NDC 62756-299 Phenytoin Sodium

Phenytoin Sodium

NDC Product Code 62756-299

NDC CODE: 62756-299

Proprietary Name: Phenytoin Sodium What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Phenytoin Sodium What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
BLUE (C48333 - BLUE TRANSPARENT)
BLUE (C48333 - LIGHT BLUE TRANSPARENT)
Shape: CAPSULE (C48336)
Size(s):
19 MM
Imprint(s):
299
Score: 1

NDC Code Structure

NDC 62756-299-08

Package Description: 100 CAPSULE, EXTENDED RELEASE in 1 BOTTLE

NDC 62756-299-13

Package Description: 500 CAPSULE, EXTENDED RELEASE in 1 BOTTLE

NDC 62756-299-83

Package Description: 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE

NDC 62756-299-88

Package Description: 100 CAPSULE, EXTENDED RELEASE in 1 BOTTLE

NDC Product Information

Phenytoin Sodium with NDC 62756-299 is a a human prescription drug product labeled by Sun Pharmaceutical Industries, Inc.. The generic name of Phenytoin Sodium is phenytoin sodium. The product's dosage form is capsule, extended release and is administered via oral form.

Labeler Name: Sun Pharmaceutical Industries, Inc.

Dosage Form: Capsule, Extended Release - A solid dosage form in which the drug is enclosed within either a hard or soft soluble container made from a suitable form of gelatin, and which releases a drug (or drugs) in such a manner to allow a reduction in dosing frequency as compared to that drug (or drugs) presented as a conventional dosage form.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Phenytoin Sodium Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • PHENYTOIN SODIUM 200 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • LACTITOL MONOHYDRATE (UNII: UH2K6W1Y64)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • TALC (UNII: 7SEV7J4R1U)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • FD&C RED NO. 40 (UNII: WZB9127XOA)
  • D&C RED NO. 28 (UNII: 767IP0Y5NH)
  • ALCOHOL (UNII: 3K9958V90M)
  • BUTYL ALCOHOL (UNII: 8PJ61P6TS3)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • AMMONIA (UNII: 5138Q19F1X)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • POTASSIUM HYDROXIDE (UNII: WZH3C48M4T)
  • SHELLAC (UNII: 46N107B71O)
  • GELATIN (UNII: 2G86QN327L)
  • FD&C RED NO. 3 (UNII: PN2ZH5LOQY)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Anti-epileptic Agent - [EPC] (Established Pharmacologic Class)
  • Decreased Central Nervous System Disorganized Electrical Activity - [PE] (Physiologic Effect)
  • Cytochrome P450 1A2 Inducers - [MoA] (Mechanism of Action)
  • Cytochrome P450 2B6 Inducers - [MoA] (Mechanism of Action)
  • Cytochrome P450 2C8 Inducers - [MoA] (Mechanism of Action)
  • Cytochrome P450 2C19 Inducers - [MoA] (Mechanism of Action)
  • Cytochrome P450 2D6 Inducers - [MoA] (Mechanism of Action)
  • Cytochrome P450 3A Inducers - [MoA] (Mechanism of Action)
  • Cytochrome P450 2C9 Inducers - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Sun Pharmaceutical Industries, Inc.
Labeler Code: 62756
FDA Application Number: ANDA040731 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 06-30-2008 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Information for Patients

Phenytoin

Phenytoin is pronounced as (fen' i toyn)

Why is phenytoin medication prescribed?
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 ...
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* Please review the disclaimer below.

Phenytoin Sodium Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Description

Phenytoin sodium is an antiepileptic drug. 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 a molecular weight of 274.25 and having the following structural formula and molecular formula:Each extended phenytoin sodium capsule, USP, for oral administration contains 200 mg or 300 mg of phenytoin sodium, USP. Each capsule also contains the following inactive ingredients: magnesium stearate, lactitol monohydrate, sodium lauryl sulfate, and talc. In addition, each of the empty gelatin capsules contains the following: gelatin, FD&C Blue # 1, FD&C Red # 40, D&C Red # 28 (200 mg) and FD&C Red # 3 (200 mg). The imprinting ink contains shellac, dehydrated alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide and potassium hydroxide. Product in vivoperformance 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 1½ to 3 hours. Extended phenytoin sodium capsules, USP 200 mg and 300 mg meet USP Dissolution Test 3.

Clinical Pharmacology

Phenytoin is an antiepileptic drug which can be used in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of posttetanic potentiation at synapses. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. The plasma half-life in man after oral administration of phenytoin averages 22 hours, with a range of 7 to 42 hours. 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. Trough levels provide information about clinically effective serum level range and confirm patient compliance and are obtained just prior to the patient’s next scheduled dose. Peak levels indicate an individual’s threshold for emergence of dose-related side effects and are obtained at the time of expected peak concentration. For extended phenytoin sodium capsules peak serum levels occur 4 to 12 hours after administration. Optimum control without clinical signs of toxicity occurs more often with serum levels between 10 and 20 mcg/mL, although some mild cases of tonic-clonic (grand mal) epilepsy may be controlled with lower serum levels of phenytoin. 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, congenital enzyme deficiency, or drug interactions which result in metabolic interference. The patient with large variations in phenytoin plasma 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. 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. Because phenytoin is hydroxylated in the liver by an enzyme system which is saturable at high plasma 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.

Indications And Usage

Extended phenytoin sodium capsules, USP are indicated for the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.Phenytoin serum level determinations may be necessary for optimal dosage adjustments (see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY).

Contraindications

Extended phenytoin sodium capsules are contraindicated in those patients who are hypersensitive to phenytoin or other hydantoins.

Warnings

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 antiepileptic medication arises, this should be done gradually. However, in the event of an allergic or hypersensitivity reaction, rapid substitution of alternative therapy may be necessary. In this case, alternative therapy should be an antiepileptic drug not belonging to the hydantoin chemical class. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including phenytoin sodium, may 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 Pooled AnalysisIndicationPlacebo Patients with Events per 1,000 PatientsDrug Patients with Events per 1,000 PatientsRelative Risk: Incidence of Events in Drug Patients/Incidence in Placebo PatientsRisk Difference: Additional Drug Patients with Events per 1,000 PatientsEpilepsy13.43.52.4Psychiatric5.78.51.52.9Other11.81.90.9Total2.44.31.81.9The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing phenytoin sodium or any other AED must balance this risk with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. There have been a number of reports suggesting a relationship between phenytoin and the development of lymphadenopathy (local or generalized) including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin’s Disease. Although a cause and effect relationship has not been established, the occurrence of lymphadenopathy indicates the need to differentiate such a condition from other types of lymph node pathology. Lymph node involvement may occur with or without symptoms and signs resembling serum sickness, e.g., fever, rash, and liver involvement. In all cases of lymphadenopathy, follow-up observation for an extended period is indicated and every effort should be made to achieve seizure control using alternative antiepileptic drugs. Acute alcoholic intake may increase phenytoin serum levels while chronic alcohol use may decrease serum levels.In view of isolated reports associating phenytoin with exacerbation of porphyria, caution should be exercised in using this medication in patients suffering from this disease. Usage in Pregnancy: Clinical: A. Risks to MotherAn increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics. Periodic measurement of plasma phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage (see PRECAUTIONS, Laboratory Tests). However, postpartum restoration of the original dosage will probably be indicated. B. Risks to the FetusIf this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential harm to the fetus.Prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes. Increased frequencies of major malformations (such as orofacial clefts and cardiac defects), minor anomalies (dysmorphic facial features, nail and digit hypoplasia), growth abnormalities (including microcephaly), and mental deficiency have been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy. There have also been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy. The overall incidence of malformations for children of epileptic women treated with antiepileptic drugs (phenytoin and/or others) during pregnancy is about 10%, or 2- to 3-fold that in the general population. However, the relative contributions of antiepileptic drugs and other factors associated with epilepsy to this increased risk are uncertain and in most cases it has not been possible to attribute specific developmental abnormalities to particular antiepileptic drugs. Patients should consult with their physicians to weigh the risks and benefits of phenytoin during pregnancy.C. Postpartum PeriodA 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.Preclinical: Increased resorption and malformation rates have been reported following administration of phenytoin doses of 75 mg/kg or higher (approximately 120% of the maximum human loading dose or higher on a mg/m2 basis) to pregnant rabbits.

General

The liver is the chief site of biotransformation of phenytoin; patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity. A small percentage of individuals who have been treated with phenytoin have been shown to metabolize the drug slowly. Slow metabolism may be due to limited enzyme availability and lack of induction; it appears to be genetically determined. Phenytoin should be discontinued if a skin rash appears (see WARNINGS section regarding drug discontinuation). If the rash is exfoliative, purpuric, or bullous, or if lupus erythematosus, Stevens-Johnson Syndrome, or toxic epidermal necrolysis is suspected, use of this drug should not be resumed and alternative therapy should be considered. (See ADVERSE REACTIONS.) If the rash is of a milder type (measles-like or scarlatiniform), therapy may be resumed after the rash has completely disappeared. If the rash recurs upon reinstitution of therapy, further phenytoin medication is contraindicated. Phenytoin and other hydantoins are contraindicated in patients who have experienced phenytoin hypersensitivity (see CONTRAINDICATIONS). Additionally, caution should be exercised if using structurally similar compounds (e.g., barbiturates, succinamides, oxazolidinediones and other related compounds) in these same patients. Hyperglycemia, resulting from the drug’s inhibitory effects on insulin release, has been reported. Phenytoin may also raise the serum glucose level in diabetic patients. Osteomalacia has been associated with phenytoin therapy and is considered to be due to phenytoin’s interference with Vitamin D metabolism. Phenytoin is not indicated for seizures due to hypoglycemic or other metabolic causes. Appropriate diagnostic procedures should be performed as indicated. Phenytoin is not effective for absence (petit mal) seizures. If tonic-clonic (grand mal) and absence (petit mal) seizures are present, combined drug therapy is needed. Serum levels of phenytoin sustained above the optimal range may produce confusional states referred to as “delirium,” “psychosis,” or “encephalopathy,” or rarely irreversible cerebellar dysfunction. Accordingly, at the first sign of acute toxicity, plasma levels are recommended. Dose reduction of phenytoin therapy is indicated if plasma levels are excessive; if symptoms persist, termination is recommended. (See WARNINGS.)

Information For Patients

Patients taking phenytoin should be advised 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. Patients should also be cautioned on the use of other drugs or alcoholic beverages without first seeking the physician’s advice.Patients should be instructed to call their physician if skin rash develops.The importance of good dental hygiene should be stressed in order to minimize the development of gingival hyperplasia and its complications. Patients should be instructed to take phenytoin sodium only as prescribed.

Suicidal Thinking And Behavior

Patients, their caregivers, and families should be counseled that AEDs, including phenytoin sodium, may increase the risk of suicidal thoughts and behavior and should be advised 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. Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This Registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see PRECAUTIONS - Pregnancy).

Laboratory Tests:

Phenytoin serum level determinations may be necessary to achieve optimal dosage adjustments.

Drug Interactions:

  • There are many drugs which may increase or decrease phenytoin levels or which phenytoin may affect. Serum level determinations for phenytoin are especially helpful when possible drug interactions are suspected. The most commonly occurring drug interactions are listed below: Drugs which may increase phenytoin serum levels include: acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, cimetidine, diazepam, dicumarol, disulfiram, estrogens, ethosuximide, fluoxetine, H2-antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinamides, sulfonamides, ticlopidine, tolbutamide, trazodone. Drugs which may decrease phenytoin levels include: carbamazepine, chronic alcohol abuse, reserpine, and sucralfate. Moban®(Moban is a registered trademark of Endo Pharmaceuticals, Inc.) brand of molindone hydrochloride contains calcium ions which interfere with the absorption of phenytoin. Ingestion times of phenytoin and antacid preparations containing calcium should be staggered in patients with low serum phenytoin levels to prevent absorption problems. Drugs which may either increase or decrease phenytoin serum levels include: phenobarbital, sodium valproate, and valproic acid. Similarly, the effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable. Although not a true drug interaction, tricyclic antidepressants may precipitate seizures in susceptible patients and phenytoin dosage may need to be adjusted. Drugs whose efficacy is impaired by phenytoin include: corticosteroids, coumarin anticoagulants, digitoxin, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, theophylline, vitamin D.

Drug Enteral Feeding/Nutritional Preparations Interaction:

Literature reports suggest that patients who have received enteral feeding preparations and/or related nutritional supplements have lower than expected phenytoin plasma levels. It is therefore suggested that phenytoin not be administered concomitantly with an enteral feeding preparation. More frequent serum phenytoin level monitoring may be necessary in these patients.

Drug/Laboratory Test Interactions:

Phenytoin may decrease serum concentrations of T4. It may also produce lower than normal values for dexamethasone or metyrapone tests. Phenytoin may cause increased serum levels of glucose, alkaline phosphatase, and gamma glutamyl transpeptidase (GGT). Care should be taken when using immunoanalytical methods to measure plasma phenytoin concentrations.

Carcinogenesis:

See WARNINGS section for information on carcinogenesis.

Pregnancy:

Pregnancy Category DSee WARNINGS. To provide information regarding the effects of in utero exposure to phenytoin sodium, 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/.

Nursing Mothers:

Infant breast feeding is not recommended for women taking this drug because phenytoin appears to be secreted in low concentrations in human milk.

Pediatric Use:

See DOSAGE AND ADMINISTRATION.

Adverse Reactions

Central Nervous System: The most common manifestations encountered with phenytoin therapy are referable to this system and are usually dose-related. These include nystagmus, ataxia, slurred speech, decreased coordination, and mental confusion. Dizziness, insomnia, transient nervousness, motor twitchings, 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. A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.Gastrointestinal System: Nausea, vomiting, constipation, toxic hepatitis and liver damage. Integumentary System: Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. Other more serious forms which may be fatal have included bullous, exfoliative or purpuric dermatitis, lupus erythematosus, Stevens-Johnson Syndrome, and toxic epidermal necrolysis (see PRECAUTIONS). Hemopoietic System: Hemopoietic 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). Connective Tissue System: Coarsening of the facial features, enlargement of the lips, gingival hyperplasia, hypertrichosis, and Peyronie’s Disease. Immunologic: Hypersensitivity syndrome (which may include, but is not limited to, symptoms such as arthralgias, eosinophilia, fever, liver dysfunction, lymphadenopathy or rash), systemic lupus erythematosus, periarteritis nodosa and immunoglobulin abnormalities.

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, nausea, vomiting. The patient may become comatose and hypotensive. Death is due to respiratory and circulatory depression. There are marked variations among individuals with respect to phenytoin plasma levels where toxicity may occur. Nystagmus, on lateral gaze, usually appears at 20 mcg/mL, ataxia at 30 mcg/mL, dysarthria and lethargy appear when the plasma 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. 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.

Dosage And Administration

Serum concentrations should be monitored in changing from extended phenytoin sodium capsules, USP to prompt phenytoin sodium capsules, USP, and from the sodium salt to the free acid form. Extended phenytoin sodium capsules, USP 200 mg and 300 mg are formulated with the sodium salt of phenytoin. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa. General: Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum level is usually 10 to 20 mcg/mL. With recommended dosage, a period of 7 to 10 days may be required to achieve steady-state blood levels with phenytoin and changes in dosage (increase or decrease) should not be carried out at intervals shorter than 7 to 10 days. Adult Dosage: Divided Daily Dosage: Patients who have received no previous treatment may be started on one 100 mg extended phenytoin sodium capsule three times daily and the dosage then adjusted to suit individual requirements. For most adults, the satisfactory maintenance dosage will be one 100 mg capsule three to four times a day. An increase up to one 200 mg extended phenytoin sodium capsules, USP three times a day may be made, if necessary. 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 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 plasma 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 phenytoin capsules is divided into three doses (400 mg, 300 mg, 300 mg) and administered at 2 hour intervals. Normal maintenance dosage is then instituted 24 hours after the loading dose, with frequent serum level determinations. Pediatric Dosage: 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 old and adolescents may require the minimum adult dose (300 mg/day).

How Supplied

Extended Phenytoin Sodium Capsules, USP are available containing 200 mg or 300 mg of phenytoin sodium, USP.The 200 mg capsule has a blue transparent cap and a light blue transparent body. The hard-shell gelatin capsule is filled with white to off-white powder. The capsule is printed axially with 299 in black ink on both the cap and the body. They are available as follows:Bottle of 30's with Child Resistant Cap...................NDC 62756-299-83Bottle of 100's with Child Resistant Cap.................NDC 62756-299-88Bottle of 100's with Non Child Resistant Cap.........NDC 62756-299-08Bottle of 500's with Non Child Resistant Cap.........NDC 62756-299-13The 300 mg capsule has a light blue transparent cap and a light blue transparent body. The hard-shell gelatin capsule is filled with white to off-white powder. The capsule is printed axially with 432 in black ink on both the cap and the body. They are available as follows:Bottle of 30's with Child Resistant Cap...................NDC 62756-432-83Bottle of 100's with Child Resistant Cap.................NDC 62756-432-88Bottle of 100's with Non Child Resistant Cap.........NDC 62756-432-08Bottle of 500's with Non Child Resistant Cap.........NDC 62756-432-13Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP for 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.Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 Manufactured by: Sun Pharmaceutical Industries Ltd. Halol-Baroda Highway, Halol-389 350, Gujarat, India. ISS. 01/2015 PJPI0071C

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