Plain-language summary, compiled from the cited regulatory records
Phenytoin is an anti-seizure medication belonging to the hydantoin derivative class [1]. It is approved for the treatment of generalized tonic-clonic status epilepticus [1]. Additionally, it is indicated for the prevention and treatment of seizures that may occur during neurosurgery [1]. Intravenous administration of phenytoin can be used as a short-term substitute for oral phenytoin when oral administration is not feasible [1].
In the past 12 months, there have been 901 adverse event reports associated with this active ingredient [2]. The most frequently reported reactions include "Drug Ineffective," "Seizure," "Off Label Use," "Drug Interaction," and "Toxicity To Various Agents" [2].
This is not medical advice. Consult a qualified healthcare professional.
GBOfficial regulatory label· revised April 17, 2026[1]
Phenytoin Sodium Hard Capsules are indicated for control of tonic-clonic seizures (grand mal epilepsy), partial seizures (focal including temporal lobe) or a combination of these, and for the prevention and treatment of seizures occurring during or following neurosurgery and/or severe head injury.
Phenytoin Sodium Hard Capsules has also been employed in the treatment of trigeminal neuralgia but it should only be used as second line therapy if carbamazepine is ineffective or patients are intolerant to carbamazepine.
How to take
USUnited States· FDA
6 products
Uses
USOfficial regulatory label· revised April 29, 2026[2]
1 INDICATIONS AND USAGE Phenytoin chewable tablets are indicated for the treatment of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.
Phenytoin chewable tablets are indicated for the treatment of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.
( 1 )
How to take
CACanada· Health Canada
6 products
Uses
CAOfficial regulatory label· revised March 22, 2025[3]
DILANTIN INFATABS (phenytoin chewable tablets), DILANTIN-30 SUSPENSION and DILANTIN- 125 SUSPENSION (phenytoin oral suspensions) are indicated for: • the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures.
Phenytoin is not effective for absence (petit mal) seizures, and not indicated for seizures due to hypoglycemic or other metabolic causes. 2 Recommended Dose and Dosage Adjustments, Pediatrics. 2 Geriatrics Evidence from clinical studies and experience suggests that use in the geriatric population is associated with differences in safety or effectiveness.
2 Recommended Dose and Dosage Adjustments, Geriatrics.
How to take
Drug interactions
Known interactions involving Phenytoin. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 600. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
Sources & citations
[1]MHRA (UK) · PL045692038 · revised April 17, 2026
[2]FDA DailyMed · 08a9d26b-4419-43… · revised April 29, 2026 [PDF]
[3]Health Canada (DPD) · 00023698 · revised March 22, 2025
[4]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
GBOfficial regulatory label· revised April 17, 2026[1]
Phenytoin Sodium Hard Capsules contain phenytoin sodium. Although 100 mg of phenytoin sodium is equivalent to 92 mg of phenytoin on a molecular weight basis, these molecular equivalents are not necessarily biologically equivalent. Physicians should therefore exercise care in those situations where it is necessary to change the dosage form and serum level monitoring is advised.
Posology Dosage should be individualized as there may be wide interpatient variability in phenytoin serum levels with equivalent dosage. Phenytoin Sodium Hard Capsules should be introduced in small dosages with gradual increments until control is achieved or until toxic effects appear.
In some cases serum level determinations, may be necessary for optimal dosage adjustments - the clinically effective level is usually 10-20mg/l (40-80 micromoles/l) although some cases of tonic-clonic seizures may be controlled with lower serum levels of phenytoin.
With recommended dosage, a period of seven to ten days may be required to achieve steady state serum levels with Phenytoin Sodium Hard Capsules and changes in dosage should not be carried out at intervals shorter than seven to ten days.
Maintenance of treatment should be the lowest dose of anticonvulsant consistent with control of seizures.
Adult Dosage for Seizures:
Initially 3 to 4mg/kg/day with subsequent dosage adjustment if necessary. For most adults, a satisfactory maintenance dose will be 200 to 500mg daily in single or divided doses. Exceptionally, a daily dose outside this range may be indicated.
Dosage should normally be adjusted according to serum levels where assay facilities exist.
Adult Dosage for Trigeminal Neuralgia:
The clinically effective dose has not been established in clinical trials. In adults, 300- 500 mg given in divided daily doses have been reported in the literature. Dosing should be adjusted based on clinical response. Determination of serum phenytoin level is advised.
Levels of total phenytoin should not exceed 20 mcg/ml. 2 Pharmacokinetic properties-Age). As with adults the dosage of Phenytoin Sodium Hard Capsules should be titrated to the patient's individual requirements using the same guidelines.
As elderly patients tend to receive multiple drug therapies, the possibility of drug interactions should be borne in mind.
Infants and Children:
Initially, 5mg/kg/day in two divided doses, with subsequent dosage individualised to a maximum of 300mg daily. A recommended daily maintenance dosage is usually 4 mg/kg to 8 mg/kg.
Neonates:
The absorption of phenytoin following oral administration in neonates is unpredictable. Furthermore, the metabolism of phenytoin may be depressed. It is therefore especially important to monitor serum levels in the neonate.
Patients with Renal or Hepatic Disease:
Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution. Unbound concentration of phenytoin may be elevated in patients with hyperbilirubinemia.
Unbound phenytoin concentrations may be more useful in these patient populations (see section
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised April 17, 2026[1]
The following adverse reactions have been reported with phenytoin (frequency unknown – cannot be estimated from available data): Immune system reactions: Anaphylactoid reaction, and anaphylaxis.
Central Nervous System:
Adverse reactions in this body system are common and are usually dose-related. Reactions include nystagmus, ataxia, slurred speech, decreased co-ordination, mental confusion. Cerebellar atrophy has been reported and appears more likely in settings of high PHE levels and/or long-term PHE use.
4 Special warnings and precautions for use – Central Nervous System Effect). Dizziness, vertigo, insomnia, transient nervousness, motor twitchings, taste perversion, headache, paresthesia and somnolence have also been observed. There have also been rare reports of phenytoin induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs.
A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.
Gastrointestinal System:
Vomiting, nausea and constipation. 4 Special warnings and precautions for use – Hepatic Injury).
Skin and subcutaneous tissue disorders:
Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. 4 Special warnings and precautions for use – Serious Dermatologic Reactions).
Urticaria also has been reported.
Connective Tissue System:
Coarsening of the facial features, enlargement of the lips, gingival hyperplasia, hirsutism, hypertrichosis, Peyronie's Disease and Dupuytren's contracture may occur rarely.
Haemopoietic System:
Haemopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leucopenia, granulocytopenia, agranulocytosis, pancytopenia with or without bone marrow suppression.
Macrocytosis and megaloblastic anaemia have occurred. Lymphadenopathy including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin's disease have been reported. 4 Special warnings and precautions for use – Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms), systemic lupus erythematosus, periarteritis nodosa, and immunoglobulin abnormalities.
4 Special warnings and precautions for use - Angioedema).
Investigations:
Thyroid function test abnormal Other: Polyarthropathy, interstitial nephritis, pneumonitis.
Musculoskeletal System:
There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with phenytoin. The mechanism by which phenytoin affects bone metabolism has not been identified. However, phenytoin has been shown to induce the CYP450 enzyme, which can affect bone mineral metabolism indirectly by increasing the metabolism of Vitamin D3.
This may lead to Vitamin D deficiency and heightened risk of osteomalacia, bone fractures, osteoporosis, hypocalcemia, and hypophosphatemia in chronically treated epileptic patients. Other disorders of bone metabolism such as hypocalcemia, hypophosphatemia and decreased levels of Vitamin D metabolites have also been reported.
Paediatric population The adverse event profile of phenytoin is generally similar between children and adults, however, gingival hyperplasia occurs more frequently in paediatric patients and in patients with poor oral hygiene. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised April 17, 2026[1]
General). Method of administration For oral administration only. 1, or other hydantoins. 4 Special warnings and precautions for use General Phenytoin is not effective for absence (petit mal) seizures. If tonic-clonic (grand mal) and absence seizures are present together, combined drug therapy is needed.
Phenytoin may affect glucose metabolism and inhibit insulin release. Hyperglycaemia has been reported in association with toxic levels. Phenytoin is not indicated for seizures due to hypoglycaemia or other metabolic causes. Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus.
When, in the judgement of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative anti-epileptic medication arises, this should be done gradually. However, in the event of an allergic or hypersensitivity reaction, rapid substitution of alternative therapy may be necessary.
In this case, alternative therapy should be an anti-epileptic drug not belonging to the hydantoin chemical class. Phenytoin may precipitate or aggravate absence seizures and myoclonic seizures. 5). Women of Childbearing Potential Phenytoin Sodium Hard Capsules may cause foetal harm when administered to a pregnant woman.
6). Phenytoin Sodium Hard Capsules should not be used in women of childbearing potential unless the benefit is judged to outweigh the risks following careful consideration of alternative suitable treatment options. Before the initiation of treatment with phenytoin in a woman of childbearing potential, pregnancy testing should be considered.
Women of childbearing potential should be fully informed of the potential risk to the foetus if they take phenytoin during pregnancy. 6). Women of childbearing potential should be counselled to contact their doctor immediately if they become pregnant or might be pregnant and are taking phenytoin.
Women of childbearing potential should use effective contraception during treatment and for one month after stopping treatment. ” Suicide Suicidal ideation and behaviour have been reported in patients treated with anti- epileptic agents in several indications.
A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for Phenytoin Sodium.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised April 17, 2026[1]
1, or other hydantoins.
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised April 29, 2026[2]
1 ) • Adult starting dose in patients who have received no previous treatment is two phenytoin chewable tablets three times a day, with dose adjustments as necessary. For most adults, the satisfactory maintenance dose will be six to eight phenytoin chewable tablets daily; an increase to twelve phenytoin chewable tablets daily may be made, if necessary.
2 ) • Pediatric starting dose is 5 mg/kg/day in two to three equally divided doses, with dosage adjustments as necessary, up to a maximum of 300 mg daily. Maintenance dosage is 4 mg/kg/day to 8 mg/kg/day. 3 ) • Serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum total concentration is 10 mcg/mL to 20 mcg/mL (unbound phenytoin concentration is 1 mcg/mL to 2 mcg/mL).
1 Important Administration Instructions NOT FOR ONCE-A-DAY DOSING. Phenytoin chewable tablets can be either chewed thoroughly before being swallowed or swallowed whole. 2 Adult Dosage The recommended starting dosage for adult patients who have received no previous treatment is two 50 mg phenytoin chewable tablets by mouth three times daily.
Adjust the dosage to suit individual requirements up to a maximum of twelve phenytoin chewable tablets daily. For most adults, the satisfactory maintenance dosage will be six to eight phenytoin chewable tablets daily. 3 Pediatric Dosage The recommended starting dosage for pediatric patients is 5 mg/kg/day by mouth in two or three equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily in divided doses.
A recommended daily maintenance dosage is usually 4 mg/kg/day to 8 mg/kg/day in equally divided doses. Children over 6 years and adolescents may require the minimum adult dosage (300 mg/day). If the daily dosage cannot be divided equally, the larger dose should be given before retiring.
4 Dosage Adjustments Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments. Trough levels provide information about clinically effective serum level range and confirm patient compliance, and are obtained just prior to the patient's next scheduled dose.
Peak levels indicate an individual's threshold for emergence of dose-related side effects and are obtained at the time of expected peak concentration. Therapeutic effect without clinical signs of toxicity occurs more often with serum total concentrations between 10 mcg/mL and 20 mcg/mL (unbound phenytoin concentrations of 1 mcg/mL to 2 mcg/mL), although some mild cases of tonic-clonic (grand mal) epilepsy may be controlled with lower serum levels of phenytoin.
6) ] . With recommended dosage, a period of seven to ten days may be required to achieve steady-state blood levels with phenytoin and changes in dosage (increase or decrease) should not be carried out at intervals shorter than seven to ten days.
5 Switching Between Phenytoin Formulations The free acid form of phenytoin is used in phenytoin oral suspension and phenytoin chewable tablets. Extended phenytoin sodium capsules and parenteral phenytoin are formulated with the sodium salt of phenytoin.
Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa.
6) ] . 3) ] . 8 Dosing during Pregnancy Decreased serum concentrations of phenytoin may occur during pregnancy because of altered phenytoin pharmacokinetics. Periodic measurement of serum phenytoin concentrations should be performed during pregnancy, and the phenytoin chewable tablets dosage should be adjusted as necessary.
1) ] . Because of potential changes in protein binding during pregnancy, the monitoring of phenytoin serum levels should be based on the unbound fraction.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 901 reports total. [4]
Drug Ineffective 171
Seizure 102
Off Label Use 101
Drug Interaction 62
Toxicity To Various Agents 51
Dizziness 48
Drug Reaction With Eosinophilia And Systemic Symptoms 43
Somnolence 34
Nausea 30
Status Epilepticus 29
Drug Ineffective For Unapproved Indication 28
Headache 28
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised April 29, 2026[2]
14) ] The following adverse reactions associated with the use of phenytoin were identified in clinical studies or postmarketing reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
7) ] . Anaphylaxis has also been reported. There have also been reports of coarsening of facial features, systemic lupus erythematosus, periarteritis nodosa, and immunoglobulin abnormalities.
Digestive System:
Acute hepatic failure, toxic hepatitis, liver damage, nausea, vomiting, constipation, enlargement of the lips, and gingival hyperplasia.
Hematologic and Lymphatic System:
Hematopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression.
While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy. 9) ] . Pure red cell aplasia has also been reported.
Laboratory Test Abnormality:
Phenytoin may decrease serum concentrations of thyroid hormone (T4 and T3), sometimes with an accompanying increase in thyroid-stimulating hormone (TSH), but usually in the absence of clinical hypothyroidism. Phenytoin may also produce lower than normal values for dexamethasone or metyrapone tests.
14) ], alkaline phosphatase, and gamma glutamyl transpeptidase (GGT).
Nervous System:
The most common adverse reactions encountered with phenytoin therapy are nervous system reactions and are usually dose-related. Reactions include nystagmus, ataxia, slurred speech, decreased coordination, somnolence, and mental confusion.
Dizziness, vertigo, insomnia, transient nervousness, motor twitchings, paresthesias, and headaches have also been observed. There have also been rare reports of phenytoin-induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs.
15) ] . A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.
Skin and Appendages:
Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. 3) ] . There have also been reports of hypertrichosis and urticaria.
Special Senses:
Altered taste sensation including metallic taste.
Urogenital:
Peyronie's disease The most common adverse reactions are nervous system reactions, including nystagmus, ataxia, slurred speech, decreased coordination, somnolence, and mental confusion. gov/medwatch.
USOfficial regulatory label· Warnings and precautions· revised April 29, 2026[2]
5 WARNINGS AND PRECAUTIONS • Withdrawal Precipitated Seizure: May precipitate status epilepticus. Dose reductions or discontinuation should be done gradually. 1 ) • Suicidal Behavior and Ideation: Monitor patients for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
2 ) • Serious Dermatologic Reactions: Discontinue phenytoin chewable tablets at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered.
3 ) • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity: If signs or symptoms of hypersensitivity are present, evaluate the patient immediately. Discontinue if an alternative etiology cannot be established.
4 ) • Cardiac Effects: Bradycardia and cardiac arrest have been reported. 6 ) • Angioedema: Discontinue immediately if symptoms of angioedema such as facial, perioral, or upper airway swelling occur. 7 ) • Hepatic Injury: Cases of acute hepatotoxicity have been reported with phenytoin chewable tablets.
If this occurs, immediately discontinue. 8 ) • Hematopoietic Complications: If occurs, follow-up observation is indicated and an alternative antiepileptic treatment should be used. 1 Withdrawal Precipitated Seizure, Status Epilepticus Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus.
When, in the judgment of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative anticonvulsant medication arises, this should be done gradually. However, in the event of an allergic or hypersensitivity reaction, more rapid substitution of alternative therapy may be necessary.
In this case, alternative therapy should be an anticonvulsant not belonging to the hydantoin chemical class. 2 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including phenytoin chewable tablets, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication.
Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. 7) of suicidal thinking or behavior compared to patients randomized to placebo.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised April 29, 2026[2]
5) ] . Reactions have included angioedema. 8) ] . • Coadministration with delavirdine because of the potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.
8 ) • Coadministration with delavirdine ( 4 )
This is not medical advice. Consult a qualified healthcare professional.
CAOfficial regulatory label· revised March 22, 2025[3]
1 Dosing Considerations Dosage should be individualized to provide maximum benefit. There may be wide interpatient variability in phenytoin serum levels with equivalent dosages. Phenytoin is highly bound to plasma protein and is subject to saturable metabolism.
Consequently: • small dose increases may substantially raise serum phenytoin concentration (and risk of DILANTIN INFATABS and DILANTIN SUSPENSIONS (phenytoin) Page 5 of 39 toxicity), when levels are already in or above the upper therapeutic range; and • phenytoin is subject to many drug interactions, which may increase serum concentrations.
3 Pharmacokinetics; and 9 DRUG INTERACTIONS. Serum blood level determinations may be necessary for optimal dosage adjustments. The clinically effective serum level is usually 40-80 micromol/L (10-20 mcg/mL). Serum blood level determinations are especially helpful when: • drug or other interactions are suspected; • treating geriatric patients; • patients have renal or hepatic impairment, or hypoalbuminemia, or hyperbilirubinemia (in which case unbound phenytoin levels should be monitored).
2 Renal or Hepatic Disease. Switch carefully between sodium salt and free acid phenytoin products. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments may be necessary and serum phenytoin concentrations should be monitored when switching between free acid and sodium salt formulations.
• The sodium salt of phenytoin is used in DILANTIN extended capsules. • The free acid form of phenytoin is used in DILANTIN-30 SUSPENSION, DILANTIN-125 SUSPENSION and DILANTIN INFATABS. • DILANTIN SUSPENSIONS ARE FOR ORAL USE, NOT PARENTERAL USE.
Phenytoin should not be abruptly discontinued because of the possibility of increased seizure frequency, including status epilepticus. See 7 WARNINGS AND PRECAUTIONS, General, Withdrawal Precipitated Seizures. 2 Recommended Dose and Dosage Adjustment DILANTIN INFATABS, DILANTIN-30 SUSPENSION and DILANTIN-125 SUSPENSION are not for once-a-day dosing.
With recommended dosage, a period of 7 to 10 days may be required to achieve therapeutic blood levels with DILANTIN INFATABS, DILANTIN-30 SUSPENSION and DILANTIN-125 SUSPENSION and changes in dosage (increase or decrease) should not be carried out at intervals shorter than 7 to 10 days.
• Adults Patients who have received no previous treatment may be started on 2 DILANTIN INFATABS 3 times daily or on 1 teaspoonful (5 mL) of DILANTIN-125 SUSPENSION 3 times daily, and the dose then adjusted to suit individual requirements.
For some adults, the satisfactory maintenance dosage will be 8 DILANTIN INFATABS daily; an increase to 12 DILANTIN INFATABS may be made, if necessary. With DILANTIN-125 SUSPENSION, an increase to 5 teaspoonfuls (25 mL) daily may be made if necessary.
DILANTIN INFATABS and DILANTIN SUSPENSIONS (phenytoin) Page 6 of 39 • Pediatrics (< 18 years of age) Initially, 5 mg/kg/day of DILANTIN INFATABS, DILANTIN-30 SUSPENSION or DILANTIN-125 SUSPENSION may be given in 2 or 3 equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily.
A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years may require the minimum adult dose (300 mg/day). If the daily dosage cannot be divided equally, the larger dose should be given at bedtime. • Geriatrics (> 65 years of age) Phenytoin clearance is decreased slightly in elderly patients.
Lower doses than the doses recommended for adults may be required when initiating treatment. 3 Pharmacokinetics, Geriatrics). • Renal or Hepatic Disease In patients with renal or hepatic impairment or in those with hypoalbuminemia, plasma levels of unbound phenytoin are elevated.
Unbound phenytoin concentrations may be more useful in these patient populations. 1 Dosing Considerations; and 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic and Renal). 5 Missed Dose The patient/caregiver should be advised that if a dose is missed, the missed dose should be taken as soon as it is remembered.
If it is almost time for the next dose, the missed dose should not be taken. Instead, take the next scheduled dose. The patient/caregiver should be advised to not to make up for a missed dose by taking a double dose next time.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[3]
). g. fosphenytoin) are contraindicated in patients who have experienced phenytoin hypersensitivity (see 2 CONTRAINDICATIONS). , trimethadione) in these patients or immediate family members, other alternatives should be considered. See also 7 WARNINGS AND PRECAUTIONS, Skin.
Angioedema Angioedema has been reported in patients treated with phenytoin. Phenytoin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur. Monitoring and Laboratory Tests Phenytoin serum level determinations may be necessary to achieve optimal dosage adjustments.
7 Drug-Laboratory Test Interactions. 5 Post- Market Adverse Reactions). Phenytoin and other anticonvulsants that have been shown to induce the CYP450 enzyme are thought to affect bone mineral metabolism indirectly by increasing the metabolism of Vitamin D3.
This may lead to Vitamin D deficiency and heightened risk of osteomalacia, bone fractures, osteoporosis, hypocalcemia, and hypophosphatemia in chronically treated epileptic patients. Consideration should be given to monitoring with bone-related laboratory and radiological tests and initiating treatment plans, as appropriate.
Neurologic Central Nervous System Serum levels of phenytoin sustained above the optimal range may produce confusional states referred to as "delirium", "psychosis" or "encephalopathy", or rarely irreversible cerebellar DILANTIN INFATABS and DILANTIN SUSPENSIONS (phenytoin) Page 12 of 39 dysfunction and/or cerebellar atrophy.
Accordingly, at the first sign of acute toxicity, serum drug level determinations are recommended. 3 Pharmacokinetics, Absorption, 7 WARNINGS AND PRECAUTIONS, General). Psychiatric Suicidal ideation and behaviour Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications.
An FDA meta-analysis of randomized placebo-controlled trials, in which antiepileptic drugs were used for various indications, has shown a small increased risk of suicidal ideation and behaviour in patients treated with these drugs.
The mechanism of this risk is not known. All patients treated with antiepileptic drugs, irrespective of indication, should be monitored for signs of suicidal ideation and behaviour and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
There were 43,892 patients treated in the placebo controlled clinical trials that were included in the meta-analysis. Approximately 75% of patients in these clinical trials were treated for indications other than epilepsy and, for the majority of non-epilepsy indications the treatment (antiepileptic drug or placebo) was administered as monotherapy.
, patients in both treatment arms were being treated with one or more antiepileptic drug). 24% for patients on placebo) is based largely on patients that received monotherapy treatment (antiepileptic drug or placebo) for non-epilepsy indications.
The study design does not allow an estimation of the risk of suicidal ideation and behaviour for patients with epilepsy that are taking antiepileptic drugs, due both to this population being the minority in the study, and the drug-placebo comparison in this population being confounded by the presence of adjunct antiepileptic drug treatment in both arms.
Renal In patients with renal impairment, plasma levels of unbound phenytoin are elevated. 2 Recommended Dose and Dosage Adjustment, Renal or Hepatic Disease). 1 Pregnant Women, Risks to Fetus. DILANTIN INFATABS and DILANTIN SUSPENSIONS (phenytoin) Page 13 of 39 Skin Serious Dermatological Reactions Phenytoin can cause rare, severe cutaneous adverse reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), exfoliative dermatitis, Steven-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be fatal.
Although serious skin reactions may occur without warning, patients should be alert for the occurrence of rash and other symptoms of hypersensitivity syndrome (HSS)/DRESS. Hypersensitivity Syndrome / Drug Reaction with Eosinophilia and Systemic Symptoms Hypersensitivity Syndrome (HSS) or Drug rash with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking anticonvulsant drugs, including phenytoin.
Some of these events have been fatal or life threatening. HSS/DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, myositis or pneumonitis.
Initial symptoms […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[3]
, Hypersensitivity; and Skin). • Patients being treated with delavirdine (a non-nucleoside reverse transcriptase inhibitor). 4 Drug-Drug Interactions. • Patients who currently suffer from sick sinus syndrome, sinus bradycardia, sinoatrial block, second- and third-degree atrioventricular (A-V) block, QT interval prolongation, Adams-Stokes syndrome, or other heart rhythm disorders.
This is due to the effect of phenytoin on ventricular automaticity. See 7 WARNINGS AND PRECAUTIONS, Cardiovascular; and 5 OVERDOSAGE. 1 Dosing Considerations Dosage should be individualized to provide maximum benefit. There may be wide interpatient variability in phenytoin serum levels with equivalent dosages.
Phenytoin is highly bound to plasma protein and is subject to saturable metabolism. Consequently: • small dose increases may substantially raise serum phenytoin concentration (and risk of DILANTIN INFATABS and DILANTIN SUSPENSIONS (phenytoin) Page 5 of 39 toxicity), when levels are already in or above the upper therapeutic range; and • phenytoin is subject to many drug interactions, which may increase serum concentrations.
3 Pharmacokinetics; and 9 DRUG INTERACTIONS. Serum blood level determinations may be necessary for optimal dosage adjustments. The clinically effective serum level is usually 40-80 micromol/L (10-20 mcg/mL). Serum blood level determinations are especially helpful when: • drug or other interactions are suspected; • treating geriatric patients; • patients have renal or hepatic impairment, or hypoalbuminemia, or hyperbilirubinemia (in which case unbound phenytoin levels should be monitored).
2 Renal or Hepatic Disease. Switch carefully between sodium salt and free acid phenytoin products. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments may be necessary and serum phenytoin concentrations should be monitored when switching between free acid and sodium salt formulations.
• The sodium salt of phenytoin is used in DILANTIN extended capsules. • The free acid form of phenytoin is used in DILANTIN-30 SUSPENSION, DILANTIN-125 SUSPENSION and DILANTIN INFATABS. • DILANTIN SUSPENSIONS ARE FOR ORAL USE, NOT PARENTERAL USE.
Phenytoin should not be abruptly discontinued because of the possibility of increased seizure frequency, including status epilepticus. See 7 WARNINGS AND PRECAUTIONS, General, Withdrawal Precipitated Seizures. 2 Recommended Dose and Dosage Adjustment DILANTIN INFATABS, DILANTIN-30 SUSPENSION and DILANTIN-125 SUSPENSION are not for once-a-day dosing.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[3]
Phenytoin is contraindicated in: • Patients who are hypersensitive to phenytoin, other hydantoins, or any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING; and 7 WARNINGS AND PRECAUTIONS, Hypersensitivity; and Skin).
• Patients being treated with delavirdine (a non-nucleoside reverse transcriptase inhibitor). 4 Drug-Drug Interactions. • Patients who currently suffer from sick sinus syndrome, sinus bradycardia, sinoatrial block, second- and third-degree atrioventricular (A-V) block, QT interval prolongation, Adams-Stokes syndrome, or other heart rhythm disorders.
This is due to the effect of phenytoin on ventricular automaticity. See 7 WARNINGS AND PRECAUTIONS, Cardiovascular; and 5 OVERDOSAGE.
This is not medical advice. Consult a qualified healthcare professional.
Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
9), but also at recommended phenytoin doses and levels. Hypersensitivity Syndrome / Drug Reaction with Eosinophilia and Systemic Symptoms Hypersensitivity syndrome (HSS) or drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported in patients taking anticonvulsant drugs, including phenytoin.
Some of these events have been fatal or life threatening. HSS/DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, myositis or pneumonitis.
Initial symptoms may resemble an acute viral infection. Other common manifestations include arthralgias, jaundice, hepatomegaly, leukocytosis, and eosinophilia. The interval between the first drug exposure and symptoms is usually 2 to 4 weeks but has been reported in individuals receiving anticonvulsants for 3 or more months.
If such signs and symptoms occur, the patient should be evaluated immediately. Phenytoin should be discontinued if an alternative etiology for the signs and symptoms cannot be established. Patients at higher risk for developing HSS/DRESS include black patients, patients who have experienced this syndrome in the past (with phenytoin or other anticonvulsant drugs), patients who have a family history of this syndrome, and immunosuppressed patients.
The syndrome is more severe in previously sensitized individuals. 8 undesirable effects –Skin and subcutaneous tissue disorders), exfoliative dermatitis, Stevens - Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and DRESS which can be fatal.
4 Special warnings and precautions for use –Hypersensitivity Syndrome/Drug Reaction with Eosinophilia […]
24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication.
The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs. 9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing phenytoin chewable tablets or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior.
Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
Behaviors of concern should be reported immediately to healthcare providers. 3 Serious Dermatologic Reactions Phenytoin can cause severe cutaneous adverse reactions (SCARs), which may be fatal. 4) ]. The onset of symptoms is usually within 28 days, but can occur later.
Phenytoin should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest a severe cutaneous adverse reaction, use of this drug should not be resumed and alternative therapy should be considered.
If a rash occurs, the patient should be evaluated for signs and symptoms of SCARs. Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene, in patients using carbamazepine.
Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. In addition, retrospective, case-control, genome-wide association studies in patients of southeast Asian ancestry have also identified an increased risk of SCARs in carriers of the decreased function CYP2C9*3 variant, which has also been associated with decreased clearance of phenytoin.
5) ] . The use of HLA-B*1502 or CYP2C9 genotyping has important limitations and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dose, compliance, concomitant medications, comorbidities, and the level of dermatologic monitoring have not been studied.
4 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including phenytoin.
Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection.
Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.
If such signs or symptoms are present, the patient should be evaluated immediately. Phenytoin should be discontinued if an alternative etiology for the signs or symptoms cannot be established. 7) ] . , trimethadione) in these same patients.
Similarly, if there is a history of hypersensitivity reactions to these structurally similar drugs in the patient or immediate family members, consider alternatives to phenytoin. 6 Cardiac Effects Cases of bradycardia and cardiac arrest have been reported in phenytoin-treated patients, both at recommended phenytoin doses and levels, and in association with phenytoin toxicity [see Overdosage (10) ].
Most of the reports of cardiac arrest occurred in patients with underlying cardiac disease. 7 Angioedema Angioedema has been reported in patients treated with phenytoin in the postmarketing setting. Phenytoin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur.
Phenytoin should be discontinued permanently if a clear alternative etiology for the reaction cannot be established. 8 Hepatic Injury Cases of acute hepatotoxicity, including infrequent cases of acute hepatic failure, have been reported with phenytoin.
4) ] . Other common manifestations include jaundice, hepatomegaly, elevated serum transaminase levels, leukocytosis, and eosinophilia. The clinical course of acute phenytoin hepatotoxicity ranges from prompt recovery to fatal outcomes.
In these patients with acute hepatotoxicity, phenytoin should be immediately discontinued and not readministered. 9 Hematopoietic Complications Hematopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin.
These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression. There have been a number of reports suggesting a relationship between phenytoin and the development of lymphadenopathy (local or generalized) including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin's disease.
Although a cause and effect relationship has not been established, the occurrence of lymphadenopathy indicates the need to differentiate such a condition from other types of lymph node pathology. 4) ] . In all cases of lymphadenopathy, follow-up observation for an extended period is indicated and every effort should be made to achieve seizure control using alternative antiepileptic drugs.
10 Effects on Vitamin D and Bone The chronic use of phenytoin in patients with epilepsy has been associated with decreased bone mineral density (osteopenia, osteoporosis, and osteomalacia) and bone fractures. Phenytoin induces hepatic metabolizing enzymes.
This may enhance the metabolism of vitamin D and decrease vitamin D levels, which may lead to vitamin D deficiency, hypocalcemia, and hypophosphatemia. Consideration should be given to screening with bone-related laboratory and radiological tests as appropriate and initiating treatment plans according to established guidelines.
11 Renal or Hepatic Impairment or Hypoalbuminemia Because the fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound fraction in those patients.
12 Exacerbation of Porphyria In view of isolated reports associating phenytoin with exacerbation of porphyria, caution should be exercised in using this medication in patients suffering from this disease. 13 Teratogenicity and Other Harm to the Newborn Phenytoin may cause fetal harm when administered to a pregnant woman.
1) ] . Increased frequencies of major malformations (such as orofacial clefts and cardiac defects), and abnormalities characteristic of fetal hydantoin syndrome, including dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits, have been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy.
There have been several reported cases of malignancies, including neuroblastoma. A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors may occur in newborns exposed to phenytoin in utero .
This drug-induced condition can be prevented with vitamin K administration to the mother before delivery and to the neonate after birth. 14 Hyperglycemia Hyperglycemia, resulting from the drug's inhibitory effects on insulin release, has been reported.
Phenytoin may also raise the serum glucose level in diabetic patients. 15 Serum Phenytoin Levels above Therapeutic Range Serum levels of phenytoin sustained above the therapeutic range may produce confusional states referred to as "delirium," "psychosis," or "encephalopathy," or rarely irreversible cerebellar dysfunction and/or cerebellar atrophy.
Accordingly, at the first sign of acute toxicity, serum levels should be immediately checked. Dose reduction of phenytoin therapy is indicated if serum levels are excessive; if symptoms persist, termination is recommended.
With recommended dosage, a period of 7 to 10 days may be required to achieve therapeutic blood levels with DILANTIN INFATABS, DILANTIN-30 SUSPENSION and DILANTIN-125 SUSPENSION and changes in dosage (increase or decrease) should not be carried out at intervals shorter than 7 to 10 days.
• Adults Patients who have received no previous treatment may be started on 2 DILANTIN INFATABS 3 times daily or on 1 teaspoonful (5 mL) of DILANTIN-125 SUSPENSION 3 times daily, and the dose then adjusted to suit individual requirements.
For some adults, the satisfactory maintenance dosage will be 8 DILANTIN INFATABS daily; an increase to 12 DILANTIN INFATABS may be made, if necessary. With DILANTIN-125 SUSPENSION, an increase to 5 teaspoonfuls (25 mL) daily may be made if necessary.
DILANTIN INFATABS and DILANTIN SUSPENSIONS (phenytoin) Page 6 of 39 • Pediatrics (< 18 years of age) Initially, 5 mg/kg/day of DILANTIN INFATABS, DILANTIN-30 SUSPENSION or DILANTIN-125 SUSPENSION may be given in 2 or 3 equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily.
A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years may require the minimum adult dose (300 mg/day). If the daily dosage cannot be divided equally, the larger dose should be given at bedtime. • Geriatrics (> 65 years of age) Phenytoin clearance is decreased slightly in elderly patients.
Lower doses than the doses recommended for adults may be required when initiating treatment. 3 Pharmacokinetics, Geriatrics). • Renal or Hepatic Disease In patients with renal or hepatic impairment or in those with hypoalbuminemia, plasma levels of unbound phenytoin are elevated.
Unbound phenytoin concentrations may be more useful in these patient populations. 1 Dosing Considerations; and 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic and Renal). 5 Missed Dose The patient/caregiver should be advised that if a dose is missed, the missed dose should be taken as soon as it is remembered.
If it is almost time for the next dose, the missed dose should not be taken. Instead, take the next scheduled dose. The patient/caregiver should be advised to not to make up for a missed dose by taking a double dose next time. 5 OVERDOSAGE The lethal dose of DILANTIN INFATABS, DILANTIN-30 SUSPENSION and DILANTIN-125 SUSPENSION in pediatric patients is not known.
The lethal dose of phenytoin in adults is estimated to be 2 to 5 grams. The initial symptoms are nystagmus, ataxia, and dysarthria. Other signs are tremor, hyperreflexia, somnolence, drowsiness, lethargy, slurred speech, blurred vision, nausea, vomiting.
The patient may become comatose and hypotensive. Bradycardia and asystole/cardiac arrest have been reported (see 7 WARNINGS AND PRECAUTIONS, Cardiac effects). Death is due to respiratory and circulatory depression. There are marked variations among individuals with respect to phenytoin plasma levels where toxicity may occur.
Nystagmus on lateral gaze, usually appears at 80 micromol/L (20 mcg/mL), ataxia at 119 micromol/L (30 mcg/mL). Dysarthria and lethargy appear […]