Aduvanz

​Aduvanz® is indicated for the treatment of:

• ​Attention Deficit Hyperactivity Disorder (ADHD)
• ​Moderate to Severe Binge Eating Disorder (BED).

​Limitation of Use:

​Aduvanz is 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 Aduvanz for the treatment of obesity have not been established.

Aduvanz dimesylate is used to treat attention deficit hyperactivity disorder (ADHD) in adults and children 6 years of age and older. Aduvanz dimesylate is also used to treat moderate to severe binge eating disorder (BED). It belongs to the group of medicines called central nervous system (CNS) stimulants.

Aduvanz dimesylate increases attention and decreases restlessness in children and adults who are overactive, cannot concentrate for very long, or are easily distracted and impulsive. Aduvanz dimesylate is used as part of a total treatment program that also includes social, educational, and psychological treatment.

Aduvanz dimesylate is available only with your doctor's prescription.

Pre-treatment Screening

Prior to treating children, adolescents, and adults with CNS stimulants, including Aduvanz, assess for the presence of cardiac disease (e.g., a careful history, family history of sudden death or ventricular arrhythmia, and physical exam).

To reduce the abuse of CNS stimulants including Aduvanz, 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 Aduvanz use.

General Instructions For Use

Take Aduvanz by mouth in the morning with or without food; avoid afternoon doses because of the potential for insomnia. Aduvanz may be administered in one of the following ways:

• Swallow Aduvanz capsules whole, or
• Open capsules, empty and mix the entire contents with yogurt, water, or orange juice. Ifthe contents of the capsule include any compacted powder, a spoon may be used to breakapart the powder. The contents should be mixed until completely dispersed. Consume theentire mixture immediately. It should not be stored. The active ingredient dissolves completely once dispersed; however, a film containing the inactive ingredients may remain in the glass or container once the mixture is consumed. Do not take anything less than one capsule per day, and a single capsule should not be divided.

Dosage For Treatment Of ADHD

The recommended starting dose is 30 mg once daily in the morning in patients ages 6 and above. Dosage may be adjusted in increments of 10 mg or 20 mg at approximately weekly intervals up to maximum dose of 70 mg/day.

Dosage For Treatment Of Moderate To Severe BED In Adults

The recommended starting dose is 30 mg/day to be titrated in increments of 20 mg at approximately weekly intervals to achieve the recommended target dose of 50 to 70 mg/day. The maximum dose is 70 mg/day. Discontinue Aduvanz if binge eating does not improve.

Dosage In Patients With Renal Impairment

In patients with severe renal impairment (GFR 15 to < 30 mL/min/1.73 m²), the maximum dose should not exceed 50 mg/day. In patients with end stage renal disease (ESRD, GFR < 15 mL/min/1.73 m²), the maximum recommended dose is 30 mg/day.

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 Aduvanz dosage accordingly.

How supplied

Dosage Forms And Strengths

Capsules 10 mg: pink body/pink cap (imprinted with S489 and 10 mg)

Capsules 20 mg: ivory body/ivory cap (imprinted with S489 and 20 mg)

Capsules 30 mg: white body/orange cap (imprinted with S489 and 30 mg)

Capsules 40 mg: white body/blue green cap (imprinted with S489 and 40 mg)

Capsules 50 mg: white body/blue cap (imprinted with S489 and 50 mg)

Capsules 60 mg: aqua blue body/aqua blue cap (imprinted with S489 and 60 mg)

Capsules 70 mg: blue body/orange cap (imprinted with S489 and 70 mg)

Aduvanz capsules 10 mg: pink body/pink cap (imprinted with S489 and 10 mg), bottles of 100, NDC 59417-101-10

Aduvanz capsules 20 mg: ivory body/ivory cap (imprinted with S489 and 20 mg), bottles of 100, NDC 59417-102-10

Aduvanz capsules 30 mg: white body/orange cap (imprinted with S489 and 30 mg), bottles of 100, NDC 59417-103-10

Aduvanz capsules 40 mg: white body/blue green cap (imprinted with S489 and 40 mg), bottles of 100, NDC 59417-104-10

Aduvanz capsules 50 mg: white body/blue cap (imprinted with S489 and 50 mg), bottles of 100, NDC 59417-105-10

Aduvanz capsules 60 mg: aqua blue body/aqua blue cap (imprinted with S489 and 60 mg), bottles of 100, NDC 59417-106-10

Aduvanz capsules 70 mg: blue body/orange cap (imprinted with S489 and 70 mg), bottles of 100, NDC 59417-107-10

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 to 86° F).

Disposal

Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining, unused, or expired Aduvanz by a medicine take-back program.

Manufactured for: Shire US Inc., 300 Shire Way, Lexington, MA 02421. Revised: Oct 2016

See also:
What is the most important information I should know about Aduvanz?

Do not use Aduvanz if you have used an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), rasagiline (Azilect), or selegiline (Eldepryl, Emsam) within the past 14 days. Serious, life-threatening side effects can occur if you take Aduvanz before the MAO inhibitor has cleared from your body.

Do not use this medication if you are allergic to Aduvanz, or if you have hardened arteries (arteriosclerosis), heart disease, moderate to severe high blood pressure (hypertension), overactive thyroid, glaucoma, severe anxiety or agitation, or a history of drug or alcohol addiction.

Some stimulants have caused sudden death in children and adolescents with serious heart problems or congenital heart defects. Before taking Aduvanz, tell your doctor if you have any type of heart problems.

Aduvanz is a drug of abuse and may be habit-forming. Keep track of the amount of medicine used from each new bottle. You should be aware if anyone is using your medicine improperly or without a prescription. Using this medication improperly can cause death or serious side effects on the heart.

Use Aduvanz as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Aduvanz comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Aduvanz refilled.
• Take Aduvanz by mouth in the morning with or without food.
• Swallow Aduvanz whole. Do not break, crush, or chew before swallowing. If you cannot swallow the capsule whole, you may open it and mix the contents with water. If needed, a spoon may be used to break apart any powder that is stuck together. Stir well until completely mixed. Drink the mixture right away. Do not store the mixture for future use. It is normal to see a filmy coating on the inside of your glass after you take Aduvanz.
• Take Aduvanz on a regular schedule to get the most benefit from it. Taking Aduvanz at the same time each day will help you remember to take it.
• If you miss a dose of Aduvanz, take it as soon as possible if you remember that morning. If it is past noon, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Aduvanz.

Use: Labeled Indications

Attention-deficit/hyperactivity disorder: Treatment of attention-deficit/hyperactivity disorder (ADHD).

Binge eating disorder: Treatment of moderate to severe binge eating disorder in adults.

See also:
What other drugs will affect Aduvanz?

Drugs Having Clinically Important Interactions With Amphetamines

Table 5 : Drugs having clinically important interactions with amphetamines.

Drugs Having No Clinically Important Interactions With Aduvanz

From a pharmacokinetic perspective, no dose adjustment of Aduvanz is necessary when Aduvanz is co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when Aduvanz is co-administered.

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 Aduvanz is co-administered.

Drug Abuse And Dependence

Controlled Substance

Aduvanz contains Lisdexamfetamine, a prodrug of amphetamine, a Schedule II controlled substance.

Abuse

CNS stimulants, including Aduvanz, other amphetamines, and methylphenidate-containing products have a high potential for abuse. Abuse is characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving.

Signs and symptoms of CNS stimulant 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.

To reduce the abuse of CNS stimulants, including Aduvanz, 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 Aduvanz use.

Studies Of Aduvanz 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 Aduvanz, 40 mg of immediate-release d-amphetamine sulphate (a controlled II substance), and 200 mg of diethylpropion hydrochloride (a controlled IV substance). Aduvanz 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 Aduvanz demonstrated similar “Drug-Liking Effects” compared to 40 mg of d-amphetamine and 200 mg of diethylpropion.

Intravenous administration of 50 mg Aduvanz 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.

Dependence

Tolerance

Tolerance (a state of adaptation in which exposure to a drug results in a reduction of the drug's desired and/or undesired effects over time) may occur during the chronic therapy of CNS stimulants including Aduvanz.

Dependence

Physical dependence (a state of adaptation manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist) may occur in patients treated with CNS stimulants including Aduvanz. Withdrawal symptoms after abrupt cessation following prolonged high-dosage administration of CNS stimulants include extreme fatigue and depression.

See also:
What are the possible side effects of Aduvanz?

The following adverse reactions are discussed in greater detail in other sections of the labeling

• Known hypersensitivity to amphetamine products or other ingredients of Aduvanz
• Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors
• Drug Dependence
• Serious Cardiovascular Reactions
• Blood Pressure and Heart Rate Increases
• Psychiatric Adverse Reactions
• Suppression of Growth
• Peripheral Vasculopathy, including Raynaud's phenomenon

Clinical Trial 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.

Attention Deficit Hyperactivity Disorder

The safety data in this section is based on data from the 4-week parallel-group controlled clinical studies of Aduvanz in pediatric and adult patients with ADHD.

Adverse Reactions Associated With Discontinuation Of Treatment In ADHD Clinical Trials

In the controlled trial in patients ages 6 to 12 years (Study 1), 9% (20/218) of Aduvanz-treated patients discontinued due to adverse reactions compared to 1% (1/72) of placebo-treated patients. The most frequent adverse reactions leading to discontinuation (i.e. leading to discontinuation in at least 1% of Aduvanz-treated patients and at a rate at least twice that of placebo) were ECG voltage criteria for ventricular hypertrophy, tic, vomiting, psychomotor hyperactivity, insomnia, and rash [2 instances for each adverse reaction, i.e., 2/218 (1%)]. In the controlled trial in patients ages 13 to 17 years (Study 4), 4% (10/233) of Aduvanz-treated patients discontinued due to adverse reactions compared to 1% (1/77) of placebo-treated patients. The most frequent adverse reactions leading to discontinuation were irritability (3/233; 1%), decreased appetite (2/233; 1%), and insomnia (2/233; 1%).

In the controlled adult trial (Study 7), 6% (21/358) of Aduvanz-treated patients discontinued due to adverse reactions compared to 2% (1/62) of placebo-treated patients. The most frequent adverse reactions leading to discontinuation (i.e. leading to discontinuation in at least 1% of Aduvanz-treated patients and at a rate at least twice that of placebo) were insomnia (8/358; 2%), tachycardia (3/358; 1%), irritability (2/358; 1%), hypertension (4/358; 1%), headache (2/358; 1%), anxiety (2/358; 1%), and dyspnea (3/358; 1%).

The most common adverse reactions (incidence ≥ 5% and at a rate at least twice placebo) reported in children, adolescents, and/or adults were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting.

Adverse Reactions Occurring At An Incidence Of 2% Or More Among Aduvanz Treated Patients With ADHD In Clinical Trials

Adverse reactions reported in the controlled trials in pediatric patients ages 6 to 12 years (Study 1), adolescent patients ages 13 to 17 years (Study 4), and adult patients (Study 7) treated with Aduvanz or placebo are presented in Tables 1, 2, and 3 below.

Table 1 : Adverse Reactions Reported by 2% or More of Children (Ages 6 to 12 Years)with ADHD Taking Aduvanz and at least Twice the Incidence in PatientsTaking Placebo in a 4-Week Clinical Trial (Study 1)

Table 2 : Adverse Reactions Reported by 2% or More of Adolescent (Ages 13 to 17 Years) Patients with ADHD Taking Aduvanz and at least Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 4)

Table 3 : Adverse Reactions Reported by 2% or More of Adult Patients with ADHD Taking Aduvanz and at least Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 7)

In addition, in the adult population erectile dysfunction was observed in 2.6% of males on Aduvanz and 0% on placebo; decreased libido was observed in 1.4% of subjects on Aduvanz and 0% on placebo.

Weight Loss And Slowing Growth Rate In Pediatric Patients With ADHD

In a controlled trial of Aduvanz in children ages 6 to 12 years (Study 1), mean weight loss from baseline after 4 weeks of therapy was -0.9, -1.9, and -2.5 pounds, respectively, for patients receiving 30 mg, 50 mg, and 70 mg of Aduvanz, compared to a 1 pound weight gain for patients receiving placebo. Higher doses were associated with greater weight loss with 4 weeks of treatment. Careful follow-up for weight in children ages 6 to 12 years who received Aduvanz over 12 months suggests that consistently medicated children (i.e. treatment for 7 days per week throughout the year) have a slowing in growth rate, measured by body weight as demonstrated by an age- and sex-normalized mean change from baseline in percentile, of -13.4 over 1 year (average percentiles at baseline and 12 months were 60.9 and 47.2, respectively). In a 4-week controlled trial of Aduvanz in adolescents ages 13 to 17 years, mean weight loss from baseline to endpoint was -2.7, -4.3, and -4.8 lbs., respectively, for patients receiving 30 mg, 50 mg, and 70 mg of Aduvanz, compared to a 2.0 pound weight gain for patients receiving placebo.

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e. treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. In a controlled trial of amphetamine (d- to l-enantiomer ratio of 3:1) in adolescents, mean weight change from baseline within the initial 4 weeks of therapy was -1.1 pounds and -2.8 pounds, respectively, for patients receiving 10 mg and 20 mg of amphetamine. Higher doses were associated with greater weight loss within the initial 4 weeks of treatment.

Weight Loss In Adults With ADHD

In the controlled adult trial (Study 7), mean weight loss after 4 weeks of therapy was 2.8 pounds, 3.1 pounds, and 4.3 pounds, for patients receiving final doses of 30 mg, 50 mg, and 70 mg of Aduvanz, respectively, compared to a mean weight gain of 0.5 pounds for patients receiving placebo.

Binge Eating Disorder

The safety data in this section is based on data from two 12 week parallel group, flexible-dose, placebo-controlled studies in adults with BED. Patients with cardiovascular risk factors other than obesity and smoking were excluded.

Adverse Reactions Associated With Discontinuation Of Treatment In BED Clinical Trials

In controlled trials of patients ages 18 to 55 years, 5.1% (19/373) of Aduvanz-treated patients discontinued due to adverse reactions compared to 2.4% (9/372) of placebo-treated patients. No single adverse reaction led to discontinuation in 1% or more of Aduvanz-treated patients.

The most common adverse reactions (incidence ≥ 5% and at a rate at least twice placebo) reported in adults were dry mouth, insomnia, decreased appetite, increased heart rate, constipation, feeling jittery, and anxiety.

Adverse reactions reported in the pooled controlled trials in adult patients (Study 11 and 12) treated with Aduvanz or placebo are presented in Table 4 below.

Table 4 : Adverse Reactions Reported by 2% or More of Adult Patients with BED Taking Aduvanz and at least Twice the Incidence in Patients Taking Placebo in 12-Week Clinical Trials (Study 11 and 12)

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Aduvanz. 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. These events are as follows: palpitations, cardiomyopathy, mydriasis, diplopia, difficulties with visual accommodation, blurred vision, eosinophilic hepatitis, anaphylactic reaction, hypersensitivity, dyskinesia, dysgeusia, tics, bruxism, depression, dermatillomania, aggression, Stevens-Johnson Syndrome, angioedema, urticaria, seizures, libido changes, frequent or prolonged erections, constipation, and rhabdomyolysis.

Aduvanz (L-lysine-d-amphetamine) is a prodrug of the psychostimulant d-amphetamine coupled with the essential amino acid L-lysine. It was developed so that the amphetamine psychostimulant is released and activated more slowly as the prodrug molecule is hydrolyzed consequently cleaving off the amino acid-during the first pass through the intestines and/or the liver. Amphetamines target the trace amine-associated receptor 1 (TAAR1). Amphetamine is also believed to exert its effects by binding to the monoamine transporters (the dopamine transporter or DAT) and increasing extracellular levels of the biogenic amines dopamine, norepinephrine (noradrenaline) and serotonin.