Get your patient on Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, And Amphetamine Sulfate - Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, And Amphetamine Sulfate tablet (Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, And Amphetamine Sulfate)

Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and Narcolepsy.

Attention Deficit Hyperactivity Disorder (ADHD)

A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV ^® ) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; “on the go;” excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.

Special Diagnostic Considerations

Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the child and not solely on the presence of the required number of DSM-IV ^® characteristics.

Need for Comprehensive Treatment Program

Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets are indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all children with this syndrome. Stimulants are not intended for use in the child who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician's assessment of the chronicity and severity of the child's symptoms.

Long-Term Use

The effectiveness of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets for long-term use has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Regardless of indication, amphetamines should be administered at the lowest effective dosage, and dosage should be individually adjusted according to the therapeutic needs and response of the patient. Late evening doses should be avoided because of the resulting insomnia.

Attention Deficit Hyperactivity Disorder

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 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.

Narcolepsy

Usual dose 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 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.

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

Agitated states.

Known hypersensitivity or idiosyncrasy to amphetamine.

Patients with a history of drug abuse.

In patients known to be hypersensitive to amphetamine, or other components of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products [see ADVERSE REACTIONS ].

Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis [see WARNINGS and DRUG INTERACTIONS ].

Cardiovascular

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

Central Nervous System

Psychotic episodes at recommended doses, overstimulation, restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, tics, aggression, anger, logorrhea, dermatillomania.

Eye Disorders

Vision blurred, mydriasis.

Gastrointestinal

Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects.

Allergic

Urticaria, rash, hypersensitivity reactions including angioedema and anaphylaxis. Serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.

Endocrine

Impotence, changes in libido, frequent or prolonged erections.

Skin

Alopecia.

Musculoskeletal

Rhabdomyolysis.

A single-entity amphetamine product combining the neutral sulfate salts of dextroamphetamine and amphetamine, with the dextro isomer of amphetamine saccharate and d, l-amphetamine aspartate monohydrate.

•   1.25 mg of Amphetamine Aspartate Monohydrate equivalent to 1.17 mg Amphetamine Aspartate (Anhydrous) as supplied

†   1.875 mg of Amphetamine Aspartate Monohydrate equivalent to 1.755 mg Amphetamine Aspartate (Anhydrous) as supplied

‡    2.5 mg of Amphetamine Aspartate Monohydrate equivalent to 2.34 mg Amphetamine Aspartate (Anhydrous) as supplied

§    3.125 mg of Amphetamine Aspartate Monohydrate equivalent to 2.925 mg Amphetamine Aspartate (Anhydrous) as supplied

¶    3.75 mg of Amphetamine Aspartate Monohydrate equivalent to 3.51 mg Amphetamine Aspartate (Anhydrous) as supplied

#    5 mg of Amphetamine Aspartate Monohydrate equivalent to 4 .6 mg Amphetamine Aspartate (Anhydrous) as supplied

Þ    7.5 mg of Amphetamine Aspartate Monohydrate equivalent to 7.03 mg Amphetamine Aspartate (Anhydrous) as supplied

Inactive Ingredients:

Microcrystalline cellulose, saccharin sodium, maltodextrin, corn starch, colloidal silicon dioxide, sucrose, magnesium stearate.

Colors:

Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets 5 mg is a white to off-white tablet, which contains no color additives.

Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets 7.5 mg and 10 mg contain FD&C Blue #2 as a color additive.

Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets 12.5 mg, 15 mg, 20 mg and 30 mg contain FD&C Yellow #6 Aluminum lake as a color additive.

Pharmacodynamics

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

Pharmacokinetics

Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets contain d-amphetamine and l-amphetamine salts in the ratio of 3:1. Following administration of a single dose 10 or 30 mg of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets to healthy volunteers under fasted conditions, peak plasma concentrations occurred approximately 3 hours post-dose for both d-amphetamine and l-amphetamine. The mean elimination half-life (t _1/2 ) for d-amphetamine was shorter than the t _1/2 of the l-isomer (9.77 to 11 hours vs. 11.5 to 13.8 hours). The PK parameters (C _max , AUC _0-inf ) of d-and l-amphetamine increased approximately three-fold from 10 mg to 30 mg indicating dose-proportional pharmacokinetics.

The effect of food on the bioavailability of dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets has not been studied.

Metabolism and Excretion

Amphetamine is reported to be oxidized at the 4 position of the benzene ring to form 4-hydroxyamphetamine, or on the side chain α or β carbons to form alpha-hydroxy-amphetamine or norephedrine, respectively. Norephedrine and 4-hydroxy-amphetamine are both active and each is subsequently oxidized to form 4-hydroxy-norephedrine. Alpha-hydroxy-amphetamine undergoes deamination to form phenylacetone, which ultimately forms benzoic acid and its glucuronide and the glycine conjugate hippuric acid. Although the enzymes involved in amphetamine metabolism have not been clearly defined, CYP2D6 is known to be involved with formation of 4-hydroxy-amphetamine. Since CYP2D6 is genetically polymorphic, population variations in amphetamine metabolism are a possibility.

Amphetamine is known to inhibit monoamine oxidase, whereas the ability of amphetamine and its metabolites to inhibit various P450 isozymes and other enzymes has not been adequately elucidated. In vitro experiments with human microsomes indicate minor inhibition of CYP2D6 by amphetamine and minor inhibition of CYP1A2, 2D6, and 3A4 by one or more metabolites. However, due to the probability of auto-inhibition and the lack of information on the concentration of these metabolites relative to in vivo concentrations, no predications regarding the potential for amphetamine or its metabolites to inhibit the metabolism of other drugs by CYP isozymes in vivo can be made.

With normal urine pHs approximately half of an administered dose of amphetamine is recoverable in urine as derivatives of alpha-hydroxy-amphetamine and approximately another 30% to 40% of the dose is recoverable in urine as amphetamine itself. Since amphetamine has a pKa of 9.9, urinary recovery of amphetamine is highly dependent on pH and urine flow rates. Alkaline urine pHs result in less ionization and reduced renal elimination, and acidic pHs and high flow rates result in increased renal elimination with clearances greater than glomerular filtration rates, indicating the involvement of active secretion. Urinary recovery of amphetamine has been reported to range from 1% to 75%, depending on urinary pH, with the remaining fraction of the dose hepatically metabolized. Consequently, both hepatic and renal dysfunction have the potential to inhibit the elimination of amphetamine and result in prolonged exposures. In addition, drugs that affect urinary pH are known to alter the elimination of amphetamine, and any decrease in amphetamine’s metabolism that might occur due to drug interactions or genetic polymorphisms is more likely to be clinically significant when renal elimination is decreased [see PRECAUTIONS ].

Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablets is supplied as follows:

5 mg: White to off white round tablets with ‘T370’ debossed on one side and four partial bisects on other side.
NDC 43602-370-01 bottles of 100 tablets
NDC 43602-370-05 bottles of 500 tablets

7.5 mg: Light blue color oval tablet, one side debossed with ‘T371’ with two partial bisects and other side with two partial bisects and one full bisect.
NDC 43602-371-01 bottles of 100 tablets
NDC 43602-371-05 bottles of 500 tablets

10 mg: Light blue color round shaped tablet debossed with T over 372 on one side and other side with one full bisect and two partial bisects.
NDC 43602-372-01 bottles of 100 tablets
NDC 43602-372-05 bottles of 500 tablets

12.5 mg: Light to dark peach colored, round beveled edge tablet, debossed with “T” over “373” on one side and one full bisect and two partial bisects on other side.
NDC 43602-373-01 bottles of 100 tablets
NDC 43602-373-05 bottles of 500 tablets

15 mg: Light to dark peach colored oval shaped tablet, debossed with ‘T374’ with two partial bisects on one side, and one full bisect and two partial bisects on other side.
NDC 43602-374-01 bottles of 100 tablets
NDC 43602-374-05 bottles of 500 tablets

20 mg: Light to dark peach colored round tablet, debossed with T over 375 on one side and other side with one full bisect and two partial bisects.
NDC 43602-375-01 bottles of 100 tablets
NDC 43602-375-05 bottles of 500 tablets

30 mg: Light to dark peach round, flat faced, beveled edge tablets with one full bisect and two partial bisect lines on one side, and debossed with “T” over “376” on other side.
NDC 43602-376-01 bottles of 100 tablets
NDC 43602-376-05 bottles of 500 tablets

Dispense in a tight, light-resistant container.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Manufactured by:
Ascent Pharmaceuticals, Inc.
Central Islip, NY 11722

Rev: 04/21