concentration rather than total serum concentration in such patients.195 268

Common Adverse Effects

Adverse GI effects include nausea and vomiting, constipation, epigastric pain, dysphagia, loss of taste, anorexia, and weight loss.b Adverse CNS effects include mental confusion, nystagmus, ataxia, blurred vision, diplopia, toxic amblyopia, dizziness, insomnia, transient nervousness, motor twitching, and headache.b

Phenytoin frequently produces gingival hyperplasia, especially in children, which occasionally is so severe that it may require surgical removal.b

Interactions for Phenytoin Sodium

Involved in multiple drug interactions because of extensive plasma protein binding, saturable metabolism, and potent hepatic enzyme-inducing properties.195

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Metabolized by CYP2C9 and CYP2C19.195 Potent inducer of CYP isoenzymes.195

Concomitant use with drugs that inhibit or induce CYP2C9 and CYP2C19 can alter serum phenytoin concentrations.195 258 Particularly susceptible to inhibitory interactions because of saturable metabolism.195 If a drug interaction is suspected, monitor serum phenytoin concentrations and adjust dosage of phenytoin as necessary.195

Because of its potent CYP-inducing properties, phenytoin can decrease plasma concentrations and possibly reduce efficacy of many drugs.195 241 258 Dosage adjustment of the concomitant drug may be necessary when phenytoin is added to or withdrawn from concomitant therapy.195

Protein-bound Drugs

Phenytoin is extensively bound to plasma proteins.195 Potential for phenytoin to displace or to be displaced by other protein-bound drugs.195

Specific Drugs or Laboratory Tests

Drug or Test

Interaction

Comments

Albendazole

Possible decreased plasma concentrations of albendazole195

Dosage adjustment of albendazole may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Alcohol intake, acute

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Alcohol abuse, chronic

Possible decreased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Amiodarone

Concomitant administration has resulted in a twofold to threefold increase in serum concentrations of phenytoin and subsequent toxicity (e.g., nystagmus, ataxia, lethargy) 195 b

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Antacids (e.g., calcium carbonate, aluminum hydroxide, magnesium hydroxide)

May interfere with GI absorption and decrease serum concentrations of phenytoin195

Do not take antacids and phenytoin at the same time of day195

Anticonvulsants

Certain anticonvulsants may increase (e.g., ethosuximide, oxcarbazepine, methsuximide, felbamate, topiramate) or decrease (e.g., vigabatrin, carbamazepine) serum phenytoin concentrations195

Phenytoin may decrease plasma concentrations of lamotrigine, felbamate, carbamazepine, oxcarbazepine, and topiramate195

Phenobarbital and valproate may increase or decrease serum phenytoin concentrations; effect of phenytoin on phenobarbital and valproate concentrations is unpredictable195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Dosage adjustment of some anticonvulsants may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Antifungals, azoles

Certain antifungal agents (e.g., fluconazole, itraconazole, ketoconazole, miconazole, voriconazole) may increase serum phenytoin concentrations195

Efficacy of certain antifungals (e.g., fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole) may be impaired by phenytoin195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Dosage adjustment of some antifungal agents may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Antineoplastic agents

Certain antineoplastic agents may increase (e.g., capecitabine, fluorouracil) or decrease (e.g., bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate) serum phenytoin concentrations195

Efficacy of certain antineoplastic agents (e.g., irinotecan, paclitaxel, teniposide) may be impaired by phenytoin195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Dosage adjustment of some antineoplastic agents may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Calcium-channel blocking agents

Phenytoin may decrease plasma concentrations of nifedipine, nimodipine, nisoldipine, and verapamil195

Dosage adjustment of the calcium-channel blocking agent may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Chloramphenicol

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Chlordiazepoxide

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Chlorpropamide

Possible decreased plasma chlorpropamide concentrations195

Dosage adjustment of chlorpropamide may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Cimetidine

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Clozapine

Possible decreased plasma clozapine concentrations195

Dosage adjustment of clozapine may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Corticosteroids

Efficacy may be impaired by phenytoin195

Dosage adjustment of the corticosteroid may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Cyclosporine

Possible decreased plasma cyclosporine concentrations195

Dosage adjustment of cyclosporine may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Delavirdine

Phenytoin can substantially decrease serum concentrations of delavirdine, resulting in loss of virologic response and possible resistance195

Concomitant use contraindicated195

Diazepam

Possible decreased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Diazoxide

Possible decreased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Digoxin

Possible decreased plasma digoxin concentrations195

Dosage adjustment of digoxin may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Disopyramide

Possible decreased plasma disopyramide concentrations195

Dosage adjustment of disopyramide may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Disulfiram

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Doxycycline

Efficacy may be impaired by phenytoin195

Dosage adjustment of doxycycline may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Efavirenz

Possible decreased plasma efavirenz concentrations195

Dosage adjustment of efavirenz may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Estrogens

Possible increased serum phenytoin concentrations195

Efficacy of estrogens may be impaired by phenytoin195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Dosage adjustment of estrogens may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Folic acid

Possible decreased serum phenytoin concentrations195

Possible decreased plasma concentrations of folic acid195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Dosage adjustment of folic acid may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Furosemide

Efficacy may be impaired by phenytoin195

Dosage adjustment of furosemide may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

HIV protease inhibitors (PIs)

Some HIV PIs (e.g., fosamprenavir, nelfinavir, ritonavir) may decrease serum phenytoin concentrations195

Phenytoin may decrease plasma concentrations of nelfinavir, ritonavir, lopinavir/ritonavir, indinavir, and saquinavir195

Effect of phenytoin on fosamprenavir varies depending on whether fosamprenavir is administered alone or in conjunction with ritonavir195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Dosage adjustment of some HIV PIs may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

HMG-CoA reductase inhibitors (statins)

Fluvastatin may increase serum phenytoin concentrations195

Phenytoin may decrease plasma concentrations of atorvastatin, fluvastatin, and simvastatin195

Fluvastatin: Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Atorvastatin, fluvastatin, simvastatin: Dosage adjustment of the statin may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Isoniazid

Possible increased serum phenytoin concentrations195

Phenytoin toxicity reported in about 25% of patients receiving concomitant therapyb

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Methadone

Possible decreased plasma methadone concentrations195

Dosage adjustment of methadone may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Methylphenidate

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Mexiletine

Possible decreased plasma mexiletine concentrations 195

Dosage adjustment of mexiletine may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Neuromuscular blocking agents

Cisatracurium, pancuronium, rocuronium, vecuronium: Resistance to these nondepolarizing neuromuscular blocking agents has occurred in patients receiving long-term phenytoin therapy; whether same effect occurs with other nondepolarizing neuromuscular blocking agents not known195

Monitor closely for more rapid than expected recovery from neuromuscular blockade; increase dosage of the neuromuscular blocking agent if necessary195

Omeprazole

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Oral contraceptives

Phenytoin can induce metabolism and decrease concentrations of estrogens and/or progestins;232 258 may lead to contraceptive failure195 258

Phenothiazines

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Praziquantel

Possible decreased plasma praziquantel concentrations195

Dosage adjustment of praziquantel may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Quetiapine

Possible decreased plasma quetiapine concentrations195

Dosage adjustment of quetiapine may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Quinidine

Efficacy may be impaired by phenytoin195

Dosage adjustment of quinidine may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Rifampin

Possible decreased serum phenytoin concentrations195

Efficacy of rifampin may be impaired by phenytoin195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Dosage adjustment of rifampin may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Salicylates

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

SSRIs

Some SSRIs (e.g., fluoxetine, fluvoxamine, sertraline) may increase serum phenytoin concentrations195

Phenytoin may impair efficacy of paroxetine and sertraline 195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Dosage adjustment of paroxetine and sertraline may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

St. John's wort

Possible decreased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Sucralfate

Possible decreased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Sulfonamides

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Test, alkaline phosphatase, serum

Phenytoin may increase serum alkaline phosphatase concentrationsb

Test, dexamethasone

Phenytoin may cause slight decreases in urinary 17-hydroxycorticosteroids and 17-ketosteroids while urinary 6-β-hydroxycortisol excretion is increasedb

Phenytoin may produce lower than normal values for the dexamethasone testb

Test, γ-glutamyl transferase (γ-glutamyltranspeptidase, GGT, GGTP)

Phenytoin may produce increased serum γ-glutamyl transferase concentrations

Test, metyrapone

Phenytoin may cause slight decreases in urinary 17-hydroxycorticosteroids and 17-ketosteroids while urinary 6-β-hydroxycortisol excretion is increasedb

Phenytoin may produce lower than normal values for the metyrapone testsb

Test, protein-bound iodine (PBI)

Patients receiving phenytoin have shown reduced protein-bound iodine (PBI) test values without lowered triiodothyronine (T3) values and without clinical symptoms of hypothyroidism; free thyroxine concentrations may also be decreasedb

The 24-hour I 131 thyroidal uptake is apparently not affected

Phenytoin may produce increased resin or red cell T3 uptake valuesb

Lowered PBI values do not occur unless phenytoin is administered for 1 week or longer, and altered values persist for 7–10 days after phenytoin is discontinuedb

Theophylline

Possible decreased serum phenytoin concentrations195

Efficacy of theophylline may be impaired by phenytoin195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Dosage adjustment of theophylline may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Ticlopidine

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Tolbutamide

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Trazodone

Possible increased serum phenytoin concentrations195

Monitor serum phenytoin concentrations and adjust dosage of phenytoin accordingly195

Vitamin D

Efficacy may be impaired by phenytoin195

Dosage adjustment of vitamin D may be necessary when phenytoin is added to or withdrawn from concomitant therapy195

Warfarin

Several interactions are possible and the net effects are difficult to predict106 195

Warfarin may increase serum phenytoin concentrations; phenytoin may induce hepatic metabolism of warfarin and/or displace the anticoagulant from its protein-binding sites106 195 232

PT/INR response may be increased or decreased106 195

Closely monitor patient and adjust dosage of warfarin or phenytoin as necessary106 195

Phenytoin Sodium Pharmacokinetics

Absorption

Bioavailability

Studies using Dilantin have shown that phenytoin and its sodium salt are usually completely absorbed from the GI tract.b

Bioavailability may vary enough among oral phenytoin sodium preparations of different manufacturers to result in toxic serum concentrations or a loss of seizure control; this should be considered before dispensing a brand or dosage form that differs from that currently taken by a patient.b Consult FDA’s Approved Drug Products and Therapeutic Equivalence Evaluations (Orange Book).

IM: Absorption may be erratic due to precipitation at injection site.200 b

Plasma Concentrations

Anticonvulsant effect: 10–20 mcg/mL.200

Antiarrhythmic effect: 10–20 mcg/mL.200

Extended-release phenytoin sodium, peak: 4–12 hours.b

Therapeutic plasma concentrations, oral: Achieved after about 1 week of therapy.b

Following oral administration, therapeutic plasma concentrations can be obtained more rapidly and maintained by administering an initial oral loading dose.b

Therapeutic plasma concentrations, IV: Within 1–2 hours.b

Distribution

Extent

Crosses the placenta.201

Distributed into milk.201 b

Elimination

Plasma Protein Binding

Approximately 95%.b

Metabolism

Metabolized by hepatic CYP enzymes.195 Metabolized to an inactive metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH).b

This metabolism is a saturable process; therefore, small increases in dosage may produce substantial increases in plasma phenytoin concentrations.b

A small percentage of individuals metabolize phenytoin slowly.195 (See Slow Metabolizers under Cautions.)

Elimination Route

Capacity-limited elimination, decreasing with increasing concentration.200

Inactive metabolite (HPPH) is excreted in urine, mainly as the glucuronide;b approximately 60–75% of the daily dose is excreted in this form.b

Half-life

Oral: About 22 hours.b

IV: Ranges from 10–15 hours.b

Special Populations

Total plasma phenytoin concentrations are lower in chronic uremic patients than in non-uremic patients, which suggests an altered metabolic disposition of the drug in patients with uremia.b

Stability

Storage

Oral

Tablets

20–25°C; protect from moisture.196

Suspension

20–25°C; protect from light and avoid freezing.197

Extended-release Capsules

Tight, light- and moisture-resistant containers at 20–25°C.195 198

Parenteral

Injection

20–25°C (may be exposed to 15–30°C).194

A precipitate may form if the injection is refrigerated or frozen; however, this will dissolve after warming to room temperature and the injection may still be used.194

Slight yellowish discoloration of the injection will not affect potency, but the injection should not be used if the solution is not clear or if a precipitate is present.194

Precipitation of free phenytoin will occur at a pH of ≤11.5.b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Phenytoin sodium injection is physically and/or chemically incompatible with some drugs, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature).b

Solution CompatibilityHID

Incompatible

Dextrose 5% in sodium chloride 0.9%

Dextrose 5% in water

Fat emulsion 10%, IV

Ringer’s injection, lactated

Sodium chloride 0.45%HID

Variable

Sodium chloride 0.9%HID

Drug Compatibility
Admixture CompatibilityHID

Compatible

Verapamil HCl

Incompatible

Amikacin sulfate

Dobutamine HCl

Lidocaine HCl

Nitroglycerin

Y-site CompatibilityHID

Compatible

Esmolol HCl

Famotidine

Fluconazole

Tacrolimus

Incompatible

Amphotericin B cholesteryl sulfate complex

Cefepime HCI

Ceftazidime

Ceftolozane sulfate-tazobactam sodium

Ciprofloxacin

Clarithromycin

Cloxacillin sodium

Diltiazem HCl

Enalaprilat

Fenoldopam mesylate

Fentanyl citrate

Heparin sodium

Heparin sodium with hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Isavuconazonium sulfate

Linezolid

Meropenem-vaborbactam

Methadone HCl

Micafungin sodium

Morphine sulfate

Oritavancin diphosphate

Potassium chloride

Propofol

Tedizolid phosphate

Theophylline

Vasopressin

Actions

  • Limitation of seizure propagation by reduction of post-tetanic potentiation (PTP), possibly by reducing the passive influx of sodium ions or by increasing the efficiency of the sodium pump so that excess accumulation of intracellular sodium does not occur during tetanic stimulation.c

  • Loss of PTP also prevents cortical seizure foci from detonating adjacent cortical areas.c

  • Exhibits antiarrhythmic properties similar to those of quinidine or procainamide.b

  • Although little effect on the electrical excitability of cardiac muscle, it decreases the force of contraction, depresses pacemaker action, and improves AV conduction, particularly when it has been depressed by digitalis glycosides.b

  • Prolongs the effective refractory period relative to the action potential duration.b

  • May produce hypotension following IV administration.b

  • Little hypnotic activity.b

Advice to Patients

  • Importance of advising patients to read the patient information (medication guide).195

  • Risk of suicidality (oral anticonvulsants, including phenytoin, may increase risk of suicidal thoughts or actions in about 1 in 500 people).100 195 196 Importance of patients, family, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one’s life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).100 195

  • Importance of immediately reporting early manifestations of hematologic, dermatologic, hypersensitivity, or hepatic reactions such as fever, sore throat, infection, rash, mouth ulcers, easy bruising, lymphadenopathy, facial swelling, petechial or purpuric hemorrhage, anorexia, nausea/vomiting, or jaundice.195 Advise patients to report these manifestations even if they are mild in severity or occur after extended use.195

  • Importance of seeking immediate medical care if signs or symptoms of angioedema (e.g., facial, perioral, or upper airway swelling) occur.195

  • Risk of severe hypotension and cardiac arrhythmias with rapid IV administration; advise patients to report any possible manifestations to their clinician.195

  • Risk of dizziness, gait disturbance, decreased coordination, and somnolence; advise patients to avoid driving, operating machinery, or performing hazardous tasks until such effects on the individual are known.195

  • Importance of not abruptly discontinuing therapy.195

  • Importance of cautioning patients not to use other drugs or alcoholic beverages without first seeking the clinician’s advice.195

  • Importance of stressing good dental hygiene in order to minimize the development of gingival hyperplasia and its complications.195

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

  • Warn women of childbearing potential that phenytoin can cause teratogenic effects and neonatal clotting disorders.194 195 Advise women of childbearing potential to use effective contraceptive methods during phenytoin therapy.195 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; discuss therapeutic options with their clinician if pregnancy is planned.195 Importance of clinicians informing women about the existence of and encouraging enrollment in the NAAED pregnancy registry (see Pregnancy under Cautions).193 195

  • Importance of informing patients of other important precautionary information.194 195 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Phenytoin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

125 mg/5 mL*

Dilantin-125

Pfizer

Phenytoin Oral Suspension

Tablets, chewable

50 mg*

Dilantin Infatabs

Pfizer

Phenytoin Chewable Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Phenytoin Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release

30 mg

Dilantin

Pfizer

100 mg*

Dilantin

Pfizer

Phenytoin Sodium Extended-release Capsules

200 mg*

Phenytek

Mylan

300 mg*

Phenytek

Mylan

Parenteral

Injection

50 mg/mL*

Phenytoin Sodium Injection

AHFS DI Essentials™. © Copyright 2020, Selected Revisions October 28, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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