Extended Phenytoin Sodium 100 mg Capsule, 500-count
Past resolved recalls for this product (2)
🆔 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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💊 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 35SW5USQ3G
A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
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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.
4 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 | $0.134 | $67.00 / 500 capsules |
| Medicaid paysCMS SDUD · 12 mo | $0.2650 | $132.50 / 500 capsules |
| Medicare drug plans payPart D · Q2 2026 | $0.2087 | $104.35 / 500 capsules |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Extended Phenytoin Sodium 100 mgthis 65162-0212-50 | Amneal | 500 capsules | $0.134 | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 00904-7416-61 | Major | 1 capsule | $0.147 | AB | Availability likely | +10% |
| Phenytoin Sodium 100 mg 50268-0719-13 | AvPAK | 1 capsule | $0.147 | AB | Availability likely | +10% |
| Extended Phenytoin Sodium 100 mg 60687-0841-01 | American | 100 capsules | $0.147 | AB | Availability likely | +10% |
| Phenytoin Sodium 100 mg 65862-0692-01 | Aurobindo | 100 capsules | $0.147 | — | Availability likely | +10% |
| Dilantin 100 mg 58151-0110-01 | Viatris | 100 capsules | $1.739 | — | Availability likely | +1198% |
| Extended Phenytoin Sodium 100 mg 00615-8556-39 | NCS | 30 capsules | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 29300-0379-01 | Unichem | 100 capsules | — | — | FDA listed | — |
| Phenytoin Sodium 100 mg 50090-3539-00 | A-S | 100 capsules | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 50090-5700-00 | A-S | 100 capsules | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 51407-0982-01 | Golden | 100 capsules | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 51672-4111-00 | Sun | 10 capsules | — | AB | Discontinued | — |
| Phenytoin Sodium 100 mg 61919-0815-30 | DIRECT | 30 capsules | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 67046-0585-03 | Coupler | 30 capsules | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 70518-0107-00 | REMEDYREPACK | 30 capsules | — | AB | FDA listed | — |
| Extended Phenytoin Sodium 100 mg 70518-2227-00 | REMEDYREPACK | 30 capsules | — | AB | Discontinued | — |
| Phenytoin Sodium 100 mg 70518-2293-01 | REMEDYREPACK | 1 capsule | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 71610-0869-92 | Aphena | 270 capsules | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 71610-0934-92 | Aphena | 270 capsules | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 72162-1646-00 | Bryant | 1000 capsules | — | AB | Discontinued | — |
| Extended Phenytoin Sodium 100 mg 72162-2514-00 | Bryant | 1000 capsules | — | AB | FDA listed | — |
| Phenytoin Sodium 100 mg 82804-0269-72 | Proficient | 120 capsules | — | AB | FDA listed | — |
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⏳ 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 |
|---|---|---|---|---|---|
| 65162-0212-03 | 30 CAPSULE in 1 BOTTLE (65162-212-03) | — | — | 2009-12-16 | Active |
| 65162-0212-10 | 100 CAPSULE in 1 BOTTLE (65162-212-10) | $0.1340 / ea | $13.40 | 2009-12-16 | Active |
| 65162-0212-11 | 1000 CAPSULE in 1 BOTTLE (65162-212-11) | $0.1340 / ea | $133.97 | 2009-12-16 | Active |
| 65162-0212-50 You're viewing this | 500 CAPSULE in 1 BOTTLE (65162-212-50) | $0.1340 / ea | $66.99 | 2009-12-16 | Active |
You're viewing one of 4 pack sizes for this product.
This pack effectively ties for the lowest per-ea cost of the 3 priced pack sizes ($0.1340 NADAC).
Pack size FAQ
What quantity is in NDC 65162-0212-50?
What is the difference between NDC 65162-0212-50 and NDC 65162-0212-03?
What NDC number is used to bill for this package of Extended Phenytoin Sodium 100 mg Capsule?
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 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. 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. (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 extended phenytoin sodium 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 extended phenytoin sodium 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 extended phenytoin sodium 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 extended phenytoin sodium 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 Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Extended phenytoin sodium capsules, USP are available as: 100 mg: white opaque/light lavender opaque, hard gelatin capsules imprinted with “IP 212” on both cap and body. Extended phenytoin sodium capsules, USP are available as 100 mg capsules. (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Phenytoin 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) ].
Co-administration 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 ) Co-administration 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 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. 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 phenytoin sodium, 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 antiepileptic drugs in the…
🤒 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 (meas…
🔄 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 a 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 b , sucralfate, theophylline Drugs that may either increase or decrease phenytoin serum levels Antiepileptic drugs Phenobarbital, valproate sodium c , valproic acid c a Antacids may affect absorption of phenytoin. b The induction potency of St. John’s wort may vary widely based on preparation. c Valproate sodium and valproic acid are similar medications. The term valproate has been used to represent these medications.
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. Whethe…
👥 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 phenytoin sodium, during pregnancy. Physicians are advised to recommend that pregnant patients taking phenytoin sodium enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free 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.
8.2 La…
🤰 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 sodium, during pregnancy. Physicians are advised to recommend that pregnant patients taking phenytoin sodium enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free 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.
🧒 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 extended phenytoin sodium capsules, peak serum levels occur 4 to 12 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 (2.6) ]. 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. 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 Extended phenytoin sodium capsules, USP 100 mg are supplied as white opaque/light lavender opaque, hard gelatin capsules imprinted with "IP 212" on both cap and body. They are supplied as follows: Bottles of 100: NDC 65162-212-10 Bottles of 500: NDC 65162-212-50 Bottles of 1000: NDC 65162-212-11
16.2Storage and Handling Store at 20 o to 25 o C (68 o to 77 o F) [see USP Controlled Room Temperature]. Preserve in tight, light-resistant containers. Protect from moisture.
📋 Description ▾
11 DESCRIPTION Phenytoin sodium, USP 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 extended phenytoin sodium capsule, USP for oral administration contains 100 mg phenytoin sodium, USP. Each capsule also contains the following inactive ingredients: D&C Red #28, D&C Red #33, FD&C Blue #1, gelatin, hydroxypropyl cellulose, mannitol, magnesium stearate, talc and titanium dioxide.
The imprinting ink contains D&C Yellow #10, FD&C Blue #1, FD&C Blue #2, FD&C Red # 40 and ferrosoferric oxide. 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 , USP with a rapid rate of absorption with peak blood concentration expected in 1 1/2; to 3 hours. Meets USP Dissolution Test 5.
Struct Form.
💬 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 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 extended phenytoin sodium 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 phenytoin sodium 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 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 associated with phenytoin. Use in Pregnancy Inform pregn…
💬 Medication Guide ▾
MEDICATION GUIDE Extended phenytoin sodium (fen‘ i toyn soe‘ dee um) capsules What is the most important information I should know about extended phenytoin sodium capsules? 1. Do not stop taking extended phenytoin sodium capsules without first talking to your healthcare provider.
Stopping extended phenytoin sodium 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, extended phenytoin sodium 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 New or worse anxiety Trouble sleeping (insomnia) Acting on dangerous impulses Attempts to commit suicide Feeling agitated or restless New or worse irritability An extreme increase in activity and talking (mania) New or worse depression Panic attacks Acting aggressive, being angry, or violent 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.
Extended phenytoin sodium 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 Sore throat Not wanting to eat (anorexia) Rash Sores in your mouth Nausea Swollen lymph glands Bruise easily Vomiting Swelling of your face, eye, lips, or tongue Trouble swallowing or breathing Purple or red spots on your skin Increase infections 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 extended phenytoin sodium capsules for an extended period of time.
These symptoms can be a sign of a serious allergic reaction. 4. Extended phenytoin sodium 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 extended phenytoin sodium capsules? Extended phenytoin sodium 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 extended phenytoin sodium capsules if you: Are allergic to phenytoin or any of the ingredients in extended phenytoin sodium capsules.
See the end of this leaflet for a complete list of ingredients in extended phenytoin sodium 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 extended phenytoin sodium 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 extended phenytoin sodium 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.
Extended ph…