Phenytek phenytoin sodium 300 mg Capsule, Extended Release, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Anti-epileptic Agent class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Phenytoin is used to control certain type of seizures, and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Phenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
Read the full MedlinePlus article ↗- 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
Phenytoin may be associated with lower levels of 13 nutrients — worth a chat with your pharmacist, not a cause for alarm.
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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.
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UNII CQ3XH3DET6
D&C Yellow No. 10 Aluminum Lake is a yellow colorant made by combining a dye with aluminum salts. It's used in medicines to add color for product identification and visual appeal.
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FD&C Blue No. 1 Aluminum Lake is a blue colorant made by combining FD&C Blue No. 1 dye with aluminum salts. It is used to color tablets, capsules, and other medicines for easy identification and appearance.
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UNII L06K8R7DQK
A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
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UNII WZB9127XOA
A synthetic red dye used to color medications and make them easier to identify. It serves as a colorant in tablets, capsules, and liquid formulations.
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UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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UNII S38J6RZN16
Hydroxyethyl cellulose is a plant-derived thickening agent made from cellulose. In medicines, it acts as a binder to hold ingredients together, a thickener to adjust product texture, and a film-former to create smooth coatings on tablets.
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UNII 3A3U0GI71G
Magnesium oxide is a mineral compound that acts as a buffer and filler in medications. It helps neutralize stomach acid and adds bulk to the tablet or capsule formulation.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII PNR0YF693Y
A plant-based powder made from purified wood cellulose. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in the stomach.
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UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII 46N107B71O
Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
16 inactive ingredients listed in the exact product block matched to this NDC.
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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
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💲 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 ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $2.098 | $62.95 / 30 capsules |
| Medicaid paysCMS SDUD · 12 mo | $2.07 | $62.00 / 30 capsules |
| Medicare drug plans payPart D · Q2 2026 | $1.34 | $40.35 / 30 capsules |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Phenytek 300 mgthis 00378-3750-93 | Mylan | 30 capsules | $2.098 | — | Availability likely | — |
| phenytoin sodium 300 mg 62756-0432-08 | Sun | 100 capsules | — | — | 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
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 00378-3750-01 | 100 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (0378-3750-01) | $2.10 / ea | $209.84 | 2001-12-10 | Active |
| 00378-3750-93 You're viewing this | 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (0378-3750-93) | $2.10 / ea | $62.95 | 2001-12-10 | Active |
You're viewing the smallest of 2 pack sizes for this product.
This pack effectively ties for the lowest per-ea cost of the 2 priced pack sizes ($2.10 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 73% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 00378-3750-93?
What is the difference between NDC 00378-3750-93 and NDC 00378-3750-01?
What NDC number is used to bill for this package of Phenytek phenytoin sodium 300 mg Capsule, Extended Release?
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 PHENYTEK ® capsules (extended phenytoin sodium capsules) are indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. PHENYTEK ® CAPSULES are indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Adult starting dose in patients who have received no previous treatment is one 100 mg extended phenytoin sodium capsule three times a day, with dose adjustments as necessary. For most adults, the satisfactory maintenance dose will be one capsule three to four times a day. An increase, up to two capsules three times a day may be made, if necessary.
( 2.1 ) • Adult once-a-day dose: If seizure control is established with divided doses of three 100 mg extended phenytoin sodium capsules daily, once-a-day dosage with 300 mg PHENYTEK ® capsules may be considered. ( 2.1 ) • Adult loading dose: reserved for patients in a clinic or hospital setting who require rapid steady-state serum levels and where intravenous administration is not desired. Refer to full prescribing information.
( 2.1 ) • 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 to 8 mg/kg/day. ( 2.2 ) • Serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum total concentration is 10 to 20 mcg/mL (unbound phenytoin concentration is 1 to 2 mcg/mL).
( 2.3 )
2.1Adult Dosage Divided Daily Dosage The recommended starting dose for adult patients who have received no previous treatment is one 100-mg extended phenytoin sodium capsule by mouth three times daily. Adjust the dosage to suit individual requirements up to a maximum of two capsules three times a day. For most adults, the satisfactory maintenance dosage will be one capsule three to four times a day.
Once-a-Day Dosage In adults, if seizure control is established with divided doses of three 100-mg extended phenytoin sodium capsules daily, once-a-day dosage with 300 mg of PHENYTEK ® capsules may be considered. Studies comparing divided doses of 300 mg with a single daily dose of this quantity indicated absorption, peak serum levels, biologic half-life, difference between peak and minimum values, and urinary recovery were equivalent. Once-a-day dosage offers a convenience to the individual patient or to nursing personnel for institutionalized patients and is intended to be used only for patients requiring this amount of drug daily.
A major problem in motivating noncompliant patients may also be lessened when the patient can take this drug once a day. However, patients should be cautioned not to miss a dose, inadvertently. Only PHENYTEK ® capsules are recommended for once-a-day dosing.
Inherent differences in dissolution characteristics and resultant absorption rates of phenytoin due to different manufacturing procedures and/or dosage forms preclude such recommendation for other phenytoin products. When a change in the dosage form or brand is prescribed, careful monitoring of phenytoin serum levels should be carried out. Loading Dose Some authorities have advocated use of an oral loading dose of phenytoin in adults who require rapid steady-state serum levels and where intravenous administration is not desirable.
This dosing regimen should be reserved for patients in a clinic or hospital setting where phenytoin serum levels can be closely monitored. Patients with a history of renal or liver disease should not receive the oral loading regimen. Initially, one gram of PHENYTEK ® capsules is divided into three doses (400 mg, 300 mg, 300 mg) and administered at two-hour intervals.
Normal maintenance dosage is then instituted 24 hours after the loading dose, with frequent serum level determinations.
2.2Pediatric 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 to 8 mg/kg/day in equally divided doses. Children over 6 years and adolescents may require the minimum adult dosage (300 mg/day).
2.3 Dosage Adjustments Dosage s…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS PHENYTEK ® CAPSULES (extended phenytoin sodium capsules, USP) are available containing 200 mg or 300 mg of phenytoin sodium, USP. • The 200 mg capsules have a dark blue opaque cap and a blue opaque body. The hard-shell gelatin capsules are filled with two white to off-white round tablets. The capsules are rectified radial printed with BERTEK over 670 in black ink on both the cap and the body. • The 300 mg capsules have a blue opaque cap and a blue opaque body.
The hard-shell gelatin capsules are filled with three white to off-white round tablets. The capsules are rectified radial printed with BERTEK over 750 in black ink on both the cap and the body. PHENYTEK ® capsules are available as 200 mg or 300 mg extended phenytoin sodium capsules.
( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS PHENYTEK ® capsules are 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 PHENYTEK ® capsules 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 PHENYTEK ® capsules. 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 drug not belonging to the hydantoin chemical class.
5.2Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including PHENYTEK ® capsules, 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 Ind…
🤒 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 PHENYTEK ® capsules 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…
🔄 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 to phenytoin 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 PHENYTEK ® capsules, during pregnancy. Physicians are advised to recommend that pregnant patients taking PHENYTEK ® capsules 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 (2.3 , 2.7) ] .
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, 75, and 12.5 mg/kg, respectivel…
🤰 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 PHENYTEK ® capsules, during pregnancy. Physicians are advised to recommend that pregnant patients taking PHENYTEK ® capsules 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 (2.3 , 2.7) ] .
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, 75, and 12.5 mg/kg, respectively.
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.
🧒 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 to 8 mg/kg. Children over 6 years and adolescents may require the minimum adult dosage (300 mg/day) [see Dosage and Administration (2.2) ] .
🧓 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 (2.6) ] .
🆘 Overdosage ▾
10 OVERDOSAGE The lethal dose in pediatric patients is not known. The lethal dose in adults is estimated to be 2 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 PHENYTEK ® capsules, peak serum levels occur 4 to 12 hours after administration. Steady-state therapeutic levels are achieved at least 7 to 10 days (5-7 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 5-7 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 (2.6) ] . 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 or nonfunctio…
🧬 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 PHENYTEK ® CAPSULES (extended phenytoin sodium capsules, USP) are available containing 200 mg or 300 mg of phenytoin sodium, USP. The 200 mg capsules have a dark blue opaque cap and a blue opaque body. The hard-shell gelatin capsules are filled with two white to off-white round tablets.
The capsules are rectified radial printed with BERTEK over 670 in black ink on both the cap and the body. They are available as follows: NDC 0378-2670-93 bottles of 30 capsules NDC 0378-2670-01 bottles of 100 capsules The 300 mg capsules have a blue opaque cap and a blue opaque body. The hard-shell gelatin capsules are filled with three white to off-white round tablets.
The capsules are rectified radial printed with BERTEK over 750 in black ink on both the cap and the body. They are available as follows: NDC 0378-3750-93 bottles of 30 capsules NDC 0378-3750-01 bottles of 100 capsules
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. PHARMACIST: Dispense a Medication Guide with each prescription.
📋 Description ▾
11 DESCRIPTION Phenytoin sodium is related to the barbiturates in chemical structure, but has a five-membered ring. The chemical name is 5,5-Diphenylhydantoin sodium salt, having the following structural formula: Each 200 mg or 300 mg PHENYTEK ® capsule (extended phenytoin sodium capsule, USP) for oral administration contains 200 mg or 300 mg phenytoin sodium, USP. Also contains colloidal silicon dioxide, FD&C Blue No.
1, gelatin, hydroxyethyl cellulose, magnesium oxide, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate and titanium dioxide. In addition, the imprinting ink contains black iron oxide, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No.
1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, propylene glycol and shellac glaze.
Product in vivo performance is characterized by a slow and extended rate of absorption with peak blood concentrations expected in 4 to 12 hours as contrasted to prompt phenytoin sodium capsules with a rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours. Meets USP Dissolution Test 3. Phenytoin Structural Formula
💬 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. Advise patients not to use capsules which are discolored.
Withdrawal of Antiepileptic Drugs: Advise patients not to discontinue use of PHENYTEK ® capsules without consulting with their healthcare provider. PHENYTEK ® capsules 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 PHENYTEK ® capsules, 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 PHENYTEK ® capsules 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 [ 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 PHENYTEK ® capsules 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 PHENYTEK ® capsules may cause dizziness, gait disturbance, decreased coordination and somnolence.
Advise patients taking PHENYTEK ® capsules not to drive, operate complex machinery, or engage in other hazardous activities until they have become accustomed to any such effects associ…
💬 Medication Guide ▾
Medication Guide PHENYTEK ® CAPSULES (extended phenytoin sodium capsules) (fen′ i toin soe′ dee um) What is the most important information I should know about PHENYTEK ® CAPSULES? 1. Do not stop taking PHENYTEK ® CAPSULES without first talking to your healthcare provider. • Stopping PHENYTEK ® CAPSULES 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).
2. Like other antiepileptic drugs, PHENYTEK ® CAPSULES 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.
3. PHENYTEK ® CAPSULES 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 • 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 PHENYTEK ® CAPSULES for an extended period of time.
These symptoms can be a sign of a serious allergic reaction. 4. PHENYTEK ® CAPSULES 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 are PHENYTEK ® CAPSULES? PHENYTEK ® CAPSULES are a prescription medicine used to treat certain types of seizures called tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures. Do not take PHENYTEK ® CAPSULES if you: • Are allergic to phenytoin or any of the ingredients in PHENYTEK ® CAPSULES.
See the end of this leaflet for a complete list of ingredients in PHENYTEK ® CAPSULES. • Have had an allergic reaction to CEREBYX ® (fosphenytoin), PEGANONE ® (ethotoin), or MESANTOIN ® (mephenytoin). • Have had liver problems from taking phenytoin. • Take delavirdine. Before taking PHENYTEK ® CAPSULES, 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 PHENYTEK ® CAPSULES 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 sodium may harm your unborn baby. • If you take PHENYTEK ® CAPSULES during pregnancy, your baby is at risk for serious birth de…