 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Dextroamphetamine
Dexedrine (dextroamphetamine sulfate) is the dextro isomer of the compound d,1-amphetamine sulfate, a sympathomimetic amine of the amphetamine group. Chemically, dextroamphetamine is d-a-methylphenethylamine, and is present in all forms of Dexedrine as the neutral sulfate. Spansule® Capsules Each Spansule sustained release capsule is so prepared that an initial dose is released promptly and the remaining medication is released gradually over a prolonged period. Inactive ingredients consist of acacia, benzyl alcohol, calcium sulfate, cetylpyridinium chloride, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 5 (tartrazine), FD&C Yellow No. 6, gelatin, glyceryl distearate, glyceryl monostearate, sodium lauryl sulfate, starch, sucrose, wax and trace amounts of other inactive ingredients. Tablets Each tablet contains dextroamphetamine sulfate, 5 mg. Inactive ingredients consist of calcium
sulfate, FD&C Yellow No. 5 (tartrazine), FD&C Yellow No.
6, gelatin, lactose, mineral
oil, starch, stearic acid,
sucrose, talc and trace
amounts of other inactive ingredients.
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. There is neither specific evidence which clearly establishes the mechanism whereby amphetamines produce mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system. Dexedrine (dextroamphetamine sulfate) Spansule capsules are formulated to release the active drug substance in vivo in a more gradual fashion than the standard formulation, as demonstrated by blood levels. The formulation has not been shown superior in effectiveness over the same dosage of the standard, noncontrolled-release formulations given in divided doses. Pharmacokinetics Tablet : The single ingestion of two 5 mg tablets by healthy volunteers produced an average peak dextroamphetamine blood level of 29.2 ng/mL at 2 hours post-administration. The average half-life was 10-25 hours. The average urinary recovery was 45% in 48 hours. Spansule Capsule: Ingestion of a Spansule capsule
containing 15 mg radiolabeled
dextroamphetamine sulfate
by healthy volunteers
produced a peak blood
level of radioactivity,
on the average at 8
to 10 hours post-administration with peak urinary
recovery seen at 12
to 24 hours.
Dexedrine (dextroamphetamine sulfate) is indicated: 1. In Narcolepsy. 2. In 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 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, emotional 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.
Amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses-particularly with the Spansule capsule form-should be avoided because of the resulting insomnia. Narcolepsy Usual dose 5 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 Dexedrine (dextroamphetamine sulfate) 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. Spansule capsules may be used for once-a-day dosage wherever appropriate. With tablets 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, by tablet 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. Spansule capsules may be used for once-a-day dosage wherever appropriate. With tablets, 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. HOW SUPPLIED Dexedrine Spansule Capsules Each capsule, with brown cap and clear body, contains dextroamphetamine sulfate. The 5 mg capsule is imprinted 5 mg and 3512 on the brown cap and is imprinted 5 mg and SB on the clear body. The 10 mg capsule is imprinted 10 mg and 3513 on the brown cap and is imprinted 10 mg and SB on the clear body. The 15 mg capsule is imprinted 15 mg and 3514 on the brown cap and is imprinted 15 mg and SB on the clear body. Available: 5 mg, 10 mg, and 15 mg in bottles of 50. Store between 15° and 30° C (59° and 86° F). Dispense in a tight, light-resistant container. Dexedrine (dextroamphetamine sulfate) Tablets Triangular, orange scored debossed SKF and E19. Available: 5 mg in bottles of 100. 5 mg 100's: NDC 0007-3519-20 Store between 15° and 30° C (59° and 86° F). Dispense
in a tight, light-resistant container.
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 phonic tics and Tourette's syndrome. Gastrointestinal Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects. Allergic Urticaria. Endocrine Impotence, changes in libido. DRUG ABUSE AND DEPENDENCE Dextroamphetamine 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 that 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 dermatoses, 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.
Acidifying Agents Gastrointestinal acidifying agents (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 by agents increase blood levels and therefore potentiate the action of amphetamines. Antidepressants tricyclic: Amphetamines may enhance the activity of tricyclic or sympathometic 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. 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. 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 norepinephrins 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 administration of phenobarbital and may produce an intestinal absorption of phenobarbital; coadministration of phenobarbital may produce a co-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.
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 NONTHERAPEUTIC USE OR DISTRIBUTION TO OTHERS AND THE DRUGS SHOULD BE PRESCRIBED OR DISPENSED SPARINGLY
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. These products contain FD&C Yellow No. 5 (tartrazine), which, may cause allergic type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. 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 Dexedrine (dextroamphetamine sulfate) have not been performed. Pregnancy Teratogenic Effects: Pregnancy Category C: Dexedrine 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. While there are no adequate and well-controlled studies in pregnant women, there has been one report of severe congenital bony deformity, tracheoesophageal fistula, and anal atresia (Vater association) in a baby born to a woman who took dextroamphetamine sulfate with lovastatin during the first trimester of pregnancy. Dexedrine 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 pediatric patients have not been well established. Amphetamines are not recommended for use in pediatric patients 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 are 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.
|
| |||