Dilantin Information
Dilantin (Phenytoin sodium) 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 sodium 5,5-diphenyl-2, 4-imidazolidinedione, having the following structural formula:
Each Dilantin (Phenytoin sodium) ——contains 100 mg phenytoin sodium. Also contains lactose monohydrate, NF; confectioner's sugar, NF; talc, USP; and magnesium stearate, NF. The capsule body contains titanium dioxide, USP and gelatin, NF. The capsule cap contains FD&C red No. 28; FD&C yellow No. 6; and gelatin NF. Product performance is characterized by a slow and extended rate of absorption with peak blood concentrations expected in 4 to 12 hours as contrasted to , USP with a rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.
Dilantin (Phenytoin sodium) 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 where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, phenytoin tends to 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 (5–7 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. 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 Dilantin (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.
Dilantin (Phenytoin sodium) Indications And Usage
Dilantin (Phenytoin sodium) is 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 and sections).
Dilantin (Phenytoin sodium) Contraindications
Phenytoin is contraindicated in those patients who are hypersensitive to phenytoin or its inactive ingredients or other hydantoins.
Dilantin (Phenytoin sodium) Warnings
Antiepileptic drugs (AEDs), including Dilantin (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 (5–100 years) in the clinical trials analyzed.
Table 1 shows absolute and relative risk by indication for all evaluated AEDs.
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Dilantin (Phenytoin sodium) or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
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.
Dilantin (Phenytoin sodium) can cause rare, serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs hypersensitivity such as itching, and should seek medical advice from their physician immediately when observing any indicative signs or symptoms. The physician should advise the patient to discontinue treatment if the rash appears (see section regarding drug discontinuation). 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 Dilantin (Phenytoin sodium) medication is contraindicated. Published literature has suggested that there may be an increased, although still rare, risk of hypersensitivity reactions, including skin rash, SJS, TEN, hepatotoxicity, and Anticonvulsant Hypersensitivity Syndrome in black patients.
Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene, in patients using another anticonvulsive drug. Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding use of drugs associated with SJS/TEN, including Dilantin (Phenytoin sodium) , in HLA-B*1502 positive patients when alternative therapies are otherwise equally available.
Anticonvulsant Hypersensitivity Syndrome (AHS) is a rare drug induced, multiorgan syndrome which is potentially fatal and occurs in some patients taking anticonvulsant medication. It is characterized by fever, rash, lymphadenopathy, and other multiorgan pathologies, often hepatic. The mechanism is unknown. The interval between first drug exposure and symptoms is usually 2–4 weeks but has been reported in individuals receiving anticonvulsants for 3 or more months. Although up to 1 in 5 patients on Dilantin (Phenytoin sodium) may develop cutaneous eruptions, only a small proportion will progress to AHS.
Patients at higher risk for developing AHS include black patients, patients who have a family history of or who have experienced this syndrome in the past, and immuno-suppressed patients. The syndrome is more severe in previously sensitized individuals. If a patient is diagnosed with AHS, discontinue the Dilantin (Phenytoin sodium) and provide appropriate supportive measures.
Dilantin (Phenytoin sodium) Precautions
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.
Published literature has suggested that there may be an increased, although still rare, risk of hypersensitivity reactions, including skin rash, SJS, TEN, hepatotoxicity, and Anticonvulsant Hypersensitivity Syndrome in black patients. (See section).
Phenytoin should be discontinued if a skin rash appears (see 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 section.) 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 ). Additionally, caution should be exercised if using structurally similar compounds (e.g., barbiturates, succinimides, 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.
Phenytoin and other anticonvulsants that have been shown to induce the CYP450 enzyme are thought to affect bone mineral metabolism indirectly by increasing the metabolism of Vitamin D. This may lead to Vitamin D deficiency and heightened risk of osteomalacia, bone fractures, osteoporosis, hypocalcemia, and hypophosphatemia in chronically treated epileptic patients.
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 section.)
Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking Dilantin (Phenytoin sodium) . Instruct patients to take Dilantin (Phenytoin sodium) only as prescribed.
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, their caregivers, and families should be counseled that AEDs, including Dilantin (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 antiepileptics drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see section).
Do not use capsules which are discolored.
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.
Dilantin (Phenytoin sodium) Adverse Reactions
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, paresthesias, somnolence 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.
Dilantin (Phenytoin sodium) 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.
Dilantin (Phenytoin sodium) Dosage And Administration
Serum concentrations should be monitored in changing from Dilantin (Phenytoin sodium) (extended phenytoin sodium capsules, USP to Prompt Phenytoin Sodium Capsules, USP, and from the sodium salt to the free acid form.
Dilantin (Phenytoin sodium) (extended phenytoin sodium capsules, USP) are formulated with the sodium salt of phenytoin. The free acid form of phenytoin is used in Dilantin (Phenytoin sodium) -125 Suspension and Dilantin (Phenytoin sodium) Infatabs. 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.
Dilantin (Phenytoin sodium) How Supplied
Hard, filled No. 3 capsules containing a white powder. The medium orange cap having "PD" printed in black ink and the white, opaque body having "Dilantin (Phenytoin sodium) " over "100 mg" printed in black ink.
100's (NDC 0071-0369-24)1,000's (NDC 0071-0369-32)Unit Dose 100's (NDC 0071-0369-40)
Dilantin (Phenytoin sodium)
Dilantin (Phenytoin sodium) Medication Guide
Read this Medication Guide before you start taking Dilantin (Phenytoin sodium) and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about Dilantin (Phenytoin sodium) , ask your healthcare provider or pharmacist.
Stopping Dilantin (Phenytoin sodium) suddenly can cause serious problems.
Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
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.
Dilantin (Phenytoin sodium) is a prescription medicine used to treat tonic-clonic (grand mal), complex partial (psychomotor or temporal lobe) seizures, and to prevent and treat seizures that happen during or after brain surgery.
Do not take Dilantin (Phenytoin sodium) if you:
Before you take Dilantin (Phenytoin sodium) , tell your healthcare provider if you:
Taking Dilantin (Phenytoin sodium) with certain other medicines can cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider.
Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.
Do not drink alcohol while you take Dilantin (Phenytoin sodium) without first talking to your healthcare provider. Drinking alcohol while taking Dilantin (Phenytoin sodium) may change your blood levels of Dilantin (Phenytoin sodium) which can cause serious problems.
Do not drive, operate heavy machinery, or do other dangerous activities until you know how Dilantin (Phenytoin sodium) affects you. Dilantin (Phenytoin sodium) can slow your thinking and motor skills.
See "
The most common side effects of Dilantin (Phenytoin sodium) include:
These are not all the possible side effects of Dilantin (Phenytoin sodium) . For more information, ask your healthcare provider or pharmacist.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Dilantin (Phenytoin sodium) for a condition for which it was not prescribed. Do not give Dilantin (Phenytoin sodium) to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about Dilantin (Phenytoin sodium) . If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Dilantin (Phenytoin sodium) that was written for healthcare professionals.
For more information about Dilantin (Phenytoin sodium) , visit http://www.pfizer.com or call 1-800-438-1985.
Active ingredient: phenytoin
Inactive ingredients: USP; alcohol, USP (maximum content not greater than 0.6 percent); banana flavor; carboxymethylcellulose sodium, USP; citric acid, anhydrous, USP; glycerin, USP; magnesium aluminum silicate, NF; orange oil concentrate; polysorbate 40, NF; purified water, USP; sodium benzoate, NF; sucrose, NF; vanillin, NF; and FD&C yellow No. 6.
Each tablet is a yellow triangular scored chewable tablet.
Active ingredient: 50 mg phenytoin
Inactive ingredients: D & C yellow No. 10, A1 lake, FD&C yellow No. 6, flavor, saccharin sodium, sucrose, talc, and other ingredients.
Dilantin (Phenytoin sodium) 100mg: Each capsule contains a white powder. The medium orange cap has "PD" imprinted in black ink and the white, opaque body has "Dilantin (Phenytoin sodium) " over "100 mg" printed in black ink.
Active ingredient: 100 mg phenytoin sodium
Inactive ingredients: lactose monohydrate, confectioner's sugar, talc, and magnesium stearate. The capsule body contains titanium dioxide and gelatin. The capsule cap contains FD&C red No. 28, FD&C yellow No. 6, and gelatin.
Dilantin (Phenytoin sodium) 30mg: Each capsule contains a white powder. The small pale pink opaque cap has "PD" imprinted in black ink and the white, opaque body has "Dilantin (Phenytoin sodium) 30 mg" printed in black ink.
Active ingredient: 30 mg phenytoin sodium
Inactive ingredients: lactose monohydrate, confectioner's sugar, talc, and magnesium stearate. The capsule shell cap and body contain Titanium Dioxide (cap and body); gelatin (cap and body); D&C yellow No. 10 (cap); FD&C red No. 3 (cap).
This Medication Guide has been approved by the U.S. Food and Drug Administration.
LAB-0398-2.0
July 2011
Dilantin (Phenytoin sodium) Principal Display Panel - Mg Capsule Carton
UNIT DOSE
NDC 0071-0369-40
For in-institution use only
