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®) 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.
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, 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 before initiating Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate (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
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 ].
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, motor and verbal tics, aggression, anger, logorrhea, dermatillomania.
Eye Disorders
Vision blurred, mydriasis.
Gastrointestinal
Dryness of the mouth, unpleasant taste, diarrhea, constipation, intestinal ischemia, 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.
Drug Abuse and Dependence
Controlled Substance
Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets a Schedule II controlled substances.
Abuse
Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablets has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see WARNINGS and PRECAUTIONS]. Dextroamphetamine saccharate, amphetamine aspartate , dextroamphetamine sulfate and amphetamine sulfate tablets can be diverted for non-medical use into illicit channels or distribution.
Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.
Misuse and abuse of amphetamines may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate, 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.
Dependence
Physical Dependence
Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
Tolerance
Dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Overdosage
Clinical Effects of Overdose
Overdose of CNS stimulants is characterized by the following sympathomimetic effects:
Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension.
Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop.
CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur.
Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop.
Overdose Management
Consider the possibility of multiple drug ingestion. D-amphetamine is not dialyzable. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
Description
A single-entity amphetamine product combining the neutral sulfate salts of Dextroamphetamine and amphetamine, with the Dextro isomer of amphetamine Saccharate and d, 1-amphetamine aspartate.
|
EACH TABLET CONTAINS
|
5 mg
|
7.5 mg
|
10 mg
|
15 mg
|
20 mg
|
30 mg
|
| Dextroamphetamine Saccharate |
1.25 mg |
1.875 mg |
2.5 mg |
3.75 mg |
5 mg |
7.5 mg |
| Amphetamine Aspartate Monohydrate Equivalent |
1.25 mg1
|
1.875 mg2
|
2.5 mg3
|
3.75 mg4
|
5 mg5
|
7.5 mg6
|
| Dextroamphetamine Sulfate, USP |
1.25 mg |
1.875 mg |
2.5 mg |
3.75 mg |
5 mg |
7.5 mg |
| Amphetamine Sulfate, USP |
1.25 mg |
1.875 mg |
2.5 mg |
3.75 mg |
5 mg |
7.5 mg |
| Total Amphetamine Base Equivalence |
3.13 mg |
4.7 mg |
6.3 mg |
9.4 mg |
12.6 mg |
18.8 mg |
11.25 mg of Amphetamine Aspartate Monohydrate equivalent to 1.17 mg Amphetamine Aspartate (Anhydrous) as supplied
21.875 mg of Amphetamine Aspartate Monohydrate equivalent to 1.755 mg Amphetamine Aspartate (Anhydrous) as supplied
32.5 mg of Amphetamine Aspartate Monohydrate equivalent to 2.34 mg Amphetamine Aspartate (Anhydrous) as supplied
43.75 mg of Amphetamine Aspartate Monohydrate equivalent to 3.51 mg Amphetamine Aspartate (Anhydrous) as supplied
55 mg of Amphetamine Aspartate Monohydrate equivalent to 4.6 mg Amphetamine Aspartate (Anhydrous) as supplied
67.5 mg of Amphetamine Aspartate Monohydrate equivalent to 7.03 mg Amphetamine Aspartate (Anhydrous) as supplied
Inactive Ingredients
In addition, each tablet contains: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, povidone, and pregelatinized starch.
Colors
The 5 mg, 7.5 mg, and 10 mg tablets contain the color additive FD&C Blue #1 Aluminum Lake.
The 15 mg, 20 mg, and 30 mg tablets contain the color additive FD&C Yellow #6 Aluminum Lake.
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 extra neuronal 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 (t1/2) for d-amphetamine was shorter than the t1/2 of the 1-isomer (9.77 to 11 hours vs. 11.5 to 13.8 hours). The PK parameters (Cmax, AUC0-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 phenyl acetone, 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] .
How Supplied / Storage and Handling
Dextroamphetamine Saccharate, amphetamine aspartate, Dextroamphetamine sulfate and amphetamine sulfate tablets are supplied as:
5 mg Tablets - Light blue to blue colored, mottled, round, flat-faced, beveled edge tablets debossed with ‘U25’ on one side and quadrisect on other side.
Bottles of 100 16714-948-01
7.5 mg Tablets - Light blue to blue colored, mottled, round, convex tablets debossed with ‘U26’ on one side and quadrisect on other side.
Bottles of 100 16714-949-01
10 mg Tablets - Light blue to blue colored, mottled, round, convex tablets debossed with ‘U27’ on one side and quadrisect on other side.
Bottles of 100 16714-950-01
15 mg Tablets - Light orange to orange colored, mottled, round, convex tablets debossed with ‘U29’ on one side and quadrisect on other side.
Bottles of 100 16714-952-01
20 mg Tablets - Light orange to orange colored, mottled, round, convex tablets debossed with ‘U30’ on one side and quadrisect on other side.
Bottles of 100 16714-953-01
30 mg Tablets - are light orange to orange colored, mottled, round, flat-faced, beveled edge tablets debossed with ‘U31’ on one side and quadrisect on other side.
Bottles of 100 16714-954-01
Dispense in a tight, light-resistant container as described in the USP.
KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense with Medication Guide available at www.northstarrxllc.com/products or call 1-800-206-7821
Manufactured for:
Northstar Rx LLC, Memphis, TN 38141.
Manufactured by:
Corepharma LLC, Middlesex, NJ 08846
Issued: 02/2025