Dintospina

Amphetamine Sulfate:

• Warning
• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warning
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Medication guideevekeo® (amphetamine sulfate tablets, usp)
• Dintospina (Amphetamine Sulfate) reviews

WARNING

AMPHETAMINES HAVE A HIGH POTENTIAL FOR ABUSE. ADMINISTRATION OF AMPHETAMINES FOR PROLONGED PERIODS OF TIME MAY LEAD TO DRUG DEPENDENCE AND MUST BE AVOIDED. PARTICULAR ATTENTION SHOULD BE PAID TO THE POSSIBILITY OF SUBJECTS OBTAINING AMPHETAMINES FOR NON-THERAPEUTIC USE OR DISTRIBUTION TO OTHERS, AND THE DRUGS SHOULD BE PRESCRIBED OR DISPENSED SPARINGLY.

MISUSE OF AMPHETAMINE MAY CAUSE SUDDEN DEATH AND SERIOUS CARDIOVASCULAR ADVERSE EVENTS.

DESCRIPTION

Dintospina (Amphetamine Sulfate) is a sympathomimetic amino of the amphetamine group. It is a white, odorless crystalline powder. It has a slightly bitter taste. Its solutions are acid to litmus, having a pH of 5 to 8. It is freely soluble in water, slightly soluble in alcohol and practically insoluble in ether.

Each tablet, for oral administration contains 5 mg or 10 mg of Dintospina (Amphetamine Sulfate). Each tablet also contains the following inactive ingredients: crospovidone, silicified microcrystalline cellulose and stearic acid. The 10 mg tablet also contains FD&C Blue #1.

Structural Formula:

Chemical Structure

CLINICAL PHARMACOLOGY

Amphetamines are non-catecholamine, sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures, and weak bronchodilator, and respiratory stimulant action.

Amphetamine, as the racemic form, differs from dextroamphetamine in a number of ways. The l-isomer is more potent than the d-isomer in cardiovascular activity, but much less potent in causing CNS excitatory effects. The racemic mixture also is less effective as an appetite suppressant when compared to dextroamphetamine. There is neither specific evidence which clearly establishes the mechanism whereby amphetamines produce mental and behavioral effects in children, nor conclusive evidence regarding how those effects relate to the condition of the central nervous system.

Drugs in this class used in obesity are commonly known as "anorectics" or "anorexigenics." It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects, may be involved, for example. Adult obese subjects instructed in dietary management and treated with "anorectic" drugs lose more weight on the average than these treated with placebo and diet, as determined in relatively short- term clinical trials.

The magnitude of increased weight loss of drug-treated patients over placebo-treated patients is only a fraction of a pound a week. The rate of weight loss is greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. The origins of the increased weight loss due to the various possible drug effects are not established. The amount of weight loss associated with the use of an "anorectic" drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician-investigator, the population treated, and the diet prescribed. Studies do not permit conclusions as to the relative importance of the drug and nondrug factors on weight loss.

The natural history of obesity is measured in years, whereas the studies cited are restricted to few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered clinically limited.

INDICATIONS AND USAGE

Dintospina (Amphetamine Sulfate)^® (amphetamine sulfate tablets, USP) is indicated for:

• Narcolepsy
• Attention Deficit Disorder with Hyperactivity as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of the syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or not be warranted.
• Exogenous Obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction for patients refractory to alternative therapy, e.g., repeated diets, group programs, and other drugs. The limited usefulness of amphetamines should be weighed against possible risks inherent in use of the drug, such as those described below.

CONTRAINDICATIONS

Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines.

Agitated states.

Patients with a history of drug abuse.

During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result).

WARNING

Serious Cardiovascular Events

Sudden Death and Pre-Existing Structural Cardiac Abnormalities or Other Serious Heart Problems

Children and Adolescents

Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

Adults

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.

Hypertension and other Cardiovascular Conditions

Stimulant medications cause a modest increase in average blood pressure and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.

Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications

Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.

Psychiatric Adverse Events

Pre-Existing Psychosis

Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.

Bipolar Illness

Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

Emergence of New Psychotic or Manic Symptoms

Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% of stimulant-treated patients compared to 0 in placebo-treated patients.

Aggression

Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility.

Long-Term Suppression of Growth

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months, suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

Seizures

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Peripheral Vasculopathy, including Raynaud's phenomenon

Stimulants, including Dintospina, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Serotonin Syndrome

Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort. Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism. The potential for a pharmacokinetic interaction exists with the co-administration of CYP2D6 inhibitors which may increase the risk with increased exposure to Dintospina (Amphetamine Sulfate). In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6.

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Concomitant use of Dintospina (Amphetamine Sulfate) with MAOI drugs is contraindicated.

Discontinue treatment with Dintospina (Amphetamine Sulfate) and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Dintospina (Amphetamine Sulfate) with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Dintospina (Amphetamine Sulfate) with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.

Visual Disturbance

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

PRECAUTIONS

General

Caution is to be exercised in prescribing amphetamines for patients with even mild hypertension.

The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.

Information for Patients

Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicle; the patient should therefore be cautioned accordingly.

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon]

• Instruct patients beginning treatment with Dintospina about the risk of peripheral vasculopathy, including Raynaud's Phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.
• Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.
• Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking Dintospina (Amphetamine Sulfate).
• Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Drug Interactions

Acidifying agents

Gastrointestinal acidifying agents lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines.

Adrenergic blockers

Adrenergic blockers are inhibited by amphetamines.

Alkalinizing agents

Gastrointestinal alkalinizing agents increase absorption of amphetamines. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentiate the action of amphetamines.

Antidepressants tricyclic

Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d- amphetamine in the brain; cardiovascular effects can be potentiated.

CYP2D6 Inhibitors

The concomitant use of Dintospina and CYP2D6 inhibitors may increase the exposure of Dintospina (Amphetamine Sulfate) compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during Dintospina (Amphetamine Sulfate) initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Dintospina (Amphetamine Sulfate) and the CYP2D6 inhibitor. Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir.

Serotonergic Drugs

The concomitant use of Dintospina (Amphetamine Sulfate) and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during Dintospina (Amphetamine Sulfate) initiation or dosage increase. If serotonin syndrome occurs, discontinue Dintospina (Amphetamine Sulfate) and the concomitant serotonergic drug(s). Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort.

MAO inhibitors

MAOI antidepressants, as well as a metabolic of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their affect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results.

Antihistamines

Amphetamines may counteract the sedative effect of antihistamines.

Antihypertensives

Amphetamines may antagonize the hypotensive effects of antihypertensives.

Chlorpromazine

Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamine, and can be used to treat amphetamine poisoning.

Ethosuximide

Amphetamines may delay intestinal absorption of ethosuximide.

Haloperidol

Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant affects of amphetamines.

Lithium carbonate

The antiobesity and stimulatory effects of amphetamines may be inhibited by lithium carbonate.

Meperidine

Amphetamines potentiate the analgesic effect of meperidine.

Methenamine therapy

Urinary excretion of amphetamines is increased, and efficacy is reduced by acidifying agents used in methenamine therapy.

Norepinephrine

Amphetamines enhance the adrenergic effect of norepinephrine.

Phenobarbital

Amphetamines may delay intestinal absorption of Phenobarbital. Co- administration of phenobarbital may produce a synergistic anticonvulsant action.

Phenytoin

Amphetamines may delay intestinal absorption of phenytoin; co- administration of phenytoin may produce a synergistic anticonvulsant action.

Propoxyphene

In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.

Veratrum alkaloids

Amphetamines inhibit the hypotensive effect of veratrum alkaloids.

Drug/Laboratory Test interactions

Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.

Carcinogenesis/Mutagenesis

Mutagenicity studies and long term studies in animals to determine the carcinogenic potential of Dintospina have not been performed.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Dextroamphetamine sulfate has been shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses approximately 41 times the maximum human dose. Embryotoxic effects were not seen in New Zealand white rabbits given the drug in doses 7 times the human dose nor in rats given 12.5 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. Dintospina should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.

Nursing Mothers

Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.

Pediatric Use

Long-term effects of amphetamines in children have not been well established.

Amphetamines are not recommended for use as anorectic agents in children under 12 years of age, or in children under 3 years of age with Attention Deficit Disorder with Hyperactivity described under INDICATIONS AND USAGE.

Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder.

Amphetamines have been reported to exacerbate motor and phonic tics and Tourette's syndrome. Therefore clinical evaluation for tics and Tourette's syndrome in children and their families should precede use of stimulant medications.

Data is inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore growth should be monitored during treatment. Drug Treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines should depend on the physician's assessment of the chronicity and severity of the child's symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics.

When these symptoms are associated with acute stress reactions, treatment with amphetamines is usually not indicated.

ADVERSE REACTIONS

Cardiovascular

Palpitations, tachycardia, elevation of blood pressure. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Central Nervous System

Psychotic episodes at recommended doses, overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of motor and phonic tics and Tourette's syndrome.

Gastrointestinal

Dryness of the mouth, unpleasant taste, diarrhea, constipation and other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects when amphetamines are used for other than the anorectic effect.

Allergic

Urticaria

Endocrine

Impotence, changes in libido, and frequent or prolonged erections.

Musculoskeletal

Rhabdomyolysis

DRUG ABUSE AND DEPENDENCE

Dintospina (Amphetamine Sulfate) is a Schedule II controlled substance. Amphetamines have been extensively abused. Tolerance, extreme psychological dependence, and severe social disability have occurred. There are reports of patients who have increased the dosage to many times the recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG. Manifestations of chronic intoxication with amphetamines include severe dermatosis, marked insomnia, irritability, hyperactivity and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia. This is rare with oral amphetamines.

OVERDOSAGE

Individual patient response to amphetamines varies widely. While toxic symptoms occasionally occur as an idiosyncrasy at doses as low as 2 mg, they are rare with doses of less than 15 mg; 30 mg can produce severe reactions, yet doses of 400 to 500 mg are not necessarily fatal.

In rats, the oral LD₅₀ of dextroamphetamine sulfate is 96.8 mg/Kg.

Symptoms

Manifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rhabdomyolysis, rapid respiration, hyperpyrexia, confusion, assaultiveness, hallucinations, panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension, or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.

Treatment

Management of acute amphetamine intoxication is largely symptomatic and includes gastric lavage and sedation with a barbiturate. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendation in this regard. Acidification of the urine increases amphetamine excretion. If acute, severe hypertension complicates amphetamine overdosage, administration of intravenous phentolamine has been suggested. However, a gradual drop in blood pressure will usually result when sufficient sedation has been achieved. Chlorpromazine antagonizes the central stimulant effects of amphetamines and can be used to treat amphetamine intoxication.

DOSAGE AND ADMINISTRATION

Regardless of indication, amphetamine should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of resulting insomnia.

Narcolepsy

Usual dose is 5 to 60 milligrams per day in divided doses depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, Dintospina may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia) dosage should be reduced. Give the first dose on awakening; additional doses (5 or 10 mg) at intervals of 4 to 6 hours.

Attention Deficit Disorder with Hyperactivity

Not recommended for children under 3 years of age.

In children from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In children 6 years of age or older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 milligrams per day.

With tablets give first dose on awakening; additional doses (1 to 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

Exogenous Obesity

Usual dosage is up to 30 mg daily, taken in divided doses of 5 to 10 mg, 30 to 60 minutes before meals. Not recommended for this use in children under 12 years of age.

HOW SUPPLIED

Dintospina (Amphetamine Sulfate) (amphetamine sulfate tablets, USP) is supplied as follows:

5 mg: White, round tablet, debossed "EVK" on one side, and "5" with a score on the other side in bottles of 100 tablets, NDC 24338-022-10.

10 mg: Blue, round tablet, debossed "EVK" on one side, and "10" with double scores on the other side in bottles of 100 tablets, NDC 24338-026-10.

Store at 20° to 25°C (68° to 77°F). Dispense in a well-closed container, as defined in the USP.

Manufactured by:

Mikart, Inc.

Atlanta, GA 30318

Manufactured for:

Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

AM-PI-08

Rev. 09/16

MEDICATION GUIDE

Dintospina ^® (amphetamine sulfate tablets, USP)

Read this Medication Guide before you or your child starts taking Dintospina (Amphetamine Sulfate) and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about you or your child's treatment.

What is the most important information I should know about Dintospina (Amphetamine Sulfate) tablets? Dintospina (Amphetamine Sulfate) is a stimulant medicine. Some people have had the following problems when taking stimulant medicines such as Dintospina (Amphetamine Sulfate): Heart-related problems: sudden death in people who have heart problems or heart defects stroke and heart attack in adults increased blood pressure and heart rate Tell your doctor if you or your child has any heart problems, heart defects, high blood pressure, or a family history of these problems. Your doctor should check you or your child carefully for heart problems before starting Dintospina (Amphetamine Sulfate). Your doctor should check you or your child's blood pressure and heart rate regularly during treatment with Dintospina (Amphetamine Sulfate). Call your doctor right away if you or your child have any signs of heart problems such as chest pain, shortness of breath, or fainting while taking Dintospina (Amphetamine Sulfate). Mental (Psychiatric) problems including: In children, teenagers, and adults: new or worse behavior and thought problems new or worse bipolar illness new or worse aggressive behavior or hostility In Children and Teenagers who have psychiatric problems, new psychotic symptoms such as: hearing voices seeing things that are not real believing things that are not true being suspicious new manic symptoms Tell your doctor about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression. Call your doctor right away if you or your child have any new or worsening mental symptoms or problems while taking Dintospina (Amphetamine Sulfate), especially: seeing or hearing things that are not real believing things that are not real being suspicious Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon]. Fingers or toes may feel numb, cool, painful Fingers or toes may change color from pale, to blue, to red Tell your doctor if you have or your child has numbness, pain, skin color change, or sensitivity to temperature in your fingers or toes. Call your doctor right away if you have or your child has any signs of unexplained wounds appearing on fingers or toes while taking Dintospina (Amphetamine Sulfate).

What is Dintospina (Amphetamine Sulfate)?

• Dintospina (Amphetamine Sulfate) is a central nervous system stimulant prescription medicine used for the treatment of:
  • a sleep disorder called narcolepsy.
  • Attention-Deficit Hyperactivity Disorder (ADHD).
    

    Dintospina (Amphetamine Sulfate) may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD. Dintospina (Amphetamine Sulfate) should be used as part of a total treatment program for ADHD that may include counseling or other therapies.
    

  • exogenous obesity. Dintospina (Amphetamine Sulfate) may be used as part of a short-term, weight reduction program for obesity.
• Dintospina (Amphetamine Sulfate) is not for use as an anorectic agent for exogenous obesity in children less than 12 years of age.
• Dintospina (Amphetamine Sulfate) is not for use for ADHD in children less than 3 years old.
• The effects of long term use of Dintospina (Amphetamine Sulfate) in children are not known.

Dintospina (Amphetamine Sulfate) is a federally controlled substance (CII) because it contains amphetamine that can be a target for people who abuse prescription medicines or street drugs. Keep Dintospina (Amphetamine Sulfate) in a safe place to protect it from theft. Never give your Dintospina (Amphetamine Sulfate) to anyone else, because it may cause death or harm them. Selling or giving away Dintospina (Amphetamine Sulfate) is against the law.

Tell your doctor if you or your child has (or has a family history of) ever abused or been dependent on alcohol, prescription medicines or street drugs.

Who should not take Dintospina (Amphetamine Sulfate)?

Do not take Dintospina (Amphetamine Sulfate) if you or your

Child:

• have heart problems or hardening of the arteries
• have moderate to severe high blood pressure
• have hyperthyroidism
• are very anxious, tense, or agitated
• have a history of drug abuse
• are taking or have taken within the past 14 days an anti-depression medicine called a monoamine oxidase inhibitor or MAOI
• are sensitive to, allergic to, or had a reaction to other stimulant medicines

What should I tell my doctor before taking Dintospina (Amphetamine Sulfate)?

Before you or your child takes Dintospina (Amphetamine Sulfate), tell your doctor if you or your child has or if there is a family history of:

• heart problems, heart defects, high blood pressure
• mental problems including psychosis, mania, bipolar illness, or depression
• tics or Tourette's syndrome
• thyroid problems
• seizures or have had an abnormal brain wave test ( EEG )
• circulation problems in fingers and toes

Tell your doctor if:

• you or your child are pregnant or planning to become pregnant. It is not known if Dintospina (Amphetamine Sulfate) will harm your unborn baby.
• you or your child are breastfeeding or plan to breastfeed. Dintospina (Amphetamine Sulfate) can pass into your milk and may harm your baby. Talk to your doctor about the best way to feed your baby if you take Dintospina (Amphetamine Sulfate). Do not breastfeed while taking Dintospina (Amphetamine Sulfate).

Tell your doctor about all the medicines that you or your child takes, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Dintospina (Amphetamine Sulfate) and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking Dintospina (Amphetamine Sulfate).

Your doctor will decide whether Dintospina (Amphetamine Sulfate) can be taken with other medicines.

Especially tell your doctor if you or your child takes:

• stomach acid medicines
• anti-depression medicines including MAOIs
• anti-psychotic medicines
• lithium
• cold or allergy medicines that contain decongestants
• blood pressure medicines
• narcotic pain medicines
• seizure medicines
• blood thinner medicines

Know the medicines that you or your child takes.

Keep a list of your medicines with you to show your doctor and pharmacist when you get a new medicine.

Do not start any new medicine while taking Dintospina (Amphetamine Sulfate) without talking to your doctor first.

How should I take Dintospina (Amphetamine Sulfate)?

• Take Dintospina (Amphetamine Sulfate) exactly as your doctor tells you to take it.
• Your doctor may change the dose until it is right for you or your child.
• The first dose of the day is usually taken when you first wake in the morning.
• Dintospina (Amphetamine Sulfate) may cause problems sleeping if taken late at night.
• Dintospina (Amphetamine Sulfate) can be taken with or without food.
• From time to time, your doctor may stop Dintospina (Amphetamine Sulfate) treatment for a while to check ADHD symptoms.
• Your doctor may do regular checks of the blood, heart, and blood pressure while taking Dintospina (Amphetamine Sulfate).
• Children should have their height and weight checked often while taking Dintospina (Amphetamine Sulfate). Dintospina (Amphetamine Sulfate) treatment may be stopped if a problem is found during these check-ups.
• If you or your child takes too much Dintospina (Amphetamine Sulfate), call your doctor right away, or go to the nearest hospital emergency room.

What should I avoid while taking Dintospina (Amphetamine Sulfate)?

Do not drive, operate machinery, or do other dangerous activities until you know how Dintospina (Amphetamine Sulfate) affects you.

What are possible side effects of Dintospina (Amphetamine Sulfate)?

Dintospina (Amphetamine Sulfate) may cause serious side effects, including:

See "What is the most important information I should know about Dintospina (Amphetamine Sulfate)?" for information on reported heart and mental problems.

Other serious side effects include:

• slowing of growth (height and weight) in children
• seizures, mainly in people with a history of seizures
• eyesight changes or blurred vision
• Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when medicines such as Dintospina (Amphetamine Sulfate) are taken with certain other medicines. Symptoms of serotonin syndrome may include:
  • agitation, hallucinations, coma or other changes in mental status
  • problems controlling your movements or muscle twitching
  • fast heartbeat
  • high or low blood pressure
  • sweating or fever
  • nausea or vomiting
  • diarrhea
  • muscle stiffness or tightness

The most common side effects of Dintospina (Amphetamine Sulfate) include:

• headache
• stomach ache
• trouble sleeping
• decreased appetite
• unpleasant taste
• nervousness
• dizziness
• sexual problems (impotence in males)
• vomiting
• itching
• diarrhea or constipation
• dry mouth
• weight loss
• mood swings

Talk to your doctor if you or your child have side effects that are bothersome or do not go away.

These are not all the possible side effects of Dintospina (Amphetamine Sulfate). For more information ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to Arbor Pharmaceuticals, LLC, Medical Information at 1-866-516-4950 or FDA at 1-800-FDA-1088.

How should I store Dintospina (Amphetamine Sulfate)?

• Store Dintospina (Amphetamine Sulfate) at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep Dintospina (Amphetamine Sulfate) and all medicines out of the reach of children.

General information about the safe and effective use of Dintospina (Amphetamine Sulfate).

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Dintospina (Amphetamine Sulfate) for a condition for which it was not prescribed. Do not give Dintospina (Amphetamine Sulfate) to other people, even if they have the same condition. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about Dintospina (Amphetamine Sulfate). If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Dintospina (Amphetamine Sulfate) that was written for healthcare professionals.

For more information about Dintospina (Amphetamine Sulfate), please contact Arbor Pharmaceuticals, LLC at 1-866-516-4950.

What are the ingredients in Dintospina (Amphetamine Sulfate)?

Active Ingredient: amphetamine sulfate

Inactive Ingredients: crospovidone, silicifed microcrystalline cellulose, and stearic acid. The 10 mg tablets also contain FD&C Blue #1.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Mikart, Inc.

Atlanta, GA 30318

Manufactured for:

Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

AM-MG-06

Rev. 09/16

NDC 24338-022-10

100 tablets

Dintospina (Amphetamine Sulfate)^®

CII

(amphetamine sulfate

tablets, USP)

5 mg

Rx only

Pharmacist: Dispense the

Medication Guide provided

separately to each patient.

Mfd. for Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

NDC 24338-026-10

100 tablets

Dintospina (Amphetamine Sulfate)^®

CII

(amphetamine sulfate

tablets, USP)

10 mg

Rx only

Pharmacist: Dispense the

Medication Guide provided

separately to each patient.

Mfd. for Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

Mephobarbital:

• Dintospina (Mephobarbital) reviews

This medication is used to relieve anxiety and tension. Dintospina (Mephobarbital) is also used to control seizures (tonic-clonic and absence types). Controlling and reducing seizures lets you do more of your normal daily activities, reduces your risk of harm when you loose consciousness, and lessens your risk for a possibly life-threatening condition of frequent, repeated seizures. Dintospina (Mephobarbital) belongs to a class of drugs known as barbiturates. It works by restoring the balance of certain natural substances (neurotransmitters) in the brain to produce a calming effect.

Phenytoin Sodium:

• Description section
• Clinical pharmacology section
• Indications & usage section
• Contraindications section
• Warnings section
• Precautions section
• Adverse reactions section
• Overdosage section
• Dosage & administration section
• How supplied section
• Spl medguide section
• Dintospina (Phenytoin Sodium) reviews

DESCRIPTION SECTION

Dintospina (Phenytoin Sodium), USP 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 extended Dintospina (Phenytoin Sodium) capsule, USP contains 100 mg Dintospina (Phenytoin Sodium), USP. Each capsule also contains the following inactive ingredients: D&C Red #28, D&C Red #33, FD&C Blue #1, gelatin, hydroxypropyl cellulose, mannitol, magnesium stearate, talc and titanium dioxide. Product in vivo performance is characterized by a slow and extended rate of absorption with peak blood concentrations expected in 4 to 12 hours as contrasted to Prompt Dintospina (Phenytoin Sodium) Capsules, USP with a rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.

CLINICAL PHARMACOLOGY SECTION

Mechanism of Action

Phenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post tetanic potentiation at synapses. Loss of post tetanic 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.

Pharmacokinetics and Drug Metabolism

The plasma half-life in man after oral administration of phenytoin averages 22 hours, with a range of 7 to 42 hours. Steady-state therapeutic levels are achieved at least 7 to 10 days (5 to 7 half-lives) after initiation of therapy with recommended doses of 300 mg/day.

When serum level determinations are necessary, they should be obtained at least 5 to 7 half-lives after treatment initiation, dosage change, or addition or subtraction of another drug to the regimen so that equilibrium or steady-state will have been achieved. Trough levels provide information about clinically effective serum level range and confirm patient compliance and are obtained just prior to the patient’s next scheduled dose. Peak levels indicate an individual’s threshold for emergence of dose-related side effects and are obtained at the time of expected peak concentration. For extended Dintospina (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, variant CYP2C9 and CYP2C19 alleles, 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.

Special Populations

Patients with Renal or Hepatic Disease: Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution. Unbound phenytoin concentrations may be more useful in these patient populations.

Age: Phenytoin clearance tends to decrease with increasing age (20% less in patients over 70 years of age relative to that in patients 20 to 30 years of age). Phenytoin dosing requirements are highly variable and must be individualized.

Gender and Race: Gender and race have no significant impact on phenytoin pharmacokinetics.

Pediatrics: Initially, 5 mg/kg/day in two or three equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily. A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years and adolescents may require the minimum adult dose (300 mg/day).

INDICATIONS & USAGE SECTION

Extended Dintospina (Phenytoin Sodium) capsules, USP are indicated for the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.

Phenytoin serum level determinations may be necessary for optimal dosage adjustments.

CONTRAINDICATIONS SECTION

Phenytoin, USP is contraindicated in those patients with a history of hypersensitivity to phenytoin, USP, its inactive ingredients, or other hydantoins.

Coadministration of extended Dintospina (Phenytoin Sodium) is contraindicated with delavirdine due to potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.

WARNINGS SECTION

Effects of Abrupt Withdrawal

Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus. When, in the judgment of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative antiepileptic medication arises, this should be done gradually. In the event of an allergic or hypersensitivity reaction, more rapid substitution of alternative therapy may be necessary. In this case, alternative therapy should be an antiepileptic drug not belonging to the hydantoin chemical class.

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including extended Dintospina (Phenytoin Sodium), increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed.

Table 1 shows absolute and relative risk by indication for all evaluated AEDs.

Indication	Placebo Patients with Events Per 1000 Patients	Drug Patients with Events Per 1000 Patients	RelativeRisk: Incidence of Events inDrug Patients/Incidence in Placebo Patients	Risk Difference:Additional DrugPatients with Events Per1000 Patients
Epilepsy	1	3.4	3.5	2.4
Psychiatric	5.7	8.5	1.5	2.9
Other	1	1.8	1.9	0.9
Total	2.4	4.3	1.8	1.9

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 extended Dintospina (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.

Serious Dermatologic Reactions

Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported with phenytoin treatment. The onset of symptoms is usually within 28 days, but can occur later. Extended Dintospina (Phenytoin Sodium) should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. If a rash occurs, the patient should be evaluated for signs and symptoms of Drug Reaction with Eosinophilia and Systemic Symptoms.

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 carbamazepine. Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding phenytoin as an alternative for carbamazepine in patients positive for HLA-B*1502.

The use of HLA-B*1502 genotyping has important limitations and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dose, compliance, concomitant medications, comorbidities and the level of dermatologic monitoring have not been studied.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including extended Dintospina (Phenytoin Sodium). Some of these events have been fatal or life-threatening. 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, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Extended Dintospina (Phenytoin Sodium) should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

Hypersensitivity

Extended Dintospina (Phenytoin Sodium) and other hydantoins are contraindicated in patients who have experienced phenytoin hypersensitivity. Additionally, consider alternatives to structurally similar drugs such as carboxamides (e.g., carbamazepine), barbiturates, succinimides and oxazolidinediones (e.g., trimethadione) in these same patients. Similarly, if there is a history of hypersensitivity reactions to these structurally similar drugs in the patient or immediate family members, consider alternatives to extended Dintospina (Phenytoin Sodium).

Hepatic Injury

Cases of acute hepatotoxicity, including infrequent cases of acute hepatic failure, have been reported with extended Dintospina (Phenytoin Sodium). These events may be part of the spectrum of DRESS or may occur in isolation. Other common manifestations include 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, extended Dintospina (Phenytoin Sodium) should be immediately discontinued and not readministered.

Hematopoietic System

Hematopoietic complications, some fatal, have occasionally been reported in association with administration of extended Dintospina (Phenytoin Sodium). 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 of DRESS.

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.

Effects on Vitamin D and Bone

The chronic use of phenytoin in patients with epilepsy has been associated with decreased bone mineral density (osteopenia, osteoporosis and osteomalacia) and bone fractures. Phenytoin induces hepatic metabolizing enzymes. This may enhance the metabolism of vitamin D and decrease vitamin D levels, which may lead to vitamin D deficiency, hypocalcemia and hypophosphatemia. Consideration should be given to screening with bone-related laboratory and radiological tests as appropriate and initiating treatment plans according to established guidelines.

Effects of Alcohol Use on Phenytoin Serum Levels

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

Exacerbation of 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.

Usage In Pregnancy:

Clinical:

• 
  

  Risks to Mother. An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics. Periodic measurement of plasma phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage. However, postpartum restoration of the original dosage will probably be indicated.
  

• 
  

  Risks to the Fetus. 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.
  

Prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes. Increased frequencies of major malformations (such as orofacial clefts and cardiac defects), minor anomalies (dysmorphic facial features, nail and digit hypoplasia), growth abnormalities (including microcephaly) and mental deficiency have been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy. There have also been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy. The overall incidence of malformations for children of epileptic women treated with antiepileptic drugs (phenytoin and/or others) during pregnancy is about 10%, or two- to three-fold that in the general population. However, the relative contributions of antiepileptic drugs and other factors associated with epilepsy to this increased risk are uncertain and in most cases it has not been possible to attribute specific developmental abnormalities to particular antiepileptic drugs.

Patients should consult with their physicians to weigh the risks and benefits of phenytoin during pregnancy.

Postpartum Period. 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.

Preclinical:

Increased resorption and malformation rates have been reported following administration of phenytoin doses of 75 mg/kg or higher (approximately 120% of the maximum human loading dose or higher on a mg/m2 basis) to pregnant rabbits.

PRECAUTIONS SECTION

General:

The liver is the chief site of biotransformation of phenytoin; patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity.

A small percentage of individuals who have been treated with phenytoin have been shown to metabolize the drug slowly. Slow metabolism may be due to limited enzyme availability and lack of induction; it appears to be genetically determined. If early signs of dose-related CNS toxicity develop, plasma levels should be checked immediately.

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 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.

Information for Patients

Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking extended Dintospina (Phenytoin Sodium). Instruct patients to take extended Dintospina (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 be made aware 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 also be cautioned on the use of other drugs or alcoholic beverages without first seeking the physician’s advice.

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 extended Dintospina (Phenytoin Sodium), may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.

Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334.

Do not use capsules which are discolored.

Laboratory Tests:

Phenytoin serum level determinations may be necessary to achieve optimal dosage adjustments. Phenytoin doses are usually selected to attain therapeutic plasma total phenytoin concentrations of 10 to 20 mcg/mL (unbound phenytoin concentrations of 1 to 2 mcg/mL).

Drug Interactions:

Phenytoin is extensively bound to serum plasma proteins and is prone to competitive displacement. Phenytoin is metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19, and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes. Serum level determinations for phenytoin are especially helpful when possible drug interactions are suspected.

The most commonly occurring drug interactions are listed below:

Note: The list is not intended to be inclusive or comprehensive. Individual drug package inserts should be consulted.

Drugs that affect phenytoin concentrations:

• Drugs that may increase phenytoin serum levels include: acute alcohol intake, amiodarone, anti-epileptic agents (ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate), azoles (fluconazole, ketoconazole, itraconazole, voriconazole), capecitabine, chloramphenicol, chlordiazepoxide, diazepam, disulfiram, estrogens, fluorouracil, fluoxetine, fluvastatin, fluvoxamine, H2-antagonists (e.g. cimetidine), halothane, isoniazid, methylphenidate, omeprazole, phenothiazines, salicylates, sertraline, succinimides, sulfonamides (e.g., sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole-trimethoprim), ticlopidine, tolbutamide, trazodone and warfarin.
• Drugs that may decrease phenytoin levels, include: anti-cancer drugs usually in combination (e.g., bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate) carbamazepine, chronic alcohol abuse, folic acid, fosamprenavir, nelfinavir, reserpine, ritonavir, St. John’s Wort, sucralfate and vigabatrin.
• Administration of phenytoin with preparations that increase gastric pH (e.g., supplements or antacids containing calcium carbonate, aluminum hydroxide and magnesium hydroxide) may affect the absorption of phenytoin. In most cases where interactions were seen, the effect is a decrease in phenytoin levels when the drugs are taken at the same time. When possible, phenytoin and these products should not be taken at the same time of day.
• Drugs that may either increase or decrease phenytoin serum levels, include: phenobarbital, sodium valproate and valproic acid. Similarly, the effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable.
• The addition or withdrawal of these agents in patients on phenytoin therapy may require an adjustment of the phenytoin dose to achieve optimal clinical outcome.

Drugs affected by phenytoin:

• Drugs that should not be coadministered with phenytoin: Delavirdine.
• Drugs whose efficacy is impaired by phenytoin include: azoles (fluconazole, ketoconazole, itraconazole, voriconazole, posaconazole), corticosteroids, doxycycline, estrogens, furosemide, irinotecan, oral contraceptives, paclitaxel, paroxetine, quinidine, rifampin, sertraline, teniposide, theophylline and vitamin D.
• Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin.
• Phenytoin decreases plasma concentrations of active metabolites of albendazole, certain HIV antivirals (efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir), anti-epileptic agents (felbamate, topiramate, oxcarbazepine, quetiapine) atorvastatin, cyclosporine, digoxin, fluvastatin, folic acid, mexiletine, nisoldipine, praziquantel and simvastatin.
• Phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite. Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir.
• Resistance to the neuromuscular blocking action of the non-depolarizing neuromuscular blocking agents pancuronium, vecuronium, rocuronium and cisatracurium has occurred in patients chronically administered phenytoin. Whether or not phenytoin has the same effect on other non-depolarizing agents is unknown. Patients should be monitored closely for more rapid recovery from neuromuscular blockade than expected, and infusion rate requirements may be higher.
• The addition or withdrawal of phenytoin during concomitant therapy with these agents may require adjustment of the dose of these agents to achieve optimal clinical outcome.

Drug Enteral Feeding/Nutritional Preparations Interaction:

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

Drug/Laboratory Test Interactions:

Phenytoin may decrease serum concentrations of T4. It may also produce lower than normal values for dexamethasone or metyrapone tests. Phenytoin may cause increased serum levels of glucose, alkaline phosphatase and gamma glutamyl transpeptidase (GGT).

Care should be taken when using immunoanalytical methods to measure plasma phenytoin concentrations.

Carcinogenesis:

See WARNINGS section for information on carcinogenesis.

Pregnancy: Pregnancy Category D; See WARNINGS section.

To provide information regarding the effects of in utero exposure to extended Dintospina (Phenytoin Sodium), physicians are advised to recommend that pregnant patients taking extended Dintospina (Phenytoin Sodium) enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.

Nursing Mothers:

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

Pediatric Use: See DOSAGE AND ADMINISTRATION section.

Geriatric Use: Phenytoin clearance tends to decrease with increasing age.

ADVERSE REACTIONS SECTION

Body as a Whole: Allergic reactions in the form of rash and rarely more serious forms 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.

Nervous System: The most common manifestations adverse reactions encountered with phenytoin therapy are referable to this nervous system reactions and are usually dose-related. These Reactions include nystagmus, ataxia, slurred speech, decreased coordination, somnolence and mental confusion. Dizziness, vertigo, insomnia, transient nervousness, motor twitchings, paresthesias and headaches have also been observed. There have also been rare reports of phenytoin induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs.

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

Digestive System: Acute hepatic failure, toxic hepatitis, liver damage, Nnausea, vomiting, constipation, enlargement of the lips,and gingival hyperplasia, toxic hepatitis and liver damage.

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.

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.

Special Senses: Altered taste sensation including metallic taste.

Urogenital: Peyronie’s disease.

OVERDOSAGE SECTION

The lethal dose in pediatric patients is not known. The lethal dose in adults is estimated to be 2 to 5 grams. The initial symptoms are nystagmus, ataxia and dysarthria. Other signs are tremor, hyperreflexia, lethargy, slurred speech, nausea, vomiting. The patient may become comatose and hypotensive. Death is due to respiratory and circulatory depression.

There are marked variations among individuals with respect to phenytoin plasma levels where toxicity may occur. Nystagmus, on lateral gaze, usually appears at 20 mcg/mL, ataxia at 30 mcg/mL; dysarthria and lethargy appear when the plasma concentration is over 40 mcg/mL, but as high a concentration as 50 mcg/mL has been reported without evidence of toxicity. As much as 25 times the therapeutic dose has been taken to result in a serum concentration over 100 mcg/mL with complete recovery.

Treatment:

Treatment is nonspecific since there is no known antidote.

The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate supportive measures employed. Hemodialysis can be considered since phenytoin is not completely bound to plasma proteins. Total exchange transfusion has been used in the treatment of severe intoxication in pediatric patients.

In acute overdosage, the possibility of other CNS depressants, including alcohol, should be borne in mind.

DOSAGE & ADMINISTRATION SECTION

Serum concentrations should be monitored in changing from extended Dintospina (Phenytoin Sodium) capsules, USP to Prompt Dintospina (Phenytoin Sodium) Capsules, USP, and from the sodium salt to the free acid form.

Extended Dintospina (Phenytoin Sodium) capsules, USP are formulated with the sodium salt of phenytoin. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa.

General:

Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments-the clinically effective serum level is usually 10 to 20 mcg/mL. With recommended dosage, a period of seven to ten days may be required to achieve steady-state blood levels with phenytoin and changes in dosage (increase or decrease) should not be carried out at intervals shorter than seven to ten days.

Adult

Dosage:

Divided daily

Dosage:

Patients who have received no previous treatment may be started on one 100-mg extended Dintospina (Phenytoin Sodium) capsule, USP three times daily and the dosage then adjusted to suit individual requirements. For most adults, the satisfactory maintenance dosage will be one capsule three to four times a day. An increase up to two capsules three times a day may be made, if necessary.

Once-a-day

Dosage:

In adults, if seizure control is established with divided doses of three 100-mg extended Dintospina (Phenytoin Sodium) capsules, USP daily, once-a-day dosage with 300 mg of extended Dintospina (Phenytoin Sodium) capsules, USP may be considered. Studies comparing divided doses of 300 mg with a single daily dose of this quantity indicated absorption, peak plasma levels, biologic half-life, difference between peak and minimum values, and urinary recovery were equivalent. Once-a-day dosage offers a convenience to the individual patient or to nursing personnel for institutionalized patients and is intended to be used only for patients requiring this amount of drug daily. A major problem in motivating noncompliant patients may also be lessened when the patient can take this drug once a day. However, patients should be cautioned not to miss a dose, inadvertently.

Only extended Dintospina (Phenytoin Sodium) capsules, USP are recommended for once-a-day dosing. Inherent differences in dissolution characteristics and resultant absorption rates of phenytoin due to different manufacturing procedures and/or dosage forms preclude such recommendation for other phenytoin products. When a change in the dosage form or brand is prescribed, careful monitoring of phenytoin serum levels should be carried out.

Loading dose:

Some authorities have advocated use of an oral loading dose of phenytoin in adults who require rapid steady-state serum levels and where intravenous administration is not desirable. This dosing regimen should be reserved for patients in a clinic or hospital setting where phenytoin serum levels can be closely monitored. Patients with a history of renal or liver disease should not receive the oral loading regimen.

Initially, one gram of extended Dintospina (Phenytoin Sodium) capsules, USP is divided into three doses (400 mg, 300 mg, 300 mg) and administered at two-hour intervals. Normal maintenance dosage is then instituted 24 hours after the loading dose, with frequent serum level determinations.

Dosing in Special Populations

Patients with Renal or Hepatic Disease: Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution. Unbound phenytoin concentrations may be more useful in these patient populations.

Elderly Patients: Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required.

Pediatric: Initially, 5 mg/kg/day in two or three equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily. A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years old and adolescents may require the minimum adult dose (300 mg/day).

HOW SUPPLIED SECTION

Extended Dintospina (Phenytoin Sodium) Capsules, USP 100 mg are supplied as white opaque / light lavender opaque, hard gelatin capsules imprinted with "IP 212" on both cap and body.

They are available as follows:

Bottles of 30: NDC 65162-212-03

Bottles of 100: NDC 65162-212-10

Bottles of 500: NDC 65162-212-50

Bottles of 1000: NDC 65162-212-11

Store at 20° to 25°C (68° to 77°F). Preserve in tight, light-resistant containers. Protect from moisture.

Rx only

SPL MEDGUIDE SECTION

Extended Phenytoin (FEN-i-toyn) Sodium Capsules


Read this Medication Guide before you start taking extended Dintospina (Phenytoin Sodium) capsules 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 extended Dintospina (Phenytoin Sodium) capsules, ask your healthcare provider or pharmacist.


What is the most important information I should know about extendedphenytoin sodium capsules?


Do not stop taking extended Dintospina (Phenytoin Sodium) capsules without first talking to your healthcare provider. Stopping extended Dintospina (Phenytoin Sodium) capsules suddenly can cause serious problems.


Extended Dintospina (Phenytoin Sodium) capsules can cause serious side effects including:


1. Like other antiepileptic drugs, extended Dintospina (Phenytoin Sodium) capsules may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.


Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:


• thoughts about suicide or dying
• attempts to commit suicide
• new or worse depression
• new or worse anxiety
• feeling agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood



How can I watch for early symptoms of suicidal thoughts and actions?


• Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
• Keep all follow-up visits with your healthcare provider as scheduled.



Call your healthcare provider between visits as needed, especially if you are worried about


symptoms.


Do not stop taking extended Dintospina (Phenytoin Sodium) capsules without first talking to a healthcare provider.


Stopping extended Dintospina (Phenytoin Sodium) capsules suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).


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.


2. Extended Dintospina (Phenytoin Sodium) capsules may harm your unborn baby.


• If you take extended Dintospina (Phenytoin Sodium) capsules during pregnancy, your baby is at risk for serious birth defects.
• Birth defects may occur even in children born to women who are not taking any medicines and do not have other risk factors.
• If you take extended Dintospina (Phenytoin Sodium) capsules during pregnancy, your baby is also at risk for bleeding problems right after birth. Your healthcare provider may give you and your baby medicine to prevent this.
• All women of child-bearing age should talk to their healthcare provider about using other possible treatments instead of extended Dintospina (Phenytoin Sodium) capsules. If the decision is made to use extended Dintospina (Phenytoin Sodium) capsules, you should use effective birth control (contraception) unless you are planning to become pregnant.
• Tell your healthcare provider right away if you become pregnant while taking extended Dintospina (Phenytoin Sodium) capsules. You and your healthcare provider should decide if you will take extended Dintospina (Phenytoin Sodium) capsules while you are pregnant.
• Pregnancy Registry: If you become pregnant while taking extended Dintospina (Phenytoin Sodium) capsules, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy.



3. Swollen glands (lymph nodes)


4. Allergic reactions or serious problems which may affect organs and other parts of your body like the liver or blood cells. You may or may not have a rash with these types of reactions. Symptoms can include any of the following:


• swelling of your face, eyes, lips, or tongue
• trouble swallowing or breathing
• a skin rash
• hives
• fever, swollen glands (lymph nodes), or sore throat that do not go away or come and go
• painful sores in the mouth or around your eyes
• yellowing of your skin or eyes
• bruising or bleeding
• severe fatigue or weakness
• severe muscle pain
• frequent infections or an infection that does not go away
• loss of appetite (anorexia)
• nausea or vomiting



Call your healthcare provider right away if you have any of the symptoms listed above.


What are extended Dintospina (Phenytoin Sodium) capsules?


Extended Dintospina (Phenytoin Sodium) capsules are 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.


Who should not take extended Dintospina (Phenytoin Sodium) capsules?


Do not take extended Dintospina (Phenytoin Sodium) capsules if you:


• are allergic to phenytoin or any of the ingredients in extended Dintospina (Phenytoin Sodium) capsules. See the end of this leaflet for a complete list of ingredients in extended Dintospina (Phenytoin Sodium) capsules.
• have had an allergic reaction to CEREBYX (fosphenytoin), PEGANONE (ethotoin), or MESANTOIN (mephenytoin).
• take delavirdine



What should I tell my healthcare provider before taking extended Dintospina (Phenytoin Sodium) capsules?


Before you take extended Dintospina (Phenytoin Sodium) capsules, tell your healthcare provider if you:


• Have or had liver disease
• Have or had porphyria
• Have or had diabetes
• Have or have had depression, mood problems, or suicidal thoughts or behavior
• Are pregnant or plan to become pregnant. If you become pregnant while taking extended Dintospina (Phenytoin Sodium) capsules, the level of extended Dintospina (Phenytoin Sodium) in your blood may decrease, causing your seizures to become worse. Your healthcare provider may change your dose of extended Dintospina (Phenytoin Sodium) capsules.
• Are breast feeding or plan to breastfeed. Extended Dintospina (Phenytoin Sodium) can pass into breast milk. You and your healthcare provider should decide if you will take extended Dintospina (Phenytoin Sodium) capsules or breastfeed. You should not do both.



Tell your healthcare provider about all the medicines you take, including prescription and


• 
  

  non-prescription medicines, vitamins and herbal supplements.
  

  Taking extended Dintospina (Phenytoin Sodium) capsules 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.
  

  How should I take extended Dintospina (Phenytoin Sodium) capsules?
  

• 
  

  Take extended Dintospina (Phenytoin Sodium) capsules exactly as prescribed. Your healthcare provider will tell you how much extended Dintospina (Phenytoin Sodium) capsules to take.
  

• Your healthcare provider may change your dose. Do not change your dose of extended Dintospina (Phenytoin Sodium) capsules without talking to your healthcare provider.
• Extended Dintospina (Phenytoin Sodium) capsules can cause overgrowth of your gums. Brushing and flossing your teeth and seeing a dentist regularly while taking extended Dintospina (Phenytoin Sodium) capsules can help prevent this.
• If you take too much extended Dintospina (Phenytoin Sodium) capsules, call your healthcare provider or local Poison Control Center right away.
• Do not stop taking extended Dintospina (Phenytoin Sodium) capsules without first talking to your healthcare provider. Stopping extended Dintospina (Phenytoin Sodium) capsules suddenly can cause serious problems.



What should I avoid while taking extended Dintospina (Phenytoin Sodium) capsules?


• Do not drink alcohol while you take extended Dintospina (Phenytoin Sodium) capsules without first talking to your healthcare provider. Drinking alcohol while taking extended Dintospina (Phenytoin Sodium) capsules may change your blood levels of extended Dintospina (Phenytoin Sodium) capsules which can cause serious problems.
• Do not drive, operate heavy machinery, or do other dangerous activities until you know how extended Dintospina (Phenytoin Sodium) capsules affect you. Extended Dintospina (Phenytoin Sodium) capsules can slow your thinking and motor skills.



What are the possible side effects of extended Dintospina (Phenytoin Sodium) capsules?


See “What is the most important information I should know about extended Dintospina (Phenytoin Sodium) capsules?”


Extended Dintospina (Phenytoin Sodium) capsules may cause other serious side effects including:


• Softening of your bones (osteopenia, osteoporosis and osteomalacia). This can cause broken bones.
  

  Call your healthcare provider right away, if you have any of the symptoms listed above.
  

  The most common side effects of extended Dintospina (Phenytoin Sodium) capsules include:
  

• problems with walking and coordination
• slurred speech
• confusion
• dizziness
• trouble sleeping
• nervousness
• tremor
• headache
• nausea
• vomiting
• constipation
• rash



These are not all the possible side effects of extended Dintospina (Phenytoin Sodium) capsules. 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.


Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


How should I store extended Dintospina (Phenytoin Sodium) capsules?


• Store extended Dintospina (Phenytoin Sodium) capsules at room temperature between 68°F to 77°F (20°C to 25°C) in tight, light-resistant containers. Protect from moisture.



Keep extended phenytoin sodiumcapsules and all medicines out of the reach of children.


General information about extended Dintospina (Phenytoin Sodium) capsules


Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use extended Dintospina (Phenytoin Sodium) capsules for a condition for which it was not prescribed. Do not give extended Dintospina (Phenytoin Sodium) capsules 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 extended Dintospina (Phenytoin Sodium) capsules. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about extended Dintospina (Phenytoin Sodium) capsules that was written for healthcare professionals.


For more information about extended Dintospina (Phenytoin Sodium) capsules, visit www.amneal.com or call 1-877-835-5472.


What are the ingredients in extended Dintospina (Phenytoin Sodium) capsules?


Extended Oral Capsule


Extended Dintospina (Phenytoin Sodium) capsule 100mg: White opaque/lavender opaque, hard gelatin capsules imprinted “IP 212” on both cap and body.


Active ingredient: 100 mg Dintospina (Phenytoin Sodium)


Inactive ingredients: D&C Red #28, D&C Red #33, FD&C Blue #1, gelatin, hydroxypropyl cellulose, mannitol, magnesium stearate, talc and titanium dioxide.


This Medication Guide has been approved by the U.S. Food and Drug Administration.


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