FDA Label for Lisdexamfetamine Dimesylate
View Indications, Usage & Precautions
- WARNING: ABUSE AND DEPENDENCE
- 2.1 PRE-TREATMENT SCREENING
- 2.2 GENERAL INSTRUCTIONS FOR USE
- 2.3 DOSAGE FOR TREATMENT OF ADHD
- 2.4 DOSAGE FOR TREATMENT OF MODERATE TO SEVERE BED IN ADULTS
- 2.5 DOSAGE IN PATIENTS WITH RENAL IMPAIRMENT
- 2.6 DOSAGE MODIFICATIONS DUE TO DRUG INTERACTIONS
- 4 CONTRAINDICATIONS
- 5.1 POTENTIAL FOR ABUSE AND DEPENDENCE
- 5.2 SERIOUS CARDIOVASCULAR REACTIONS
- 5.3 BLOOD PRESSURE AND HEART RATE INCREASES
- 5.5 SUPPRESSION OF GROWTH
- 5.6 PERIPHERAL VASCULOPATHY, INCLUDING RAYNAUD'S PHENOMENON
- 5.7 SEROTONIN SYNDROME
- 6 ADVERSE REACTIONS
- 6.1 CLINICAL TRIALS EXPERIENCE
- 6.2 POSTMARKETING EXPERIENCE
- 7.1 DRUGS HAVING CLINICALLY IMPORTANT INTERACTIONS WITH AMPHETAMINES
- 7.2 DRUGS HAVING NO CLINICALLY IMPORTANT INTERACTIONS WITH LISDEXAMFETAMINE DIMESYLATE CAPSULES
- 8.5 GERIATRIC USE
- 8.6 RENAL IMPAIRMENT
- 9.1 CONTROLLED SUBSTANCE
- 9.2 ABUSE
- 10 OVERDOSAGE
- 11 DESCRIPTION
- 12.1 MECHANISM OF ACTION
- 12.2 PHARMACODYNAMICS
- 12.3 PHARMACOKINETICS
- 13.2 ANIMAL TOXICOLOGY AND/OR PHARMACOLOGY
- 14.2 BINGE EATING DISORDER (BED)
- 16.2 STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
- PRINCIPAL DISPLAY PANEL - 10 MG CAPSULE BOTTLE LABEL
- PRINCIPAL DISPLAY PANEL - 20 MG CAPSULE BOTTLE LABEL
- PRINCIPAL DISPLAY PANEL - 30 MG CAPSULE BOTTLE LABEL
- PRINCIPAL DISPLAY PANEL - 40 MG CAPSULE BOTTLE LABEL
- PRINCIPAL DISPLAY PANEL - 50 MG CAPSULE BOTTLE LABEL
- PRINCIPAL DISPLAY PANEL - 60 MG CAPSULE BOTTLE LABEL
- PRINCIPAL DISPLAY PANEL - 70 MG CAPSULE BOTTLE LABEL
Lisdexamfetamine Dimesylate Product Label
The following document was submitted to the FDA by the labeler of this product Lannett Company, Inc.. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.
Warning: Abuse And Dependence
CNS stimulants, including lisdexamfetamine dimesylate capsules, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy [see Warnings and Precautions (5.1), and Drug Abuse and Dependence (9.2, 9.3)].
2.1 Pre-Treatment Screening
Prior to treating patients with CNS stimulants, including lisdexamfetamine dimesylate capsules, assess for the presence of cardiac disease (e.g., a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)].
To reduce the abuse of CNS stimulants including lisdexamfetamine dimesylate capsules, assess the risk of abuse, prior to prescribing. After prescribing, keep careful prescription records, educate patients about abuse, monitor for signs of abuse and overdose, and re-evaluate the need for lisdexamfetamine dimesylate capsules use [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9)].
2.2 General Instructions For Use
Take lisdexamfetamine dimesylate capsules by mouth in the morning with or without food; avoid afternoon doses because of the potential for insomnia. Lisdexamfetamine dimesylate capsules may be administered in one of the following ways:
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 lisdexamfetamine dimesylate capsules 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 m2), the maximum dosage should not exceed 50 mg once daily. In patients with end stage renal disease (ESRD, GFR < 15 mL/min/1.73 m2), 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 lisdexamfetamine dimesylate capsules dosage accordingly [see Drug Interactions (7.1)].
4 Contraindications
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)].
5.1 Potential For Abuse And Dependence
CNS stimulants, including lisdexamfetamine dimesylate capsules, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Drug Abuse and Dependence (9.2, 9.3)].
5.2 Serious Cardiovascular Reactions
Sudden death, stroke, and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during lisdexamfetamine dimesylate capsules treatment.
5.3 Blood Pressure And Heart Rate Increases
CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Monitor all patients for potential tachycardia and hypertension.
5.5 Suppression Of Growth
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including lisdexamfetamine dimesylate capsules. In a 4-week, placebo-controlled trial of lisdexamfetamine dimesylate capsules in pediatric patients ages 6 to 12 years old with ADHD, there was a dose-related decrease in weight in the lisdexamfetamine dimesylate capsules 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)].
Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. Lisdexamfetamine dimesylate capsule are not approved for use in pediatric patients below 6 years of age [see Use in Specific Populations (8.4)].
5.6 Peripheral Vasculopathy, Including Raynaud's Phenomenon
Stimulants, including lisdexamfetamine dimesylate capsules, are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
5.7 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 (7.1)]. The co-administration with cytochrome P450 2D6 (CYP2D6) inhibitors may also increase the risk with increased exposure to the active metabolite of lisdexamfetamine dimesylate capsules (dextroamphetamine). In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drug Interactions (7.1)].
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 lisdexamfetamine dimesylate capsules with MAOI drugs is contraindicated [see Contraindications (4)].
Discontinue treatment with lisdexamfetamine dimesylate capsules and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment. If concomitant use of lisdexamfetamine dimesylate capsules with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate lisdexamfetamine dimesylate capsules 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.
6 Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Known hypersensitivity to amphetamine products or other ingredients of lisdexamfetamine dimesylate capsules [see Contraindications (4)]
- Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications (4) and Drug Interactions (7.1)]
- Drug Dependence [see Boxed Warning, Warnings and Precautions (5.1), and Drug Abuse and Dependence (9.2, 9.3)]
- Serious Cardiovascular Reactions [see Warnings and Precautions (5.2)]
- Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3)]
- Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
- Suppression of Growth [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)]
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.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of lisdexamfetamine dimesylate capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events are as follows: cardiomyopathy, mydriasis, diplopia, difficulties with visual accommodation, blurred vision, eosinophilic hepatitis, anaphylactic reaction, hypersensitivity, dyskinesia, dysgeusia, tics, bruxism, depression, dermatillomania, alopecia, aggression, Stevens-Johnson Syndrome, chest pain, angioedema, urticaria, seizures, libido changes, frequent or prolonged erections, constipation, rhabdomyolysis, and intestinal ischemia.
7.1 Drugs Having Clinically Important Interactions With Amphetamines
MAO Inhibitors (MAOI) | |
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 lisdexamfetamine dimesylate capsules during or within 14 days following the administration of MAOI [see Contraindications (4)]. |
Serotonergic Drugs | |
Clinical Impact | The concomitant use of lisdexamfetamine dimesylate capsules 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 lisdexamfetamine dimesylate capsules initiation or dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the concomitant serotonergic drug(s) [see Warnings and Precautions (5.7)]. |
CYP2D6 Inhibitors | |
Clinical Impact | The concomitant use of lisdexamfetamine dimesylate capsules and CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of lisdexamfetamine dimesylate capsules compared to the use of the drug alone and increase the risk of serotonin syndrome. |
Intervention | Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during lisdexamfetamine dimesylate capsules initiation and after a dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the CYP2D6 inhibitor [see Warnings and Precautions (5.7) and Overdosage (10)]. |
Alkalinizing Agents | |
Clinical Impact | Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. |
Intervention | Co-administration of lisdexamfetamine dimesylate capsules and urinary alkalinizing agents should be avoided. |
Acidifying Agents | |
Clinical Impact | Urinary acidifying agents can lower blood levels and efficacy of amphetamines. |
Intervention | Increase dose based on clinical response. |
Tricyclic Antidepressants | |
Clinical Impact | 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. |
Intervention | Monitor frequently and adjust or use alternative therapy based on clinical response. |
7.2 Drugs Having No Clinically Important Interactions With Lisdexamfetamine Dimesylate Capsules
From a pharmacokinetic perspective, no dose adjustment of lisdexamfetamine dimesylate capsules is necessary when lisdexamfetamine dimesylate capsules are co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when lisdexamfetamine dimesylate capsules are co-administered [see Clinical Pharmacology (12.3)].
From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when lisdexamfetamine dimesylate capsules are co-administered [see Clinical Pharmacology (12.3)].
8.5 Geriatric Use
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.
8.6 Renal Impairment
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.
9.1 Controlled Substance
Lisdexamfetamine Dimesylate Capsules contain lisdexamfetamine, a prodrug of amphetamine, a Schedule II controlled substance.
9.2 Abuse
CNS stimulants, including lisdexamfetamine dimesylate capsules, other amphetamine-containing products, and methylphenidate have a high potential for abuse. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Abuse is characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving. 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 higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Both abuse and misuse may lead to addiction, and some individuals may develop addiction even when taking lisdexamfetamine dimesylate capsules as prescribed.
Signs and symptoms of amphetamine abuse may include increased heart rate, respiratory rate, blood pressure, and/or sweating, dilated pupils, hyperactivity, restlessness, insomnia, decreased appetite, loss of coordination, tremors, flushed skin, vomiting, and/or abdominal pain. Anxiety, psychosis, hostility, aggression, suicidal or homicidal ideation have also been seen. Abusers of CNS stimulants may chew, snort, inject, or use other unapproved routes of administration which can result in overdose and death [see Overdosage (10)].
To reduce the abuse of CNS stimulants, including lisdexamfetamine dimesylate capsules, assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and on proper storage and disposal of CNS stimulants. Monitor for signs of abuse while on therapy, and re-evaluate the need for lisdexamfetamine dimesylate capsules use.
10 Overdosage
Consult with a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice for treatment of overdosage. Individual patient response to amphetamines varies widely. Toxic symptoms may occur idiosyncratically at low doses.
Manifestations of amphetamine overdose include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis. Fatigue and depression usually follow the central nervous system stimulation. Serotonin syndrome has been reported with amphetamine use, including lisdexamfetamine dimesylate capsules. Cardiovascular effects include arrhythmias, hypertension or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.
Lisdexamfetamine and d-amphetamine are not dialyzable.
11 Description
Lisdexamfetamine Dimesylate Capsules, a CNS stimulant, is for once-a-day oral administration. The chemical designation for lisdexamfetamine dimesylate is (2S)-2,6-diamino-N-[(1S)-1-methyl-2-phenylethyl] hexanamide dimethanesulfonate. The molecular formula is C15H25N3O•(CH4O3S)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).
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.
12.2 Pharmacodynamics
Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine, does not bind to the sites responsible for the reuptake of norepinephrine and dopamine in vitro.
12.3 Pharmacokinetics
Pharmacokinetic studies after oral administration of lisdexamfetamine dimesylate have been conducted in healthy adult (capsule and Vyvanse chewable tablet formulations) and pediatric (6 to 12 years) patients with ADHD (capsule formulation). After single dose administration of lisdexamfetamine dimesylate, pharmacokinetics of dextroamphetamine was found to be linear between 30 mg and 70 mg in a pediatric study (6 to 12 years), and between 50 mg and 250 mg in an adult study. Dextroamphetamine pharmacokinetic parameters following administration of lisdexamfetamine dimesylate in adults exhibited low inter-subject (<25%) and intra-subject (<8%) variability. There is no accumulation of lisdexamfetamine and dextroamphetamine at steady state in healthy adults.
13.2 Animal Toxicology And/Or Pharmacology
Acute administration of high doses of amphetamine (d- or d, l-) has been shown to produce long-lasting neurotoxic effects, including irreversible nerve fiber damage, in rodents. The significance of these findings to humans is unknown.
14.2 Binge Eating Disorder (Bed)
A phase 2 study evaluated the efficacy of lisdexamfetamine dimesylate capsules 30, 50 and 70 mg/day compared to placebo in reducing the number of binge days/week in adults with at least moderate to severe BED. This randomized, double-blind, parallel-group, placebo-controlled, forced-dose titration study (Study 10) consisted of an 11-week double-blind treatment period (3 weeks of forced-dose titration followed by 8 weeks of dose maintenance). Lisdexamfetamine dimesylate capsules 30 mg/day was not statistically different from placebo on the primary endpoint. The 50 and 70 mg/day doses were statistically superior to placebo on the primary endpoint.
The efficacy of lisdexamfetamine dimesylate capsules in the treatment of BED was demonstrated in two 12-week randomized, double-blind, multi-center, parallel-group, placebo-controlled, dose-optimization studies (Study 11 and Study 12) in adults aged 18-55 years (Study 11: N=374, Study 12: N=350) with moderate to severe BED. A diagnosis of BED was confirmed using DSM-IV criteria for BED. Severity of BED was determined based on having at least 3 binge days per week for 2 weeks prior to the baseline visit and on having a Clinical Global Impression Severity (CGI-S) score of ≥4 at the baseline visit. For both studies, a binge day was defined as a day with at least 1 binge episode, as determined from the subject’s daily binge diary.
Both 12-week studies consisted of a 4-week dose-optimization period and an 8-week dose- maintenance period. During dose-optimization, subjects assigned to lisdexamfetamine dimesylate capsules began treatment at the titration dose of 30 mg/day and, after 1 week of treatment, were subsequently titrated to 50 mg/day. Additional increases to 70 mg/day were made as tolerated and clinically indicated. Following the dose-optimization period, subjects continued on their optimized dose for the duration of the dose-maintenance period.
The primary efficacy outcome for the two studies was defined as the change from baseline at Week 12 in the number of binge days per week. Baseline is defined as the weekly average of the number of binge days per week for the 14 days prior to the baseline visit. Subjects from both studies on lisdexamfetamine dimesylate capsules had a statistically significantly greater reduction from baseline in mean number of binge days per week at Week 12. In addition, subjects on lisdexamfetamine dimesylate capsules showed greater improvement as compared to placebo across key secondary outcomes with higher proportion of subjects rated improved on the CGI-I rating scale, higher proportion of subjects with 4-week binge cessation, and greater reduction in the Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) total score.
Study Number | Treatment Group | Primary Efficacy Measure: Binge Days per Week at Week 12 | ||
---|---|---|---|---|
Mean Baseline Score (SD) | LS Mean Change from Baseline (SE) | Placebo-subtracted Differencea (95% CI) | ||
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval. a Difference (drug minus placebo) in least-squares mean change from baseline. * Doses statistically significantly superior to placebo. | ||||
Study 11 | Lisdexamfetamine Dimesylate Capsules (50 or 70 mg/day)* | 4.79 (1.27) | -3.87 (0.12) | -1.35 (-1.70, -1.01) |
Placebo | 4.60 (1.21) | -2.51 (0.13) | -- | |
Study 12 | Lisdexamfetamine Dimesylate Capsules (50 or 70 mg/day)* | 4.66 (1.27) | -3.92 (0.14) | -1.66 (-2.04, -1.28) |
Placebo | 4.82 (1.42) | -2.26 (0.14) | -- |
A double-blind, placebo controlled, randomized withdrawal design study (Study 13) was conducted to evaluate maintenance of efficacy based on time to relapse between lisdexamfetamine dimesylate capsules and placebo in adults aged 18 to 55 (N=267) with moderate to severe BED. In this longer-term study patients who had responded to lisdexamfetamine dimesylate capsules in the preceding 12-week open-label treatment phase were randomized to continuation of lisdexamfetamine dimesylate capsules or placebo for up to 26 weeks of observation for relapse. Response in the open-label phase was defined as 1 or fewer binge days each week for four consecutive weeks prior to the last visit at the end of the 12-week open-label phase and a CGI-S score of 2 or less at the same visit. Relapse during the double-blind phase was defined as having 2 or more binge days each week for two consecutive weeks (14 days) prior to any visit and having an increase in CGI-S score of 2 or more points compared to the randomized- withdrawal baseline. Maintenance of efficacy for patients who had an initial response during the open-label period and then continued on lisdexamfetamine dimesylate capsules during the 26-week double-blind randomized-withdrawal phase was demonstrated with lisdexamfetamine dimesylate capsules being superior over placebo as measured by time to relapse.
Figure 8: Kaplan-Meier Estimated Proportions of Subjects with Relapse in Adults with BED (Study 13)
Examination of population subgroups based on age (there were no patients over 65), gender, and race did not reveal any clear evidence of differential responsiveness in the treatment of BED.
16.2 Storage And Handling
Dispense in a tight, light-resistant container as defined in the USP.
Store at room temperature, 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
17 Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Principal Display Panel - 10 Mg Capsule Bottle Label
NDC 0527-4661-37
Lisdexamfetamine Dimesylate Capsules
CII
10 mg
Pharmacist: Dispense the accompanying Medication Guide to each patient.
Print Medication Guides at:
www.lannett.com/med-guide/lisdexamfetamine
Rx Only
100 Capsules
Lannett
Principal Display Panel - 20 Mg Capsule Bottle Label
NDC 0527-4662-37
Lisdexamfetamine Dimesylate Capsules
CII
20 mg
Pharmacist: Dispense the accompanying Medication Guide to each patient.
Print Medication Guides at:
www.lannett.com/med-guide/lisdexamfetamine
Rx Only
100 Capsules
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Principal Display Panel - 30 Mg Capsule Bottle Label
NDC 0527-4663-37
Lisdexamfetamine Dimesylate Capsules
CII
30 mg
Pharmacist: Dispense the accompanying Medication Guide to each patient.
Print Medication Guides at:
www.lannett.com/med-guide/lisdexamfetamine
Rx Only
100 Capsules
Lannett
Principal Display Panel - 40 Mg Capsule Bottle Label
NDC 0527-4664-37
Lisdexamfetamine Dimesylate Capsules
CII
40 mg
Pharmacist: Dispense the accompanying Medication Guide to each patient.
Print Medication Guides at:
www.lannett.com/med-guide/lisdexamfetamine
Rx Only
100 Capsules
Lannett
Principal Display Panel - 50 Mg Capsule Bottle Label
NDC 0527-4665-37
Lisdexamfetamine Dimesylate Capsules
CII
50 mg
Pharmacist: Dispense the accompanying Medication Guide to each patient.
Print Medication Guides at:
www.lannett.com/med-guide/lisdexamfetamine
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100 Capsules
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Principal Display Panel - 60 Mg Capsule Bottle Label
NDC 0527-4666-37
Lisdexamfetamine Dimesylate Capsules
CII
60 mg
Pharmacist: Dispense the accompanying Medication Guide to each patient.
Print Medication Guides at:
www.lannett.com/med-guide/lisdexamfetamine
Rx Only
100 Capsules
Lannett
Principal Display Panel - 70 Mg Capsule Bottle Label
NDC 0527-4667-37
Lisdexamfetamine Dimesylate Capsules
CII
70 mg
Pharmacist: Dispense the accompanying Medication Guide to each patient.
Print Medication Guides at:
www.lannett.com/med-guide/lisdexamfetamine
Rx Only
100 Capsules
Lannett
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