WARNING: ABUSE, MISUSE, AND ADDICTION
Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablet 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 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 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets 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].
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 | 7.5 mg | 10 mg | 12.5 mg | 15 mg | 20 mg | 30 mg |
| Dextroamphetamine Saccharate | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| Amphetamine Aspartate Monohydrate | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| Dextroamphetamine Sulfate, USP | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| Amphetamine Sulfate, USP | 1.25 mg | 1.875 mg | 2.5 mg | 3.125 mg | 3.75 mg | 5 mg | 7.5 mg |
| Total Amphetamine Base Equivalence | 3.13 mg | 4.7 mg | 6.3 mg | 7.8 mg | 9.4 mg | 12.6 mg | 18.8 mg |
Inactive Ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose and pregelatinized starch.
5 mg: White to off white, oval shaped, biconvex tablets, double scored on one side and debossed with “G 5” above “111” on other side.
7.5 mg: White to off white, round, flat faced, beveled edge tablets, double scored on one side and debossed with “G 7.5” above “112” on other side.
10 mg: White to off white, oval shaped, flat faced, beveled edge tablets, double scored on one side and debossed with "G 10 " above "113" on other side.
12.5 mg: White to off white, oval shaped, biconvex tablets, double scored on one side and debossed with "G 12.5" above "114" on other side.
15 mg: White to off white, round, flat faced, beveled edge tablets, double scored on one side and debossed with “G 15” above “115” on other side.
20 mg: White to off white, oval shaped, flat faced, beveled edge tablets, double scored on one side and debossed with "G 20" above "116" on other side.
30 mg: White to off white, oval shaped, biconvex tablets, double scored on one side and debossed with “G 30” above “117” on other side.
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 Tablet 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].
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.
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].
WARNINGS
Abuse, Misuse, and Addiction
Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablet has a high potential for abuse and misuse. The use of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets can be diverted for non-medical use into illicit channels or distribution [see DRUG ABUSE AND DEPENDENCE: Abuse]. 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 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets to anyone else. Throughout Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets 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 were treated with CNS stimulant treatment at the recommended ADHD dosages.
Avoid Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets 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). Some patients may have larger increases. Monitor all Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets-treated patients for potential tachycardia and hypertension.
Psychiatric Adverse Reactions
Exacerbation of Preexisting 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 Disorder
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, consider discontinuing Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets.
Long-Term Suppression of Growth in Pediatric Patients
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets-treated pediatric patients treated with CNS stimulants.
Pediatric patients who are not growing or gaining 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 seizure, 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in postmarketing reports and at the therapeutic dosage of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant. Careful observation for digital changes is necessary during Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets-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]. The coadministration with cytochrome P450 (CYP2D6) inhibitors increase the risk with increased exposure to Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets. 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets with MAOI drugs is contraindicated [see CONTRAINDICATIONS].
Discontinue treatment with Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets, 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets, and discontinue treatment if clinically appropriate.
PRECAUTIONS
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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets, 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets in a safe place, preferably locked, and instruct patients to not give Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets 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
Advise patients that Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets can elevate blood pressure and heart rate [see
WARNINGS].
Psychiatric Adverse Reactions
Advise patients that Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets, 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets may cause slowing of growth including weight loss [see
WARNINGS].
Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, Including Raynaud’s Phenomenon]
• Instruct patients beginning treatment with Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets 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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets.
• Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
Serotonin Syndrome
Caution patients about the risk of serotonin syndrome with concomitant use of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets and other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort, and with drugs that impair metabolism of serotonin (in particular MAOIs, both those intended to treat psychiatric disorders and also others such as linezolid [see
CONTRAINDICATIONS,
WARNINGS, and
DRUG INTERACTIONS]. Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome.
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 Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets. Instruct the patients to notify their healthcare provider if emergence or worsening of tics or Tourette’s syndrome occurs [see WARNINGS].
Drug Interactions
MAO Inhibitors
Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Do not administer Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets concomitantly or within 14 days after discontinuing MAOI [see
CONTRAINDICATIONS and
WARNINGS].
Serotonergic Drugs
The concomitant use of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets and the concomitant serotonergic drug(s) [see
WARNINGS and
PRECAUTIONS].
CYP2D6 Inhibitors
The concomitant use of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets and CYP2D6 inhibitors may increase the exposure of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets and the CYP2D6 inhibitor [see
WARNINGS,
OVERDOSAGE].
Acidifying Agents
Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents and urinary acidifying agents.
Adrenergic Blockers
Adrenergic blockers are inhibited by amphetamines.
Alkalinizing Agents
Increase blood levels and potentiate the action of amphetamine. Co-administration of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents and urinary alkalinizing agents.
Tricyclic Antidepressants
May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response.
Antihistamines
Amphetamines may counteract the sedative effect of antihistamines.
Antihypertensives
Amphetamines may antagonize the hypotensive effects of antihypertensives.
Chlorpromazine
Chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning.
Ethosuximide
Amphetamines may delay intestinal absorption of ethosuximide.
Haloperidol
Haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of amphetamines.
Lithium Carbonate
The anorectic and stimulatory effects of amphetamines may be inhibited by lithium carbonate.
Meperidine
Amphetamines potentiate the analgesic effect of meperidine.
Methenamine Therapy
Urinary excretion of amphetamines is increased, and efficacy is reduced, by acidifying agents used in methenamine therapy.
Norepinephrine
Amphetamines enhance the adrenergic effect of norepinephrine.
Phenobarbital
Amphetamines may delay intestinal absorption of phenobarbital; coadministration of phenobarbital may produce a synergistic anticonvulsant action.
Phenytoin
Amphetamines may delay intestinal absorption of phenytoin; coadministration of phenytoin may produce a synergistic anticonvulsant action.
Propoxyphene
In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.
Proton Pump Inhibitors
Time to maximum concentration (T
max) of amphetamine is decreased compared to when administered alone. Monitor patients for changes in clinical effect and adjust therapy based on clinical response. An example of a proton pump inhibitor is omeprazole.
Veratrum Alkaloids
Amphetamines inhibit the hypotensive effect of veratrum alkaloids.
Drug/Laboratory Test Interactions
Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.
Carcinogenesis/Mutagenesis and Impairment of Fertility
No evidence of carcinogenicity was found in studies in which d,l-amphetamine (enantiomer ratio of 1:1) was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19 mg/kg/day in female mice, and 5 mg/kg/day in male and female rats. These doses are approximately 2.4, 1.5, and 0.8 times, respectively, the maximum recommended human dose of 30 mg/day [child] on a mg/m 2 body surface area basis.
Amphetamine, in the enantiomer ratio present in Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets (immediate-release) (d- to l- ratio of 3:1), was not clastogenic in the mouse bone marrow micronucleus test in vivo and was negative when tested in the E. coli component of the Ames test in vitro. d, l-Amphetamine (1:1 enantiomer ratio) has been reported to produce a positive response in the mouse bone marrow micronucleus test, an equivocal response in the Ames test, and negative responses in the in vitro sister chromatid exchange and chromosomal aberration assays.
Amphetamine, in the enantiomer ratio present in Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets (immediate-release) (d- to l- ratio of 3:1), did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/kg/day (approximately 5 times the maximum recommended human dose of 30 mg/day on a mg/m 2 body surface area basis).
Pregnancy
Teratogenic Effects
Amphetamine, in the enantiomer ratio present in Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets (d- to l- ratio of 3:1), had no apparent effects on embryofetal morphological development or survival when orally administered to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 6 and 16 mg/kg/day, respectively. These doses are approximately 1.5 and 8 times, respectively, the maximum recommended human dose of 30 mg/day [child] on a mg/m 2 body surface area basis. Fetal malformations and death have been reported in mice following parenteral administration of d-amphetamine doses of 50 mg/kg/day (approximately 6 times that of a human dose of 30 mg/day [child] on a mg/m 2 basis) or greater to pregnant animals. Administration of these doses was also associated with severe maternal toxicity.
A number of studies in rodents indicate that prenatal or early postnatal exposure to amphetamine (d- or d,l-), at doses similar to those used clinically, can result in long-term neurochemical and behavioral alterations. Reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function.
There are no adequate and well-controlled studies in pregnant women. There has been one report of severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia (vater association) in a baby born to a woman who took dextroamphetamine sulfate with lovastatin during the first trimester of pregnancy. Amphetamines should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects
Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.
Usage in Nursing Mothers
Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.
Pediatric Use
Long-term effects of amphetamines in children have not been well established. Amphetamines are not recommended for use in children under 3 years of age with Attention Deficit Hyperactivity Disorder described under INDICATIONS AND USAGE.
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, 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.
To report SUSPECTED ADVERSE REACTIONS, contact Granules Pharmaceuticals Inc., at 1-877-770-3183 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG ABUSE AND DEPENDENCE
Controlled Substance
Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets contains amphetamine, a Schedule II controlled substance.
Abuse
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 [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 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.
Dependence
Physical Dependence
Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets 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 Tablets 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 Tablets 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.
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.
Prior to treating patients with Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets 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 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.
HOW SUPPLIED
5 mg: White to off white, oval shaped, biconvex tablets, double scored on one side and debossed with “G 5” above “111” on other side.
Bottles of 30 Tablets NDC 70010-111-03
Bottles of 100 Tablets NDC 70010-111-01
7.5 mg: White to off white, round, flat faced, beveled edge tablets, double scored on one side and debossed with “G 7.5” above “112” on other side.
Bottles of 30 Tablets NDC 70010-112-03
Bottles of 100 Tablets NDC 70010-112-01
10 mg: White to off white, oval shaped, flat faced, beveled edge tablets, double scored on one side and debossed with “G 10” above “113” on other side.
Bottles of 30 Tablets NDC 70010-113-03
Bottles of 100 Tablets NDC 70010-113-01
12.5 mg: White to off white, oval shaped, biconvex tablets, double scored on one side and debossed with “G 12.5” above “114” on other side.
Bottles of 30 Tablets NDC 70010-114-03
Bottles of 100 Tablets NDC 70010-114-01
15 mg: White to off white, round, flat faced, beveled edge tablets, double scored on one side and debossed with “G 15” above “115” on other side.
Bottles of 30 Tablets NDC 70010-115-03
Bottles of 100 Tablets NDC 70010-115-01
20 mg: White to off white, oval shaped, flat faced, beveled edge tablets, double scored on one side and debossed with “G 20” above “116” on other side.
Bottles of 30 Tablets NDC 70010-116-03
Bottles of 100 Tablets NDC 70010-116-01
30 mg White to off white, oval shaped, biconvex tablets, double scored on one side and debossed with “G 30” above “117” on other side.
Bottles of 30 Tablets NDC 70010-117-03
Bottles of 100 Tablets NDC 70010-117-01
Dispense in a tight, light-resistant container.
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Dispense with Medication Guide available at:
https://granulespharma.com/product/mixed-salts-amphetamine-tab/
Manufactured by:
Granules Pharmaceuticals Inc.,
Chantilly, VA 20151
Rev. 06/2024
MEDICATION GUIDE
Dispense with Medication Guide available at:
https://granulespharma.com/product/mixed-salts-amphetamine-tab/
| MEDICATION GUIDE
Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate (DEX-troe-am-FET-uh-meen SACK-uh-rate, am-FET-uh-meen ass-PAR-tate, DEX-troe-am-FET-uh-meen SULL-fate, am-FET-uh-meen SULL-fate) Tablets (Mixed Salts of a Single Entity Amphetamine Product), CII |
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What is the most important information I should know about Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets?
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What are Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets?
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| Do not take Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets if you or your child:
• are allergic to amphetamine products or any of the ingredients in Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets. See the end of this Medication Guide for a complete list of ingredients in Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets. • are taking or have taken within the past 14 days, a medicine used to treat depression called a monoamine oxidase inhibitor (MAOI), including the antibiotic linezolid or the intravenous medicine methylene blue. |
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Before taking Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets, tell your healthcare provider about all of your or your child’s medical conditions, including if you or your child:
Tell your healthcare provider about all of the medicines that you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be changed during treatment with Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets. Your healthcare provider will decide if Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets can be taken with other medicines.
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| How should Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets be taken?
• Take Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets exactly as prescribed by your or your child’s healthcare provider. • Your healthcare provider may change the dose if needed. • The first dose of the day is usually taken when you first wake up. • Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets can be taken with or without food. • If you or your child take too much Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away. |
| What should I avoid while taking Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets?
Do not drive, operate heavy machinery, or do other potentially dangerous activities until you know how Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets affects you. |
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What are the possible side effects of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets?
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How should I store Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets?
Keep Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets and all medicines out of the reach of children. |
| General information about the safe and effective use of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets for a condition for which it was not prescribed. Do not give Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets to other people, even if they have the same condition. It may harm them and it is against the law. You can ask your healthcare provider or pharmacist for information about Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets that is written for healthcare professionals. |
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What are the ingredients in Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets?
Manufactured by:
For more information about Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets, please contact Granules Pharmaceuticals Inc at 1-877-770-3183. |
This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 06/2024
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 5 mg 30s Container Label
NDC 70010- 111-03
Dextroamphetamine Saccharate,
Amphetamine Aspartate,
Dextroamphetamine Sulfate
and Amphetamine Sulfate Tablets
(Mixed Salts of a Single Entity
Amphetamine Product) CII
5 mg
Pharmacist: Dispense the Medication
Guide provided separately to each patient.
30 Tablets Rx only
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 7.5 mg 30s Container label
NDC 70010- 112-03
Dextroamphetamine Saccharate,
Amphetamine Aspartate,
Dextroamphetamine Sulfate
and Amphetamine Sulfate Tablets
(Mixed Salts of a Single Entity
Amphetamine Product) CII
7.5 mg
Pharmacist: Dispense the Medication
Guide provided separately to each patient.
30 Tablets Rx only
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 10 mg 30s Container label
NDC 70010- 113-03
Dextroamphetamine Saccharate,
Amphetamine Aspartate,
Dextroamphetamine Sulfate
and Amphetamine Sulfate Tablets
(Mixed Salts of a Single Entity
Amphetamine Product)
CII
10 mg
Pharmacist: Dispense the Medication
Guide provided separately to each patient.
30 Tablets Rx only
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 12.5 mg 30s Container label
NDC 70010- 114-03
Dextroamphetamine Saccharate,
Amphetamine Aspartate,
Dextroamphetamine Sulfate
and Amphetamine Sulfate Tablets
(Mixed Salts of a Single Entity
Amphetamine Product)
CII
12.5 mg
Pharmacist: Dispense the Medication
Guide provided separately to each patient.
30 Tablets Rx only
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 15 mg 30s Container label
NDC 70010- 115-03
Dextroamphetamine Saccharate,
Amphetamine Aspartate,
Dextroamphetamine Sulfate
and Amphetamine Sulfate Tablets
(Mixed Salts of a Single Entity
Amphetamine Product)
CII
15 mg
Pharmacist: Dispense the Medication
Guide provided separately to each patient.
30 Tablets Rx only
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 20 mg 30s Container label
NDC 70010- 116-03
Dextroamphetamine Saccharate,
Amphetamine Aspartate,
Dextroamphetamine Sulfate
and Amphetamine Sulfate Tablets
(Mixed Salts of a Single Entity
Amphetamine Product)
CII
20 mg
Pharmacist: Dispense the Medication
Guide provided separately to each patient.
30 Tablets Rx only
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 30 mg 30s Container label
NDC 70010- 117-03
Dextroamphetamine Saccharate,
Amphetamine Aspartate,
Dextroamphetamine Sulfate
and Amphetamine Sulfate Tablets
(Mixed Salts of a Single Entity
Amphetamine Product)
CII
30 mg
Pharmacist: Dispense the Medication
Guide provided separately to each patient.
30 TabletsRx only
