Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 Long-Term Suppression of Growth in Pediatric Patients
Additions and/or revisions underlined:
DYANAVEL XR is not
approved for use and is not recommended in pediatric patients below 6 years of
age [see Use in Specific Populations (8.4)].
…
8
Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and effectiveness of DYANAVEL XR have not
been established in pediatric patients below the age of 6 years.
In studies evaluating extended-release amphetamine
products, patients 4 to <6 years of age had higher systemic amphetamine
exposures than those observed in older pediatric patients at the same dosage.
Pediatric patients 4 to <6 years of age also had a higher incidence of
adverse reactions, including weight loss.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
…
What
is DYANAVEL XR?
DYANAVEL XR is a central nervous system (CNS)
stimulant prescription medicine used for the treatment of Attention Deficit Hyperactivity
Disorder (ADHD) in people 6 years of age and older.
DYANAVEL
XR may help increase attention and decrease impulsiveness and hyperactivity in
people with ADHD.
DYANAVEL
XR is not recommended for use in children under 6 years of age with
ADHD.
…
Approved Drug Label (PDF)
Boxed Warning
Additions and/or
revisions underlined:
WARNING: ABUSE,
MISUSE, AND ADDICTION
DYANAVEL XR 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 DYANAVEL XR, 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
DYANAVEL XR, 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 DYANAVEL XR 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:
DYANAVEL XR has a high
potential for abuse and misuse. The use of DYANAVEL XR exposes individuals to
the risks of abuse and misuse, which can lead to the development of a substance
use disorder, including addiction. DYANAVEL XR 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 DYANAVEL XR, can result in overdose and death [see Overdosage (10)] , and this risk is
increased with higher doses and or unapproved methods of administration, such
as snorting or injection.
Before prescribing DYANAVEL XR, 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 DYANAVEL XR in
a safe place, preferably locked, and instruct patients to not give DYANAVEL XR
to anyone else. Throughout DYANAVEL XR 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 DYANAVEL
XR, assess the family history and clinically evaluate patients for tics or
Tourette’s syndrome.
Regularly monitor DYANAVEL XR-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:
…
6.2 Postmarketing
Experience
Additions
and/or revisions underlined:
…
Central
Nervous System:
restlessness, irritability, euphoria, dyskinesia, dysphoria, depression,
tremor, aggression, anger, logorrhea, and paresthesia (including formication), motor
and verbal tics
…
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 DYANAVEL XR, 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 DYANAVEL XR in a safe place, preferably locked, and
instruct patients to not give DYANAVEL XR 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 DYANAVEL XR.
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)].
…
MEDICATION GUIDE
Medication
Guide has undergone extensive changes; please refer to label.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 Long-Term Suppression of Growth
Additions
underlined
…
![]()
Patients who are
not growing or gaining height or weight as expected may need to have their
treatment interrupted
[see Use in Specific
Populations (8.4)].
6
Adverse Reactions
6.2 Postmarketing Experience
Additions underlined
…
Gastrointestinal:
unpleasant taste, constipation, intestinal ischemia, and other
gastrointestinal disturbances
…
8
Use in Specific Populations
8.1 Pregnancy
Additions
and/or revisions underlined
…
Risk Summary
…
No
effects on morphological development were observed in embryo-fetal development
studies with oral administration of amphetamine to rats and rabbits during
organogenesis at doses that are approximately 3 and 16 times,
respectively, the maximum recommended human dose (MRHD) of 20 mg/day (as base
equivalents) on a mg/m2 basis, given to adults. However, long-term
neurochemical and behavioral effects have been reported in published animal
developmental studies using clinically relevant doses of amphetamine [see Data]. In the U.S.
general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
…
Data
Animal Data
…
These doses are approximately 3 and 16 times,
respectively, the MRHD of 20 mg/day (as base equivalents) on a mg/m2 basis,
given to adults. Fetal malformations and death have been reported in mice
following parenteral administration of d-amphetamine
doses of 50 mg/kg/day (approximately 12 times the MRHD) given to adults
on a mg/m2 basis or greater to pregnant animals. Administration of these doses
was also associated with severe maternal toxicity.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions underlined
…
Dosage and
Administration Instructions
…
DYANAVEL XR extended-release tablets
o Tablets may be chewed or swallowed
whole.
…
Approved Drug Label (PDF)
6
Adverse Reactions
6.2 Postmarketing Experience
(additions
underlined)
The
following adverse reactions have been identified during post approval use of
other amphetamine products. 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.
Allergic:
urticaria, rash, hypersensitivity reactions including angioedema and
anaphylaxis. Serious skin rashes, including Stevens-Johnson Syndrome and toxic
epidermal necrolysis have been reported.
Cardiovascular:
palpitations, sudden death, myocardial infarction. There have been isolated
reports of cardiomyopathy associated with chronic amphetamine use.
Central
Nervous System: restlessness, irritability, euphoria, dyskinesia, dysphoria,
depression, tremor, aggression, anger, logorrhea, and paresthesia (including
formication).
Endocrine:
impotence, changes in libido, frequent or prolonged erections. Eye
Disorders: vision blurred, mydriasis
Gastrointestinal:
unpleasant taste, constipation, other gastrointestinal disturbances.
Musculoskeletal, Connective Tissue, and Bone Disorders: rhabdomyolysis.
Psychiatric
Disorders: dermatillomania, bruxism.
Skin: alopecia
Vascular
Disorders: Raynaud’s phenomenon
8
Use in Specific Populations
8.1 Pregnancy
(additions
underlined)
Pregnancy
Exposure Registry
There
is a pregnancy exposure registry that monitors pregnancy outcomes in women
exposed to DYANAVEL XR during pregnancy. Healthcare providers are encouraged to
register patients by calling the National Pregnancy Registry for
Psychostimulants at 1-866-961-2388 or visiting online at
https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/.
Risk Summary
…No
effects on morphological development were observed in embryo-fetal development
studies with oral administration of amphetamine to rats and rabbits during
organogenesis at doses 2 and 12 times, respectively, the maximum
recommended human dose (MRHD) of 20 mg/day (as base equivalents) given to
adolescents, on a mg/m2 basis. However, long-term neurochemical and
behavioral effects have been reported in published animal developmental studies
using clinically relevant doses of amphetamine [see Data]. In the U.S. general population, the
estimated background risk of major birth defects and miscarriage in clinically
recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
…
Data
Animal
Data
…These
doses are approximately 2 and 12 times, respectively, the MRHD of
20 mg/day (as base equivalents), given to adolescents, on a mg/m2 basis.
Fetal malformations and death have been reported in mice following parenteral
administration of d- amphetamine doses of 50 mg/kg/day (approximately 10
times the MRHD) given to adolescents on a mg/m2 basis or greater to
pregnant animals. Administration of these doses was also associated with severe
maternal toxicity.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(additions
underlined)
…
Before taking
DYANAVEL XR tell your healthcare provider about all medical conditions,
including if you or your child:
…
There is a pregnancy registry for females who are
exposed to DYANAVEL XR during pregnancy. The purpose of the registry is to
collect information about the health of females exposed to DYANAVEL XR and
their baby. If you or your child becomes pregnant during treatment with DYANAVEL
XR, talk to your healthcare provider about registering with the National
Pregnancy Registry for Psychostimulants at 1- 866-961-2388 or visit https://womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry/othermedications/.
PATIENT COUNSELING INFORMATION
(additions
underlined)
…
Pregnancy
Registry
Advise
patients that there is a pregnancy exposure registry that monitors pregnancy
outcomes in women exposed to DYANAVEL XR during pregnancy.
…
Approved Drug Label (PDF)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17. PATIENT COUNSELING INFORMATION
(Additions and/or revisions are underlined)
Advise the patient
to read the FDA-approved patient labeling (Medication Guide and Instructions
for Use).
Dosage and Administration Instructions
Provide the
following instructions on administration to the patient:
- Use with the oral dosing dispenser provided by the
pharmacist.
- Ensure that the bottle adapter has been firmly inserted into the
bottle by the pharmacist. Once the bottle adapter has been inserted into
the bottle it should not be removed.
- Shake the bottle of DYANAVEL XR before each dose.
- Measure the appropriate dose as prescribed by the physician.
- Using the filled oral dosing dispenser, dispense DYANAVEL
XR directly into mouth.
- Replace bottle cap and store bottle as directed.
- Wash oral dosing dispenser after each use.
MEDICATION GUIDE
(Additions and/or revisions are underlined)
What is the most
important information I should know about DYANAVEL XR? DYANAVEL XR can cause
serious side effects, including:
- Abuse and dependence. DYANAVEL XR, other amphetamine
containing medicines, and methylphenidate have a high chance for abuse and
can cause physical and psychological dependence. Your healthcare provider
should check you or your child for signs of abuse and dependence before,
and during, treatment with DYANAVEL XR.
- Your healthcare provider can tell you
more about the differences between physical and psychological dependence
and drug addiction.
- Heart-related problems, including:
- sudden death in children and
adolescents who have heart problems or heart defects
…Call your healthcare
provider or go the nearest hospital emergency room right away if you or
your child have any signs of heart problems such as chest pain, shortness of breath,
or fainting while taking DYANAVEL XR.
- Mental (psychiatric) problems, including:
…Call your healthcare
provider right away if you or your child have any new or worsening mental
symptoms or problems while taking DYANAVEL XR, especially hearing voices, seeing
or believing things that are not real, or new manic symptoms.
What is
DYANAVEL XR?
…DYANAVEL XR
is a federally controlled substance (CII) because it contains amphetamine that
can be a target for people who abuse prescription medicines or street drugs. Keep
DYANAVEL XR in a safe place to protect it from theft. Never give your DYANAVEL
XR to anyone else, because it may cause death or harm them. Selling or giving
away DYANAVEL XR may harm others and is against the law.
Before taking
DYANAVEL XR tell your healthcare provider about all medical conditions,
including if you or your child:
- are breastfeeding or plan to breastfeed. DYANAVEL XR passes into
breast milk. You should not breastfeed while you are taking DYANAVEL
XR.
How should I
take DYANAVEL XR?
See the
detailed “Instructions for Use” for information on how to give a dose of
DYANAVEL XR.
What are
possible side effects of DYANAVEL XR? DYANAVEL XR can cause serious side
effects, including:
- Slowing of growth (height and weight) in children. Children should have their height and
weight checked often while taking DYANAVEL XR.
- Circulation problems in fingers and
toes (peripheral vasculopathy, including Raynaud’s phenomenon). Signs and symptoms may include:
- fingers or toes may feel numb, cool,
painful
- fingers or toes may change color from
pale, to blue, to red
Tell your
healthcare provider if you or your child have numbness, pain, skin color
change, or sensitivity to temperature in your fingers or toes.
Call your
healthcare provider right away if you or your child have any signs of
unexplained wounds appearing on fingers or toes while taking DYANAVEL XR.
Approved Drug Label (PDF)
4
Contraindications
Additions and/or revisions underlined:
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). The
potential for a pharmacokinetic interaction exists with the co- administration
of CYP2D6 inhibitors which may increase the risk of serotonin syndrome with
increased exposure to DYANAVEL XR. 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 DYANAVEL XR with MAOI drugs is contraindicated.
![]()
If symptoms of serotonin syndrome
occur, discontinue all serotonergic agents immediately, and initiate supportive
symptomatic treatment. If concomitant use of DYANAVEL XR with other
serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate
DYANAVEL XR with lower doses, monitor patients for the emergence of serotonin
syndrome during drug initiation or titration, and inform patients of the
increased risk for serotonin syndrome.
6
Adverse Reactions
Addition of the following to the bulleted list:
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Addition of the following:
Read this Medication Guide that comes with DYANAVEL XR before you or your
child starts taking it and each time you get a refill. There may be new
information. This Medication Guide does not take the place of talking to your
doctor about your or your child’s treatment with DYANAVEL XR.
PATIENT COUNSELING INFORMATION
Addition of the following:
Serotonin
Syndrome
Caution patients
about the risk of serotonin syndrome with concomitant use of DYANAVEL XR 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.
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