Arynta
Lisdexamfetamine dimesylate oral · Solution · Oral
Uses
1 INDICATIONS AND USAGE ARYNTA is indicated for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older [see Clinical Studies ( 14.1 )] Moderate to severe binge eating disorder (BED) in adults [see Clinical Studies ( 14.2 )] . Limitations of Use: The use of ARYNTA 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 Warnings and Precautions ( 5.5 ), Use in Specific Populations ( 8.4 )] . ARYNTA is not indicated or recommended for weight loss. Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. The safety and effectiveness of ARYNTA for the treatment of obesity have not been established [see Warnings and Precautions ( 5.2 )] . ARYNTA is a central nervous system (CNS) stimulant indicated for the treatment of ( 1 ): Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older. Moderate to severe binge eating disorder (BED) in adults Limitations of Use : The use of ARYNTA 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 ( 5.5 , 8.4 ) ARYNTA is not indicated for weight loss. Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. The safety and effectiveness of ARYNTA for the treatment of obesity have not been established ( 5.2 )
Dosage and administration
Indicated Population Initial Dose Titration Schedule Recommended Dose Maximum Dose ADHD (Adults and pediatric patients 6 years and older) ( 2.2 ) 30 mg every morning 10 mg or 20 mg weekly 30 mg to 70 mg per day 70 mg per day BED (Adults) ( 2.3 ) 30 mg every morning 20 mg weekly 50 mg to 70 mg per day 70 mg per day
• Prior to treatment, assess for presence of cardiac disease ( 2.4 )
• Severe renal impairment: Maximum dose is 50 mg/day ( 2.5 )
• End stage renal disease (ESRD): Maximum dose is 30 mg/day ( 2.5 ) 2.1 Pretreatment Screening Prior to treating patients with ARYNTA, 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 and Precautions ( 5.2 )] .
• the family history and clinically evaluate patients for motor or verbal tics or Tourette's syndrome before initiating ARYNTA [see Warnings and Precautions ( 5.8 )] . 2.2 General Administration Information Take ARYNTA orally in the morning with or without food; avoid afternoon doses because of the potential for insomnia. Instruct caregivers/patients to read the ‘Instructions for Use’ for complete administration instructions.
• Use the oral dosing syringe and bottle adapter provided with ARYNTA.
• Ensure that the bottle adapter is firmly inserted into the bottle before first use and keep the adapter in place for the duration of the usage of the bottle.
• Throw away (discard) any remaining ARYNTA 30 days after first opening the bottle. 2.3 Dosage for Treatment of ADHD The recommended starting dosage in adults and pediatric patients 6 years and older is 30 mg once daily in the morning. Dosage may be adjusted in increments of 10 mg or 20 mg at approximately weekly intervals up to maximum recommended dosage of 70 mg once daily [see Clinical Studies ( 14.1 )] . 2.4 Dosage for Treatment of Moderate to Severe BED in Adults The recommended starting dosage in adults is 30 mg once daily to be titrated in increments of 20 mg at approximately weekly intervals to achieve the recommended target dose of 50 mg to 70 mg once daily. The maximum recommended dosage is 70 mg once daily [see Clinical Studies ( 14.2 )]. Discontinue ARYNTA if binge eating does not improve. 2.5 Dosage in Patients with Renal Impairment In patients with severe renal impairment (GFR 15 to < 30 mL/min/1.73 m 2 ), the maximum dosage should not exceed 50 mg once daily. In patients with end stage renal disease (ESRD, GFR < 15 mL/min/1.73 m 2 ), the maximum recommended dosage is 30 mg once daily [see Use in Specific Populations ( 8.6 )] . 2.6 Dosage Modifications due to Drug Interactions Agents that alter urinary pH can impact urinary excretion and alter blood levels of amphetamine. Acidifying agents (e.g., ascorbic acid) decrease blood levels, while alkalinizing agents (e.g., sodium bicarbonate) increase blood levels. Adjust ARYNTA dosage accordingly [see Drug Interactions ( 7.1 )] .
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS ARYNTA oral solution 10 mg/mL is supplied as a clear colorless solution. Oral solution: 10 mg/mL.
Contraindications
4 CONTRAINDICATIONS ARYNTA is contraindicated in patients with:
• Known hypersensitivity to amphetamine products or other ingredients of ARYNTA. Anaphylactic reactions, Stevens-Johnson Syndrome, angioedema, and urticaria have been observed in postmarketing reports [see Adverse Reactions ( 6.2 )].
• 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 Precautions ( 5.7 ) and Drug Interactions ( 7.1 )].
• Known hypersensitivity to amphetamine products or other ingredients in ARYNTA ( 4 )
• Use with monoamine oxidase (MAO) inhibitor, 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 ARYNTA, screen patients for risk factors for developing a manic episode. If new psychotic or manic symptoms occur, consider discontinuing ARYNTA. ( 5.4 )
• Long-Term Suppression of Growth in Pediatric Patients : Closely monitor growth (height and weight) in pediatric patients. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted. ( 5.5 )
• Peripheral Vasculopathy, including Raynaud's phenomenon : Careful observation for digital changes is necessary during ARYNTA treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy. ( 5.6 )
• Serotonin Syndrome : Increased risk when co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. If it occurs, discontinue ARYNTA and initiate supportive treatment. ( 4 , 5.7 , 10 )
• Motor and Verbal Tics, and Worsening of Tourette's Syndrome : Before initiating ARYNTA, 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. Discontinue treatment if clinically appropriate. ( 5.8 ) 5.1 Abuse, Misuse, and Addiction ARYNTA has a high potential for abuse and misuse. The use of ARYNTA exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. ARYNTA can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence ( 9.2 )] . Misuse and abuse of CNS stimulants, including ARYNTA, can result in overdose and death [see Overdosage ( 10 )] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing ARYNTA, 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 ARYNTA in a safe place, preferably locked, and instruct patients to not give ARYNTA to anyone else. Throughout ARYNTA treatment, reassess each patient's risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction. 5.2 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 stimulants at the recommended ADHD dosage. Avoid ARYNTA use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 5.3 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 ARYNTA -treated patients for potential tachycardia and hypertension. 5.4 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 Disorder CNS stimulants may induce a manic or mixed episode. Prior to initiating ARYNTA 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, and depression). New Psychotic or Manic Symptoms CNS stimulants, at the recommended dosage, 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 to 0% of placebo-treated patients. If such symptoms occur, consider discontinuing ARYNTA. 5.5 Long-Term Suppression of Growth in Pediatric Patients ARY NTA is not approved for use and is not recommended in pediatric patients below 6 years of age [see Use in Specific Populations ( 8.4 )] . CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. In a 4-week, placebo-controlled trial of ARYNTA in pediatric patients ages 6 to 12 years old with ADHD, there was a dose-related decrease in weight in the ARYNTA groups compared to weight gain in the placebo group. Additionally, in studies of another stimulant, there was slowing of the increase in height [see Adverse Reactions ( 6.1 )] . Closely monitor growth (weight and height) in ARYNTA-treated pediatric patients. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. 5.6 Peripheral Vasculopathy, including Raynaud's Phenomenon CNS stimulants, including ARYNTA, 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 the therapeutic dosages 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.
Side effects
The following adverse reactions are discussed in greater detail in other sections of the labeling:
• Known hypersensitivity to amphetamine products or other ingredients of ARYNTA [see Contraindications ( 4 )]
• Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications ( 4 ) and Drug Interactions ( 7.1 )]
• Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions ( 5.1 ), and Drug Abuse and Dependence ( 9.2 , 9.3 )]
• 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 )]
• Serotonin Syndrome [see Warnings and Precautions ( 5.7 )]
• Motor and Verbal Tics, and Worsening of Tourette's Syndrome [see Warnings and Precautions ( 5.8 )] Most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) in pediatric patients ages 6 to 17 years, and/or adults with ADHD were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting. ( 6.1 ) Most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) in adults with BED were dry mouth, insomnia, decreased appetite, increased heart rate, constipation, feeling jittery, and anxiety. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc., at 1-800-461-7449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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 practice. Attention Deficit Hyperactivity Disorder The safety data in this section is based on data from the 4-week controlled parallel-group clinical studies of Lisdexamfetamine Dimesylate in pediatric and adult patients with ADHD [see Clinical Studies ( 14.1 )]. Adverse Reactions Associated with Discontinuation of Treatment in ADHD Clinical Trials In the controlled trial in pediatric patients ages 6 to 12 years (Study 1), 8% (18/218) of ARYNTA-treated patients discontinued due to adverse reactions compared to 0% (0/72) of placebo-treated patients. The most frequently reported adverse reactions (1% or more and twice rate of placebo) were ECG voltage criteria for ventricular hypertrophy, tic, vomiting, psychomotor hyperactivity, insomnia, decreased appetite and rash [2 instances for each adverse reaction, i.e., 2/218 (1%)]. Less frequently reported adverse reactions (less than 1% or less than twice rate of placebo) included abdominal pain upper, dry mouth, weight decreased, dizziness, somnolence, logorrhea, chest pain, anger and hypertension. In the controlled trial in pediatric patients ages 13 to 17 years (Study 4), 3% (7/233) of ARYNTA-treated patients discontinued due to adverse reactions compared to 1% (1/77) of placebo-treated patients. The most frequently reported adverse reactions (1% or more and twice rate of placebo) were decreased appetite (2/233; 1%) and insomnia (2/233; 1%). Less frequently reported adverse reactions (less than 1% or less than twice rate of placebo) included irritability, dermatillomania, mood swings, and dyspnea. In the controlled adult trial (Study 7), 6% (21/358) of ARYNTA-treated patients discontinued due to adverse reactions compared to 2% (1/62) of placebo-treated patients. The most frequently reported adverse reactions (1% or more and twice rate of placebo) were insomnia (8/358; 2%), tachycardia (3/358; 1%), irritability (2/358; 1%), hypertension (4/358; 1%), headache (2/358; 1%), anxiety (2/358; 1%), and dyspnea (3/358; 1%). Less frequently reported adverse reactions (less than 1% or less than twice rate of placebo) included palpitations, diarrhea, nausea, decreased appetite, dizziness, agitation, depression, paranoia and restlessness. Adverse Reactions Occurring at an Incidence of ≥5% or More Among ARYNTA Treated Patients with ADHD in Clinical Trials The most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) reported in pediatric patients ages 6 to 17 years, and/or adults were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting. Adverse Reactions Occurring at an Incidence of 2% or More Among ARYNTA Treated Patients with ADHD in Clinical Trials Adverse reactions reported in the controlled trials in pediatric patients ages, 6 to 12 years (Study 1), pediatric patients ages 13 to 17 years (Study 4), and adult patients (Study 7) treated with ARYNTA or placebo are presented in Tables 1, 2 and 3 below.
Drug interactions
Acidifying and Alkalinizing Agents : Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Adjust ARYNTA dosage accordingly. ( 2.6 , 7.1 ) 7.1 Drugs Having Clinically Important Interactions with Amphetamines Table 5 Drugs Having Clinically Important Interactions with Amphetamines MAO Inhibitors (MAOI) Prevention or Management Do not administer ARYNTA during or within 14 days following the administration of MAOI [see Contraindications ( 4 )] . Mechanism and Clinical Effect(s) 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. Serotonergic Drugs Prevention or Management Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during ARYNTA initiation or dosage increase. If serotonin syndrome occurs, discontinue ARYNTA and the concomitant serotonergic drug(s) [see Warnings and Precautions ( 5.7 )] . Mechanism and Clinical Effect(s) The concomitant use of lisdexamfetamine dimesylate and serotonergic drugs increases the risk of serotonin syndrome. CYP2D6 Inhibitors Prevention or Management Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during ARYNTA initiation and after a dosage increase. If serotonin syndrome occurs, discontinue ARYNTA and the CYP2D6 inhibitor [see Warnings and Precautions ( 5.7 ) and Overdosage ( 10 )]. Mechanism and Clinical Effect(s) The concomitant use of lisdexamfetamine dimesylate and CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of lisdexamfetamine dimesylate compared to the use of the drug alone and increase the risk of serotonin syndrome. Alkalinizing Agents Prevention or Management Co-administration of ARYNTA and urinary alkalinizing agents should be avoided. Mechanism and Clinical Effect(s) Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. Acidifying Agents Prevention or Management Increase dose based on clinical response. Mechanism and Clinical Effect(s) Urinary acidifying agents can lower blood levels and efficacy of amphetamines. Tricyclic Antidepressants Prevention or Management Monitor frequently and adjust or use alternative therapy based on clinical response. Mechanism and Clinical Effect(s) 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.
Use in specific populations
• Pregnancy : May cause fetal harm ( 8.1 )
• Lactation : Breastfeeding not recommended ( 8.2 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/adhd-medications/. Risk Summary The limited available data from published literature and postmarketing reports on use of ARYNTA 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 animal reproduction studies, lisdexamfetamine dimesylate (a prodrug of d-amphetamine) had no effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis. Pre- and postnatal studies were not conducted with lisdexamfetamine dimesylate. However, amphetamine (d- to l- ratio of 3:1) administration 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 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Amphetamines, such as ARYNTA, 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 Lisdexamfetamine dimesylate had no apparent effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 40 and 120 mg/kg/day, respectively. These doses are approximately 5.5 and 33 times, respectively, the maximum recommended human dose (MRHD) of 70 mg/day given to adults, on a mg/m2 body surface area basis. A 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. 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. 8.2 Lactation Risk Summary Lisdexamfetamine is a pro-drug of dextroamphetamine. Based on limited case reports in published literature, amphetamine ( d -or d , l -) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. There are no reports of adverse effects on the breastfed infant. Long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. It is possible that large dosages of dextroamphetamine might interfere with milk production, especially in women whose lactation is not well established. Because of the potential for serious adverse reactions in nursing infants, including serious cardiovascular reactions, blood pressure and heart rate increase, suppression of growth, and peripheral vasculopathy, advise patients that breastfeeding is not recommended during treatment with ARYNTA. 8.4 Pediatric Use The safety and effectiveness of ARYNTA have not been established in pediatric patients below the age of 6 years. ADHD Safety and effectiveness of ARYNTA have been established in pediatric patients with ADHD ages 6 to 17 years [see Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.1 )]. Safety and efficacy of lisdexamfetamine dimesylate were evaluated in a double-blind, randomized, parallel-group, placebo-controlled, fixed-dose study in pediatric patients ages 4 to 5 years with ADHD, followed by a 1-year open-label extension study.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/adhd-medications/. Risk Summary The limited available data from published literature and postmarketing reports on use of ARYNTA 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 animal reproduction studies, lisdexamfetamine dimesylate (a prodrug of d-amphetamine) had no effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis. Pre- and postnatal studies were not conducted with lisdexamfetamine dimesylate. However, amphetamine (d- to l- ratio of 3:1) administration 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 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Amphetamines, such as ARYNTA, 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 Lisdexamfetamine dimesylate had no apparent effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 40 and 120 mg/kg/day, respectively. These doses are approximately 5.5 and 33 times, respectively, the maximum recommended human dose (MRHD) of 70 mg/day given to adults, on a mg/m2 body surface area basis. A 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. 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.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of ARYNTA have not been established in pediatric patients below the age of 6 years. ADHD Safety and effectiveness of ARYNTA have been established in pediatric patients with ADHD ages 6 to 17 years [see Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.1 )]. Safety and efficacy of lisdexamfetamine dimesylate were evaluated in a double-blind, randomized, parallel-group, placebo-controlled, fixed-dose study in pediatric patients ages 4 to 5 years with ADHD, followed by a 1-year open-label extension study. In these studies, patients experienced elevated rates of adverse reactions, including weight loss, decreased BMI, decreased appetite, insomnia, infections (upper respiratory and nasopharyngitis), irritability, and affect lability. With the same lisdexamfetamine dimesylate dose, mean steady state exposure of dextroamphetamine was approximately 44% higher in pediatric patients ages 4 to 5 years compared to the pediatric patients ages 6 to 11 years. BED Safety and effectiveness of ARYNTA have not been established in pediatric patients with BED less than 18 years of age. Growth Suppression Growth should be monitored during treatment with stimulants, including ARYNTA, and pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions ( 5.5 ) and Adverse Reactions ( 6.1 )]. Juvenile Animal Data Studies conducted in juvenile rats and dogs at clinically relevant doses showed growth suppression that partially or fully reversed in dogs and female rats but not in male rats after a four-week drug-free recovery period. A study was conducted in which juvenile rats received oral doses of 4, 10, or 40 mg/kg/day of lisdexamfetamine dimesylate from day 7 to day 63 of age. These doses are approximately 0.3, 0.7, and 3 times the maximum recommended human daily dose of 70 mg on a mg/m 2 basis for a child. Dose-related decreases in food consumption, bodyweight gain, and crown-rump length were seen; after a four-week drug-free recovery period, bodyweights and crown-rump lengths had significantly recovered in females but were still substantially reduced in males. Time to vaginal opening was delayed in females at the highest dose, but there were no drug effects on fertility when the animals were mated beginning on day 85 of age. In a study in which juvenile dogs received lisdexamfetamine dimesylate for 6 months beginning at 10 weeks of age, decreased bodyweight gain was seen at all doses tested (2, 5, and 12 mg/kg/day, which are approximately 0.5, 1, and 3 times the maximum recommended human daily dose on a mg/m 2 basis for a child). This effect partially or fully reversed during a four-week drug-free recovery period.
Geriatric use
8.5 Geriatric Use Clinical studies of lisdexamfetamine dimesylate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience and pharmacokinetic data [see Clinical Pharmacology ( 12.3 )] have not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
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. The pharmacokinetic profile of ARYNTA should be considered when treating patients with overdose. Lisdexamfetamine and d-amphetamine are not dialyzable. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
Description
(lisdexamfetamine dimesylate), is a CNS stimulant. The chemical designation for lisdexamfetamine dimesylate is (2S)-2,6-diamino-N-[(1S)-1-methyl-2-phenylethyl] hexanamide dimethanesulfonate. The molecular formula is C 15 H 25 N 3 O∙(CH 4 O 3 S) 2 , which corresponds to a molecular weight of 455.60. The chemical structure is: Lisdexamfetamine dimesylate is a white to off-white powder that is soluble in water (792 mg/mL). The pH is 4.24. The pKa values are 10.21 and 15.89. ARYNTA oral solution is a clear colorless solution, contains 10 mg/mL of lisdexamfetamine dimesylate (equivalent to 5.8 mg of lisdexamfetamine). Inactive ingredients: dibasic sodium phosphate dihydrate, methylparaben sodium, monobasic sodium phosphate dihydrate, propylparaben sodium, propylene glycol, saccharin sodium, hydrochloric acid, sodium hydroxide and purified water. Lisdex Structure
Mechanism of action
12.1 Mechanism of Action Lisdexamfetamine is a prodrug of dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The exact mode of therapeutic action in ADHD and BED is not known.
How supplied
16.1 How Supplied ARYNTA oral solution is a clear colorless solution contains 10 mg/mL of lisdexamfetamine dimesylate. It is packaged in 100 mL PET bottles with a child resistant closure and in 30 mL, 60 mL, 90 mL, 120 mL HDPE bottles with child resistant closures as follows: Each sealed bottle is co-packaged with one press-in bottle adapter and one oral dosing syringe. NDC Number Size 24338-019-01 100 mL 24338-103-01 30 mL 24338-160-01 60 mL 24338-109-01 90 mL 24338-162-01 120 mL 16.2 Storage and Handling ARYNTA is stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep the container tightly closed. Throw away (discard) any remaining ARYNTA 30 days after first opening the bottle.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Abuse, Misuse, and Addiction Educate patients and their families about the risks of abuse, misuse, and addiction of ARYNTA, which can lead to overdose and death, and proper disposal of any unused drug [see Warnings And Precautions (5.1), Drug Abuse and Dependence ( 9.2 ), Overdosage ( 10 )] . Advise patients to store ARYNTA in a safe place, preferably locked, and instruct patients to not give ARYNTA 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 ARYNTA 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 and Precautions ( 5.2 )]. Increased Blood Pressure and Heart Rate Instruct patients that ARYNTA can cause elevations of their blood pressure and pulse rate and they should be monitored for such effects. Psychiatric Adverse Reactions Advise patients that ARYNTA at recommended doses may cause psychotic or manic symptoms even in patients without prior history of psychotic symptoms or mania [see Warnings and Precautions ( 5.4 )]. Long-Term Suppression of Growth in Pediatric Patients Advise patients that ARYNTA may cause slowing of growth including weight loss [see Warnings and Precautions ( 5.5 )] . Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon] Instruct patients beginning treatment with ARYNTA 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 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 ARYNTA. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients [see Warnings and Precautions ( 5.6 )]. Serotonin Syndrome Caution patients about the risk of serotonin syndrome with concomitant use of ARYNTA 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 ( 4 ), Warnings and Precautions ( 5.7 ) and Drug Interactions ( 7.1 )] . Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome. Concomitant Medications Advise patients to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs because there is a potential for interactions [see Drug Interactions ( 7.1 )]. 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 ARYNTA. Instruct patients to notify their healthcare provider if emergence of new tics or worsening of tics or Tourette's syndrome occurs [see Warnings and Precautions ( 5.8 )]. Pregnancy Registry Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARYNTA during pregnancy [see Use in Specific Populations ( 8.1 )]. Pregnancy Advise patients of the potential fetal effects from the use of ARYNTA during pregnancy. Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with ARYNTA [see Use in Specific Populations ( 8.1 )]. Lactation Advise women not to breastfeed if they are taking ARYNTA [see Use in Specific Populations ( 8.2 )]. Manufactured for: Azurity Pharmaceuticals, Inc. Woburn, MA 01801 This products labeling may have been updated. For current Full Prescribing Information, please visit www.arynta.com. PN: #####-##### Rev: 04; 12/2025 INSTRUCTIONS FOR USE ARYNTA TM (AH-RIN-TAH) (lisdexamfetamine dimesylate) oral solution, CII This Instructions for Use contains information on how to measure and take a dose of ARYNTA. Important Information You Need to Know Before Taking ARYNTA:
• ARYNTA is for oral use only (taken by mouth).
• Take ARYNTA with or without food.
• Use the oral dosing syringe and bottle adapter that come with ARYNTA to measure and take a dose of ARYNTA.
• Check the expiration date (EXP) on the carton label. Do not take ARYNTA after the expiration date has passed. Call your healthcare provider or pharmacist if your medicine is expired.
• Record the date you first opened the bottle on the space provided on the bottle. Throw away (discard) any remaining ARYNTA 30 days after first opening the bottle. See “ Disposing of ARYNTA ” below. Supplies included in the ARYNTA carton (See Figure A):
• 1 bottle of ARYNTA
• 1 oral dosing syringe
• 1 bottle adapter
• 1 Prescribing Information with Medication Guide
• 1 Instructions for Use Step 1: Preparing to take ARYNTA
• Wash and dry your hands (see Figure B).
• Remove the tamper evident seal from the carton.
• Take the ARYNTA bottle, 1 oral dosing syringe, 1 bottle adapter, 1 Prescribing Information with Medication Guide, and 1 Instructions for Use out of the carton. Tell your pharmacist right away if you are missing any supplies from the carton. Step 2:
• Place the ARYNTA bottle on a flat surface like a table or countertop and remove the child resistant cap by pressing down and turning counterclockwise (see Figure C).
Label text from the FDA structured product label by Azurity Pharmaceuticals, Inc. (revised Jul 30, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Lisdexamfetamine Dimesylate in 5 products
Arynta NDC products (5)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 24338-019 | Lisdexamfetamine Dimesylate 10 mg/mL Solution | Azurity Pharmaceuticals, Inc. | NDA · DEA CII |
| 24338-103 | Lisdexamfetamine Dimesylate 10 mg/mL Solution | Azurity Pharmaceuticals, Inc. | NDA · DEA CII |
| 24338-109 | Lisdexamfetamine Dimesylate 10 mg/mL Solution | Azurity Pharmaceuticals, Inc. | NDA · DEA CII |
| 24338-160 | Lisdexamfetamine Dimesylate 10 mg/mL Solution | Azurity Pharmaceuticals, Inc. | NDA · DEA CII |
| 24338-162 | Lisdexamfetamine Dimesylate 10 mg/mL Solution | Azurity Pharmaceuticals, Inc. | NDA · DEA CII |
Frequently asked questions
What is Arynta used for?
1 INDICATIONS AND USAGE ARYNTA is indicated for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older [see Clinical Studies ( 14.1 )] Moderate to severe binge eating disorder (BED) in adults [see Clinical Studies ( 14.2 )] . Limitations of Use: The use of ARYNTA is not recommended in pediatric patients younger than 6 years of age…
What are the side effects of Arynta?
The following adverse reactions are discussed in greater detail in other sections of the labeling: • Known hypersensitivity to amphetamine products or other ingredients of ARYNTA [see Contraindications ( 4 )] • Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications ( 4 ) and Drug Interactions ( 7.1 )] • Abuse, Misuse, and Addiction [see Boxed Warning,… See the full label for the complete list.
Who makes Arynta?
Arynta is listed by 1 labeler in the FDA NDC directory, including Azurity Pharmaceuticals, Inc..