LISDEXAMFETAMINE DIMESYLATE capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

Lisdexamfetamine Dimesylate (UNII: SJT761GEGS) (Lisdexamfetamine - UNII:H645GUL8KJ)

Available from:

Apotex Corp.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Lisdexamfetamine dimesylate capsules are 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: - Pediatric patients with ADHD younger than 6 years of age experienced more long-term weight loss than patients 6 years and older [see Use in Specific Populations (8.4)] . - Lisdexamfetamine dimesylate capsules are 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 lisdexamfetamine dimesylate capsules for the treatment of obesity have not been established [see Warnings and Precautions (5.2)] . Lisdexamfetamine dimesylate capsules are contraindicated in patients with: - Known hypersensitivity to amphetamine products or other ingredients of lisdexamfetamine dimesylate capsules. 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)] . 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%20researchprograms/pregnancyregistry/adhd-medications/. Risk Summary The limited available data from published literature and postmarketing reports on use of lisdexamfetamine dimesylate capsules 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 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Amphetamines, such as lisdexamfetamine dimesylate 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 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. 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 lisdexamfetamine dimesylate capsules. ADHD Safety and effectiveness of lisdexamfetamine dimesylate capsules 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 effectiveness of lisdexamfetamine dimesylate capsules have not been established in pediatric patients below the age of 6 years. Safety and efficacy of lisdexamfetamine dimesylate capsules 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 capsules 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 lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate capsules, 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/m2 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/m2  basis for a child). This effect partially or fully reversed during a four- week drug-free recovery period. Clinical studies of lisdexamfetamine dimesylate capsules 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. Due to reduced clearance in patients with severe renal impairment (GFR 15 to < 30 mL/min/1.73 m2 ), the maximum dose should not exceed 50 mg/day. The maximum recommended dose in ESRD (GFR < 15 mL/min/1.73 m2 ) patients is 30 mg/day [see Clinical Pharmacology (12.3)] . Lisdexamfetamine and d-amphetamine are not dialyzable. Lisdexamfetamine dimesylate capsules contains lisdexamfetamine, a prodrug of amphetamine, a Schedule II controlled substance. Lisdexamfetamine dimesylate capsules has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see Warnings and Precautions (5.1)]. Lisdexamfetamine dimesylate capsules 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 lisdexamfetamine, a prodrug of amphetamine, may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including lisdexamfetamine dimesylate capsules, 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. Studies of Lisdexamfetamine Dimesylate Capsules in Drug Abusers A randomized, double-blind, placebo-control, cross-over, abuse liability study in 38 patients with a history of drug abuse was conducted with single-doses of 50, 100, or 150 mg of lisdexamfetamine dimesylate capsules, 40 mg of immediate-release d-amphetamine sulphate (a controlled II substance), and 200 mg of diethylpropion hydrochloride (a controlled IV substance). Lisdexamfetamine dimesylate capsules 100 mg produced significantly less “Drug Liking Effects” as measured by the Drug Rating Questionnaire-Subject score, compared to d-amphetamine 40 mg; and 150 mg of lisdexamfetamine dimesylate capsules demonstrated similar “Drug-Liking Effects” compared to 40 mg of d-amphetamine and 200 mg of diethylpropion. Intravenous administration of 50 mg lisdexamfetamine dimesylate to individuals with a history of drug abuse produced positive subjective responses on scales measuring "Drug Liking", "Euphoria", "Amphetamine Effects", and "Benzedrine Effects" that were greater than placebo but less than those produced by an equivalent dose (20 mg) of intravenous d-amphetamine. Physical Dependence Lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate capsules include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.   Tolerance Lisdexamfetamine dimesylate capsules 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).

Product summary:

Lisdexamfetamine Dimesylate Capsules are supplied as follows: Capsules 10 mg: Hard gelatin capsule with EEC pink opaque body and EEC pink opaque cap. Imprinted APO L10 in black ink. White to off-white granular fill. Bottles of 100, NDC 60505-4739-01   Capsules 20 mg: Hard gelatin capsule with ivory opaque body and ivory opaque cap. Imprinted APO L20 in black ink. White to off-white granular fill. Bottles of 100, NDC 60505-4740-01   Capsules 30 mg: Hard gelatin capsule with white opaque body and orange opaque cap. Imprinted APO L30 in black ink. White to off-white granular fill.   Bottles of 100, NDC 60505-4741-01   Capsules 40 mg: Hard gelatin capsule with white opaque body and dark green opaque cap. Imprinted APO L40 in black ink. White to off-white granular fill.   Bottles of 100, NDC 60505-4742-01   Capsules 50 mg: Hard gelatin capsule with white opaque body and light blue opaque cap. Imprinted APO L50 in black ink. White to off-white granular fill.   Bottles of 100, NDC 60505-4743-01   Capsules 60 mg: Hard gelatin capsule with aqua blue opaque body and aqua blue opaque cap. Imprinted APO L60 in black ink. White to off-white granular fill.   Bottles of 100, NDC 60505-4744-01   Capsules 70 mg: Hard gelatin capsule with light blue opaque body and medium orange opaque cap. Imprinted APO L70 in black ink. White to off-white granular fill.   Bottles of 100, NDC 60505-4745-01 Dispense in a tight, light-resistant container as defined in the USP. Store at room temperature, 20ºC to 25ºC (68ºF to 77ºF). Excursions permitted between 15ºC and 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

LISDEXAMFETAMINE DIMESYLATE- LISDEXAMFETAMINE DIMESYLATE CAPSULE
Apotex Corp.
----------
MEDICATION GUIDE
LisdexamfetamineDimesylate (lis dex”am fet’ a meen dye mes’ i
late) Capsules, CII
Medication Guide available at
https://www.apotex.com/products/us/mg.asp
What is the most important information I should know about
lisdexamfetamine dimesylate capsules?
Lisdexamfetamine dimesylate capsules may cause serious side effects,
including:
•
Abuse, misuse, and addiction.Lisdexamfetamine dimesylate capsules has
a high chance for abuse
and misuse and may lead to substance use problems, including
addiction. Misuse and abuse of
lisdexamfetamine dimesylate capsules, other amphetamine containing
medicines, and
methylphenidate containing medicines, can lead to overdose and death.
The risk of overdose and
death is increased with higher doses of lisdexamfetamine dimesylate
capsules or when it is used in
ways that are not approved, such as snorting or injection.
•
Your healthcare provider should check you or your child’s risk for
abuse, misuse, and addiction
before starting treatment with lisdexamfetamine dimesylate capsules
and will monitor you or your
child during treatment.
•
Lisdexamfetamine dimesylate capsules may lead to physical dependence
after prolonged use, even
if taken as directed by your healthcare provider.
•
Do not give lisdexamfetamine dimesylate capsules to anyone else. See
“What is lisdexamfetamine
dimesylate capsules?” for more information.
•
Keep lisdexamfetamine dimesylate capsules in a safe place and properly
dispose of any unused
medicine. See "How should I store lisdexamfetamine dimesylate
capsules?" for more information.
•
Tell your healthcare provider if you or your child have ever abused or
been dependent on alcohol,
prescription medicines, or street drugs.
•
Risks for people with serious heart disease. Sudden death has happened
in people who have heart
defects or other serious heart disease.
Your healthcare provider should check you or your child carefully for
heart problems b

Summary of Product characteristics

LISDEXAMFETAMINE DIMESYLATE- LISDEXAMFETAMINE DIMESYLATE CAPSULE
APOTEX CORP.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LISDEXAMFETAMINE
DIMESYLATE CAPSULES SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
LISDEXAMFETAMINE DIMESYLATE CAPSULES.
LISDEXAMFETAMINE DIMESYLATE CAPSULES, FOR ORAL USE, CII
INITIAL U.S. APPROVAL: 2007
WARNING: ABUSE, MISUSE, AND ADDICTION
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
LISDEXAMFETAMINE DIMESYLATE CAPSULES 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 LISDEXAMFETAMINE
DIMESYLATE CAPSULES,
CAN RESULT IN OVERDOSE AND DEATH (5.1, 9.2, 10):
BEFORE PRESCRIBING LISDEXAMFETAMINE DIMESYLATE CAPSULES, 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 TREATMENT, REASSESS EACH PATIENT’S RISK AND FREQUENTLY
MONITOR FOR SIGNS
AND SYMPTOMS OF ABUSE, MISUSE, AND ADDICTION.
RECENT MAJOR CHANGES
Boxed Warning 10/2023
Dosage and Administration (2.1) 10/2023
Warnings and Precautions (5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.8) 10/2023
INDICATIONS AND USAGE
Lisdexamfetamine dimesylate capsules are 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:
Pediatric patients with ADHD younger than 6 years of age experienced
more long-term weight
loss than patients 6 years and older (8.4)
Lisdexamfetamine dimesylate capsules are 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 lisdexamfetamine dimesylate
capsules for