Centrally acting sympathomimetics

Dextroamp Saccharate, Amp Aspartate, Dextroamp Sulfate and Amp Sulfate

Approved 31 Aug 2023OralCapsule, extended release

The FDA lists this product in 60 strengths and forms.

Indications

Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 13 years and older [see Clinical Studies ( 14 )] . Limitations of Use: Pediatric patients 12 years and younger experienced higher plasma exposure than patients 13 years and older at the same dose, and experienced higher rates of adverse reactions, mainly insomnia and decreased appetite [see Use in Specific Populations ( 8.4 )] .

Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules are a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 13 years and older. ( 1 ) Limitations of Use: Pediatric patients 12 years and younger experienced higher plasma exposure than patients 13 years and older at the same dose and experienced higher rates of adverse reactions, mainly insomnia and decreased appetite.

( 8.4 )

Contraindications

Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules are contraindicated in patients with: Known hypersensitivity to amphetamine, or other components of Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products [see Adverse Reactions (6.2) ] .

Concomitant treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with a monoamine oxidase inhibitor, because of an increased risk of hypertensive crisis [see Drug Interactions (7.1) ] . Known hypersensitivity to amphetamine products or other ingredients in Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules. ( 4 ) Use with monoamine oxidase (MAO) inhibitors, or within 14 days of the last MAO inhibitor dose.

( 4 , 7.1 )

Warnings and precautions

Risks to Patients with Serious Cardiac Disease : Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. ( 5.2 ) Increased Blood Pressure and Heart Rate : Monitor blood pressure and pulse. ( 5.3 ) Psychiatric Adverse Reactions : Prior to initiating Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules, screen patients for risk factors for developing a manic episode.

Interactions

Acidifying and Alkalinizing Agents: Agents that alter GI and urinary pH can alter blood levels of amphetamine. Acidifying agents (GI and urinary) decrease amphetamine blood levels, while alkalinizing agents (GI and urinary) increase amphetamine blood levels. Adjust Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules dosage accordingly. ( 2.5 , 7.1 )

7.1 Drugs Having Clinically Important Interactions with Amphetamines Table 3 Drugs Having Clinically Important Interactions with Amphetamines Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact MAOI antidepressants slow amphetamine metabolism, increasing amphetamines effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results.

Intervention Do not administer Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules during or within 14 days following the administration of MAOI [see Contraindications (4) ] . Serotonergic Drugs Clinical Impact The concomitant use of amphetamines and serotonergic drugs increases the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules initiation or dosage increase.

If serotonin syndrome occurs, discontinue Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules and concomitant serotonergic drug(s) [see Warnings and Precautions (5.7 )] . Alkalinizing Agents Clinical Impact May increase exposure to amphetamine and exacerbate the action of amphetamine. Intervention Caution should be taken when co-administering Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules and gastrointestinal and urinary alkalinizing agents.

Acidifying Agents Clinical Impact Lower blood levels and efficacy of amphetamines. Intervention Increase dose of Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules based on clinical response. Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing sustained increases in the concentration of d- amphetamine in the brain; cardiovascular effects can be potentiated.

Intervention Monitor frequently and adjust Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules dose or use alternative therapy based on clinical response. CYP2D6 Inhibitors Clinical Impact May increase the exposure of amphetamine. Intervention Start with lower doses and monitor frequently and adjust Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules dose or use alternative therapy based on clinical response.

Gastric pH Modulators Clinical Impact Potential change in shape of PK profile and exposure may occur. Intervention Monitor patients for changes in clinical effect and use alternative therapy based on clinical response.

7.2Drug/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.

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/. Risk Summary The limited available data from published literature and postmarketing reports on use of amphetamine in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage.

Adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers dependent on amphetamines [see Clinical Considerations] . In an embryofetal development study, amphetamine ( d- to l- enantiomer ratio of 3:1, the same as in Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules) had no effects on embryofetal morphological development or survival when administered to pregnant rats and rabbits throughout the period of organogenesis up to doses 10 times the maximum recommended human dose (MRHD) of 25 mg/day given to adolescents, on a mg/m 2 body surface area basis.

However, in a pre- and post-natal development study, amphetamine ( d- to l- ratio of 3:1) administered orally to pregnant rats during gestation and lactation caused a decrease in pup survival and a decrease in pup body weight that correlated with a delay in developmental landmarks at clinically relevant doses of amphetamine. In addition, adverse effects on reproductive performance were observed in pups whose mothers were treated with amphetamine.

Long-term neurochemical and behavioral effects have also been reported in animal developmental studies using clinically relevant doses of amphetamine [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations Fetal/Neonatal Adverse Reactions Amphetamines, such as Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules, cause vasoconstriction and thereby may decrease placental perfusion. In addition, amphetamines can stimulate uterine contractions increasing the risk of premature delivery. Infants born to amphetamine-dependent mothers have an increased risk of premature delivery and low birth weight.

Monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness. Data Animal Data Amphetamine ( d- to l- enantiomer ratio of 3:1, the same as in Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules) had no apparent effects on embryofetal morphological development or survival when administered orally 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 2 and 10 times, respectively, the maximum recommended human dose (MRHD) of 25 mg/day given to adolescents, 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 8 times the MRHD given to adolescents on a mg/m 2 basis) or greater to pregnant animals. Administration of these doses was also associated with severe maternal toxicity.

A pre- and postnatal development study was conducted with amphetamine ( d- to l- enantiomer ratio of 3:1) in which pregnant rats received daily oral doses of 2, 6, and 10 mg/kg from gestation day 6 to lactation day 20. These doses are approximately 0.6, 2, and 3 times the MRHD of 25 mg/day amphetamine ( d- to l- ratio of 3:1) given to adolescents, on a mg/m 2 basis. All doses caused hyperactivity and decreased weight gain in the dams.

A decrease in pup survival was seen at all doses. A decrease in pup body weight was seen at 6 and 10 mg/kg which correlated with delays in developmental landmarks, such as preputial separation and vaginal opening. Increased pup locomotor activity was seen at 10 mg/kg on day 22 postpartum but not at 5 weeks postweaning. When pups were tested for reproductive performance at maturation, gestational weight gain, number of implantations, and number of delivered pups were decreased in the group whose mothers had been given 10 mg/kg.

A number of studies from the literature 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.

Adverse reactions

The following adverse reactions are discussed in greater detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 , 9.3 )] Hypersensitivity to amphetamine products or other ingredients of Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules [see Contraindications ( 4 )] Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] Risks to Patients with Serious Cardiac Disease [see Warnings and Precautions ( 5.2 )] Increased Blood Pressure and Heart Rate [see Warnings and Precautions ( 5.3 )] Psychiatric Adverse Reactions [see Warnings and Precautions ( 5.4 )] Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions ( 5.5 )] Peripheral Vasculopathy, including Raynaud’s phenomenon [see Warnings and Precautions ( 5.6 )] Seizures [see Warnings and Precautions ( 5.7 )] Serotonin Syndrome [see Warnings and Precautions ( 5.8 )] Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions ( 5.10 )] Most common adverse reactions in patients with ADHD (incidence ≥5% and at a rate at least twice placebo) are: Pediatrics (13 years and older): insomnia, decreased appetite, decreased weight, irritability, and nausea.

( 6.1 ) Adults: insomnia, decreased appetite, decreased weight, dry mouth, increased heart rate, and anxiety. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mallinckrodt at 1-800-778-7898 or FDA at 1-800-FDA-1088 or www.fda.gov./medwatch

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules were studied in adults (18 to 55 years) and pediatric patients (13 to 17 years) who met Diagnostic and Statistical Manual of Mental Disorders, 4 th or 5 th editions (DSM-IV-TR ® or DSM-5) criteria for ADHD.

The safety data for adults were pooled from three randomized, double-blind, placebo-controlled studies in doses of 12.5 mg to 75 mg per day (1.5 times the maximum recommended dosage). Doses higher than 50 mg per day did not demonstrate additional clinical benefit and are not recommended. The safety data for pediatric patients (13 to 17 years) is from 1 randomized, double-blind, placebo-controlled study of doses of 12.5 mg to 25 mg.

The total exposure in patients treated with Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules totalled 704; this included pediatric patients, 78 adolescent patients and 626 adult patients from multiple well-controlled trials. The duration of use ranged from 4 to 7 weeks [see Clinical Studies (14) ] . Adverse Reactions Leading to Discontinuation of Treatment In pooled controlled trials of adult patients, 9% (54/626) of Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules-treated patients discontinued due to adverse reactions compared to 2% (7/328) of placebo-treated patients.

The most frequent adverse reactions leading to discontinuation (i.e., leading to discontinuation in at least 1% of Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules-treated patients and at a rate at least twice that of placebo) were insomnia (2%, n=15), blood pressure increased (2%, n=10), decreased appetite (1%, n=5), and headache (1%, n=4). In a controlled trial including adolescent patients (13 to 17 years), 5% (4/78) of Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules-treated patients discontinued due to adverse reactions compared to 0% (0/79) of placebo-treated patients.

The most frequent adverse reaction leading to discontinuation (i.e., leading to discontinuation in at least 1% of Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules-treated patients and at a rate at least twice that of placebo) were dizziness (1%, n=1), depression (1%, n=1), abdominal pain upper (1%, n=1), and viral infection (1%, n=1). Adverse Reactions Occurring at an Incidence of ≥ 2% and at Least Twice Placebo Among Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules-Treated Adults in Clinical Trials The most common adverse reactions reported in adults were insomnia, decreased appetite, dry mouth, decreased weight, heart rate increased, and anxiety.

Table 1 lists the adverse reactions that occurred ≥ 2% compared to placebo. The most common adverse reaction (insomnia) generally occurred early during treatment with Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules. Table 1 Adverse Reactions Reported by 2% or More of Adults Taking Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules and at Least Twice the Incidence in Patients Taking Placebo in 3 Clinical Trials (4, 6, and 7 Weeks) Body System Adverse Reaction Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules Includes doses up to 75 mg (1.5 times the maximum recommended dosage).

(N=626) Placebo (N=328) Nervous System Anxiety 7% 3% Feeling Jittery 2% 1% Agitation 2% 0% Bruxism 2% 0% Psychiatric Disorders Insomnia 31% 8% Depression 3% 0% Metabolism and Nutritional Disorders Decreased Appetite 30% 4% Weight Decreased 9% 0% Gastrointestinal System Dry Mouth 23% 4% Diarrhea 3% 1% Cardiovascular System Heart Rate Increased 9% 0% Palpitations 4% 2% Genitourinary System Dysmenorrhea Dysmenorrhea was observed in 11 females 4% 2% Erectile Dysfunction Erectile dysfunction was observed in 6 males 2% 1% Adverse Reactions Occurring at an Incidence of 2% or More and at Least Twice Placebo Among Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules-Treated Adolescents (13 to 17 years) in a 4-Week Clinical Trial The most common adverse reactions reported in adolescents were decreased appetite, nausea, insomnia, abdominal pain upper, irritability, and weight decreased.

Table 2 lists the adverse reactions that occurred ≥ 2% compared to placebo. Table 2 Adverse Reactions Reported by ≥ 2% or More of Adolescents Taking Mixed Salts of a Single-Entity Amphetamine Product Extended-Release Capsules and at Least Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial Body System Adverse Reaction Mixed Salts of aSingle-Entity Amphetamine Product Extended-Release Capsules (N=78) Placebo (N=79) Nervous System Dizziness 4% 0% Metabolism and Nutrition Disorders Decreased Appetite 22% 6% Weight Decreased 5% 1% Psychiatric Disorders Irritability 6% 3% Insomnia Insomnia includes terms: initial insomnia, middle insomnia, terminal insomnia and insomnia. 8% 3% Gastrointestinal Disorders Nausea 8% 4% Abdominal Pain, Upper 4% 1%

6.2Adverse Reactions Associated with the Use of Amphetamines

The following adverse reactions have been associated with the use of amphetamines. The following adverse reactions have been identified during post-approval use of amphetamines. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Allergic : Urticaria, rash, hypersensitivity reactions, including angioedema and anaphylaxis.

Serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Cardiovascular : Dyspnea, sudden death. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use. Central Nervous System : Psychotic episodes at recommended doses, overstimulation, restlessness, euphoria, dyskinesia, dysphoria, headache, tics, fatigue, aggression, anger, logorrhea, dermatillomania, and paresthesia (including form

Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA

Dextroamp Saccharate, Amp Aspartate, Dextroamp Sulfate and Amp Sulfate

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Abuse, Misuse, and Addiction Mixed Salts of a Single-Entity Amphetamine Product Extended-Release

5.2Risks to Patients with Serious Cardiac Disease

5.3Increased Blood Pressure and Heart Rate

5.4Psychiatric Adverse Reactions Exacerbation of Pre-Existing Psychosis

5.5Long-Term Suppression of Growth in Pediatric Patients

5.6Peripheral Vasculopathy, Including Raynaud's Phenomenon

Interactions

7.2Drug/Laboratory Test Interactions

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

Adverse reactions

6.1Clinical Trials Experience

6.2Adverse Reactions Associated with the Use of Amphetamines

Composition

Strengths and forms

Official product information

At a glance

Guidelines