VA Class:CN801
AHFS Class:
Generic Name(s):
Notification FDA drug safety communication (5/11/2023): To address continuing concerns of misuse, abuse, addiction, and overdose of prescription stimulants, FDA is requiring updates to the Boxed Warning and other information to ensure the prescribing information is consistent across the entire class of these drugs.500 The current prescribing information in some prescription stimulants does not provide up to date warnings about the harms of misuse and abuse, particularly when these drugs are shared with individuals for whom they are not prescribed. 500 An FDA review found that most individuals who misuse prescription stimulants obtain their drugs from family members or peers, and that such sharing of prescription stimulants was a major contributor to nonmedical use and addiction.500 Updates will include information that patients should never share their prescription stimulants with anyone, and the Boxed Warning information will describe the risks of misuse, abuse, addiction, and overdose consistently across all medicines in the class.500 The Boxed Warning will also advise healthcare professionals to monitor patients closely for signs and symptoms of misuse, abuse, and addiction.500 |
Amphetamine is a noncatechol, sympathomimetic amine with CNS-stimulating activity.
Amphetamine sulfate and amphetamine aspartate in fixed-combination preparations containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate are used in the treatment of narcolepsy and as adjuncts to psychological, educational, social, and other remedial measures in the treatment of attention deficit hyperactivity disorder (ADHD).
Narcolepsy and Attention Deficit Hyperactivity Disorder
Amphetamine sulfate and amphetamine aspartate in fixed-combination preparations containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate are used in the treatment of narcolepsy and as adjuncts to psychological, educational, social, and other remedial measures in the treatment of ADHD (hyperkinetic disorder, hyperkinetic syndrome of childhood, minimal brain dysfunction) in children, adolescents, and adults.
ADHD usually is characterized by developmentally inappropriate symptoms (e.g., moderate to severe distractibility, short attention span, hyperactivity, emotional lability, impulsivity). The final diagnosis of this disorder should not be made if these symptoms are of only comparatively recent origin. Nonlocalizing (soft) neurologic signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of CNS dysfunction may or may not be warranted. Drug therapy is not indicated in all children with ADHD, and such therapy should be considered only after a complete evaluation including medical history has been performed. The decision to use amphetamines should depend on the age of the child and the clinician's assessment of the severity and duration of symptoms and should not depend solely on one or more behavioral characteristics. When symptoms of ADHD are associated with acute stress reactions, use of amphetamines usually is not recommended. For a more detailed discussion on the management of ADHD, including the use of stimulants such as amphetamine, see Uses: Attention Deficit Hyperactivity Disorder, in Methylphenidate 28:20.32.
Administration 
Amphetamine sulfate and amphetamine aspartate in fixed-combination preparations containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate are administered orally. The commercially available extended-release capsules containing amphetamine sulfate and amphetamine aspartate in fixed-combination with dextroamphetamine saccharate and dextroamphetamine sulfate (Adderall® XR) may be swallowed intact with or without food or the entire contents of a capsule(s) may be sprinkled on a small amount of applesauce immediately prior to administration; subdividing the contents of a capsule is not recommended. The pellets contained in the capsules should not be chewed or crushed, and the sprinkle/food mixture must not be stored for use at a later time.
The initial dose of amphetamines (as conventional tablets or extended-release capsules) should be given on awakening; when amphetamines are administered as conventional tablets in divided doses (2 or 3), additional doses are given at intervals of 4-6 hours. Because of the potential for insomnia, administration of conventional tablets in the late evening or extended-release capsules in the afternoon should be avoided.
Dosage
Dosage of amphetamines should be adjusted according to individual response and tolerance; the smallest dose required to produce the desired response should always be used.
Narcolepsy
In the treatment of narcolepsy, the usual total dosage of amphetamines given in fixed-combination preparations containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate is 5-60 mg daily, depending upon the patient's age and response, usually given in divided doses. In patients 12 years of age and older, the initial dosage is 10 mg daily; daily dosage is increased by 10 mg at weekly intervals until the optimum response is attained. Although narcolepsy seldom occurs in children younger than 12 years of age, such children also may receive dextroamphetamine alone. In patients 6-12 years of age, the recommended initial dosage is 5 mg daily; daily dosage is increased by 5 mg at weekly intervals until optimum response is attained. When intolerable adverse effects (e.g., insomnia, anorexia) occur, dosage should be reduced.
Attention Deficit Hyperactivity Disorder
As an adjunct in the treatment of attention deficit hyperactivity disorder (ADHD) in children 6 years of age and older, the initial total dosage of amphetamines given in conventional fixed-combination preparations containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate is 5 mg once or twice daily; the daily dosage is increased by 5 mg at weekly intervals until the optimum response is attained. Total daily dosage rarely should exceed 40 mg. In children 3-5 years of age, the initial dosage of amphetamines given in conventional fixed-combination preparations containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate is 2.5 mg daily; the daily dosage is increased by 2.5 mg at weekly intervals until the optimum response is attained. When amphetamines are administered as conventional tablets in divided doses (2 or 3), additional doses are given at intervals of 4-6 hours.
Alternatively, in patients who are receiving drug therapy for ADHD for the first time or are being switched from therapy with another stimulant, amphetamine therapy may be initiated with extended-release capsules containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate in fixed combination (Adderall® XR). In children 6-12 years of age, the initial dosage of amphetamines as extended-release capsules (Adderall® XR) is 10 mg once daily; daily dosage may be increased in increments of 5 or 10 mg at weekly intervals to a maximum dosage of 30 mg daily. Treatment may be initiated with a dosage of 5 mg once daily when, in the opinion of the clinician, a lower initial dosage is appropriate. In adolescents 13-17 years of age, the initial dosage of amphetamines as extended-release capsules (Adderall® XR) is 10 mg once daily. Dosage may be increased to 20 mg once daily after 1 week if symptoms are not adequately controlled. In adults who are receiving drug therapy for ADHD for the first time or are being switched from therapy with another drug, the recommended dosage of amphetamines as extended-release capsules (Adderall XR®) is 20 mg once daily. Although dosages of up to 60 mg daily (as extended-release capsules) have been used in adolescents 13-17 years of age and adults in clinical studies, there is no evidence that dosages exceeding 20 mg daily provide any additional benefit in these patients. When switching from conventional tablets (Adderall®) to extended-release capsules (Adderall® XR), the total daily dosage of amphetamines may remain the same but should be given once daily.
When possible, therapy should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued treatment. Long-term use of conventional tablets or long-term use of extended-release capsules (i.e., more than 3 weeks in children or more than 4 weeks in adolescents or adults) has not been studied systematically. If conventional tablets or extended-release capsules are used for extended periods, the usefulness of the drug should be reevaluated periodically.
Chemistry and Stability
Chemistry
Amphetamine, d,l -α-methylphenethylamine, occurs as a colorless, mobile liquid with an amine odor and is sparingly soluble in water (1:50) and soluble in alcohol. The base is volatile at room temperature and has been used as an inhalant but is no longer commercially available in the US. Amphetamine sulfate occurs as a white, odorless crystalline powder and has a slightly bitter taste. Amphetamine sulfate is freely soluble in water (1:9) and slightly soluble in alcohol (about 1:500). Amphetamine aspartate and amphetamine sulfate currently are commercially available in the US only as fixed-combination preparations containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate.
Stability
The fixed-combination conventional tablets or extended-release capsules containing amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate should be stored in tight, light-resistant containers at 25°C but may be exposed to temperatures ranging from 15-30°C.
Additional Information
For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, chronic toxicity, acute toxicity, and dosage and administration of amphetamine and amphetamine sulfate, see the Amphetamines General Statement 28:20.04.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Amphetamine sulfate preparations are subject to control under the Federal Controlled Substances Act of 1970 as schedule II (C-II) drugs.
Amphetamine Sulfate Combinations
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|
Oral | Capsules, extended-release | 5 mg total amphetamine (as 1.25 mg, with Amphetamine Aspartate 1.25 mg, Dextroamphetamine Saccharate 1.25 mg, and Dextroamphetamine Sulfate 1.25 mg) | Adderall XR® (C-II) | Shire |
| | 10 mg total amphetamine (as 2.5 mg, with Amphetamine Aspartate 2.5 mg, Dextroamphetamine Saccharate 2.5 mg, and Dextroamphetamine Sulfate 2.5 mg) | Adderall XR® (C-II) | Shire |
| | 15 mg total amphetamine (as 3.75 mg, with Amphetamine Aspartate 3.75 mg, Dextroamphetamine Saccharate 3.75 mg, and Dextroamphetamine Sulfate 3.75 mg) | Adderall XR® (C-II) | Shire |
| | 20 mg total amphetamine (as 5 mg, with Amphetamine Aspartate 5 mg, Dextroamphetamine Saccharate 5 mg, and Dextroamphetamine Sulfate 5 mg) | Adderall XR® (C-II) | Shire |
| | 25 mg total amphetamine (as 6.25 mg, with Amphetamine Aspartate 6.25 mg, Dextroamphetamine Saccharate 6.25 mg, and Dextroamphetamine Sulfate 6.25 mg) | Adderall XR® (C-II) | Shire |
| | 30 mg total amphetamine (as 7.5 mg, with Amphetamine Aspartate 7.5 mg, Dextroamphetamine Saccharate 7.5 mg, and Dextroamphetamine Sulfate 7.5 mg) | Adderall XR® (C-II) | Shire |
| Tablets | 5 mg total amphetamine (as 1.25 mg, with Amphetamine Aspartate 1.25 mg, Dextroamphetamine Saccharate 1.25 mg, and Dextroamphetamine Sulfate 1.25 mg)* | Adderall® (C-II; double-scored) | Shire |
| | | Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored) | |
| | 7.5 mg total amphetamine (as 1.875 mg, with Amphetamine Aspartate 1.875 mg, Dextroamphetamine Saccharate 1.875 mg, and Dextroamphetamine Sulfate 1.875 mg)* | Adderall® (C-II; double-scored) | Shire |
| | | Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored) | |
| | 10 mg total amphetamine (as 2.5 mg, with Amphetamine Aspartate 2.5 mg, Dextroamphetamine Saccharate 2.5 mg, and Dextroamphetamine Sulfate 2.5 mg)* | Adderall® (C-II; double-scored) | Shire |
| | | Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored) | |
| | 12.5 mg total amphetamine (as 3.125 mg, with Amphetamine Aspartate 3.125 mg, Dextroamphetamine Saccharate 3.125 mg, and Dextroamphetamine Sulfate 3.125 mg)* | Adderall® (C-II; double-scored) | Shire |
| | | Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored) | |
| | 15 mg total amphetamine (as 3.75 mg, with Amphetamine Aspartate 3.75 mg, Dextroamphetamine Saccharate 3.75 mg, and Dextroamphetamine Sulfate 3.75 mg)* | Adderall® (C-II; double-scored) | Shire |
| | | Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored) | |
| | 20 mg total amphetamine (as 5 mg, with Amphetamine Aspartate 5 mg, Dextroamphetamine Saccharate 5 mg, and Dextroamphetamine Sulfate 5 mg)* | Adderall® (C-II; double-scored) | Shire |
| | | Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored) | |
| | 30 mg total amphetamine (as 7.5 mg, with Amphetamine Aspartate 7.5 mg, Dextroamphetamine Saccharate 7.5 mg, and Dextroamphetamine Sulfate 7.5 mg)* | Adderall® (C-II; double-scored) | Shire |
| | | Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (C-II; double-scored) | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions May 18, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
500. FDA drug safety communication. FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions; issued May 11 2023. From FDA website. [Web]