Get your patient on Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, Amphetamine Sulfate - Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, Amphetamine SulfateĀ tablet (Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, Amphetamine Sulfate)
Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, Amphetamine Sulfate - Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, Amphetamine SulfateĀ tablet prescribing information
WARNINGS: ABUSE, MISUSE, AND ADDICTION
Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets have a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets, can result in overdose and death (see OVERDOSAGE ), and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets, assess each patientās risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets treatment, reassess each patientās risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction (see WARNINGS and DRUG ABUSE AND DEPENDENCE ).
INDICATIONS AND USAGE
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 Ā® ) 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; āon the go;ā excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.
DOSAGE AND ADMINISTRATION
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.
Prior to treating patients with dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets assess:
ā¢ 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 ). ā¢ the family history and clinically evaluate patients for motor or verbal tics or Tourette's syndrome before initiating dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets (see WARNINGS ).
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.
CONTRAINDICATIONS
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 ].
ADVERSE REACTIONS
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, intestinal ischemia, and 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.
DESCRIPTION
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.
| EACH TABLET CONTAINS | 5 mg | 10 mg | 15 mg | 20 mg | 30 mg |
Dextroamphetamine Saccharate | 1.25 mg | 2.5 mg | 3.75 mg | 5 mg | 7.5 mg |
| Amphetamine Aspartate Monohydrate | 1.25 mg | 2.5 mg | 3.75 mg | 5 mg | 7.5 mg |
Dextroamphetamine Sulfate, USP | 1.25 mg | 2.5 mg | 3.75 mg | 5 mg | 7.5 mg |
Amphetamine Sulfate, USP | 1.25 mg | 2.5 mg | 3.75 mg | 5 mg | 7.5 mg |
| Total Amphetamine Base Equivalence | 3.13 mg | 6.3 mg | 9.4 mg | 12.6 mg | 18.8 mg |
Inactive Ingredients: microcrystalline cellulose, maltodextrin, compressible sugar, corn starch, colloidal silicon dioxide, saccharin sodium and magnesium stearate. The 15 mg, 20 mg and 30 mg tablets contain FD&C Yellow #6 Aluminum Lake as a color additive.
CLINICAL PHARMACOLOGY
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 have 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 Ī± or Ī² 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 amphetamineās 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 ].
HOW SUPPLIED
Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets are supplied as follows:
5 mg: A white to off-white, round, biconvex quadrisect tablet debossed on one side with ā5ā in the upper left quadrant. The other side is quadrisected and debossed with NP007.
Bottles of 100 Tablets NDC 55466-129-12
10 mg: A white to off-white, round, biconvex quadrisect tablet debossed on one side with ā10ā separated by a bisect in the upper quadrant. The other side is quadrisected and debossed with NP008.
Bottles of 100 Tablets NDC 55466-130-12
15 mg: An orange, round, biconvex quadrisect tablet debossed on one side with ā15ā separated by a bisect in the upper quadrant. The other side is quadrisected and debossed with NP009.
Bottles of 100 Tablets NDC 55466-131-12
20 mg: An orange, round, biconvex quadrisect tablet debossed on one side with ā20ā separated by a bisect in the upper quadrant. The other side is quadrisected and debossed with NP010.
Bottles of 100 Tablets NDC 55466-132-12
30 mg: An orange, round, biconvex quadrisect tablet debossed on one side with ā30ā separated by a bisect in the upper quadrant. The other side is quadrisected and debossed with NP011.
Bottles of 100 Tablets NDC 55466-133-12
Dispense in a tight, light-resistant container.
Store at 20Ā° to 25Ā°C (68Ā° to 77Ā°F) [See USP Controlled Room Temperature].
Manufactured and Distributed by:
Neolpharma, Inc.
Caguas, Puerto Rico 00725, USA
Issued 06/23
PP12902
