Phenytoin 125 mg/5mL Suspension
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Anti-epileptic Agent class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
- Phenytoin is an antiseizure medication — it's used to treat and prevent different types of seizures, including tonic-clonic (grand mal) seizures, complex partial seizures, and seiz...
- The most important thing is to take it exactly as prescribed and not skip doses. If you're on chewable tablets or the liquid suspension, those are not once-a-day medications — they...
- How do I take phenytoin correctly — are there any tricks I should know?
- The most common side effects involve your nervous system — things like dizziness, unsteady walking, slurred speech, drowsiness, and rapid eye movements. These are often dose-relate...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Phenytoin — tap one for details:
Phenytoin may be associated with lower levels of 13 nutrients — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII XF417D3PSL
Anhydrous citric acid is a sour, crystalline powder derived from citric acid with water removed. In medicines, it acts as a buffer to control pH, adds tartness to improve taste, and helps tablets disintegrate.
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UNII K679OBS311
Carboxymethylcellulose sodium is a plant-derived thickening agent made from cellulose. In medicines, it acts as a binder to hold ingredients together, a disintegrant to help the tablet break apart, or a thickener in liquids.
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UNII H77VEI93A8
A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
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UNII 6M3P64V0NC
A fine powder made from magnesium, aluminum, and silicon compounds. It absorbs moisture and helps keep medicine ingredients from clumping or separating, so the product stays stable and flows smoothly during manufacturing.
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UNII CAL22UVI4M
A synthetic emulsifier derived from sorbitol and fatty acids. It helps mix oil and water-based ingredients together and improves the texture and stability of the medicine.
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UNII OJ245FE5EU
Sodium benzoate is a salt derived from benzoic acid, a preservative. It's added to medicines to prevent growth of bacteria, fungi, and other microorganisms that could spoil the product.
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UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
8 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.076 | $17.92 / 237 ml |
| Medicaid paysCMS SDUD · 12 mo | $0.1037 | $24.58 / 237 ml |
| Medicare drug plans payPart D · Q2 2026 | $0.0873 | $20.69 / 237 ml |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Phenytoin 125 mg/5mLthis 51672-4069-02 | Sun | 1 bottle | $0.076 | AB | Availability likely | — |
| Phenytoin 125 mg/5mL 59762-0531-02 | Mylan | 1 bottle | $0.076 | AB | Availability likely | — |
| Phenytoin 125 mg/5mL 00121-0892-50 | PAI | 10 cups | — | AB | FDA listed | — |
| Phenytoin 125 mg/5mL 17856-4070-01 | ATLANTIC | 72 cups | — | AB | FDA listed | — |
| Dilantin-125 125 mg/5mL 58151-0115-35 | Viatris | 1 bottle | — | AB | FDA listed | — |
| Phenytoin 125 mg/5mL 60687-0275-66 | American | 10 cups | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 51672-4069-01 | 237 mL in 1 BOTTLE (51672-4069-1) | $0.0756 / mL | $17.92 | 2004-04-08 | Discontinued by firm |
| 51672-4069-02 You're viewing this | 1 BOTTLE in 1 CARTON (51672-4069-2) / 237 mL in 1 BOTTLE | $0.0756 / mL | $17.92 | 2025-07-23 | Active |
This pack effectively ties for the lowest per-mL cost of the 2 priced pack sizes ($0.0756 NADAC).
This pack accounts for about 12% of this product's recent Medicaid fills; most go to the 237 ml pack. See all packs ↓
Pack size FAQ
What quantity is in NDC 51672-4069-02?
What NDC number is used to bill for this package of Phenytoin 125 mg/5mL Suspension?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Phenytoin oral suspension is indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures. Phenytoin oral suspension is indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Adult starting dose in patients who have received no previous treatment is 5 mL three times daily, with dose adjustments as necessary, up to 25 mL daily. ( 2.2 ) 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.
( 2.3 ) 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). ( 2.1 )
2.1Important Administration Instructions FOR ORAL ADMINISTRATION ONLY; NOT FOR PARENTERAL USE A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device.
2.2Adult Dosage The recommended starting dosage for adult patients who have received no previous treatment is 5 mL (125 mg/5 mL), or one teaspoonful, by mouth three times daily. Adjust the dosage to suit individual requirements, up to a maximum of 25 mL daily [see Dosage and Administration (2.4) ] .
2.3Pediatric 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).
2.4Dosage 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. In patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of unbound phenytoin concentrations may be more relevant [see Dosage and Administration (2.6) ] .
With recommended dosages, a period of seven to ten days may be required to achieve phenytoin steady-state blood levels, and changes in dosage (increase or decrease) should not be carried out at intervals shorter than seven to ten days.
2.5Switching Between Phenytoin Formulations The free acid form of phenytoin is used in phenytoin oral suspension and DILANTIN Infatabs. DILANTIN extended capsules and parenteral DILANTIN 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.
2.6Dosing in Patients with 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 [see Warnings and Precautions (5.11) and Use in Specific Populations (8.6) ] .
2.7Geriatric Dosage Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required [see Clinical Pharmacology (12.3) ] .
2.8 Dosing during Pregnancy Decreased serum concent…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Phenytoin oral suspension is available as a 125 mg phenytoin/5 mL oral suspension of orange color with an orange-vanilla flavor. Phenytoin oral suspension is available as a 125 mg phenytoin/5 mL oral suspension. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Phenytoin oral suspension is contraindicated in patients with: A history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins [see Warnings and Precautions (5.5) ] . Reactions have included angioedema. A history of prior acute hepatotoxicity attributable to phenytoin [see Warnings and Precautions (5.8) ] .
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. Hypersensitivity to phenytoin, its ingredients, or other hydantoins ( 4 , 5.5 ) A history of prior acute hepatotoxicity attributable to phenytoin ( 4 , 5.8 ) Coadministration with delavirdine ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Withdrawal Precipitated Seizure: May precipitate status epilepticus. Dose reductions or discontinuation should be done gradually. ( 5.1 ) 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.
( 5.2 ) Serious Dermatologic Reactions: Discontinue phenytoin oral suspension 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. ( 5.3 ) 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. ( 5.4 ) Cardiac Effects: Bradycardia and cardiac arrest have been reported. ( 5.6 ) Angioedema: Discontinue immediately if symptoms of angioedema such as facial, perioral, or upper airway swelling occur.
( 5.7 ) Hepatic Injury: Cases of acute hepatotoxicity have been reported with phenytoin oral suspension. If this occurs, immediately discontinue. ( 4 , 5.8 ) Hematopoietic Complications: If occurs, follow-up observation is indicated and an alternative antiepileptic treatment should be used.
( 5.9 )
5.1Withdrawal 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.
5.2Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including phenytoin, 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. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo.
In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% 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.
Table 1 Risk by indication for antiepilep…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions (5.1) ] Suicidal Behavior and Ideation [see Warnings and Precautions (5.2) ] Serious Dermatologic Reactions [see Warnings and Precautions (5.3) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.4) ] Hypersensitivity [see Warnings and Precautions (5.5) ] Cardiac Effects [see Warnings and Precautions (5.6) ] Angioedema [see Warnings and Precautions (5.7) ] Hepatic Injury [see Warnings and Precautions (5.8) ] Hematopoietic Complications [see Warnings and Precautions (5.9) ] Effects on Vitamin D and Bone [see Warnings and Precautions (5.10) ] Exacerbation of Porphyria [see Warnings and Precautions (5.12) ] Teratogenicity and Other Harm to the Newborn [see Warnings and Precautions (5.13) ] Hyperglycemia [see Warnings and Precautions (5.14) ] 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. Body as a Whole: Allergic reactions in the form of rash and rarely more serious forms and DRESS have been observed, as has angioedema [see Warnings and Precautions (5.3 , 5.4 , 5.7) ] . 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. Lymphadenopathy including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin's disease have been reported [see Warnings and Precautions (5.9) ] .
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.
Phenytoin may cause increased serum levels of glucose [see Warnings and Precautions (5.14) ] , 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. Cerebellar atrophy has been reported, and appears more likely in settings of elevated phenytoin levels and/or long-term phenytoin use [see Warnings and Precautions (5.15) ] .
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…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Phenytoin is extensively bound to plasma proteins and is prone to competitive displacement. Phenytoin is primarily metabolized by the hepatic cytochrome P450 enzyme CYP2C9 and to a lesser extent by CYP2C19 and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity.
Monitoring of phenytoin serum levels is recommended when a drug interaction is suspected. Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes. Multiple drug interactions because of extensive plasma protein binding, saturable metabolism and potent induction of hepatic enzymes.
( 7.1 , 7.2 )
7.1Drugs that Affect Phenytoin Concentrations Table 2 includes commonly occurring drug interactions that affect phenytoin concentrations. However, this list is not intended to be inclusive or comprehensive. Individual prescribing information from relevant drugs should be consulted.
The addition or withdrawal of these agents in patients on phenytoin therapy may require an adjustment of the phenytoin dose to achieve optimal clinical outcome. Table 2: Drugs That Affect Phenytoin Concentrations Interacting Agent Examples Drugs that may increase phenytoin serum levels Antiepileptic drugs Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline Gastric acid reducing agents H 2 antagonists (cimetidine), omeprazole Sulfonamides Sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole-trimethoprim Other Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogen, fluvastatin, isoniazid, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, trazodone, warfarin Drugs that may decrease phenytoin serum levels Antacids Antacids may affect absorption of phenytoin.
Calcium carbonate, aluminum hydroxide, magnesium hydroxide Prevention or Management: Phenytoin and antacids should not be taken at the same time of day Antineoplastic agents (usually in combination) Bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate Antiviral agents Fosamprenavir, nelfinavir, ritonavir Antiepileptic drugs Carbamazepine, vigabatrin Other Chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine, rifampin, St. John's wort The induction potency of St. John's wort may vary widely based on preparation. , sucralfate, theophylline Drugs that may either increase or decrease phenytoin serum levels Antiepileptic drugs Phenobarbital, valproate sodium Valproate sodium and valproic acid are similar medications.
The term valproate has been used to represent these medications. , valproic acid
7.2Drugs Affected by Phenytoin Table 3 includes commonly occurring drug interactions affected by phenytoin. However, this list is not intended to be inclusive or comprehensive. Individual drug package inserts should be consulted.
The addition or withdrawal of phenytoin during concomitant therapy with these agents may require adjustment of the dose of these agents to achieve optimal clinical outcome. Table 3: Drugs Affected by Phenytoin Interacting Agent Examples Drugs whose efficacy is impaired by phenytoin Azoles Fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole Antineoplastic agents Irinotecan, paclitaxel, teniposide Delavirdine Phenytoin can substantially reduce the concentrations of delavirdine. This can lead to loss of virologic response and possible resistance [see Contraindications (4) ].
Neuromuscular blocking agents Cisatracurium, pancuronium, rocuronium and vecuronium: resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking agents has occurred in patients chronically administered phenytoin. Whether or not phen…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Prenatal exposure may increase the risks for congenital malformations and other adverse developmental outcomes. ( 5.13 , 8.1 ) Renal and/or Hepatic Impairment or Hypoalbuminemia: Monitor unbound phenytoin concentrations in these patients. ( 8.6 )
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as phenytoin, during pregnancy. Physicians are advised to recommend that pregnant patients taking phenytoin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the tollfree number 1-888-233-2334, and must be done by patients themselves.
Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. Risk Summary In humans, prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes. Prenatal phenytoin exposure is associated with an increased incidence of major malformations, including orofacial clefts and cardiac defects.
In addition, the fetal hydantoin syndrome, a pattern of abnormalities including dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits has been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy [see Data ] . There have been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy. Administration of phenytoin to pregnant animals resulted in an increased incidence of fetal malformations and other manifestations of developmental toxicity (including embryofetal death, growth impairment, and behavioral abnormalities) in multiple species at clinically relevant doses [see Data ] .
In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Disease-associated maternal risk An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics.
Periodic measurement of serum phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage [see Dosage and Administration (2.4 , 2.8) ] . However, postpartum restoration of the original dosage will probably be indicated [see Clinical Pharmacology (12.3) ] . Fetal/Neonatal Adverse Reactions 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. Data Human Data Meta-analyses using data from published observational studies and registries have estimated an approximately 2.4-fold increased risk for any major malformation in children with prenatal phenytoin exposure compared to controls. An increased risk of heart defects, facial clefts, and digital hypoplasia has been reported.
The fetal hydantoin syndrome is a pattern of congenital anomalies including craniofacial anomalies, nail and digital hypoplasia, prenatal-onset growth deficiency, and neurodevelopmental deficiencies. Animal Data Administration of phenytoin to pregnant rats, rabbits, and mice during organogenesis resulted in embryofetal death, fetal malformations, and decreased fetal growth. Malformations (including craniofacial, cardiovascular, neural, limb, and digit abnormalities) were observed in rats, rabbits, and mice at doses as low as 100 mg/kg, 75 mg/kg, and 12.5 mg/kg, respectively.
8.2 Lactation Risk…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as phenytoin, during pregnancy. Physicians are advised to recommend that pregnant patients taking phenytoin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the tollfree number 1-888-233-2334, and must be done by patients themselves.
Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. Risk Summary In humans, prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes. Prenatal phenytoin exposure is associated with an increased incidence of major malformations, including orofacial clefts and cardiac defects.
In addition, the fetal hydantoin syndrome, a pattern of abnormalities including dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits has been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy [see Data ] . There have been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy. Administration of phenytoin to pregnant animals resulted in an increased incidence of fetal malformations and other manifestations of developmental toxicity (including embryofetal death, growth impairment, and behavioral abnormalities) in multiple species at clinically relevant doses [see Data ] .
In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Disease-associated maternal risk An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics.
Periodic measurement of serum phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage [see Dosage and Administration (2.4 , 2.8) ] . However, postpartum restoration of the original dosage will probably be indicated [see Clinical Pharmacology (12.3) ] . Fetal/Neonatal Adverse Reactions 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. Data Human Data Meta-analyses using data from published observational studies and registries have estimated an approximately 2.4-fold increased risk for any major malformation in children with prenatal phenytoin exposure compared to controls. An increased risk of heart defects, facial clefts, and digital hypoplasia has been reported.
The fetal hydantoin syndrome is a pattern of congenital anomalies including craniofacial anomalies, nail and digital hypoplasia, prenatal-onset growth deficiency, and neurodevelopmental deficiencies. Animal Data Administration of phenytoin to pregnant rats, rabbits, and mice during organogenesis resulted in embryofetal death, fetal malformations, and decreased fetal growth. Malformations (including craniofacial, cardiovascular, neural, limb, and digit abnormalities) were observed in rats, rabbits, and mice at doses as low as 100 mg/kg, 75 mg/kg, and 12.5 mg/kg, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use Initially, 5 mg/kg/day in two or three equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily. A recommended daily maintenance dosage is usually 4 mg/kg to 8 mg/kg. Children over 6 years and adolescents may require the minimum adult dosage (300 mg/day) [see Dosage and Administration (2.3) ] .
🧓 Geriatric Use ▾
8.5Geriatric Use Phenytoin clearance tends to decrease with increasing age [see Clinical Pharmacology (12.3) ] . Lower or less frequent dosing may be required [see Dosage and Administration (2.7) ] .
🆘 Overdosage ▾
10 OVERDOSAGE The lethal dose in pediatric patients is not known. The lethal dose in adults is estimated to be 2 grams to 5 grams. The initial symptoms are nystagmus, ataxia, and dysarthria.
Other signs are tremor, hyperreflexia, lethargy, slurred speech, blurred vision, nausea, and vomiting. The patient may become comatose and hypotensive. Bradycardia and cardiac arrest have been reported [see Warnings and Precautions (5.6) ] .
Death is caused by respiratory and circulatory depression. There are marked variations among individuals with respect to phenytoin serum levels where toxicity may occur. Nystagmus, on lateral gaze, usually appears at 20 mcg/mL, ataxia at 30 mcg/mL, dysarthria and lethargy appear when the serum concentration is over 40 mcg/mL, but as high a concentration as 50 mcg/mL has been reported without evidence of toxicity.
As much as 25 times the therapeutic dose has been taken to result in a serum concentration over 100 mcg/mL with complete recovery. Irreversible cerebellar dysfunction and atrophy have been reported. Treatment: Treatment is nonspecific since there is no known antidote.
The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate supportive measures employed. Hemodialysis can be considered since phenytoin is not completely bound to plasma proteins. Total exchange transfusion has been used in the treatment of severe intoxication in pediatric patients.
In acute overdosage the possibility of other CNS depressants, including alcohol, should be borne in mind.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltage-dependent blockade of membrane sodium channels resulting in a reduction in sustained high-frequency neuronal discharges.
12.3Pharmacokinetics Absorption For phenytoin oral suspension, peak levels occur 1½ to 3 hours after administration. Steady-state therapeutic levels are achieved at least 7 to 10 days (5 to 7 half-lives) after initiation of therapy with recommended doses of 300 mg/day. When serum level determinations are necessary, they should be obtained at least 5 to 7 half-lives after treatment initiation, dosage change, or addition or subtraction of another drug to the regimen so that equilibrium or steady-state will have been achieved.
Distribution Phenytoin is extensively bound to serum plasma proteins. Elimination The plasma half-life in man after oral administration of phenytoin averages 22 hours, with a range of 7 to 42 hours. Metabolism Phenytoin is primarily metabolized by the hepatic cytochrome P450 enzyme CYP2C9 and to a lesser extent by CYP2C19.
Because phenytoin is hydroxylated in the liver by an enzyme system which is saturable at high serum levels, small incremental doses may increase the half-life and produce very substantial increases in serum levels, when these are in the upper range. The steady-state level may be disproportionately increased, with resultant intoxication, from an increase in dosage of 10% or more. In most patients maintained at a steady dosage, stable phenytoin serum levels are achieved.
There may be wide interpatient variability in phenytoin serum levels with equivalent dosages. Patients with unusually low levels may be noncompliant or hypermetabolizers of phenytoin. Unusually high levels result from liver disease, variant CYP2C9 and CYP2C19 alleles, or drug interactions which result in metabolic interference.
The patient with large variations in phenytoin serum levels, despite standard doses, presents a difficult clinical problem. Serum level determinations in such patients may be particularly helpful. As phenytoin is highly protein bound, free phenytoin levels may be altered in patients whose protein binding characteristics differ from normal.
Excretion Most of the drug is excreted in the bile as inactive metabolites which are then reabsorbed from the intestinal tract and excreted in the urine. Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion. Specific Populations Age: Geriatric Population: Phenytoin clearance tends to decrease with increasing age (20% less in patients over 70 years of age relative to that in patients 20 to 30 years of age).
Since phenytoin clearance is decreased slightly in elderly patients, lower or less frequent dosing may be required [see Dosage and Administration (2.7) ] . Sex/Race: Gender and race have no significant impact on phenytoin pharmacokinetics. Renal or Hepatic Impairment: Increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia has been reported.
Pregnancy: It has been reported in the literature that the plasma clearance of phenytoin generally increased during pregnancy, reached a peak in the third trimester and returned to the level of pre-pregnancy after few weeks or months of delivery. Drug Interaction Studies Phenytoin is primarily metabolized by the hepatic cytochrome P450 enzyme CYP2C9 and to a lesser extent by CYP2C19. Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes [see Drug Interactions (7.1 , 7.2) ] .
12.5Pharmacogenomics CYP2C9 activity is decreased in individuals with genetic variants such as the CYP2C9*2 and CYP2C9*3 alleles. Carriers of variant alleles, resulting in intermediate (e.g., *1/*3, *2/*2) or poor metabolism (e.g., *2/*3, *3/*3) have decreased clearance of phenytoin. Other decreased o…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltage-dependent blockade of membrane sodium channels resulting in a reduction in sustained high-frequency neuronal discharges.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Phenytoin Oral Suspension USP, 125 mg phenytoin/5 mL is supplied as follows: Package Configuration Strength NDC 8-oz white PET bottles 125 mg phenytoin/5 mL NDC 51672-4069-2 One 8-oz white PET bottle in One Carton 125 mg phenytoin/5mL NDC 51672-4069-2
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Do not freeze.
📦 Storage and Handling ▾
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Do not freeze.
📋 Description ▾
11 DESCRIPTION Phenytoin is related to the barbiturates in chemical structure, but has a five-membered ring. The chemical name is 5,5-diphenyl-2,4 imidazolidinedione, having the following structural formula: Each 5 mL of the oral suspension contains 125 mg of phenytoin, USP; carboxymethylcellulose sodium, citric acid anhydrous, FD&C yellow no. 6, magnesium aluminum silicate, orange flavor spray dry natural and artificial, polysorbate 60, purified water, sodium benzoate, sucrose and vanilla flavored powder artificial.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Medication Guide). Administration Information Advise patients taking phenytoin of the importance of adhering strictly to the prescribed dosage regimen, and of informing the physician of any clinical condition in which it is not possible to take the drug orally as prescribed, e.g., surgery, etc. Instruct patients to use an accurately calibrated measuring device when using this medication to ensure accurate dosing.
Withdrawal of Antiepileptic Drugs Advise patients not to discontinue use of phenytoin without consulting with their healthcare provider. Phenytoin should normally be gradually withdrawn to reduce the potential for increased seizure frequency and status epilepticus [see Warnings and Precautions (5.1) ] . Suicidal Ideation and Behavior Counsel patients, their caregivers, and families that AEDs, including phenytoin, may increase the risk of suicidal thoughts and behavior and advise them of the need to be alert for the emergence or worsening of 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 [see Warnings and Precautions (5.2) ] . Serious Dermatologic Reactions Advise patients of the early signs and symptoms of severe cutaneous adverse reactions and to report any occurrence immediately to a physician [see Warnings and Precautions (5.3) ] . Potential Signs of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Other Systemic Reactions Advise patients of the early toxic signs and symptoms of potential hematologic, dermatologic, hypersensitivity, or hepatic reactions.
These symptoms may include, but are not limited to, fever, sore throat, rash, ulcers in the mouth, easy bruising, lymphadenopathy, facial swelling, and petechial or purpuric hemorrhage, and in the case of liver reactions, anorexia, nausea/vomiting, or jaundice. Advise the patient that, because these signs and symptoms may signal a serious reaction, that they must report any occurrence immediately to a physician. In addition, advise the patient that these signs and symptoms should be reported even if mild or when occurring after extended use [see Warnings and Precautions (5.3 , 5.4 , 5.5 , 5.8 , 5.9) ] .
Cardiac Effects Counsel patients that cases of bradycardia and cardiac arrest have been reported, both at recommended phenytoin doses and levels, and in association with phenytoin toxicity. Patients should report cardiac signs or symptoms to their healthcare provider [see Warnings and Precautions (5.6) and Overdosage (10) ] . Angioedema Advise patients to discontinue phenytoin oral suspension and seek immediate medical care if they develop signs or symptoms of angioedema, such as facial, perioral, or upper airway swelling [see Warnings and Precautions (5.7) ] .
Effects of Alcohol Use and Other Drugs and Over-the-Counter Drug Interactions Caution patients against the use of other drugs or alcoholic beverages without first seeking their physician's advice [see Drug Interactions (7.1 , 7.2) ] . Inform patients that certain over-the-counter medications (e.g., antacids, cimetidine, and omeprazole), vitamins (e.g., folic acid), and herbal supplements (e.g., St. John's wort) can alter their phenytoin levels.
Hyperglycemia Advise patients that phenytoin may cause an increase in blood glucose levels [see Warnings and Precautions (5.14) ] . Gingival Hyperplasia Advise patients of the importance of good dental hygiene in order to minimize the development of gingival hyperplasia and its complications. Neurologic Effects Counsel patients that phenytoin may cause dizziness, gait disturbance, decreased coordination and somnolence.
Advise patients taking phenytoin not to drive, operate complex machinery, or engage in other hazardous activities until they have become accustomed to any such effects associat…
💬 Medication Guide ▾
This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: April 2022 Dispense with Medication Guide available at: https://www.taro.com/usa-medication-guides MEDICATION GUIDE Phenytoin (fen' i toin) Oral Suspension What is the most important information I should know about phenytoin oral suspension? Do not stop taking phenytoin oral suspension without first talking to your healthcare provider.
Stopping phenytoin oral suspension suddenly can cause serious problems. Stopping a seizure medicine suddenly can cause you to have seizures more often or seizures that will not stop (status epilepticus). Like other antiepileptic drugs, phenytoin oral suspension may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.
Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you: Thoughts about suicide or dying Attempts to commit suicide New or worse depression New or worse anxiety Feeling agitated or restless Panic attacks Trouble sleeping (insomnia) New or worse irritability Acting aggressive, being angry, or violent Acting on dangerous impulses An extreme increase in activity and talking (mania) Other unusual changes in behavior or mood Suicidal thoughts or actions can be caused by things other than medicines.
If you have suicidal thoughts or actions, your healthcare provider may check for other causes. How can I watch for early symptoms of suicidal thoughts and actions? Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you are worried about symptoms. Phenytoin oral suspension can cause a type of serious allergic reaction that may affect different parts of the body such as your liver, kidneys, blood, heart, skin or other parts of your body.
These can be very serious and cause death. Call your healthcare provider right away if you have any or all of these symptoms: Fever Rash Swollen lymph glands Swelling of your face, eye, lips, or tongue Trouble swallowing or breathing Sore throat Sores in your mouth Bruise easily Purple or red spots on your skin Increase infections Not wanting to eat (anorexia) Nausea Vomiting Yellowing of the skin and the white part of your eyes (jaundice) Call your healthcare provider even if the symptoms are mild or if you have been taking phenytoin for an extended period of time.
These symptoms can be a sign of a serious allergic reaction. Phenytoin oral suspension can cause problems with your heart, including a slow heartbeat. Let your healthcare provider know right away if you have any of these symptoms: dizziness tiredness feeling like your heart is beating slowly or skipping beats chest pain What is phenytoin oral suspension?
Phenytoin oral suspension is a prescription medicine used to treat certain types of seizures called tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures. Do not take phenytoin oral suspension if you: Are allergic to phenytoin or any of the ingredients in phenytoin oral suspension. See the end of this leaflet for a complete list of ingredients in phenytoin oral suspension.
Have had an allergic reaction to CEREBYX (fosphenytoin), PEGANONE (ethotoin), or MESANTOIN (mephenytoin). Have had liver problems from taking phenytoin. Take delavirdine.
Before taking phenytoin oral suspension, tell your healthcare provider about all of your medical conditions, including if you: Have or have had depression, mood problems, or suicidal thoughts or behavior Have had an allergic reaction to a medicine similar to phenytoin called carboxamides, barbiturates, succinimides, and oxazolidinediones Have or had liver or kidney problems Have or had an enzyme problem called porphyria Have or had high blood sugar (hyperglycemia) Drink alcohol Are pregnant or plan to become pregnant.
Phenytoin oral…