DEXEDRINESPANSULE (dextroamphetamine sulfate) capsule, extended release

DEXEDRINE has 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 DEXEDRINE, 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 DEXEDRINE, assess each patient’s 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 DEXEDRINE treatment, reassess each patient’s 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].

DEXEDRINE (dextroamphetamine sulfate) is the dextro isomer of the compound d,l-amphetamine sulfate, a sympathomimetic amine of the amphetamine group. Chemically, dextroamphetamine is d-alpha-methylphenethylamine, and is present in all forms of DEXEDRINE as the neutral sulfate.

Structural formula:

DEXEDRINE - Chemical Structure

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.

Each capsule, with brown cap and natural body, contains dextroamphetamine sulfate. The 5-mg capsule is imprinted in white with IX and 5 mg on the brown cap and is imprinted in white with 673 and 5 mg on the natural body. The 10-mg capsule is imprinted in white with IX and 10 mg on the brown cap and is imprinted in white with 674 and 10 mg on the natural body. The 15-mg capsule is imprinted in white with IX and 15 mg on the brown cap and is imprinted in white with 675 and 15 mg on the natural body. Product reformulation in 1996 has caused a minor change in the color of the time-released pellets within each capsule. Inactive ingredients now consist of cetyl alcohol, D&C Yellow No. 10, dibutyl sebacate, ethylcellulose, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 6, gelatin, hypromellose, polyethylene glycol, povidone, sodium lauryl sulfate, sugar spheres, and trace amounts of other inactive ingredients.

Amphetamines are noncatecholamine, 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 that 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 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.

DEXEDRINE is indicated in:

Narcolepsy

Attention Deficit Disorder with Hyperactivity

As an integral part of a total treatment program that typically includes other measures (psychological, educational, social) for patients (ages 6 years to 16 years) with this syndrome. A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV) implies the presence of the 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 2 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 6 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 6 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 of medical and 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 patient and not solely on the presences of the required number of DSM-IV characteristics.

Need for Comprehensive Treatment Program

DEXEDRINE is 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 patients with this syndrome. Stimulants are not intended for use in patients who exhibit 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 patient’s symptoms.

Limitations of Use

The use of DEXEDRINE is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage [see Precautions, Pediatric Use].

In patients known to be hypersensitive to amphetamine, or other components of DEXEDRINE. 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].

Abuse, Misuse, and Addiction

DEXEDRINE has a high potential for abuse and misuse. The use of DEXEDRINE exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. DEXEDRINE can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence]. Misuse and abuse of CNS stimulants, including DEXEDRINE 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 DEXEDRINE, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug. Advise patients to store amphetamine sulfate in a safe place, preferably locked, and instruct patients to not give DEXEDRINE to anyone else. Throughout DEXEDRINE treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

Risks to Patients with Serious Cardiac Disease

Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended ADHD dosages.

Avoid DEXEDRINE use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.

Increased Blood Pressure and Heart Rate

CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm).

Monitor all patients for potential tachycardia and hypertension.

Psychiatric Adverse Reactions

Exacerbation of Pre-Existing Psychosis

CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.

Induction of a Manic Episode in Patients with Bipolar Disease

CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).

New Psychotic or Manic Symptoms

CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared with 0% of placebo-treated patients. If such symptoms occur, consideration discontinuing DEXEDRINE.

Long-Term Suppression of Growth in Pediatric Patients

DEXEDRINE is not approved for use and is not recommended in pediatric patients below 6 years of age [see Precautions, Pediatric Use].

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients, including DEXEDRINE. Closely monitor growth (weight and height) in DEXEDRINE-treated pediatric patients treated with CNS stimulants.

Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted [see Precautions, Pediatric Use].

Seizures

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Peripheral Vasculopathy, including Raynaud’s phenomenon

Stimulants, including DEXEDRINE, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports and at therapeutic dosages in all age groups throughout the course of treatment. Signs and symptoms generally improve after dosage reduction or discontinuation of the CNS stimulant. Careful observation for digital changes is necessary during DEXEDRINE treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for DEXEDRINE-treated patients who develop signs or symptoms of peripheral vasculopathy.

Serotonin Syndrome

Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort [see Drug Interactions]. Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism [see Clinical Pharmacology]. The potential for a pharmacokinetic interaction exists with the co-administration of CYP2D6 inhibitors which may increase the risk with increased exposure to DEXEDRINE. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drug Interactions].

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Concomitant use of DEXEDRINE with MAOI drugs is contraindicated [see Contraindications].

Discontinue treatment with DEXEDRINE and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of DEXEDRINE with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate DEXEDRINE with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.

Motor and Verbal Tics, and Worsening of Tourette’s Syndrome

CNS stimulants, including amphetamine sulfate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported. Before initiating DEXEDRINE, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome with DEXEDRINE, and discontinue treatment if clinically appropriate.

General

The least amount feasible should be prescribed or dispensed at 1 time in order to minimize the possibility of overdosage.

Information for Patients

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Abuse, Misuse, and Addiction

Educate patients and their families about the risks of abuse, misuse, and addiction of DEXEDRINE, which can lead to overdose and death, and proper disposal of any unused drug [see Warnings, Drug Abuse and Dependence, Overdosage]. Advise patients to store DEXEDRINE in a safe place, preferably locked, and instruct patients to not give DEXEDRINE to anyone else.

Risks to Patients with Serious Cardiac Disease

Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with DEXEDRINE use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see Warnings].

Increased Blood Pressure and Heart Rate

Instruct patients that DEXEDRINE can elevate blood pressure and heart rate [see Warnings].

Psychiatric Adverse Reactions

Advise patients that DEXEDRINE, at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania [see Warnings].

Long-Term Suppression of Growth in Pediatric Patients

Advise patients that DEXEDRINE may cause slowing of growth and weight loss in pediatric patients [see Warnings].

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’s phenomenon]

• Instruct patients beginning treatment with DEXEDRINE about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.
• Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.
• Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking DEXEDRINE.
• Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients [see Warnings].

Motor and Verbal Tics, and Worsening of Tourette’s Syndrome

Advise patients that motor and verbal tics and worsening of Tourette’s Syndrome may occur during treatment with DEXEDRINE. Instruct the patients to notify their healthcare provider if emergence or worsening of tics or Tourette’s syndrome occurs [see Warnings].

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 verbal tics, and Tourette’s syndrome.

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.

Endocrine

Impotence, changes in libido, frequent or prolonged erections.

Musculoskeletal

Rhabdomyolysis.

Skin and Subcutaneous Tissue Disorders

Alopecia.

To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Controlled Substance

DEXEDRINE  contains dextroamphetamine, a Schedule II controlled substance.

Abuse

DEXEDRINE has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see Warnings]. DEXEDRINE 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 amphetamine 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 DEXEDRINE, 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

DEXEDRINE 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 DEXEDRINE include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.

Tolerance

DEXEDRINE 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).

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. The pharmacokinetic profile of DEXEDRINE should be considered when treating patients with overdose. D-amphetamine is not dialyzable. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

Amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of the resulting insomnia.

Prior to treating patients with DEXEDRINE, 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 [see Warnings].

Narcolepsy

Usual dose is 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 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 an 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 an 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.

Attention Deficit Disorder with Hyperactivity

The SPANSULE capsule formulation is not recommended for pediatric patients younger than 6 years of age.

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.

DEXEDRINE SPANSULE capsules

Each capsule, with brown cap and natural body, contains dextroamphetamine sulfate.

The 5-mg capsule is imprinted in white with IX and 5 mg on the brown cap and is imprinted in white with 673 and 5 mg on the natural body.

The 10-mg capsule is imprinted in white with IX and 10 mg on the brown cap and is imprinted in white with 674 and 10 mg on the natural body.

The 15-mg capsule is imprinted in white with IX and 15 mg on the brown cap and is imprinted in white with 675 and 15 mg on the natural body.

5 mg 90s:                                             NDC 64896-673-10

10 mg 90s:                                           NDC 64896-674-10

15 mg 90s:                                           NDC 64896-675-10

Store at controlled room temperature between 20° to 25°C (68° to 77°F) [see USP].

Dispense in a tight, light-resistant container.

Manufactured by:

Catalent Pharma Solutions

Winchester, KY 40391

Distributed by:

Amneal Specialty, a division of

Amneal Pharmaceuticals LLC

Bridgewater, NJ 08807

Rev. 09-2025-03

For additional copies of the printed medication guide, please visit www.amneal.com or contact us at 1-877-835-5472.

This Medication Guide has been approved by the U.S. Food and Drug Administration.                                                      Rev. 09-2025-01