Side effects for dilantin

Contents

Dilantin

SIDE EFFECTS

The following serious adverse reactions are described elsewhere in the labeling:

  • Cardiovascular Risk Associated with Rapid Infusion
  • Withdrawal Precipitated Seizure, Status Epilepticus
  • Serious Dermatologic Reactions
  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity
  • Hypersensitivity
  • Hepatic Injury
  • Hematopoietic Complications
  • Local toxicity (Including Purple Glove Syndrome)
  • Exacerbation of Porphyria
  • Teratogenicity and Other Harm to the Newborn
  • Hyperglycemia

The following adverse reactions associated with the use of DILANTIN 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.

The most notable signs of toxicity associated with the intravenous use of this drug are cardiovascular collapse and/or CNS depression. Hypotension does occur when the drug is administered rapidly by the intravenous route. The rate of administration is very important; it should not exceed 50 mg per minute in adults, and 1 to 3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients .

Body As A Whole

Allergic reactions in the form of rash and rarely more serious forms (see Skin and Appendages paragraph below) and DRESS have been observed. Anaphylaxis has also been reported.

There have also been reports of coarsening of facial features, systemic lupus erythematosus, periarteritis nodosa, and immunoglobulin abnormalities.

Severe cardiovascular events and fatalities have been reported with atrial and ventricular conduction depression and ventricular fibrillation. Severe complications are most commonly encountered in elderly or critically ill patients .

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 .

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 also cause increased serum levels of glucose, 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, paresthesia, 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 .

A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.

Skin And Appendages

Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-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, Stevens-Johnson syndrome, and toxic epidermal necrolysis . There have also been reports of hypertrichosis.

Local irritation, inflammation, tenderness, necrosis, and sloughing have been reported with or without extravasation of intravenous phenytoin .

Special Senses

Altered taste sensation including metallic taste.

Urogenital

Peyronie’s disease

Read the entire FDA prescribing information for Dilantin (Phenytoin)

Phenytoin, Oral Capsule

Phenytoin oral capsule can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with phenytoin are listed below.

Heart or cardiovascular drugs

Taking these drugs with phenytoin can increase the level of phenytoin in your body. This may lead to more side effects. Examples of these drugs include:

  • amiodarone
  • ticlopidine

Cholesterol drug

Using fluvastatin with phenytoin can increase the levels of both drugs in your body. This can lead to more side effects.

Anti-seizure drugs

Taking these anti-seizure drugs with phenytoin can increase the level of phenytoin in your body. This may lead to more side effects. Examples of these drugs include:

  • ethosuximide
  • felbamate
  • oxcarbazepine
  • methsuximide
  • topiramate

Taking these anti-seizure drugs with phenytoin can lower the level of phenytoin in your body. This means that it may not work as well to control your seizures. Examples of these drugs include:

  • carbamazepine
  • vigabatrin

Taking these anti-seizure drugs with phenytoin can increase or decrease the levels of phenytoin in your body. This means that you may have more side effects, or that phenytoin may not work as well. Examples of these drugs include:

  • phenobarbital
  • sodium valproate or valproic acid

Antifungal drugs

Taking certain antifungal drugs with phenytoin can increase the level of phenytoin in your body. This can lead to more side effects. Examples of these drugs include:

  • ketoconazole
  • itraconazole
  • miconazole
  • voriconazole
  • fluconazole

Taking fluconazole with phenytoin can lower the level of phenytoin in your body. This can keep phenytoin from working well.

Antibiotics

Taking certain antibiotics with phenytoin can increase the level of phenytoin in your body. This may lead to more side effects. Examples of these drugs include:

  • chloramphenicol

Cancer drugs

Taking certain cancer drugs with phenytoin can increase the level of phenytoin in your body. This may lead to more side effects. Examples of these drugs include:

  • capecitabine
  • fluorouracil

Taking other cancer drugs with phenytoin can lower the level of phenytoin in your body. This means that it may not work as well to control your seizures. Examples of these drugs include:

  • bleomycin
  • carboplatin
  • cisplatin
  • doxorubicin
  • methotrexate

Diabetes drugs

Taking certain diabetes drugs with phenytoin can increase the level of phenytoin in your body. This may lead to more side effects. Examples of these drugs include:

  • tolbutamide

Oral birth control pills

Taking phenytoin with oral birth control pills that contain estrogen can make those pills less effective. This means they won’t work as well to prevent pregnancy. You should use a backup form of birth control if taking these drugs together.

Menopause drugs

Taking phenytoin with oral pills that contain estrogen can make those pills less effective. This means they won’t work as well to prevent symptoms of menopause, such as hot flashes.

Stomach acid drugs

Taking certain stomach acid drugs with phenytoin can affect the level of phenytoin in your body. This may lead to more side effects, or make the phenytoin not work as well. Examples of these drugs include:

  • cimetidine
  • omeprazole

Tuberculosis drug

Taking isoniazid with phenytoin can increase the level of phenytoin in your body. This may lead to more side effects.

Mental health drugs

Taking certain mental health drugs with phenytoin can increase the level of phenytoin in your body. This may lead to more side effects. Examples of these drugs include:

  • chlordiazepoxide
  • disulfiram
  • fluoxetine
  • fluvoxamine
  • sertraline
  • trazodone
  • methylphenidate
  • phenothiazines, such as fluphenazine, chlorpromazine, or perphenazine

Taking diazepam with phenytoin can lower the level of phenytoin in your body. This means that it may not work as well to control your seizures.

Blood thinner

Taking warfarin with phenytoin can increase the level of phenytoin in your body. This may lead to more side effects. Also, phenytoin can affect how the body handles warfarin in several ways. Your doctor will monitor you closely when starting, stopping, or adjusting your phenytoin treatment if you also take warfarin.

Sulfonamides

Taking these drugs with phenytoin can increase the level of phenytoin in your body. This may lead to more side effects. Examples of these drugs include:

  • sulfamethizole
  • sulfaphenazole
  • sulfadiazine
  • sulfamethoxazole-trimethoprim

Respiratory drug

Taking theophylline with phenytoin can lower the levels of both drugs in your body. This means that both drugs may not work as well.

HIV drugs

Taking certain HIV drugs with phenytoin can lower the level of phenytoin in your body. This means that it may not work as well to control your seizures. Examples of these drugs include:

  • fosamprenavir
  • nelfinavir
  • ritonavir

Do not take delavirdine together with phenytoin. Taking these medications together will prevent delavirdine from working and treating HIV.

Herbal supplement

Taking St. John’s wort with phenytoin can lower the level of phenytoin in your body. This means it may not work as well to control your seizures.

Antacids or certain supplements

Taking certain antacids or supplements with phenytoin can decrease how well your body absorbs phenytoin. This can keep it from working well to control your seizures. To prevent this, try to take these supplements at a different time of day than when you take phenytoin. Examples of these drugs include supplements containing:

  • calcium carbonate
  • aluminum hydroxide
  • magnesium hydroxide

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

DILANTIN (extended phenytoin sodium capsules USP)

Warnings And Precautions

General

DILANTIN Capsules should not be abruptly discontinued because of the possibility of increased seizure frequency, including 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 hypersensitivity reaction, rapid substitution of alternative therapy may be necessary. In this case, alternative therapy should be an anticonvulsant drug which does not belong to the hydantoin chemical class.

Acute alcoholic intake may increase phenytoin serum levels while chronic alcoholic use may decrease serum levels.

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.

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.

In patients with renal or hepatic impairment or in those with hypoalbuminemia, there is increased plasma levels of unbound phenytoin. In patients with hyperbilirubinemia, plasma levels of unbound phenytoin may also be elevated. Since unbound phenytoin concentrations may be more useful in these patient populations, it may affect dosing considerations (see DOSAGE AND ADMINSTRATION, Renal or Hepatic Disease).

Skin

Serious Dermatological Reactions

Phenytoin can cause rare, severe cutaneous adverse reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), exfoliative dermatitis, Steven-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be fatal. Although serious skin reactions may occur without warning, patients should be alert for the occurrence of rash and other symptoms of hypersensitivity syndrome (HSS)/DRESS.

Hypersensitivity Syndrome / Drug Reaction with Eosinophilia and Systemic Symptoms
Hypersensitivity Syndrome (HSS) or Drug rash with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking anticonvulsant drugs, including phenytoin. Some of these events have been fatal or life threatening.

HSS/DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, myositis or pneumonitis. Initial symptoms may resemble an acute viral infection. Other common manifestations include arthralgias, jaundice, hepatomegaly, leukocytosis, and eosinophilia. 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. If such signs and symptoms occur, the patient should be evaluated immediately. Phenytoin should be discontinued if an alternative aetiology for the signs and symptoms cannot be established.

Patients at higher risk for developing HSS/DRESS include black patients, patients who have experienced HSS/DRESS in the past (with phenytoin or other anticonvulsant drugs), those with a family history of HSS/DRESS, and immune-suppressed patients. The syndrome is more severe in previously sensitized individuals.

Stevens-Johnson Syndrome, Acute Generalized Exanthematous Pustulosis and Toxic Epidermal Necrolysis
Serious and sometimes fatal dermatologic reactions, including Toxic Epidermal Necrolysis (TEN), Acute Generalized Exanthematous Pustulosis (AGEP) and Stevens-Johnson Syndrome (SJS), have been reported with phenytoin. Although serious skin reactions may occur without warning, patients should be alert for the occurrence of rash and other symptoms of DRESS (see WARNINGS AND PREACUTIONS, Skin). In countries with mainly Caucasian populations, these reactions are estimated to occur in 1 to 6 per 10,000 new users, but in some Asian countries (e.g., Taiwan, Malaysia and the Philippines) the risk is estimated to be much higher (see WARNINGS AND PRECAUTIONS, Skin – Asian Ancestry and Allelic Variation in the HLA-B Genotyping).

Literature reports suggest that the combination of phenytoin, cranial irradiation and the gradual reduction of corticosteroids may be associated with the development of erythema multiforme, and/or SJS, and/or TEN. In any of the above instances, caution should be exercised if using structurally similar compounds (eg, barbiturates, succinimides, oxazolidinediones and other related compounds) in these same patients.

Treatment recommendations for dermatological reactions
Phenytoin should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If the rash is exfoliative, purpuric, or bullous or if lupus erythematosus or SJS or TEN 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. The use of other anti-epileptic drugs associated with SJS/TEN should be avoided in patients who have shown severe dermatological reactions during phenytoin treatment. If a rash occurs and SJS or TEN is not suspected, the patient should be evaluated for signs and symptoms of DRESS (see WARNINGS AND PRECAUTIONS, Skin).

Asian Ancestry and Allelic Variation in the HLA-B Genotyping

HLA-B*1502
In studies that included small samples of patients of Asian ancestry a strong association was found between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene. The HLA-B*1502 allele is found almost exclusively in individuals with ancestry across broad areas of Asia1. Results of these studies suggest that the presence of the HLA-B *1502 allele may be one of the risk factors for phenytoin-associated SJS/TEN in patients with Asian ancestry.

Therefore, physicians should consider HLA-B *1502 genotyping as a screening tool in these patients. Until further information is available, the use of phenytoin and other anti-epileptic drugs associated with SJS/TEN should also be avoided in patients who test positive for the HLA-B*1502 allele.

1 The following rates provide a rough estimate of the prevalence of HLA-B*1502 in various populations. Greater than 15% of the population is reported positive in Hong Kong, Thailand, Malaysia, and parts of the Philippines, compared to about 10% in Taiwan and 4% in North China. South Asians, including Indians, appear to have intermediate prevalence of HLA-B*1502, averaging 2 to 4%, but this may be higher in some groups. HLA-B*1502 is present in <1% of the population in Japan and Korea. HLA-B*1502 is largely absent in individuals not of Asian origin (e.g., Caucasians, African-Americans, Hispanics, and Native Americans). The estimated prevalence rates have limitations due to the wide variability in rates that exist within ethnic groups, the difficulties in ascertaining ethnic ancestry and the likelihood of mixed ancestry.

Important Limitations of HLA-B Genotyping
HLA-B*1502 genotyping as a screening tool has important limitations and must never substitute for appropriate clinical vigilance and patient management. Many HLA-B*1502-positive Asian patients treated with phenytoin will not develop SJS/TEN, and these reactions can still occur infrequently in HLA-B*1502-negative patients of any ethnicity. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dose, compliance, concomitant medications, co-morbidities, and the level of dermatologic monitoring have not been studied.

In addition, it should be kept in mind that the majority of phenytoin treated patients who will experience SJS/TEN have this reaction within the first few months of treatment. This information may be taken into consideration when deciding whether to screen genetically at-risk patients currently on phenytoin.

Should signs and symptoms suggest a severe skin reaction such as SJS or TEN, phenytoin should be withdrawn at once.

Angioedema

Angioedema has been reported in patients treated with phenytoin. Phenytoin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur.

Hepatic/Biliary/Pancreatic

Cases of acute hepatotoxicity, including infrequent cases of acute hepatic failure, have been reported with phenytoin. These incidents have been associated with a hypersensitivity syndrome characterized by fever, skin eruptions, and lymphadenopathy, and usually occur within the first 2 months of treatment. Other common manifestations include arthralgias, rash, jaundice, hepatomegaly, elevated serum transaminase levels, leukocytosis, and eosinophilia. The clinical course of acute phenytoin hepatotoxicity ranges from prompt recovery to fatal outcomes. In these patients with acute hepatotoxicity, phenytoin should be immediately discontinued and not re-administered.

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 (see OVERDOSAGE).

Toxic hepatitis, liver damage, and hypersensitivity syndrome have been reported and may, in rare cases be fatal (see ADVERSE REACTIONS).

Immune

Hypersensitivity

Phenytoin and other hydantoins are contraindicated in patients who have experienced phenytoin hypersensitivity (see CONTRAINDICATIONS). If there is a history of hypersensitivity reactions to structurally similar drugs, such as carboxamides (e.g., carbamazepine), barbiturates, succinimides, and oxazolidinediones (e.g., trimethadione) in these patients or immediate family members, other alternatives should be considered.

Cardiovascular

Cardiac Effects

Cardiac-related adverse events have been reported in association with therapeutic and supratherapeutic levels of phenytoin in patients with or without history of cardiac disease or comorbidities and with or without other medications present. These reactions occurred in all age groups and included bradycardia, ventricular tachycardia, cardiac arrest, and death. In a number of cases, patients recovered following phenytoin dose reduction or discontinuation. Patients with any underlying cardiac conditions should be evaluated on an individual basis, and potential benefits of phenytoin treatment should be assessed against its potential risks (see CONTRAINDICATIONS, OVERDOSAGE).

Hematologic

Hematopoietic

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.

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 DRESS (see WARNINGS AND PRECAUTIONS, Skin). 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 anticonvulsant drugs.

While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy. If folic acid is added to phenytoin therapy, a decrease in seizure control may occur.

Carcinogenesis and Mutagenesis

(See WARNINGS AND PRECAUTIONS, Hematopoietic; WARNINGS AND PRECAUTIONS, Special Populations – Pregnant Women

Endocrine and Metabolism

Porphyria

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.

Hyperglycemia

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.

Musculoskeletal

Chronic use of phenytoin by patients with epilepsy has been associated with decreased bone mineral density (osteopenia, osteoporosis, osteomalacia) and bone fractures (see ADVERSE REACTIONS, Post-Market Adverse Drug Reactions).

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 D3. This may lead to Vitamin D deficiency and heightened risk of osteomalacia, bone fractures, osteoporosis, hypocalcemia, and hypophosphatemia in chronically treated epileptic patients. Consideration should be given to monitoring with bone-related laboratory and radiological tests and initiating treatment plans, as appropriate.

Neurologic

Central Nervous System

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 and/or cerebellar atrophy. Accordingly, at the first sign of acute toxicity, serum drug level determinations are recommended. Dose reduction of phenytoin therapy is indicated if serum levels are excessive; if symptoms persist, termination of phenytoin therapy is recommended (see ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics-Absorption; WARNINGS AND PRECAUTIONS, General).

Driving/Operating Machinery

Patients should be advised not to drive or operate complex machinery or engage in other hazardous activities until they have gained sufficient experience on phenytoin to gauge whether or not it affects their mental and/or motor performance adversely.

Psychiatric

Suicidal ideation and behaviour

Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications. An FDA meta-analysis of randomized placebo controlled trials, in which antiepileptic drugs were used for various indications, has shown a small increased risk of suicidal ideation and behaviour in patients treated with these drugs. The mechanism of this risk is not known.

All patients treated with antiepileptic drugs, irrespective of indication, should be monitored for signs of suicidal ideation and behaviour and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

There were 43,892 patients treated in the placebo controlled clinical trials that were included in the meta-analysis. Approximately 75% of patients in these clinical trials were treated for indications other than epilepsy and, for the majority of non-epilepsy indications the treatment (antiepileptic drug or placebo) was administered as monotherapy. Patients with epilepsy represented approximately 25% of the total number of patients treated in the placebo controlled clinical trials and, for the majority of epilepsy patients, treatment (antiepileptic drug or placebo) was administered as adjunct to other antiepileptic agents (i.e., patients in both treatment arms were being treated with one or more antiepileptic drug). Therefore, the small increased risk of suicidal ideation and behaviour reported from the meta-analysis (0.43% for patients on antiepileptic drugs compared to 0.24% for patients on placebo) is based largely on patients that received monotherapy treatment (antiepileptic drug or placebo) for non-epilepsy indications. The study design does not allow an estimation of the risk of suicidal ideation and behaviour for patients with epilepsy that are taking antiepileptic drugs, due both to this population being the minority in the study, and the drug-placebo comparison in this population being confounded by the presence of adjunct antiepileptic drug treatment in both arms.

Special Populations

Women of child-bearing potential: Anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus. The prescribing physician will wish to weigh these considerations in treating and counseling epileptic women of childbearing potential.

Pregnant Women

Risks to mother: An increase in seizure frequency during pregnancy occurs in a high proportion of patients, because of altered phenytoin absorption or metabolism. Periodic measurement of serum phenytoin levels is particularly valuable in the management of a pregnant epileptic patient as a guide to an appropriate adjustment of dosage (see ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics-Absorption). However, postpartum restoration of the original dosage will probably be indicated.

Risks to fetus: Phenytoin crosses the placental barrier and may cause fetal harm when administered to a pregnant woman. Prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse development outcomes.

Increased frequencies of major malformations (such as orofacial clefts and cardiac defects), and abnormalities characteristic of fetal hydantoin syndrome, including dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits, have been reported among children born to women with epilepsy who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy.

Risk to newborn:

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.

There have been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy.

Therefore, DILANTIN should be used during pregnancy only if the potential benefit outweighs the potential risks. If 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 from exposure to phenytoin.

Counsel pregnant women and women of childbearing potential about alternative therapeutic options. Women of childbearing potential who are not planning a pregnancy should be advised regarding the use of effective contraception during treatment. Phenytoin may result in a failure of the therapeutic effect of hormonal contraceptives (see DRUG INTERACTIONS, Drug-Drug Interactions, Table 4).

Nursing Women: Infant breast feeding is not recommended for women taking phenytoin. Phenytoin is secreted into human milk. Limited observations in patients suggest that phenytoin concentration in breast milk is approximately one-third of the corresponding maternal plasma concentration.

Geriatrics (> 65 years of age): Phenytoin clearance is decreased slightly in elderly patients (see DOSAGE AND ADMINISTRATION, Geriatrics).

Lactose: DILANTIN capsules contain lactose. Patients with rare hereditary problems of galactose intolerance or glucose-galactose malabsorption should not take DILANTIN capsules.

Monitoring and Laboratory Tests

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

Information for Patients and Caregivers

Patients and caregivers should be advised to read the Consumer Information sheet for DILANTIN prior to use. Patients receiving DILANTIN, and caregivers, should be given the following instructions by the physician and pharmacist:

  1. Patients taking phenytoin should be advised of the importance of adhering strictly to the prescribed dosage regimen, and of informing their physician of any clinical condition in which it is not possible to take the drug orally as prescribed, eg, surgery, etc.
  2. Patients should be advised 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 and petechial or purpuric hemorrhage, and in the case of liver reactions, anorexia, nausea/vomiting, or jaundice. The patient should be advised that, because these signs and symptoms may signal a serious reaction, that they must report any occurrence immediately to a physician. In addition, the patient should be advised that these signs and symptoms should be reported even if mild or when occurring after extended use. Patients should be advised that a history of hypersensitivity reactions with other antiepileptic drugs may be a risk for developing reactions with phenytoin (see WARNINGS AND PRECAUTIONS, Hematologic; Immune; Skin; Hepatic/Biliary/Pancreatic).
  3. Patients should be cautioned on the use of other drugs or alcoholic beverages without first seeking the physician’s advice (see DRUG INTERACTIONS).
  4. Patients should be instructed to call their physician if skin rash develops.
  5. The importance of good dental hygiene should be stressed in order to minimize the development of gingival hyperplasia and its complications.
  6. Patients, their caregivers, and families should be counseled that antiepileptic drugs, including DILANTIN, 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 (see WARNINGS AND PRECAUTIONS, Psychiatric).
  7. Women of child-bearing potential should be warned to consult their physician regarding the discontinuation of the drug due to the potential hazards to themselves and to the fetus if they are pregnant or intend to become pregnant (see WARNINGS AND PRECAUTIONS, Special Populations – Women of child-bearing potential, Pregnant Women, Nursing Women).
  8. Patients who become pregnant should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients themselves must call the toll free number 1-888-233-2334. Registry information can also be obtained from the Internet at http://www.massgeneral.org/aed/ (see WARNINGS AND PRECAUTIONS, Special Populations – Pregnant Women).

Dilantin Toxicity

This material must not be used for commercial purposes, or in any hospital or medical facility. Failure to comply may result in legal action.

Medically reviewed by Drugs.com. Last updated on Sep 24, 2019.

  • Care Notes
  • Overview
  • Aftercare Instructions
  • Ambulatory Care
  • En Español

What is Dilantin toxicity?

Dilantin, or phenytoin, toxicity happens when you have high levels of Dilantin in your body that become harmful. Dilantin is a medicine that is used to prevent and treat seizures. Dilantin toxicity can lead to a coma.

What increases my risk for Dilantin toxicity?

Your risk of Dilantin toxicity is higher if you are elderly. Your risk is increased if your dose is increased or you take other medicines that affect the way Dilantin works. Examples include other medicines used to treat seizures and some antibiotics. Other examples include certain medicines used to treat arrhythmias (abnormal heart rhythms), alcoholism, ulcers, and tuberculosis.

What are the symptoms of Dilantin toxicity?

  • Fast, uncontrollable eye movements or double vision
  • Dizziness, drowsiness, or confusion
  • Lack of coordination of fingers, hands, arms, legs, or body
  • Slurred speech
  • Nausea or vomiting
  • Decreased appetite, decreased activity, abdominal bloating, or irregular jerky movements in children or the elderly

How do I safely take Dilantin?

  • Take this medicine exactly as directed. Contact your healthcare provider if you miss a dose or you have any questions about how to take Dilantin.
  • Do not stop taking Dilantin or change your dose. Your risk of seizures increases if you decrease your dose or stop taking Dilantin. Even a small increase in your dose can cause toxicity.
  • Go to all your follow-up appointments. Your healthcare provider will need to monitor you closely while you are taking Dilantin. You will need regular blood and urine tests.

What else should I do while I am taking Dilantin?

Wear medical alert jewelry or carry a card that says you take Dilantin. Ask where to get these items.

What should I do if I think I or someone I know took too much Dilantin?

Call the Poison Control Center at 1-800-222-1222 immediately.

When should I seek immediate care?

  • You have fast, uncontrollable eye movements or double vision.
  • You have a lack of coordination of fingers, hands, arms, legs, or other part of your body.
  • You are dizzy, drowsy, or confused.
  • Your speech is slurred.
  • You have irregular or jerky movements.
  • You cannot be awakened.

When should I contact my healthcare provider?

  • You have frequent or unexplained falls.
  • You missed a dose of Dilantin.
  • You have nausea, or you are vomiting.
  • You have a decreased appetite.
  • Your abdomen is bloated.
  • You have questions or concerns about your condition or care.

Care Agreement

You have the right to help plan your care. Learn about your health condition and how it may be treated. Discuss treatment options with your healthcare providers to decide what care you want to receive. You always have the right to refuse treatment. The above information is an educational aid only. It is not intended as medical advice for individual conditions or treatments. Talk to your doctor, nurse or pharmacist before following any medical regimen to see if it is safe and effective for you.

© Copyright IBM Corporation 2019 Information is for End User’s use only and may not be sold, redistributed or otherwise used for commercial purposes. All illustrations and images included in CareNotes® are the copyrighted property of A.D.A.M., Inc. or IBM Watson Health

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Learn more about Dilantin Toxicity

IBM Watson Micromedex

  • Adverse Drug Reaction
  • Antibiotic Medication Allergy
  • Antiretroviral Medication Allergy
  • Digoxin Toxicity
  • Drug Allergy
  • Lithium Toxicity
  • Safe Use of Antiplatelet Medication
  • Safe Use of Nsaids

What are the Symptoms of Dilantin Toxicity?

The widely used anticonvulsant Dilantin has been linked with a number of serious issues. One of these side effects is Dilantin toxicity, which can cause problems like nausea, dizziness, lack of coordination, and may even lead to a coma.

Basics of Dilantin

Dilantin (also known by its generic name, phenytoin) is a popular anticonvulsant and anti-epilepsy oral medication manufactured by pharmaceutical giant Pfizer, Inc., and is used to control seizures. In order to reduce seizure activity in the brain, Dilantin works to slow down the rapid firing of the brain’s neurons that are indicative of a seizure.

Dilantin was first approved by the U.S. Food and Drug Administration (FDA) back in 1953 for the treatment of seizures. In the decades since, Dilantin has become one of the most widespread options available for this purpose. Unfortunately, Dilantin has also been linked with some serious and potentially permanent side effects, including Dilantin toxicity and cerebellar atrophy.

What is Dilantin Toxicity?

Essentially, Dilantin toxicity occurs when a patient has such high levels of Dilantin in their body that it actually becomes harmful. In extreme cases, Dilantin toxicity can even lead to a coma. The NIH notes that very high levels of Dilantin may even lead to seizures, the same condition the drug is meant to control.

Symptoms of Dilantin toxicity may include the following:

  • Fast, uncontrollable eye movements or double vision (nystagmus)
  • Dizziness, drowsiness, or confusion
  • Lack of coordination of fingers, hands, arms, legs, or body
  • Slurred speech
  • Nausea or vomiting
  • Decreased appetite, decreased activity, abdominal bloating, or irregular jerky movements in children or the elderly

The use of phenytoin has also been linked in studies with a side effect known as Dilantin cerebellar atrophy, a severe degenerative brain condition. As cerebellar atrophy progresses, neurons and their connections are lost, which in turn affects essential movements like balance, coordination, posture, and speech.

The precision of these movements are lost over time, leading to unsteady walking, slow or slurred speech, and rapid eye movement, among others.

When a patient is exposed to higher levels of Dilantin, especially over a longer period of time, they face an increased risk of experiencing major side effects like Dilantin toxicity or cerebellar degeneration. However, this does not mean that patients taking normal or low levels of the drug do not also face some risk of these complications.

In order to treat these Dilantin side effects, some patients may simply need to stop taking Dilantin (only if monitored by a doctor). Unfortunately, in some cases, these side effects may have permanent consequences.

Cerebellar atrophy is a serious condition. In some cases, recovery may be possible if a patient stops taking Dilantin. However, in many cases, the atrophy may be permanent. One side effect is cerebellar ataxia, which is a loss of muscle coordination that is often permanent after damage to the cerebellum has occurred, says Mayo Clinic.

Filing a lawsuit may be one way to help deal with the costs of managing Dilantin toxicity. Cerebellar degeneration can make life complicated for many people and may be disabling.

Managing the condition may require extensive therapy and care. Occupational therapy and movement therapy can help people with movement problems from cerebellar ataxia move around safely and comfortably. Some patients may require ongoing care for the rest of their lives.

Additionally, devices like wheelchairs and walkers can also become necessary. These devices can be extremely costly. Filing a Dilantin toxicity lawsuit can help you get the funds needed to provide these devices for your loved ones or yourself.

The financial hit of medical devices, on top of possible lost wages and decreased productivity, may be a serious financial strain, and filing a lawsuit can be helpful in managing these costs.

People with cerebellar ataxia have higher rates of anxiety and depression, which can take their own toll and can also require management. Ataxia patients who need help with daily tasks are especially at risk for anxiety and depression, says Healthline.

Filing a Dilantin Lawsuit

A growing number of Dilantin users are turning to litigation, alleging that they were not adequately warned about various severe complications associated with the use of Dilantin.

If you or someone you love have suffered from side effects of Dilantin, including Dilantin toxicity, you may be able to file a lawsuit and pursue compensation. Of course, filing a lawsuit cannot take away the pain and suffering caused by Dilantin complications, but it can at least help to alleviate the financial burden incurred by medical expenses, lost wages, and more.

Phenytoin intoxication can occur either with repeated supra therapeutic dosing or an acute overdose. Dose-dependent CNS depression occurs. Most presentations are benign and have good outcomes with supportive care. The main risk to patients is falling which can last days.

Toxic Mechanism:

Phenytoin is a sodium channel blocker, this is why you should never give it as an intravenous bolus. It would cause acute sodium channel blockade like a tricyclic antidepressant causing widening of the QRS with risk of dysrhythmias including VT. Specifically it suppresses membrane post-titanic potentiation and hyper excitability.

Toxicokinetics:

  • Slow and erratic absorption orally.
  • Peak levels are delayed by 24 – 48 hours
  • Volume of distribution is 0.6 L/kg
  • Protein binding is high (90%)
  • It is metabolised in the liver, importantly this metabolism is saturable and plasma levels can rise dramatically with only a slight increase in daily dosing.
  • Elimination half-lives in a poisoned patient can vary between 24 to 230 hours.

Resuscitation:

  • Attention to ABC, if there is a reduced GCS or an unprotected airway or respiratory depression, intubation and ventilation will need to be performed.
  • Ventricular dysrhythmias (seen if phenytoin is given rapidly as an IV push, not with an oral overdose):
    • Sodium bicarbonate 2 mmol/kg IV repeated every 1-2 minutes to restore a perfusing rhythm, multiple doses maybe required.
    • It is unlikely that defibrillation will work.
    • Lignocaine 1.5 mg/kg IV is third line when the pH is >7.5
    • If the QRS persists in widening after boluses of sodium bicarbonate then the patient will require intubation and ventilation to maintain a pH>7.5
  • Seizures: IV benzodiazepines incrementally dosed every 5 minutes to effect.
    • Check the patient is not in a dysrhythmia
    • Can be managed with benzodiazepines (varying doses in the textbooks, easy method is 0.1mg/kg IV for lorazepam (max 4mg) / midazolam (max 10mg) / diazepam (max 10mg). Or…
    • Lorazepam 0.1mg/kg max 4mg
    • Diazepam 0.15mg/kg max 10mg
    • Midazolam 0.2mg/kg max 10mg

Risk Assessment

  • Dose-dependent CNS effects are seen. Mainly cerebellar features (ataxia, nystagmus, slurred speech, tremor, involuntary movements and ophthalmoplegia). These findings may be subtle in a patient with chronic toxicity, consider in anyone who has fallen on phenytoin.
    • 10 – 15 mg/kg = Standard therapeutic loading
    • >20 mg/kg = Ataxia, dysarthria and nystagmus
    • >100 mg/kg = Potential for coma and seizures
  • Coma and seizures are rare
  • Cardiovascular effects are only seen with rapid intravenous administration (hypotension, bradycardia, ventricular dysrhythmias and asystole)
  • Symptoms take hours to precipitate and 2 – 4 days to resolve as levels slowly fall.
  • Children: Ingestion of one to two 100 mg tablets is insufficient to cause symptoms.

Supportive Care

  • General supportive care
  • The main consideration is a falls risk secondary to the ataxia. Bed rails should be used along with assistance to mobilise.
  • If intubated consider FASTHUGSINBED Please

Investigations

  • Screening: 12 lead ECG, BSL, Paracetamol level
  • Specific:
    • EUC, VBG and serum osmolality – hypernatraemia and hyperglycaemia can occur from a non-ketotic hyperosmolar coma in large overdoses.
    • Phenytoin levels – useful to confirm the diagnosis and levels correlate with toxicity:
      • Nystagmus >20 mg/L (80 micromol/L)
      • Severe ataxia 30 – 40 mg/L (120 -160 micromol/L)
      • Coma >50 mg/L (200 micromol/L)
    • ECG monitoring is not required for oral toxicity

Decontamination:

  • 50 g (1 g/kg in a child) of activated charcoal can be given within 4 hours of an acute oral overdose and may reduce the length of stay in hospital.

Enhanced Elimination

  • Both Multiple dose activated charcoal and charcoal haemoperfusion and plasmapheresis are all possible given the pharmacokinetics of phenytoin but are not routine choices. Consult a clinical toxicologist for advice as these can be utilised in massive overdoses.

Antidote

  • None available

Disposition

  • Children only require assessment and observation if they become symptomatic (ataxia or drowsiness) otherwise they can remain at home.
  • Patients who are asymptomatic 6 hours post ingestion (GCS 15, can heel-toe-walk) are medically fit for discharge. Discharge should not occur over night.
  • Those who develop symptoms will require the appropriate treatment and level of observation, usually on the ward. Most symptoms resolve within 2 – 4 days. Once asymptomatic and can walk they are medically fit for discharge.
  • Patients who require intubation and ventilation will require ICU.

Additional Resources and References:

Additional Resources:

  • Tox conundrum 023 – Toxic seizures
  • CCC – Sodium channel blockers

Video: Sodium Channel Blockade and the ECG

Toxicology Library

DRUGS and TOXICANTS

PHENYTOIN AS THE FIRST OPTION IN FEMALE EPILEPTIC PATIENTS?

PAULO CÉSAR TREVISOL-BITTENCOURT, VICTOR REIS DA SILVA, MÁRCIO ALCIDES MOLINARI, ANDRÉ RIBEIRO TROIANO

ABSTRACT ¾ Objective: Phenytoin (PHT) is one of the first-choice drugs in several epileptic syndromes, mostly in partial epilepsies, in which case it is effective as carbamazepine and phenobarbital. However, like any other anti-epileptic drug (AED), unpleasant side-effects are not rare. The aim of this study is the evaluation of dermatological troubles related to chronic PHT usage in female patients. Method: Between 1990-93, 731 new patients underwent investigation for epilepsy at the Multidisciplinary Clinic for Epilepsy in our State. In this sample 283 were AED users at the time of the first assessment. Sixty one female patients taking PHT were identified. They were taking PHT in a dosage ranging from 100 to 300 mg daily, in mono or polytherapy regimen, during 1-5 previous years. Results: More than 50% of the sample showed coarse facial features made by the combination of several degrees of acne, hirsutism and gingival hyperplasia. Conclusion: Except in emergency situations, PHT should not be prescribed as the first option to the treatment of female epileptic patients, because not uncommonly the cosmetic side-effects are more socially handicapping than the epileptic syndrome by itself.

KEY WORDS: epilepsy, phenytoin, gingival hyperplasia, hirsutism.

Fenitoína como primeira opção em mulheres com epilepsia ?

RESUMO ¾ Objetivo: Fenitoína (PHT) é uma das principais drogas no tratamento de epilepsias diversas, principalmente as parciais, para a qual ela é tão eficaz quanto carbamazepina e fenobarbital. Entretanto, como qualquer outra droga anti-epiléptica (DAE) da atualidade, efeitos desagradáveis não são raros. O alvo deste estudo é a avaliação dos efeitos dermatológicos relacionados com o uso prolongado de PHT em pacientes femininas. Método: Entre 1990-93, foram admitidos para avaliação 731 novos pacientes na Clínica Multidisciplinar de Epilepsia/SUS, Florianópolis/SC. Destes, 238 já estavam em uso de DAE, sendo que 61 eram mulheres usuárias de fenitoína, numa dosagem que variava de 100-300 mg/dia, em mono ou politerapia, por um período prévio de 1-5 anos. Resultados: Mais de 50 % das pacientes exibiam alterações faciais grosseiras, decorrentes da combinação em diferentes níveis de severidade de acne, hirsutismo e hiperplasia gengival,. Conclusão: Exceto em situações de emergência, PHT não deveria ser usada como primeira escolha no tratamento de mulheres com epilepsia; seus frequentes efeitos colaterais dermatológicos causam mais transtornos médico-sociais que a epilepsia por si própria.

PALAVRAS-CHAVE: epilepsia, fenitoína, hiperplasia gengival, hirsutismo.

Overall, phenytoin (PHT) is known to be effective in the treatment of several epileptic syndromes, specially in partial epilepsies1. However it has been associated with a lot of undesirable bad effects and cosmetic-dermatological troubles are quite common. Since Kimball, 1939, first reported gingival hiperplasia (GH) as a side-effect of PHT, many efforts have been done to approach this manifestation. The pathogenesis of the GH is still debatable and several theories have been developed in an attempt to elucidate such issue. The most reasonables are IgA deficiency in serum and saliva leading to local immune reactions 2; decreased serum levels of folic acid causing deterioration of the gingival saccular epitelium3 and low Ca+ in gingival fibroblasts4.

Moreover PHT may generate a sizeable list of unpleasant side-effects, such as teratogenies, cognitive impairment, cutaneous syndromes, metabolic and hematologic disorders; however cosmetic side-effects are some of the most socially undesirable5-7. Hirsutism for instance, is a common undisguiseable trait of PHT long-term use and the first criticism on it was made by Kerr in 19758. Since then very few neurologists have done comments on this important negative aspect and paradoxically it has never been taken into account on evaluating epileptic patient´s quality of life.

We hope to add few inroads into the era of the modern epileptology, and allow the idea of socially stigmatising sequelae as a result of PHT use.

METHOD

In a cohort study with 3-years of longitudinal follow-up, 1990-93, 731 new patients were assessed in the outpatient Multidisciplinary Clinic of Epilepsy (MCE) of the Brazilian National Health Service for investigation of seizures. All this sample was screened by a multidisciplinary team consisting of neurology, psychiatry, psychology, nursing and social workers. All patients previously taking anti-epileptic drugs (AEDs) were identified. Those female patients who presented unequivocal dermatological troubles were separated and correlation with previous treatment was made. As the mainstain inclusion criteria, the presence of PHT as the solely causative factor for the cluster of dermatologic side-effects was identified together with a minucious assessment of the clinical findings by a multidisciplinary team.

RESULTS

Among the 283 patients using AEDs, 61 were female PHT users in mono or polytherapy, in a dosage ranging from 100 to 300 mg daily. Mean time of PHT use prior to the initial assessment was 3 years and 7 months. Mean age was 32 years (14 to 56). Most of the sample, 52.46% (32 patients), exhibited bizarre facial features in a gamut of severity. Essentially they were a combination of acne, hirsutism and gum hyperplasia (Fig 1). Halitosis secondary to gingival bleeding was remarkable in the vast majority of this group.

DISCUSSION

Initially, we would like to emphasize our agreement that PHT is a major and accessible anti-epileptic drug. Actually, we use to prescribe PHT as the first choice drug to many patients suffering from epilepsy at the MCE. Unfortunately there is no safe side, being the list of side effects of PHT, like any other AED, manifold. The crippling combination of hirsutism and facial coarsening with thickening of the subcutaneous tissue, have been reported as common long-term complications PHT use. Also, there is a tendency for GH to be associated with high serum levels of the drug and duration of treatment9. However was noteworthy to see very few reports on this important subject. In our study for example, more than 50% of the female epileptic users showed undesirable features as a deplorable consequence of treatment. Unlike changes frequently seen, these unpleasant side-effects did not return to normal, keeping the patients with this lifetime scar. And now, these already stigmatised patients have to live not only with abnormal phenomena of their brain, but also with these iatrogenical and social limiting side-effects. Many unfortunate patients showed an “ugly-man” appearance that we defined as rasputinian facies. Most of them were unsuccessfully attempting to keep a charming feminine look, with endless shavings, as a result of the grossly deformed hairy face. The odd appearance was made by coarsened facial features, where GH was a clear cause of several bleeding episodes triggered by chewing or tooth brushing. Thus, halitosis became a natural aroma exhibited by most of these patients. Also, it was something surreal to notice that no one, including doctors, had paid attention to these symptoms. A considerable slice of these sample was exposed to chronic and enormously expensive psychological, dental and dermatological treatments, which gives testimony of a good deal of our reigning ignorance and consequent failure to recognize such obvious aetiology. Perhaps, for many doctors, patients and their relatives as well, epilepsy is still been identified as a terrible lifetime condition. So, these vulgar side-effects are usually neglected or misenterpreted as a kind of natural tribute that epileptic patients must pay to get freedom from seizures10.

The association between those cosmetic effects and the lack of knowledge about epilepsy made even worse the psychological scenery among patients with epilepsy and their interaction in society. Medical and social importance given to these alterations differ from place to place, and doctors are prone to give attention or not to these side effects depending on the environment they grew up and learned their medical skills. So, we can not expect physicians from different lineages to have the same attitude and opinion before such situation.

Finally, our readers should noticed that as brazilians we belong to latin tribe, where good look is important to get active social life. Maybe, this aspect represents the bias side of our study. However, we suspect that artificial ugliness does not help people suffering from epilepsy to get better quality of life, does not matter which society they are living. For these reasons, we believe that except on an emergency basis, PHT should not be used as the first option in the treatment of female epileptic patients, because usually the dermatological side-effects are more socially handicapping than the epileptic syndrome by itself.

2. Fontana A, Sauter R, Grob PJ. IgA deficiency epilepsy and hydantoin-medication. Lancet 1976;2:228-231.

3. Poppell TD, Kelling SD, Collins JF, Hassel TM. Effect of folic acid on recurrence of phenytoin induced gingival overgrowth following gengivectomy. J Clin Periodontol 1991;18:134-139.

4. Modeer T, Brunius G, Mendez C, Juntti Berggren L, Berggren PO. Influence of phenytoin on cytoplasmatic free Ca+ level in human gingival fibroblasts. Scand J Dent Res 1991;99:310-315.

5. Dahllöf G, Preber H, Eliasson S, et al. Periodontal condition of epileptic adults treated long-term with phenytoin or carbamazepine. Epilepsia 1993;34:960-964.

6. Reynolds EH. Chronic antiepileptic toxicity: a review. Epilepsia 1975;16:319-352.

8. Kerr WC: Phenytoin: reevaluation necessary (letter). Med J Aust 1975;13:2:918.

10. Trevisol-Bittencourt PC, Silva VR. Alternative medicine in patients with epilepsy in Santa Catarina, southern Brazil. Epicadec News 1998;12:12-16.

Neurology Professor, University Hospital, Santa Catarina Federal University (UFSC), Neurosurgery Resident, University of Toronto, Canada; Medical Student, Santa Catarina Federal University. Aceite: 29-junho-1999.

Generic Name: phenytoin (oral) (FEN i toyn)
Brand Names: Dilantin, Phenytek

Medically reviewed by P. Thornton, DipPharm Last updated on Jan 21, 2019.

  • Overview
  • Side Effects
  • Dosage
  • Professional
  • Interactions
  • More

What is Dilantin?

Dilantin (phenytoin) is an anti-epileptic drug, also called an anticonvulsant. It works by slowing down impulses in the brain that cause seizures.

Dilantin is used to control seizures. Phenytoin does not treat all types of seizures, and your doctor will determine if it is the right medicine for you.

Important Information

You should not use Dilantin if you also take delavirdine (Rescriptor), or if you are allergic to phenytoin, ethotoin (Peganone), fosphenytoin (Cerebyx), or mephenytoin (Mesantoin). If you are pregnant, DO NOT START TAKING this medicine unless your doctor tells you to. Phenytoin may cause harm to an unborn baby, but having a seizure during pregnancy could harm both the mother and the baby. If you become pregnant while taking Dilantin, DO NOT STOP TAKING the medicine without your doctor’s advice. Seizure control is very important during pregnancy and the benefits of preventing seizures may outweigh any risks posed by using phenytoin.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, depression, anxiety, or if you feel agitated, hostile, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.

Before taking this medicine

You should not use Dilantin if you are allergic to phenytoin, or if you have ever had:

  • liver problems caused by phenytoin;

  • an allergy to similar medicines such as ethotoin, fosDilantin, or meDilantin; or

  • if you currently take delavirdine (Rescriptor).

To make sure Dilantin is safe for you, tell your doctor if you have ever had:

  • heart problems;

  • liver disease;

  • diabetes;

  • depression;

  • suicidal thoughts or actions;

  • a vitamin D deficiency or any other condition that causes thinning of the bones;

  • porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system); or

  • if you are of Asian ancestry (you may need a special blood test to determine your risk for having a skin reaction to phenytoin).

Some people have thoughts about suicide while taking Dilantin. Your doctor will need to check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Seizure control is very important during pregnancy. Do not start or stop taking Dilantin without your doctor’s advice if you are pregnant. Phenytoin may harm an unborn baby, but having a seizure during pregnancy could harm both mother and baby. Tell your doctor right away if you become pregnant while taking this medicine.

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of phenytoin on the baby.

If you have taken phenytoin during pregnancy, be sure to tell the doctor who delivers your baby about your Dilantin use. Both you and the baby may need to receive medications to prevent excessive bleeding during delivery and just after birth.

Phenytoin can make birth control pills less effective. Ask your doctor about using a non-hormonal birth control (condom, diaphragm with spermicide) to prevent pregnancy.

It may not be safe to breast-feed while using this medicine. Ask your doctor about any risk.

How should I take Dilantin?

Take Dilantin exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Swallow an extended-release capsule whole and do not crush, chew, break, or open it.

Dilantin Infatabs chewable tablets are not for once-per-day dosing. You must take them 2 or 3 times per day. Follow your doctor’s dosing instructions very carefully.

Shake the oral suspension (liquid) before you measure a dose. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

You may need frequent blood tests. You may also need a blood test when switching from one form of phenytoin to another. Visit your doctor regularly.

Tell your doctor if Dilantin does not seem to work as well in controlling your seizures. Do not stop using Dilantin suddenly, even if you feel fine. Stopping suddenly may cause increased seizures. Follow your doctor’s instructions about tapering your dose.

In case of emergency, wear or carry medical identification to let others know you have seizures.

Phenytoin can cause swelling in your gums. Brush and floss your teeth and visit your dentist regularly to help prevent this problem.

Store at room temperature away from moisture, light, and heat.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of phenytoin can be fatal. Overdose symptoms may include twitching eye movements, slurred speech, loss of balance, tremor, muscle stiffness or weakness, nausea, vomiting, feeling light-headed, fainting, and slow or shallow breathing.

What should I avoid while taking Dilantin?

Avoid drinking alcohol while you are taking Dilantin. Alcohol use can increase your blood levels of phenytoin and may increase side effects. Daily alcohol use can decrease your blood levels of phenytoin, which can increase your risk of seizures.

Ask a doctor or pharmacist before using over-the-counter medicines such as cimetidine, omeprazole, St. John’s wort, or vitamins and mineral supplements that contain folic acid.

Avoid driving or hazardous activity until you know how Dilantin will affect you. Your reactions could be impaired.

Avoid taking antacids at the same time you take Dilantin. Antacids can make it harder for your body to absorb the medication.

Dilantin side effects

Get emergency medical help if you have signs of an allergic reaction to Dilantin (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

  • slow or uneven heartbeats, chest pain, fluttering in your chest, and dizziness (like you might pass out);

  • any skin rash, no matter how mild;

  • fever, chills, sore throat, swollen glands;

  • red or swollen gums, mouth sores;

  • easy bruising, unusual bleeding, purple or red spots under your skin; or

  • liver problems – loss of appetite, upper stomach pain, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common Dilantin side effects may include:

  • drowsiness, confusion;

  • slurred speech;

  • abnormal eye movement; or

  • problems with balance or muscle movement.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Dilantin?

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Many drugs can interact with phenytoin. Not all possible interactions are listed here. TELL YOUR DOCTOR ABOUT ALL OTHER MEDICINES YOU USE, and any you start or stop using during treatment with Dilantin. This includes prescription and over-the-counter medicines, vitamins, and herbal products.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Dilantin only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2020 Cerner Multum, Inc. Version: 18.02.

Medical Disclaimer

More about Dilantin (phenytoin)

  • Side Effects
  • During Pregnancy or Breastfeeding
  • Dosage Information
  • Drug Images
  • Drug Interactions
  • Compare Alternatives
  • Support Group
  • Pricing & Coupons
  • 63 Reviews
  • Generic Availability
  • Drug class: group I antiarrhythmics
  • FDA Alerts (2)

Consumer resources

  • Dilantin
  • Dilantin Infatabs
  • Dilantin Kapseals
  • Dilantin (Advanced Reading)
  • Dilantin Infatabs (Advanced Reading)
  • … +2 more

Other brands: Phenytek

Professional resources

  • Dilantin (FDA)
  • … +4 more

Related treatment guides

  • Neurosurgery
  • Seizures
  • Epilepsy
  • Seizure Prophylaxis During or Following Neurosurgery
  • Status Epilepticus

It is very important that your doctor check your or your child’s progress at regular visits while using this medicine to see if it is working properly and to allow for a change in the dose. Blood and urine tests may be needed to check for any unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Do not use this medicine if you or your child are also using delavirdine (Rescriptor®). Using these medicines together may cause unwanted effects.

Lymph node problems may occur while using this medicine. Check with your doctor right away if you or your child have swollen, painful, or tender lymph glands in your neck, armpit, or groin.

Do not stop using this medicine without first checking with your doctor. Your doctor may want you or your child to gradually reduce the amount you are using before stopping completely.

This medicine may cause serious allergic reactions, including angioedema. These can be life-threatening and require immediate medical attention. Tell your doctor right away if you or your child have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after using this medicine.

Serious skin reactions can occur with this medicine. Check with your doctor right away if you or your child have blistering, peeling, or loose skin, red skin lesions, severe acne or skin rash, sores or ulcers on the skin, a fever, or chills while you are using this medicine.

Tell your doctor right away if you or your child develop a fever, rash, swollen, painful, or tender lymph glands in the neck, armpit, or groin, unusual bleeding or bruising, or yellow eyes or skin after using this medicine. These may be symptoms of a serious and life-threatening condition called drug reaction with eosinophilia and systemic symptoms (DRESS).

Phenytoin may cause heart problems, including a slow heartbeat. Check with your doctor right away if you have chest pain, dizziness, or tiredness.

This medicine may cause liver damage. Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin.

Phenytoin can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

  • If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
  • Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
  • Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
  • Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
  • Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
  • Avoid contact sports or other situations where bruising or injury could occur.

This medicine may decrease bone mineral density. A low bone mineral density can cause weak bones or osteoporosis. If you or your child have any questions about this ask your doctor.

This medicine may affect blood sugar levels. If you or your child notice a change in the results of your blood or urine sugar tests or if you have any questions, check with your doctor.

This medicine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you, your child, or your caregiver notice any of these side effects, tell your or your child’s doctor right away.

In some patients (usually younger patients), tenderness, swelling, or bleeding of the gums (gingival hyperplasia) may appear soon after phenytoin treatment is started. To help prevent this, brush and floss your teeth carefully and regularly and massage your gums. Also, see your dentist every 6 months to have your teeth cleaned. If you have any questions about how to take care of your teeth and gums, or if you notice any tenderness, swelling, or bleeding of your gums, check with your doctor or dentist.

Before you have any medical tests, tell the medical doctor in charge that you or your child are taking this medicine. The results of some tests may be affected by this medicine.

This medicine may cause drowsiness, trouble thinking, or trouble in controlling movements. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

Avoid drinking alcohol while you are using this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter ) medicines and herbal or vitamin supplements.

Phenytoin toxicity

Background

  • Mortality is extremely rare after intentional overdose if good supportive care is provided
  • Rapid IV dosing carries greatest risk (due to propylene glycol constituent of IV form → myocardia depression & cardiac arrest)
  • 90% protein bound; dialysis ineffective

Clinical Features

  • CV (only with IV form)
    • Bradycardia
    • Hypotension
    • Vfib
    • Asystole
  • Neuro
    • Nystagmus
      • First only with forced lateral gaze; later becomes spontaneous
      • May disappear at higher levels
    • Ataxia
    • Decreased LOC
  • GI
    • Nausea and vomiting
  • Skin
    • tissue infiltration (IV) → “Purple glove syndrome”
    • edema, pain, ischemia, tissue necrosis, compartment syndrome
  • Anticonvulsant hypersensitivity syndrome
    • Fever, eosinophilia, rash, pseudolymphoma, SLE, pancytopenia, hepatitis, pneumonitis, pharyngitis, rhabdomyolysis
    • Mortality rate of 10%

Differential Diagnosis

Toxicity symptoms by phenytoin level^

Level Sypmtoms
>10 Usually no symptoms
10-20 Occasional mild nystagmus
20-30 Nystagmus
30-40 Ataxia, slurred speech, Nausea/vomiting
40-50 Lethargy, confusion
>50 Coma, seizure (rare)

^Provides a rough guide only; neither sensitive nor specific

  • Correct for albumin level
    • Free phenytoin concentration determines toxicity
    • Hypoalbuminemia results in higher free phenytoin concentration
  • Other laboratory testing
    • LFTs, hepatic dysfunction increases risk of phenytoin toxicity
    • CBC, frequently show eosinophilia or marked leukocytosis
    • Total CK
    • ECG, may see arrhythmias, AV block, or sinus arrest with junctional or ventricular escape
    • POC glucose, rule out hypoglycemia as cause of AMS
    • Acetaminophen and salicylate levels, rule out common coingestion
    • Urine pregnancy test

Management

  • Supportive care is mainstay of treatment
  • If intubation needed, standard RSI meds ok, avoid lidocaine (same antidysrhythmic properties as phenytoin)
  • If symptomatic bradyarrhythmia:
    • ACLS: Bradycardia, Atropine, epinephrine, dopamine are first line
    • May consider transcutaneous or transvenous pacing
  • Hypotension
    • IVF bolus
  • Detoxification
    • Activated charcoal PO
    • Gastric lavage and whole bowel irrigation are NOT recommended

Disposition

  • Cannot base on phenytoin level (erratic absorption after PO overdose)
    • Consider discharge if patient has only mild symptoms and serial phenytoin levels decline

See Also

  • Phenytoin

About the author

Leave a Reply

Your email address will not be published. Required fields are marked *