Vyvanse (Page 3 of 7)

6.2 Postmarketing Reports

The following adverse reactions have been identified during post approval use of Vyvanse. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders — Palpitation

Eye Disorders — Vision blurred, mydriasis, diplopia

General Disorders and Administration Site Conditions — Fatigue

Hepatobiliary Disorders — Eosinophilic Hepatitis

Immune System Disorders — Anaphylactic reaction, hypersensitivity

Nervous System Disorders — Somnolence, seizure, dyskinesia

Psychiatric Disorder — Psychotic episodes, mania, hallucination, depression, aggression, dysphoria, euphoria, logorrhoea, dermatillomania

Skin and Subcutaneous Tissue Disorder — Stevens-Johnson Syndrome, angioedema, urticaria

6.3 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.

7 DRUG INTERACTIONS

7.1 Agents Whose Blood Levels May be Impacted by Vyvanse

Extended release guanfacine: In a drug interaction study (N=40), administration of an extended release guanfacine (4 mg) in combination with Vyvanse (50 mg) increased guanfacine maximum plasma concentration by 19%, whereas, exposure (area under the curve; AUC) was increased by 7%. These small changes are not expected to be clinically meaningful. In this study, no effect on d-amphetamine exposure was observed following co-administration of extended release guanfacine and Vyvanse.

7.2 Agents that Lower Blood Levels of Amphetamines

Urinary Acidifying Agents

These agents (ammonium chloride, sodium acid phosphate, etc.) increase the concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion.

Methenamine Therapy

Urinary excretion of amphetamines is increased, and efficacy is reduced, by acidifying agents used in methenamine therapy.

7.3 Agents that Increase Blood Levels of Amphetamines

Urinary Alkalinizing Agents

These agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion.

Monoamine Oxidase Inhibitors

MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results.

7.4 Agents Whose Effects May be Reduced by Amphetamines

Adrenergic Blockers

Adrenergic blockers are inhibited by amphetamines.

Antihistamines

Amphetamines may counteract the sedative effect of antihistamines.

Antihypertensives

Amphetamines may antagonize the hypotensive effects of antihypertensives.

Veratrum Alkaloids

Amphetamines inhibit the hypotensive effect of veratrum alkaloids.

Ethosuximide

Amphetamines may delay intestinal absorption of ethosuximide.

7.5 Agents Whose Effects May be Potentiated by Amphetamines

Antidepressants, Tricyclic

Amphetamines may enhance the activity of tricyclic antidepressants or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated.

Meperidine

Amphetamines potentiate the analgesic effect of meperidine.

Phenobarbital

Amphetamines may delay intestinal absorption of phenobarbital; co-administration of phenobarbital may produce a synergistic anticonvulsant action.

Phenytoin

Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action.

7.6 Agents that May Reduce the Effects of Amphetamines

Chlorpromazine

Chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning.

Haloperidol

Haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of amphetamines.

Lithium Carbonate

The anorectic and stimulatory effects of amphetamines may be inhibited by lithium carbonate.

7.7 Agents that May Potentiate the Effects of Amphetamines

Norepinephrine

Amphetamines enhance the adrenergic effect of norepinephrine.

Propoxyphene Overdosage

In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.

7.8 Drug/Laboratory Test Interactions

Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamine may interfere with urinary steroid determinations.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Animal reproduction studies of lisdexamfetamine dimesylate have not been performed. Studies have been performed with the active metabolite of lisdexamfetamine, d-amphetamine, either alone or in combination with l-amphetamine, as noted below.

Teratogenic Effects

Pregnancy Category C

Amphetamine (d- to l-enantiomer ratio of 3:1) had no apparent effects on embryofetal morphological development or survival when orally administered to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 6 and 16 mg/kg/day, respectively. Fetal malformations and death have been reported in mice following parenteral administration of d-amphetamine doses of 50 mg/kg/day or greater to pregnant animals. Administration of these doses was also associated with severe maternal toxicity.

A number of studies 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 longterm neurochemical and behavioral alterations. Reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function.

There are no adequate and well-controlled studies in pregnant women. There has been one report of severe congenital bony deformity, tracheo-esophageal fistula, and anal atresia (vater association) in a baby born to a woman who took dextroamphetamine sulfate with lovastatin during the first trimester of pregnancy. Amphetamines should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.