Approved Drug Label (PDF)
Boxed Warning
Additions and/or
revisions underlined:
VYVANSE has a high
potential for abuse and misuse, which can lead to the development of a
substance use disorder, including addiction. Misuse and abuse of CNS
stimulants, including VYVANSE, can result in overdose and death [see Overdosage (10)], and this risk is
increased with higher doses or unapproved methods of administration, such as
snorting or injection.
Before prescribing
VYVANSE, assess each patient’s risk for abuse, misuse, and addiction.
Educate patients and their families about these risks, proper storage of the
drug, and proper disposal of any unused drug. Throughout VYVANSE treatment,
reassess each patient’s risk of abuse, misuse, and addiction and frequently
monitor for signs and symptoms of abuse, misuse, and addiction [see Warnings and Precautions (5.1), Drug
Abuse and Dependence (9.2)].
5
Warnings and Precautions
5.1 Abuse, Misuse, and Addiction
Additions and/or revisions underlined:
VYVANSE has a high
potential for abuse and misuse. The use of VYVANSE exposes individuals to
the risks of abuse and misuse, which can lead to the development of a
substance use disorder, including addiction. VYVANSE can be diverted for
non-medical use into illicit channels or distribution [see Drug Abuse and Dependence (9.2 )]. Misuse and abuse of CNS stimulants, including VYVANSE, can result in
overdose and death [see
Overdosage (10)], and this risk is increased with higher
doses or unapproved methods of administration, such as snorting or injection.
Before prescribing VYVANSE, assess each patient’s
risk for abuse, misuse, and addiction. Educate patients and their families
about these risks and proper disposal of any unused drug. Advise patients to
store VYVANSE in a safe place, preferably locked, and instruct patients to not
give VYVANSE to anyone else. Throughout VYVANSE treatment, reassess each
patient’s risk of abuse, misuse, and addiction and frequently monitor for signs
and symptoms of abuse, misuse, and addiction.
5.8 Motor and Verbal Tics, and Worsening of Tourette’s Syndrome
New
subsection added:
CNS stimulants, including amphetamine, have been
associated with the onset or exacerbation of motor and verbal tics. Worsening
of Tourette’s syndrome has also been reported [see Adverse Reactions (6.2)].
Before initiating VYVANSE, assess the family history
and clinically evaluate patients for tics or Tourette’s syndrome. Regularly
monitor VYVANSE-treated patients for the emergence or worsening of tics or
Tourette’s syndrome, and discontinue treatment if clinically appropriate.
6
Adverse Reactions
Additions and/or
revisions underlined:
The following adverse reactions are discussed in
greater detail in other sections of the labeling:
…
Abuse, Misuse, and
Addiction [see Boxed Warning, Warnings and Precautions
(5.1), and Drug Abuse and Dependence (9.2, 9.3)]
…
6.2 Postmarketing
Experience
Additions
and/or revisions underlined
… These events are
as follows: cardiomyopathy, mydriasis, diplopia, difficulties with visual
accommodation, blurred vision, eosinophilic hepatitis, anaphylactic reaction,
hypersensitivity, dyskinesia, dysgeusia, motor and verbal 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.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined
…
Abuse,
Misuse, and Addiction
Educate
patients
and their families about the risks of abuse, misuse, and addiction of
VYVANSE, which can lead to overdose and death, and proper disposal of any
unused drug [see Warnings and Precautions
(5.1), Drug Abuse and Dependence
(9.2), Overdosage (10)]. Advise patients to store VYVANSE in
a safe place, preferably locked, and instruct patients to not give
VYVANSE to anyone else.
…
Motor
and Verbal Tics, and Worsening of Tourette’s Syndrome
Advise
patients that motor and verbal tics and worsening of Tourette’s Syndrome may
occur during treatment with VYVANSE. Instruct patients to notify their
healthcare provider if emergence of new tics or worsening of tics or Tourette’s
syndrome occurs [see Warnings and
Precautions (5.8)].
Pregnancy
Registry
Advise
patients that there is a pregnancy exposure registry that monitors pregnancy
outcomes in women exposed to VYVANSE during pregnancy [see Use in Specific Populations (8.1)].
…
MEDICATION GUIDE
Medication Guide has undergone extensive changes;
please refer to label.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 Suppression of Growth
Additions
underlined
![]()
…
Patients
who are not growing or gaining height or weight as expected may need to have
their treatment interrupted. VYVANSE is not approved for use in pediatric
patients below 6 years of
age [see Use in Specific Populations
(8.4)].
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions
underlined
…
Attention Deficit Hyperactivity Disorder
…
Adverse
Reactions Occurring at an Incidence of greater than or equal to 5% or More Among
VYVANSE Treated Patients with ADHD in Clinical Trials
The most common adverse reactions (incidence greater
than or equal to 5% and at a rate at least twice placebo) reported in pediatric
patients ages 6 to 17 years, and/or adults were anorexia, anxiety, decreased
appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia,
nausea, upper abdominal pain, and vomiting.
…
Weight
Loss and Slowing Growth Rate in Pediatric Patients with ADHD
…
Careful follow-up
of weight and height in pediatric patients 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 pediatric patients over 36 months (to the
ages of 10 to 13 years), suggests that consistently medicated pediatric patients
ages 7 to 13 years (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 pediatric patients
ages 13 to 17 years, 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 [see Warnings and Precautions (5.5)].
Binge Eating Disorder
…
Adverse Reactions Occurring
at an Incidence of 5% or More and At Least Twice Placebo Among VYVANSE Treated
Patients with BED in Clinical Trials
The
most common adverse reactions (incidence greater than or equal to 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
Occurring at an Incidence of 2% or More and At Least Twice Placebo Among
VYVANSE Treated Patients with BED in Clinical Trials
Adverse
reactions reported in the pooled controlled trials in adult patients (Study 11
and 12) treated with VYVANSE or placebo are presented in Table 4 below.
Please
refer to label to view Table 4
8
Use in Specific Populations
8.1 Pregnancy
8.4 Pediatric Use
Additions
underlined
ADHD
Safety
and effectiveness of VYVANSE have been established in pediatric patients with
ADHD ages 6 to 17 years [see Dosage and
Administration (2.3), Adverse Reactions (6.1), Clinical Pharmacology (12.3),
and Clinical Studies (14.1)].
Safety
and effectiveness of VYVANSE have not been established in pediatric patients
below the age of 6 years.
Safety
and efficacy of VYVANSE were evaluated in a double-blind, randomized,
parallel-group, placebo-controlled, fixed-dose study in pediatric patients ages
4 to 5 years with ADHD, followed by a 1-year open-label extension study. In
these studies, patients experienced elevated rates of adverse reactions,
including weight loss, decreased BMI, decreased appetite, insomnia, infections
(upper respiratory and nasopharyngitis), irritability, and affect lability.
With
the same VYVANSE dose, mean steady state exposure of dextroamphetamine was
approximately 44% higher in pediatric patients ages 4 to 5 years compared to
the pediatric patients ages 6 to 11 years.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Extensive additions and/or revisions, please refer
to label for complete information.
PATIENT COUNSELING INFORMATION
Additions
underlined
…
Administration
Instructions
Capsules: Advise
patients to take the capsules whole or empty and mix the entire contents with
yogurt, water, or orange juice. Advise patients to consume the mixture
immediately and not to store for future use [see Dosage and Administration (2.2)].
Chewable tablets:
Advise patients that chewable tablets must be chewed thoroughly before
swallowing [see Dosage and Administration
(2.2)].
Approved Drug Label (PDF)
6
Adverse Reactions
Table
1 Adverse Reactions Reported by 2% of More of Children (Ages 6-12 years) with
ADHD Taking VYVANSE and at least Twice the Incidence in Patients Taking Placebo
in a 4-Week Clinical Trial (Study 1)
Under
the VYVANSE column, Insomnia changes from 23 to 22%
Anorexia
added to table, 2% under VYVANSE column, and 0% under placebo column
Table
2 Adverse Reactions Reported by 2% or More of Adolescent (Ages 13 to 17 Years
(Patients with ADHD Taking VYVANSE and at least Twice the Incidence of Patients
Taking Placebo in a 4-Week Clinical Trial (Study 4)
Addition
of Palpitations,
Anorexia, and Tremor to table. All have 2% under VYVNASE column, and 0%
under Placebo column.
Table
3 Adverse Reactions Reported by 2% or More of Adult Patients with ADHD Taking
Vyvanse and at least Twice the Incidence in Patients Taking Placebo in a 4-Week
Clinical Trial (Study 7)
Addition
of Palpitations to table; 2% under VYVANSE column and 0%
under Placebo column.
6.1 Clinical Trial Experience
Attention Deficit Hyperactivity Disorder
Adverse
Reactions Associated with Discontinuation of Treatment in ADHD Clinical Trials
Additions
and/or revisions underlined:
In the controlled trials in patients
ages 6 to 12 years (Study 1), 8% (18/218) of VYVANSE-treated patients
discontinued due to adverse reactions compared to 0% (0/72) of placebo-treated
patients. The most frequently reported adverse
reactions (1% or more and twice rate of placebo) were ECG voltage
criteria for ventricular hypertrophy, tic, vomiting, psychomotor hyperactivity,
insomnia, decreased appetite and rash [2 instances for each adverse reactions,
i.e., 2/218 (1%)]. Less frequently
reported adverse reactions (less than 1% or less than twice rate of placebo)
included abdominal pain upper, dry mouth, weight decreased, dizziness,
somnolence, logorrhea, chest pain, anger, and hypertension.
In the controlled trial in patients ages
13 to 17 years (Study 4), 3% (7/233) of VYVANSE –treated patients
discontinued due to adverse reactions compared to 1% (7/233) of placebo-treated
patients. The most frequently reported
adverse reactions (1% or more and twice rate of placebo) were decreased
appetite (2/233; 1%) and insomnia (2/233; 1%).
Less frequently reported adverse reactions (less than 1% or less than
twice rate of placebo) included irritability, dermatillomania, mood swings, and
dyspnea.
In the controlled adult trial (Study 7),
6% (21/358) of VYVANSE-treated patients discontinued due to adverse reactions
compared to 2% (1/62) of placebo-treated patients. The most frequently reported adverse reactions
(1% or more and twice rate of placebo) were insomnia (8/358; 2%),
tachycardia (3/358; 1%), irritability (2/358; 1%), hypertension (4/358; 1%),
headache (28/358; 1%), anxiety (2/358; 1%), and dyspnea (3/358; 1%). Less frequently reported adverse reactions
(less than 1% or less than twice rate of placebo) included palpitations,
diarrhea, nausea, decreased appetite, dizziness, agitation, depression,
paranoia and restlessness.
Adverse
Reactions Occurring at an Incidence of greater than or equal to 5% or More
Among VYVANSE Treated Patients with ADHD in Clinical Trials
The most common adverse reactions
(incidence …
6.2 Postmarketing Experience
Addition
of chest
pain to listing of adverse reactions
identified during post approval use of VYVANSE.
Approved Drug Label (PDF)
6
Adverse Reactions
6.2 Postmarketing Experience
(Additions and/or revisions
are underlined)
…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, alopecia, …
Approved Drug Label (PDF)
4
Contraindications
Additions
and/or revisions underlined:
VYVANSE administration is
contraindicated in patients with the following conditions:
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.
5
Warnings and Precautions
5.7 Serotonin Syndrome
Newly
added subsection:
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. Amphetamines and amphetamine derivatives are known to be
metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor
inhibition of CYP2D6 metabolism. The potential for a pharmacokinetic
interaction exists with the co-administration of CYP2D6 inhibitors which may
increase the risk with increased exposure to the active metabolite of VYVANSE
(dextroamphetamine). In these situations, consider an alternative
non-serotonergic drug or an alternative drug that does not inhibit CYP2D6.
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 VYVANSE with MAOI
drugs is contraindicated.
Discontinue treatment with VYVANSE and
any concomitant serotonergic agents immediately if symptoms of serotonin syndrome
occur, and initiate supportive symptomatic treatment. Concomitant use of
VYVANSE with other serotonergic drugs or CYP2D6 inhibitors should be used only
if the potential benefit justifies the potential risk. If clinically warranted,
consider initiating VYVANSE with lower doses, monitoring patients for the
emergence of serotonin syndrome during drug initiation or titration, and
informing 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:
Addition
of the following:
Serotonin Syndrome
7
Drug Interactions
7.1 Drugs Having Clinically Important Interactions with Amphetamines
Table
5 Drugs having clinically important interactions with amphetamines
Addition
of Serotonergic Drugs and CYP2D6 Inhibitors to table; please refer to label.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additional
subsections added:
Serotonin Syndrome
Caution patients about the risk of
serotonin syndrome with concomitant use of VYVANSE and other serotonergic drugs
including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium,
tramadol, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism
of serotonin (in particular MAOIs, both those intended to treat psychiatric
disorders and also others such as linezolid. Advise patients to contact their
healthcare provider or report to the
emergency room if they experience signs or symptoms of serotonin syndrome.
Concomitant Medications
Advise patients to notify their
physicians if they are taking, or plan to take, any prescription or
over-the-counter drugs because there is a potential for interactions.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.4 Psychiatric Adverse Reactions
Induction of a Manic Episode in Patients with
Bipolar Disorder (addition underlined)
CNS stimulants may induce a
mixed/manic episode in patients with bipolar disorder. Prior to initiating
treatment, screen patients for risk factors for developing a manic episode (e.g.,
comorbid or history of depressive symptoms or a family history of suicide,
bipolar disorder, and depression).
6
Adverse Reactions
6.2 Postmarketing Experience (addition underlined)
…, 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.
7
Drug Interactions
Tables 5 and 6 revised, please
refer to label.
8
Use in Specific Populations
8.1
Pregnancy (PLLR conversion)
8.2 Lactation
(PLLR conversion)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION (addition underlined)
Pregnancy
Advise patients of
the potential fetal effects from the use of VYVANSE during pregnancy. Advise
patients to notify their healthcare provider if they become pregnant or intend
to become pregnant during treatment with VYVANSE.
Lactation
Advise women not to
breastfeed if they are taking VYVANSE.
Get Email Alerts |
Guide
