PROCENTRA

INDICATIONS AND USAGE Dextroamphetamine Sulfate Oral Solution is indicated in: Narcolepsy Attention Deficit Disorder with Hyperactivity: As an integral part of a total treatment program that typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in pediatric patients (ages 3 years to 16 years) with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: Moderate to severe distractibility, short attention span, hyperactivity, emotionally lability, and impulsivity. The diagnosis of this 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 may not be warranted.

DOSAGE AND ADMINISTRATION Amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of the resulting insomnia. Narcolepsy: Usual dose is 5 mg to 60 mg 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, Dextroamphetamine Sulfate Oral Solution 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 is 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 first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours. Attention Deficit Disorder with Hyperactivity: Not recommended for pediatric patients under 3 years of age. In pediatric patients 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 pediatric patients 6 years of age and 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 mg per day. Give first dose on awakening; additional doses (1 or 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. Prior to treating patients with dextroamphetamine sulfate assess: for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) (see WARNINGS ) . the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome ( see WARNINGS )

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 (rare), overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of motor and verbal tics and Tourette’s syndrome. Gastrointestinal: Dryness of the mouth, unpleasant taste, diarrhea, constipation, intestinal ischemia and other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects. Allergic: Urticaria. Endocrine: Impotence, changes in libido. Musculoskeletal: Rhabdomyolysis.

Drug Interactions MAO Inhibitors - MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect 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. Serotonergic Drugs - The concomitant use of dextroamphetamine sulfate oral solution 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 dextroamphetamine sulfate oral solution initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine sulfate oral solution and the concomitant serotonergic drug(s) [see WARNINGS, PRECAUTIONS ] . 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. CYP2D6 Inhibitors - The concomitant use of dextroamphetamine sulfate oral solution and CYP2D6 inhibitors may increase the exposure of dextroamphetamine sulfate oral solution 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 dextroamphetamine sulfate oral solution initiation and after a dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine sulfate oral solution and the CYP2D6 inhibitor [see WARNINGS, OVERDOSAGE] . Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. Acidifying Agents - Gastrointestinal acidifying reagents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase the 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 (sodium bicarbonate, etc.) 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 actions 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. 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 amphetamines, 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 effects of amphetamines. Lithium Carbonate - The 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 absorptions 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.