Included as part of the PRECAUTIONS section.
Potential For Abuse And Dependence
CNS stimulants, including MYDAYIS, other
amphetamine-containing products, and methylphenidate, have a high potential for
abuse and dependence. Assess the risk of abuse prior to prescribing, and
monitor for signs of abuse and dependence while on therapy [see BOXED
WARNING, Drug Abuse and Dependence].
Serious Cardiovascular Reactions
Sudden death, stroke and myocardial infarction have been
reported in adults with CNS stimulant treatment at recommended doses. Sudden
death has been reported in pediatric patients with structural cardiac
abnormalities and other serious heart problems while taking CNS stimulants at
recommended doses for ADHD. Avoid use in patients with known structural cardiac
abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery
disease, and other serious heart problems. Further evaluate patients who
develop exertional chest pain, unexplained syncope, or arrhythmias during
Blood Pressure And Heart Rate Increases
CNS stimulants cause an increase in blood pressure (mean
increase about 2-4 mm Hg) and heart rate (mean increase about 3-6 bpm). Monitor
all patients for potential tachycardia and hypertension [see ADVERSE
Psychiatric Adverse Reactions
Exacerbation Of Pre-existing Psychosis
CNS stimulants may
exacerbate symptoms of behavior disturbance and thought disorder in patients
with a pre-existing psychotic disorder.
Induction Of A Manic Episode In Patients With Bipolar
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).
New Psychotic Or Manic Symptoms
CNS stimulants, at
recommended doses, may cause psychotic or manic symptoms, e.g., hallucinations,
delusional thinking, or mania in patients without a prior history of psychotic
illness or mania. If such symptoms occur, consider discontinuing MYDAYIS. In a
pooled analysis of multiple short-term, placebo-controlled studies of CNS
stimulants, psychotic or manic symptoms occurred in 0.1% of CNS
stimulant-treated patients compared to 0% in placebo-treated patients.
Long-Term Suppression Of Growth
CNS stimulants have been associated with weight loss and
slowing of growth rate in pediatric patients. Closely monitor growth (weight
and height) in pediatric patients treated with CNS stimulants, including
MYDAYIS. In a 4-week, placebo-controlled trial of MYDAYIS in patients ages 6 to
17 years old with ADHD, there was a decrease in weight in the MYDAYIS groups
compared to weight gain in the placebo group [see ADVERSE REACTIONS].
Patients who are not growing or gaining weight as
expected may need to have their treatment interrupted. MYDAYIS is not approved
for use in pediatric patients 12 years and younger [Use in Specific Populations].
Peripheral Vasculopathy, Including Raynaud's Phenomenon
Stimulants, including MYDAYIS, used to treat ADHD are
associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs
and symptoms are usually intermittent and mild; however, very rare sequelae
include digital ulceration and/or soft tissue breakdown. Effects of peripheral
vasculopathy, including Raynaud's phenomenon, were observed in post-marketing
reports at different times and at therapeutic doses in all age groups
throughout the course of treatment. Signs and symptoms generally improve after
reduction in dose or discontinuation of drug. Careful observation for digital
changes is necessary during treatment with ADHD stimulants. Further clinical
evaluation (e.g., rheumatology referral) may be appropriate for certain
MYDAYIS may lower the convulsive threshold in patients
with prior history of seizure, in patients with prior EEG abnormalities in the
absence of seizures, and in patients without a history of seizures and no prior
EEG evidence of seizures. In the presence of seizures, MYDAYIS should be
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 [see DRUG INTERACTIONS]. The co-administration with
cytochrome P450 2D6 (CYP2D6) inhibitors may also increase the risk with
increased exposure to MYDAYIS. In these situations, consider an alternative
non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see DRUG
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 MYDAYIS with MAOI drugs is contraindicated
Discontinue treatment with MYDAYIS and any concomitant
serotonergic agents immediately if the above symptoms occur, and initiate
supportive symptomatic treatment. If concomitant use of MYDAYIS with other
serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate
MYDAYIS 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.
Potential For Overdose Due To Medication Errors
Medication errors, including substitution and dispensing
errors, between MYDAYIS and other amphetamine products could occur, leading to
possible overdosage. To avoid substitution errors and overdosage, do not substitute
for other amphetamine products on a milligram-per-milligram basis because of
different amphetamine base compositions and differing pharmacokinetic profiles [see
DOSAGE AND ADMINISTRATION and OVERDOSAGE].
Patient Counseling Information
Advise the patient to read the
FDA-approved patient labeling (Medication Guide).
Status/High Potential For Abuse and Dependence
Advise patients and their
caregivers that MYDAYIS is a federally controlled substance because it can be
abused or lead to dependence. Advise patients to store MYDAYIS in a safe place,
preferably locked, to prevent abuse. Advise patients to comply with laws and
regulations on drug disposal. Advise patients to dispose of remaining, unused,
or expired MYDAYIS by a medicine take-back program if available [see BOXED
WARNING, WARNINGS AND PRECAUTIONS, Drug
Abuse and Dependence].
Serious Cardiovascular Risks
Advise patients, caregivers,
and family members that there is a potential serious cardiovascular risk
including sudden death, myocardial infarction, stroke, and hypertension with
MYDAYIS use. Instruct patients to contact a healthcare provider immediately if
they develop symptoms such as exertional chest pain, unexplained syncope, or
other symptoms suggestive of cardiac disease [see WARNINGS AND
Blood Pressure And Heart Rate
Instruct patients that MYDAYIS
can cause elevations of their blood pressure and pulse rate and they should be
monitored for such effects [see WARNINGS AND PRECAUTIONS].
Advise patients that MYDAYIS,
at recommended doses, may cause psychotic or manic symptoms even in patients
without prior history of psychotic symptoms or mania [see WARNINGS
Long-Term Suppression Of Growth
Advise patients, family members,
and caregivers that amphetamines may cause slowing of growth including weight
loss [see WARNINGS AND PRECAUTIONS].
Circulation Problems In Fingers
And Toes [Peripheral Vasculopathy, including Raynaud's Phenomenon]
Instruct patients beginning
treatment with MYDAYIS about the risk of peripheral vasculopathy, including
Raynaud's phenomenon, and associated signs and symptoms: fingers or toes may
feel numb, cool, painful, and/or may change from pale, to blue, to red.
Instruct patients to report to their physician any new numbness, pain, skin
color change, or sensitivity to temperature in fingers or toes. Instruct
patients to call their physician immediately with any signs of unexplained
wounds appearing on fingers or toes while taking MYDAYIS. Further clinical
evaluation (e.g. rheumatology referral) may be appropriate for certain patients
[see WARNINGS AND PRECAUTIONS].
Caution patient that MYDAYIS
may lower the convulsive threshold. Advise patients to contact their healthcare
provider immediately and to discontinue MYDAYIS if a seizure occurs [see WARNINGS
Caution patients about the risk
of serotonin syndrome with concomitant use of MYDAYIS 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 [see CONTRAINDICATIONS, WARNINGS
AND PRECAUTIONS and DRUG INTERACTIONS]. Advise patients to contact their healthcare provider or
report to the emergency room if they experience signs or symptoms of serotonin
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 [see DRUG
Advise patients of the
potential fetal effects from the use of MYDAYIS during pregnancy. Advise
patients to notify their healthcare provider if they become pregnant or
intend to become pregnant during treatment with MYDAYIS [see Use in Specific
Advise women not to breastfeed if they are taking MYDAYIS
[see Use in Specific Populations].
Advise patients to avoid alcohol while taking MYDAYIS.
Consumption of alcohol while taking MYDAYIS may result in a more rapid release of the dose of mixed amphetamine salts
[see CLINICAL PHARMACOLOGY].
Impairment Of Fertility
No evidence of carcinogenicity was found in studies in
which d, l-amphetamine (enantiomer ratio of 1:1) was administered to mice and
rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19
mg/kg/day in female mice, and 5 mg/kg/day in male and female rats. These doses
are approximately 3, 2, and 1 times, respectively, the maximum recommended
human dose of 50 mg/day on a mg/m² body surface area basis in adults.
Amphetamine, in the enantiomer
ratio present, d-to l-ratio of 3:1, was not clastogenic in the mouse bone
marrow micronucleus test in vivo and was negative when tested in the E. coli
component of the Ames test in vitro. d, l-Amphetamine (1:1 enantiomer ratio)
has been reported to produce a positive response in the mouse bone marrow
micronucleus test, an equivocal response in the Ames test, and negative
responses in the in vitro sister chromatid exchange and chromosomal aberration
Impairment Of Fertility
Amphetamines, in the enantiomer ratio, d-to l-ratio of
3:1, did not adversely affect fertility or early embryonic development in the
rat at doses of up to 20 mg/kg/day (approximately 6 times the maximum
recommended human dose of 25 mg/day given to adolescents on a mg/m² body
surface area basis).
Use In Specific Populations
The limited available data from published literature and
postmarketing reports on use of amphetamine in pregnant women are not
sufficient to inform a drug-associated risk for major birth defects and
miscarriage. Adverse pregnancy outcomes, including premature delivery and low
birth weight, have been seen in infants born to mothers dependent on
amphetamines [see Clinical Considerations].
In an embryofetal development study, amphetamine (d-to l-enantiomer
ratio of 3:1, the same as in MYDAYIS) had no effects on embryofetal
morphological development or survival when administered to pregnant rats and
rabbits throughout the period of organogenesis up to doses 10 times the maximum
recommended human dose (MRHD) of 25 mg/day given to adolescents, on a mg/m² body
surface area basis. However, in a pre-and post-natal development study,
amphetamine (d-to l-ratio of 3:1) administered orally to pregnant rats during
gestation and lactation caused a decrease in pup survival and a decrease in pup
body weight that correlated with a delay in developmental landmarks at
clinically relevant doses of amphetamine. In addition, adverse effects on
reproductive performance were observed in pups whose mothers were treated with
amphetamine. Long-term neurochemical and behavioral effects have also been
reported in animal developmental studies using clinically relevant doses of
amphetamine [see Data].
The estimated background risk of major birth defects and
miscarriage for the indicated population is unknown. All pregnancies have a
background risk of birth defect, loss or other adverse outcomes. In the U.S.
general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2-4% and 1520%,
Fetal/Neonatal Adverse Reactions
Amphetamines, such as MYDAYIS,
cause vasoconstriction and thereby may decrease placental perfusion. In
addition, amphetamines can stimulate uterine contractions increasing the risk
of premature delivery. Infants born to amphetamine-dependent mothers have an
increased risk of premature delivery and low birth weight.
Monitor infants born to mothers
taking amphetamines for symptoms of withdrawal such as feeding difficulties,
irritability, agitation, and excessive drowsiness.
Amphetamine (d-to l-enantiomer ratio of 3:1, the same as
in MYDAYIS) had no apparent effects on embryofetal morphological development or
survival when administered orally to pregnant rats and rabbits throughout the
period of organogenesis at doses of up to 6 and 16 mg/kg/day, respectively.
These doses are approximately 2 and 10 times, respectively, the maximum
recommended human dose (MRHD) of 25 mg/day given to adolescents, on a mg/m² body
surface area basis. Fetal malformations and death have been reported in mice
following parenteral administration of d-amphetamine doses of 50 mg/kg/day
(approximately 8 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.
A pre-and postnatal development study was conducted with
amphetamine (d-to l-enantiomer ratio of 3:1) in which pregnant rats received
daily oral doses of 2, 6, and 10 mg/kg from gestation day 6 to lactation day
20. These doses are approximately 0.6, 2, and 3 times the MRHD of 25 mg/day
amphetamine (d-to l-ratio of 3:1) given to adolescents, on a mg/m² basis. All
doses caused hyperactivity and decreased weight gain in the dams. A decrease in
pup survival was seen at all doses. A decrease in pup body weight was seen at 6
and 10 mg/kg which correlated with delays in developmental landmarks, such as
preputial separation and vaginal opening. Increased pup locomotor activity was
seen at 10 mg/kg on day 22 postpartum but not at 5 weeks postweaning. When pups
were tested for reproductive performance at maturation, gestational weight
gain, number of implantations, and number of delivered pups were decreased in
the group whose mothers had been given 10 mg/kg.
A number of studies from the literature 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 long-term neurochemical
and behavioral alterations. Reported behavioral effects include learning and
memory deficits, altered locomotor activity, and changes in sexual function.
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 breastfed 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. 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 breastfeeding is not recommended
during treatment with MYDAYIS.
Safety and effectiveness in
pediatric patients with ADHD ages 13 to 17 years have been established in two
placebo-controlled clinical studies [see ADVERSE REACTIONS, CLINICAL
PHARMACOLOGY, Clinical Studies].
Safety and effectiveness have
not been established in pediatric patients ages 12 years and younger.
In clinical trials, pediatric
patients 6 to 12 years of age experienced higher rates of adverse reactions in
some cases compared to patients 13 years and older, including higher rates of
insomnia (30% versus 8%) and appetite decreased (43% versus 22%). In addition,
amphetamine systemic exposures (both d-and l-) in patients 6 to 12 years of age
following a single dose were higher than those observed in adults at the same
dose (72-79% higher Cmax and approximately 83% higher AUC).
Growth should be monitored
during treatment with stimulants, including MYDAYIS, in pediatric patients 13
to 17 years who are not growing or gaining weight as expected may need to have
their treatment interrupted [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS].
Juvenile Animal Toxicity Data
Juvenile rats treated with mixed amphetamine salts (same
as in MYDAYIS) early in the postnatal period through sexual maturation
demonstrated transient changes in motor activity. Learning and memory was
impaired at approximately 8 times the maximum recommended human dose (MRHD)
given to children on a mg/m² basis. No recovery was seen following a drug free
period. A delay in sexual maturation was observed at a dose approximately 8
times the MRHD given to children on a mg/m² basis, although there was no effect
In a juvenile developmental study, rats received daily
oral doses of amphetamine (d to l enantiomer ratio of 3:1, the same as in
MYDAYIS) of 2, 6, or 20 mg/kg on days 7-13 of age; from day 14 to approximately
day 60 of age these doses were given b.i.d. for total daily doses of 4, 12, or
40 mg/kg. The latter doses are approximately 0.8, 2, and 8 times the MRHD of 25
mg/day given to children on a mg/m² basis. Post-dosing hyperactivity was seen
at all doses; motor activity measured prior to the daily dose was decreased
during the dosing period but the decreased motor activity was largely absent after
an 18 day drug-free recovery period. Performance in the Morris water maze test
for learning and memory was impaired at the 40 mg/kg dose, and sporadically at
the lower doses, when measured prior to the daily dose during the treatment
period; no recovery was seen after a 19 day drug-free period. A delay in the
developmental milestones of vaginal opening and preputial separation was seen
at 40 mg/kg but there was no effect on fertility.
Clinical studies of MYDAYIS did
not include sufficient numbers of subjects aged 65 and over to determine
whether they respond differently from younger subjects. Other reported clinical
experience has not identified differences in responses between the elderly and
younger patients. In general, dose selection for an elderly patient should
start 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.
Due to reduced clearance of amphetamine in patients with
severe renal insufficiency (GFR 15 to < 30 mL/min/1.73 m²), the maximum dose
in adults should be reduced. Pediatric patients ages 13 to 17 years with severe
renal insufficiency can be given the recommended starting dose if tolerated,
but the dose should not be escalated. MYDAYIS is not recommended in patients
with ESRD (GFR < 15 mL/min/1.73 m²) [see DOSAGE AND ADMINISTRATION, CLINICAL
D-amphetamine is not