VYVANSE 30mg. Capsules.

BOXED WARNING

Stimulants, such as lisdexamfetamine, have a high potential for substance abuse and dependence. Assess the risk for abuse and dependence prior to initiating lisdexamfetamine treatment, to include evaluating the child or adult patient for a personal or family history of abuse of prescription medicines or street drugs, or abuse or dependence on alcohol (alcoholism). All patients should be monitored for signs of abuse and dependence while receiving lisdexamfetamine. Administration of amphetamines for a prolonged period of time may lead to physical and psychological drug dependence. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion. Symptoms of chronic intoxication include insomnia, irritability, change in personality, and psychotic symptoms that may be clinically indistinguishable from psychotic disorders.

DEA CLASS

Rx, schedule II

DESCRIPTION

Oral CNS stimulant in the amphetamine class and pro-drug of dextroamphetamine
Indicated for ADHD in adult and pediatric patients 6 years and older; efficacious for binge-eating disorder (BED) in adults 18 to 55 years
Assess the risk of substance abuse prior to prescribing; monitor for abuse and dependence during treatment

COMMON BRAND NAMES

Vyvanse

HOW SUPPLIED

Vyvanse Oral Cap: 10mg, 20mg, 30mg, 40mg, 50mg, 60mg, 70mg
Vyvanse Oral Tab Chew: 10mg, 20mg, 30mg, 40mg, 50mg, 60mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

70 mg/day PO.

70 mg/day PO.

70 mg/day PO.

>= 6 years: 70 mg/day PO.
< 6 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Hepatic dysfunction has the potential to slow the elimination of amphetamines; use with caution and titrate dosages carefully.

GFR 30 mL/minute/1.73 m2 or more: Specific dosage adjustments not specified; titrate dosage carefully in patients with renal impairment.
GFR 15 to 29 mL/minute/1.73 m2: Do not exceed 50 mg/day PO.
GFR less than 15 mL/minute/1.73 m2: Do not exceed 30 mg/day PO.

Intermittent hemodialysis
Lisdexamfetamine and d-amphetamine are not dialyzable.

ADMINISTRATION

STORAGE

Vyvanse:
– Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

Lisdexamfetamine is contraindicated for use in patients with known hypersensitivity to amphetamines or any component of the lisdexamfetamine product.

Stimulants, such as lisdexamfetamine, have a high potential for substance abuse and dependence. Assess the risk for abuse and dependence prior to initiating lisdexamfetamine treatment, to include evaluating the child or adult patient for a personal or family history of abuse of prescription medicines or street drugs, or abuse or dependence on alcohol (alcoholism). All patients should be monitored for signs of abuse and dependence while receiving lisdexamfetamine. Administration of amphetamines for a prolonged period of time may lead to physical and psychological drug dependence. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. The least amount reasonable should be prescribed or dispensed at one time in order to limit the potential for overuse or drug diversion. Symptoms of chronic intoxication include insomnia, irritability, change in personality, and psychotic symptoms that may be clinically indistinguishable from psychotic disorders.

Lisdexamfetamine should be used with caution in patients in an agitated state. Stimulants such as lisdexamfetamine should be used cautiously in those with bipolar disorder and/or mania due to the potential for manic episodes to occur. An assessment should be performed prior to initiation of therapy to determine the risk for developing a manic episode (e.g., comorbid history of depressive symptoms or a family history of suicide, bipolar disorder, and depression). Due to its toxic effects in overdose, lisdexamfetamine should only be used in those with major depression or suicidal ideation when absolutely necessary. Appropriate stimulant therapy should not suppress normal emotions or intellectual ability; the occurrence of certain side effects may indicate a need for dosage reduction or discontinuation. Not all pediatric patients with ADHD will require medication; non-drug measures are often instituted concurrently with drug therapy. Monitoring of the effectiveness of stimulant therapy by the health care prescriber, parents, and teachers is important; periodic reassessment of the need for medication is recommended. It is recommended to monitor for signs of aggression or worsening of pre-existing aggressive behavior when treatment is initiated. Aggression, hostility, and suicidal ideation or behaviors have been reported in both clinical trials and post-marketing experience with ADHD medications. Although causality has not been established and these behaviors may be inherent to ADHD, close monitoring is recommended. Patients and their caregivers should be advised to promptly report any changes in mood or behavior. If suicide-related events emerge during treatment, consideration should be given to dose reduction or drug discontinuation, especially if symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. In psychotic individuals (e.g., schizophrenia), amphetamines may exacerbate behavioral disturbances, psychosis, or thought disorders. New onset psychotic symptoms (e.g., hallucinations, delusional thinking, mania) may occur in individuals without a prior history of psychosis. If such symptoms occur, discontinuation of treatment should be considered.

Lisdexamfetamine should be used with caution in patients with pre-existing hypertension or tachycardia; prior to initiating treatment, with lisdexamfetamine, the adult, child, or adolescent should be assessed for the presence of cardiovascular disease (e.g., a careful history, family history of arrhythmia or cardiovascular death, and a physical exam).. Stimulant medications must be used very cautiously in patients with even mild hypertension or other conditions in which a modest increase in blood pressure or heart rate could be detrimental. Stimulant medications cause a modest increase in average blood pressure (approximately 2 to 4 mmHg) and average heart rate (approximately 3 to 6 bpm); however, some individuals may have larger increases. Although these mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Advise patients that there is a potential serious cardiovascular risk including hypertension with lisdexamfetamine use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained fainting, or other symptoms suggestive of heart disease. Further evaluate patients who develop exertional chest pain, unexplained fainting, or heart rate abnormalities during treatment. Elevated blood pressure may require a dose reduction, discontinuation, and/or initiation of appropriate antihypertensive medication.

According to American Heart Association (AHA) guidance and the manufacturer, all patients being considered for treatment with amphetamines should be assessed for cardiac disease (e.g., a careful history, family history of sudden death or ventricular arrhythmias, and physical exam). Further, the AHA recommends a cardiac evaluation including an ECG and echocardiogram if cardiac disease is suspected. For pediatric patients, the AHA states that it may be useful to obtain a baseline ECG. If a child or adolescent has any significant findings on physical exam, ECG, or family history, a pediatric cardiologist should be consulted before treatment. The manufacturer recommends avoiding use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias (e.g., ventricular arrhythmias), coronary artery disease, and other serious heart problems that may be exacerbated by the noradrenergic effects of amphetamines (e.g., aortic stenosis, prosthetic heart valves, valvular heart disease, cardiomyopathy, advanced arteriosclerosis, ventricular dysfunction, heart failure, acute myocardial infarction). Because amphetamines can increase blood pressure, all patients should be monitored for tachycardia and hypertension. Patients who develop exertional chest pain, unexplained syncope, or arrhythmias should be promptly evaluated. Sudden death, stroke and myocardial infarction (MI) have been reported in adults receiving CNS stimulants at recommended doses, and sudden death has been reported in children and adolescents with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. The AHA states that it is reasonable to consider ADHD medications in pediatric patients with congenital heart disease without current hemodynamic or arrhythmic concerns or congenital heart disease that the patient’s pediatric cardiologist considers stable and without specific concerns. These patients should be closely monitored and treatment discontinuation should be considered if any of the following conditions develop: heart condition associated with sudden cardiac death (SCD), arrhythmia requiring cardiopulmonary resuscitation, direct current cardioversion/defibrillation, or overdrive pacing, arrhythmia associated with SCD, any clinically significant arrhythmia that is not treated or controlled, QTc interval on ECG of more than 0.46 sec, or heart rate or blood pressure more than 2 standard deviations above the mean for age. Despite earlier reports of an increased risk, it appears that the short-term risk of serious cardiac events is not significantly increased in otherwise healthy pediatric patients. A large retrospective cohort study of over 1.2 million children, adolescents, and young adults 2 to 24 years of age did not find an increased risk of serious cardiac events in current users of ADHD drugs compared to nonusers. Similar results were seen when current users of ADHD drugs were compared to former users and when current users with severe underlying cardiac disease were included in the analysis. The authors concluded that although the absolute magnitude of risk appears to be low, a modest increased risk could not be ruled out. This data is supported by results from another large population-based retrospective cohort study (patients aged 3 to 18 years) that found no increase in short-term risk of severe cardiac events in stimulant users versus nonusers. Unlike other trials, this second study also included high risk patients (e.g., malignancy, HIV, congenital heart disease, or cardiomyopathy); the odds ratio in the high risk group was 1.02 (95% CI 0.28 to 3.69). The portion of patients specifically using amphetamines in either study is unknown. The authors of both studies concluded that although the absolute magnitude of risk appears to be low, a modest increase in risk could not be ruled out. The effect of long-term use in pediatric patients has not been evaluated. Advise patients/caregivers that there are potentially severe cardiac risks including sudden death, MI, stroke, and hypertension, and to contact a healthcare provider immediately if they develop exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease.

Stimulants, such as lisdexamfetamine, should be used with caution in patients with hyperthyroidism, including thyrotoxicosis, because sympathomimetic stimulation may induce cardiac arrhythmias or other side effects.

Lisdexamfetamine is contraindicated in patients who are receiving monoamine oxidase inhibitors (MAOI therapy), including linezolid or intravenous methylene blue, or who have received MAOI therapy within the past 14 days because of the possibility of precipitating a hypertensive crisis. MAOI antidepressants slow amphetamine metabolism, potentiating their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings. This may precipitate hypertensive crisis, malignant hyperthermia, serotonin syndrome, and a variety of toxic neurologic effects; these events can be fatal. Increased risk for serotonin syndrome also may occur when amphetamines are co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans, and others), and may also occur during overdosage situations. If serotonin syndrome occurs, discontinue lisdexamfetamine and all other serotonergic agents, and initiate supportive treatment.

Amphetamines, such as lisdexamfetamine, should be used with caution in patients with glaucoma. The sympathetic stimulation of amphetamines blocks aqueous outflow and raises intraocular pressure. Occasionally, visual disturbance, such as change in visual accomodation or blurred vision, have been reported in individuals without ocular disease while they are taking amphetamines. Patients should report any new visual disturbance; ophthalmic evaluation may be needed.

Lisdexamfetamine, like other amphetamines, may precipitate motor or phonetic tics in those with Tourette’s syndrome. Some patients with Tourette’s syndrome may actually benefit from stimulant therapy; administer under close supervision and at the lowest effective dose.

The use of lisdexamfetamine may cause dizziness, mask signs of fatigue or the need for rest, or impair the ability of a patient to participate in activities that require mental alertness. Patients should not perform such tasks, including driving or operating machinery, until they are aware of how this medication affects them.

Use lisdexamfetamine with caution in patients with a history of a seizure disorder. Stimulants can lower the seizure threshold, particularly during excess CNS stimulation (i.e., amphetamine overdosage). The effects of amphetamines on the seizure threshold, in normal therapeutic dosages, are less clear. Seizure threshold may be reduced in those with electroencephalogram (EEG) abnormalities and rarely in patients without a seizure history or EEG abnormalities. Seizures have been reported during postmarketing use of lisdexamfetamine; however, the frequency is unknown. If seizures occur, discontinuation of therapy is recommended. Because of a potential increased risk of seizures, amphetamines should not be used during intrathecal radiographic contrast administration. Based upon recommendations for other amphetamines, lisdexamfetamine should be discontinued 48 hours before the myelography and should not be resumed until at least 24 hours after the procedure.

The use of inhalational anesthetics during surgery may sensitize the myocardium to the effects of amphetamines and other sympathomimetic drugs. Patients should check with their surgeon prior to elective surgery regarding any adjustments needed in timing of medications for surgical procedures.

Lisdexamfetamine may cause hypercortisolism, as amphetamines can cause a significant elevation in plasma corticosteroid concentrations. The elevation is greatest in the evening. Amphetamines may interfere with urinary steroid determinations; consider the possible effect of lisdexamfetamine if determination of plasma corticosteroid concentrations is desired.

Use lisdexamfetamine with caution in patients with significant hepatic disease or renal impairment. The elimination of amphetamine is dependent on hepatic metabolism, urinary pH and urinary flow rates, as well as active secretion; dysfunction of either system may inhibit elimination and result in prolonged exposure. The mean clearance of lisdexamfetamine’s active moiety, d-amphetamine, is reduced in patients with severe renal impairment or renal failure; therefore, reduced maximum daily dosages are recommended. Dialysis does not significantly affect the clearance of d-amphetamine.

In rare instances, stimulant medications may cause prolonged and sometimes painful erections (priapism). All male patients and their caregivers should be counseled on the signs and symptoms of priapism and the importance of seeking immediate medical attention if an erection lasting more than 4 hours occurs. Immediate diagnosis and treatment are essential to avoid tissue damage. Priapism can occur in males of any age; younger males, particularly those who have not reached puberty, may not recognize the problem or may be embarrassed to tell anyone if it occurs. In a review of methylphenidate products by the FDA, the median age of patients who experienced priapism was 12.5 years (range: 8 to 33 years). Reported cases have occurred after a period of time on stimulant therapy and often subsequent to a dose increase. Priapism has also been reported during periods of drug withdrawal (e.g., drug holidays or discontinuation). Practitioners should be aware that both methylphenidate and amphetamine products have been associated with post-marketing reports of priapism; however, causality in relation to the amphetamine products is uncertain because patients had been taking other medications thought to cause priapism. Caution should be used when considering changing male patients from stimulant to non-stimulant medications; atomoxetine is also associated with priapism in young males and appears to carry a higher risk of the condition compared to stimulant medications.

Stimulant medications are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Worsening of peripheral vascular disease is possible. Effects on circulation have been observed with therapeutic doses at different times throughout therapy in all age groups. Signs and symptoms are usually intermittent and mild and generally improve after reduction in dose or discontinuation of drug. However, very rare sequelae include digital skin ulcer and/or soft tissue breakdown. Carefully monitor all patients for digital changes during treatment with stimulant medications, especially those with pre-existing circulation problems. Instruct patients to seek immediate medical attention if any new digital numbness, pain, skin discoloration, or temperature sensitivity occur, or if unexplained wounds appear on their fingers or toes. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Lisdexamfetamine is specifically FDA approved to assist patients with binge-eating disorder (BED). Other eating disorders, such as anorexia nervosa or bulimia nervosa, should be ruled out prior to treatment with lisdexamfetamine for either BED or for attention deficit (ADD/ADHD). Patients with eating disorders may have physiologic complications, such as metabolic and electrolyte abnormalities, which increase their susceptibility to the adverse effects of stimulants. Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. Lisdexamfetamine is not indicated or recommended to promote generalized weight loss. The safety and effectiveness of lisdexamfetamine for obesity treatment have not been established.

Administration of amphetamines for a prolonged period of time may lead to physical and psychological drug dependence. Abrupt discontinuation after chronic use (therapeutic and recreational) may result in severe depressive symptoms, extreme fatigue, sleep EEG changes, and symptoms of withdrawal. Close supervision during gradual withdrawal of therapy is recommended. Of note, drug ‘holidays’, the temporary discontinuation of drug during weekends, holidays, summer vacations, and etc. in patients with well-controlled attention-deficit hyperactivity disorder (ADHD) symptoms, are not usually associated with drug withdrawal symptoms.

Pediatric patients 3 years and older have been successfully treated for attention-deficit hyperactivity disorder (ADHD) with amphetamines; however, safe and effective use for lisdexamfetamine have not been established in children and infants less than 6 years of age for ADHD, and safety and efficacy are not established in pediatric patients for the treatment of binge-eating disorder (BED). The potential for growth inhibition in pediatric patients should be monitored during stimulant therapy with lisdexamfetamine. Monitor height and weight parameters relative to age at treatment initiation and periodically thereafter (at minimum yearly). Patients who are not growing or gaining weight as expected may need to have their treatment interrupted. In a study of children aged 6 to 12 years receiving lisdexamfetamine 30 mg, 50 mg, and 70 mg mean weight loss from baseline over 4 weeks was -0.9, -1.9, and -2.5 pounds, respectively, compared to a 1 pound weight gain for patients receiving placebo. Adolescents aged 13 to 17 years had a mean weight loss from baseline of -2.7, -4.3, and -4.8 pounds when receiving the same doses over 4 weeks compared to a 2 pound weight gain for patients receiving placebo. Follow-up of children aged 6 to 12 years who were consistently medicated (treatment for 7 days/week) over a 12 month period showed a slowing in growth rate. Data obtained on the effects of stimulants on growth suppression in children 7 to 10 years of age suggested that regularly medicated children (7 days/week) had a temporary average slowing in growth of 2 cm in height and 2.7 kg in weight over 3 years. Data are inadequate to determine whether chronic use of stimulants causes long-term growth inhibition. Although data are limited, available studies do not indicate that stimulant use compromises the attainment of normal adult height and weight in most children.

Amphetamines should be avoided during pregnancy if possible. The limited available data from published literature and postmarketing reports on use of lisdexamfetamine during human pregnancy are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. However, amphetamines have been shown to have both embryotoxic and teratogenic effects in some animals when administered at high doses. In addition, because amphetamines cause vasoconstriction, they may decrease placental perfusion. Amphetamines can stimulate uterine contractions increasing the risk of premature labor and there is no essential use of the drugs during labor or obstetric delivery. Neonates born to amphetamine-dependent mothers are at increased risk for premature delivery and low birth weight. Physical withdrawal symptoms (e.g., abnormal sleep patterns, poor feeding, tremor, irritability, agitation, excessive drowsiness, and hypertonia) may occur in the neonate following delivery. There is 1 case of a neonate born with a severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia following maternal exposure to dextroamphetamine sulfate and lovastatin during the first trimester of pregnancy. However, most available data indicate that amphetamines are not teratogenic in humans. Of 671 mother-child pairs enrolled in the Collaborative Perinatal Project who had first trimester exposure to amphetamines and 1898 mother-child pairs with amphetamine exposures at any time during pregnancy, there was no evidence suggesting a relationship to large categories of major or minor malformations. In a prospective comparison study, neonates exposed to cocaine, methamphetamine, or a combination of cocaine and narcotic in utero had a 35.1% incidence of cranial abnormalities (i.e., intraventricular hemorrhage, echodensities known to be associated with necrosis, and cavitary lesions) compared to a 5.3% incidence in normal infants as assessed by cranial ultrasonography; the authors attributed the findings to the vasoconstrictive properties of the drugs.

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 breast-feeding is not recommended during treatment with lisdexamfetamine. 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 breast-fed 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. The effect of stimulant medication exposure via breast milk on the neurological development of the infant has not been well studied. In a study of 4 women with attention deficit hyperactivity disorder receiving d-amphetamine (median dose 18 mg/day) while breast-feeding, the mean relative infant dose was 5.7% of the weight-adjusted maternal dose (range: 3.9 to 13.8%). Of the 3 infants in whom blood samples were obtained, plasma d-amphetamine levels were undetectable in 1 infant; d-amphetamine levels were approximately 6% and 14% of the corresponding maternal plasma concentrations in the remaining 2 infants. None of the 4 infants in the study showed any adverse effects. If breast-feeding cannot be avoided during administration of a stimulant, the nursing infant should be monitored for signs of central nervous system hyperactivity, including decreased appetite, insomnia, and irritability. If possible, long-term infant exposure to stimulants through breast milk should be avoided since the consequences of such exposure are unknown. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

Clinical studies for lisdexamphetamine for attention-deficit hyperactivity disorder (ADHD) did not include sufficient numbers of geriatric adults 65 years of age or older to determine whether they respond differently from younger adults. Clinical studies for binge-eating disorder (BED) did not include adult and geriatric patients older than 55 years of age; therefore, dosing recommendations are not available for this condition. Other reported clinical experience has not identified differences in responses. In general, dose selection for an elderly patient should be cautious, usually starting 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. Stimulant medications are used as the treatments of choice in the adult patient over 50 years of age with ADHD when behavioral and lifestyle modifications alone have failed to improve concerns associated with inattention, such as task focus and completion, or organization and time management. Medication should be titrated with low doses initially and with a slow increase.[60888] Debilitated or geriatric patients may be more susceptible to the CNS and sympathomimetic side effects of the amphetamines; use with caution in the older adult. Side effects of amphetamines or other stimulants are usually mild but may include mood or behavior changes, tremor, insomnia, increased blood pressure, headache, or gastroesophageal reflux or other GI complaints. Adults should have their blood pressure and heart rate checked at baseline and periodically during treatment. If treatment is considered necessary, periodically re-evaluate the long-term usefulness of the drug for the individual patient. According to the Beers Criteria, stimulants such as amphetamines are considered potentially inappropriate medications (PIMs) for use in geriatric patients with insomnia and should be avoided due to the potential for drug-induced CNS stimulant effects.