Top Export, Import, company in world [Meterra ( lisdexamfetamine dimesylate)]

DRUG DESCRIPTION Meterra is designed as a capsule for once-a-day oral administration.Meterra capsules contain 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg of lisdexamfetamine dimesylate and the following inactive ingredients: microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. INDICATIONS Attention Deficit Hyperactivity Disorder Meterra™ is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). The efficacy of Meterra in the treatment of ADHD was established on the basis of two controlled trials in children aged 6 to 12 and one controlled trial in adults. A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV®) implies the presence of hyperactive-impulsive and/or inattentive symptoms that cause impairment and were present before the age of 7 years. The symptoms must cause clinically significant impairment, e.g. in social, academic, or occupational functioning, and be present in two or more settings, e.g. school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least 6 of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least 6 of the following symptoms (or adult equivalent symptoms) must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; “on the go”; excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met. Special Diagnostic Considerations Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but also of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of DSM-IV characteristics. Need for Comprehensive Treatment Program Meterra is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all patients with this syndrome. Stimulants are not intended for use in patients who exhibit symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational/vocational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician's assessment of the chronicity and severity of the patient's symptoms and on the level of functional impairment. Long-Term Use The effectiveness of Meterra for long-term use, i.e., for more than 4 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Meterra for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

DOSAGE AND ADMINISTRATION Dosage should be individualized according to the therapeutic needs and response of the patient. Meterra should be administered at the lowest effective dosage. In children 6 to12 years of age or adults who are either starting treatment for the first time or switching from another medication, 30 mg once daily in the morning is the recommended dose. If the decision is made in the judgment of the clinician to increase the dose beyond 30 mg/day, daily dosage may be adjusted in increments of 10 mg or 20 mg at approximately weekly intervals. The maximum recommended dose is 70 mg/day; doses greater than 70 mg/day of Meterra have not been studied. Amphetamines are not recommended for children under 3 years of age. Meterra has not been studied in children under 6 years of age or over 12 years of age. Meterra should be taken in the morning. Afternoon doses should be avoided because of the potential for insomnia. Meterra may be taken with or without food. Meterra capsules may be taken whole, or the capsule may be opened and the entire contents dissolved in a glass of water. The solution should be consumed immediately and should not be stored. The dose of a single capsule should not be divided. The contents of the entire capsule should be taken, and patients should not take anything less than one capsule per day. SIDE EFFECTS Weight Loss – In the controlled adult trial, mean weight loss after 4 weeks of therapy was 2.8 lbs, 3.1 lbs, and 4.3 lbs, for patients receiving final doses of 30 mg, 50 mg, and 70 mg of Meterra, respectively, compared to a mean weight gain of 0.5 lbs for patients receiving placebo. Cardiac Disorders – palpitation Eye Disorders – vision blurred, mydriasis, diplopia Immune System Disorders – hypersensitivity Nervous System Disorders – seizure, dyskinesia Psychiatric Disorder – psychotic episodes, mania, hallucination, depression, aggression, dysphoria, euphoria, logorrhea Skin and Subcutaneous Tissue Disorder – angioedema, urticaria Adverse Reactions Associated with the Use of Amphetamine Cardiovascular Palpitations, tachycardia, elevation of blood pressure, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use. Central Nervous System - Psychotic episodes at recommended doses, overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, depression, tremor, headache, exacerbation of motor and phonic tics and Tourette's syndrome, seizures, stroke. Gastrointestinal - Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances. Allergic - Urticaria, rashes, and hypersensitivity reactions, including angioedema and anaphylaxis. Serious skin reactions, including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis have been reported. Endocrine - Impotence, changes in libido. WARNINGS Serious Cardiovascular Events Sudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug [see CONTRAINDICATIONS]. Adults Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs [see CONTRAINDICATIONS]. CONTRAINDICATIONS * Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncratic reaction to sympathomimetic amines, glaucoma * Agitated states * Patients with a history of drug abuse * During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result) Presentation Meterra Capsules Blister of 10 Capsules Taj pharmaceuticals(lisdexamfetamine dimesylate) is designed as a capsule 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, Lisdexamfetamine dimesylate is a white to off-white powder that is soluble in water (792 mg/mL). Vyvanse capsules contain 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg of lisdexamfetamine dimesylate and the following inactive. Methods This 4-week, phase 3, double-blind, forced-dose escalation study of adults aged 18 to 55 years with ADHD randomized participants to receive placebo (n = 62), or 30 (n = 119), 50 (n = 117), or 70 (n = 122) mg/d LDX, taken once a day in the morning. The self-rated Pittsburgh Sleep Quality Index (PSQI) was administered at baseline and at week 4 to assess sleep quality. The PSQI global score assesses 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) each scored from 0 (no difficulty) to 3 (severe difficulty). Attention deficit/hyperactivity disorder (ADHD), characterized by a pattern of inattention and/or hyperactivity, is one of the most prevalent psychiatric disorders worldwide. Often diagnosed in childhood, ADHD is thought to affect as many as 8% of children globally Symptoms of ADHD persist into adolescence and adulthood for approximately two-thirds of childhood cases The prevalence of ADHD in adults in the United States is estimated to be 4.4% Subjective reports of sleep problems are frequent among both adult and pediatric patients with ADHD The relationship between sleep and ADHD is complex and appears to be bidirectional in that ADHD affects sleep patterns while sleep patterns can impact ADHD symptoms .The mechanisms by which ADHD can disturb sleep have not been fully elucidated but may involve changes in noradrenergic and/or dopaminergic systems. Furthermore, anatomical and functional regions of the central nervous system responsible for ADHD symptoms and those involved in sleep regulation seemingly overlap . Patient reports of disturbed sleep are also significantly associated with their current ADHD symptom severity. A study by Kass et al demonstrated that daytime sleepiness and insomnia were predictors of increased ADHD symptomatology as assessed by the Adult Behavior Checklist in young adults . Sleep disturbances in ADHD may be a manifestation of ADHD, itself, but may also result from medications used to treat ADHD Sleep disturbances may also be secondary to comorbid conditions .It is possible that sleep disturbances secondary to ADHD and/or pharmacotherapy may also be contributing factors in driving-related problems known to be associated with ADHD. The increased prevalence of sleep disturbances in adults with ADHD may also be secondary to other behaviors or conditions associated with ADHD. For instance, cigarette use, which is significantly more common in adolescents and adults with ADHD than in healthy controls, has been shown to independently result in sleep disturbances, including, but not limited to, less total sleep time, extended sleep onset latency, and dissatisfaction with sleep quality . Caffeine intake is well known to adversely affect sleep , but at the same time, may be used to some extent for self-medication in adults with ADHD. There also appears to be an association between obesity and ADHD. Obesity is an important risk factor for obstructive sleep apnea-hypopnea syndrome, a disorder associated with sleep fragmentation and frequent nocturnal arousals leading to daytime sleepiness . Although subjective reports of sleep disturbances in adults with ADHD are frequent in the clinical literature, to date, there is scant direct evidence of the occurrence of specific sleep disorders in adults with ADHD . Wagner et al noted that ADHD symptoms were more common (26%) in a cohort of subjects with restless leg syndrome (RLS) than those with primary insomnia (6%) or normal controls (5%) suggesting a link between ADHD and RLS in adults. A recent small (N = 6) pilot study found polysomnographic evidence of sleep-disordered breathing to support subjective reports of sleep disturbances in adult subjects with carefully diagnosed ADHD. Another case study further supports the notion that ADHD and sleep-disordered breathing in the form of obstructive sleep apnea may be associated . A number of studies have investigated the sleep patterns of subjects with ADHD compared with healthy adults. Schredl et al demonstrated that adults with ADHD rated their sleep quality and feeling of being refreshed in the morning much lower than healthy controls; sleep latency and nocturnal awakenings were marginally significantly different from controls. The cross-sectional study did not demonstrate any effect of medication on sleep parameters as assessed by patient-completed questionnaires. Using a combination of sleep log and actigraph results, Kooij and colleagues reported that adults with ADHD demonstrated significantly poorer sleep quality and higher nocturnal motor activity than their matched controls but did not differ in reported total time in bed, sleep latency, or number of awakenings . Along with Surman et al above , other studies have provided further objective (eg, polysomnography or sleep actigraphy) data regarding the relationship between ADHD and sleep disturbances. Another study comparing adults with ADHD to healthy control subjects demonstrated significantly increased nocturnal motor activity and more frequent arousals in the patients with ADHD but did not find differences in other polysomnography parameters, despite these patients with ADHD reporting subjectively worse sleep quality than controls. A recent study by Sobanski et al demonstrated reduced sleep efficiency, longer sleep onset latency, more frequent nocturnal awakenings, and altered sleep architecture in adults with ADHD compared with controls . In children with ADHD, subjective parental and patient reports of sleep disturbances are common .Recent reports have linked ADHD in children to RLS, periodic limb movement disorder (PLMD), and sleep-disordered breathing , Notably, however, objective sleep data have not demonstrated uniform results regarding sleep continuity or sleep architecture abnormalities in children with ADHD . Moreover, there have been relatively few studies examining the effects of ADHD medications on sleep parameters in children with ADHD, and most evaluate the effects of short-acting stimulants. Stimulants are the mainstay of pharmacologic therapy for adults with ADHD in 2007 .Their effectiveness in reducing the symptoms of ADHD in adults is well documented . Despite the lack of objective documentation of sleep difficulties, clinical studies commonly report sleep difficulties, namely delay of sleep onset and insomnia . As stimulants wear off, they are sometimes associated with a rebound effect and a return of ADHD symptoms. Depending on the timing of the last dose of medication and the duration of effect for the drug, this can coincide with bedtime and may result in a delay of sleep onset .However, the effects of stimulants on sleep patterns in patients with ADHD have not been fully elucidated , and it is clear that stimulants can cause insomnia and result in sleep disturbances in some patients . There is some evidence that stimulants may improve sleep in patients with ADHD. In one study, after 3 weeks of treatment with stimulants, adults with ADHD demonstrated reduced nocturnal motor activity and improved sleep quality . In another study, treatment with methylphenidate (MPH) resulted in significant reduction in sleep onset latency and improved sleep efficiency, but did not alter other parameters as measured by polysomnography. Studies of sleep actigraphy measuring gross body movements over extended periods of time in adults with ADHD demonstrated that although adults treated with MPH experienced prolonged sleep onset latency and decreased total sleep time, they also experienced a decrease in nocturnal awakenings leading to more consolidated sleep reported as improved quality . A recent study by Faraone et al suggests that neither once-daily OROS MPH nor transdermal MPH reliably caused sleep problems (or worsened existing sleep problems) in children with ADHD In another pediatric study, MPH significantly prolonged sleep-onset latency while atomoxetine decreased it . In the same study, however, treatment with atomoxetine was associated with significantly more sleep interruptions than MPH .So while it may be apparent that stimulants can cause sleep disturbances in some patients, the evidence is inconsistent. Lisdexamfetamine dimesylate (LDX) is approved for the treatment of ADHD in children aged 6 to 12 years and in adults, and is the first prodrug stimulant. LDX is a therapeutically inactive molecule. After oral ingestion, LDX is converted to l-lysine and active d-amphetamine, which is responsible for the therapeutic effect. While a small amount of LDX is hydrolyzed to d-amphetamine in the gastrointestinal (GI) tract, the conversion of LDX into active d-amphetamine occurs primarily in the blood. The combination of l-lysine and d-amphetamine created a new chemical entity with a prodrug technology of delivery of d-amphetamine The absorption of LDX and its conversion to d-amphetamine are not affected by the pH of the GI system and is unlikely to be influenced by normal variations in GI transit times . LDX has demonstrated efficacy in treating children and adults with ADHD in multiple randomized, double-blind, clinical trials. LDX has demonstrated significant efficacy over placebo in improving ADHD rating scale Version IV (ADHD-RS-IV-IV) scores, Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale scores, and Permanent Product Measure of Performance (PERMP) scores compared with placebo in children with ADHD LDX was effective for up to 13 hours in a phase 3, randomized, controlled trial in children in a laboratory classroom study .Adverse events (AEs) were consistent with other pediatric studies of LDX. In a large, randomized, controlled trial in adults with ADHD, treatment with LDX resulted in significant improvements in ADHD-RS-IV and Clinical Global Impression (CGI) scores compared with placebo LDX was generally well tolerated in this study, and subjects reported common nonsleep-related adverse events including dry mouth and decreased appetite as well as insomnia. The results of this study were previously published. The present analysis, using the data-set from this previously published study , evaluated the effects of LDX on sleep parameters in adults with ADHD utilizing the Pittsburgh Sleep Quality Index (PSQI), a validated scale designed to measure overall sleep quality and related aspects of sleep This analysis was undertaken to describe the effects of LDX on sleep using the PSQI. Previously, the PSQI scale has not been extensively studied in adult patients with ADHD. Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders affecting children. The symptoms often persist into adolescence and adulthood, causing significant impairments. ADHD often remains undiagnosed and untreated, and because of its potential long-term impact, recognition, diagnosis, and management in children have become increasingly important. Education about ADHD and the available therapy options is important for both the patient and the caregiver to achieve more effective treatment. Efficacy and safety data on stimulant medications have provided evidence for their effectiveness in treating ADHD. Although they remain the first-line treatment, the need for multiple daily dosing and concerns about the general risk profile of stimulants have led to the development of new agents, including once-daily formulations that provide prolonged duration of action. However, pharmacokinetic variability of these formulations can result in inconsistent effects in some patients. The use of prodrug technology and the development of the only prodrug stimulant, lisdexamfetamine dimesylate (LDX), provide a promising treatment option for ADHD with an improved overdose potential risk profile when compared to d-amphetamine. This review of LDX, which presents the efficacy, safety, and pharmacokinetic profile of this new class of stimulant, is designed to help the physician better understand the clinical use of this agent in treating ADHD. Introduction Attention deficit hyperactivity disorder (ADHD) is one of the most common behavioral disorders in childhood, estimated to occur worldwide in as many as eight percent to 12 percent of children. Childhood ADHD persists into adolescence and adulthood in an estimated 10 percent to 70 percent of cases, with impairing symptoms experienced by at least 50 percent of these patients.1 A US epidemiologic adult ADHD study reported a prevalence of 4.4 percent, yet only a small fraction of adults with ADHD (10.9%) had received treatment prior to the survey. Stimulants have the most evidence for efficacy and safety for the treatment of ADHD and remain the first-line therapy for ADHD. Concerns about the general risk profile of stimulant medications in clinical practice are common, including the association between ADHD and substance use disorder. Tampering, including mechanical manipulation, of some formulations has allowed misuse through administration via intended or non-intended routes and has led to the need for the development of new agents, including nonstimulants, developed as nonabusable alternatives for ADHD. Since 2000, once-daily, modified-release stimulant formulations that provide prolonged delivery have been developed for the treatment of ADHD.[9] While it is not known if this pharmacokinetic variability contributes to therapeutic duration variability, formulations with less pharmacokinetic variability may provide more consistent clinical results. More recently, development of long-acting formulations has included a prodrug stimulant representing a new class of agents for the treatment of ADHD that has less pharmacokinetic variability and the potential to produce more consistent clinical effects and less abuse potential. Description Lisdexamfetamine dimesylate belongs to the group of medicines called central nervous system (CNS) stimulants. It is used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children 6 to 12 years of age and in adults . Lisdexamfetamine dimesylate increases attention and decreases restlessness in children and adults who are overactive, cannot concentrate for very long, or are easily distracted and impulsive. This medicine is used as part of a total treatment program that also includes social, educational, and psychological treatment . This medicine is available only with your doctor's prescription . Mechanism of Action and Pharmacology Vyvanse is a pro-drug of dextroamphetamine. After oral administration, lisdexamfetamine dimesylate is rapidly absorbed from the gastrointestinal tract and converted to dextroamphetamine, which is responsible for the drug’s activity. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in Attention-Deficit/Hyperactivity Disorder (ADHD) is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine, does not bind to the sites responsible for the reuptake of norepinephrine and dopamine in vitro. Children ages 6 to 12: Individualize dosage based on therapeutic needs and response. For child starting treatment for first time or switching from another drug, recommended dosage is 30 mg P.O. once daily in morning. If daily dosage will be increased above 30 mg, adjust in increments of 20 mg/day at approximately weekly intervals. Maximum recommended dosage is 70 mg/day. Contraindications • Hypersensitivity or idiosyncratic reaction to sympathomimetic amines • Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, glaucoma, agitated state • History of drug abuse • During or within 14 days of MAO inhibitor therapy. Results LDX treatment significantly improved scores on SKAMP-deportment, SKAMP-attention, PERMP-attempted, PERMP-correct, and CGI-improvement from baseline. Adverse events were similar for both active treatments.