Included as part of the PRECAUTIONS section.
Potential For Abuse and Dependence
CNS stimulants, including QUILLIVANT XR, other
methylphenidate-containing products, and amphetamines, 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 Drug Abuse And
Serious Cardiovascular Reactions
Stroke and myocardial infarction have occurred in adults
treated with CNS stimulants at recommended doses. Sudden death has occurred in
children and adolescents with structural cardiac abnormalities and other
serious cardiac problems, and in adults taking CNS stimulants at recommended
doses for ADHD. Avoid use in patients with known structural cardiac abnormalities,
cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other
serious cardiac problems. Further evaluate patients who develop exertional
chest pain, unexplained syncope, or arrhythmias during treatment with QUILLIVANT
Blood Pressure And Heart Rate Increases
CNS stimulants cause an increase in blood pressure (mean
increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately
3 to 6 bpm). Individuals may have larger increases. Monitor all patients for
hypertension and tachycardia.
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
Induction Of A Manic Episode In Patients With Bipolar
CNS stimulants may induce a manic or mixed episode in
patients. 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, or 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 QUILLIVANT XR. In a pooled analysis of
multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or
manic symptoms occurred in approximately 0.1% of CNS stimulant-treated
patients, compared to 0 in placebo-treated patients.
Prolonged and painful erections, sometimes requiring
surgical intervention, have been reported with methylphenidate products in both
pediatric and adult patients. Priapism was not reported with drug initiation
but developed after some time on the drug, often subsequent to an increase in
dose. Priapism has also appeared during a period of drug withdrawal (drug
holidays or during discontinuation). Patients who develop abnormally sustained
or frequent and painful erections should seek immediate medical attention.
Peripheral Vasculopathy, Including Raynaud's Phenomenon
CNS stimulants, including QUILLIVANT XR, 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 of
digital changes is necessary during treatment with ADHD stimulants. Further
clinical evaluation (e.g., rheumatology referral) may be appropriate for
Long-Term Suppression Of Growth
CNS stimulants have been associated with weight loss and
slowing of growth rate in pediatric patients. Careful follow-up of weight and
height in pediatric patients ages 7 to 10 years who were randomized to either
methylphenidate or nonmedication treatment groups over 14 months, as well as in
naturalistic subgroups of newly methylphenidate-treated and nonmedicationtreated
pediatric patients over 36 months (to the ages of 10 to 13 years), suggests
that consistently medicated pediatric patients (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
Closely monitor growth (weight and height) in pediatric
patients treated with CNS stimulants, including QUILLIVANT XR. Patients who are
not growing or gaining height or weight as expected may need to have their
Patient Counseling Information
Advise patients to read the FDA-approved patient labeling
(Medication Guide and Instructions for Use).
Controlled Substance Status/Potential For Abuse And Dependence
Advise patients and their caregivers that QUILLIVANT XR
is a federally controlled substance, and it can be abused and lead to dependence
[see Drug Abuse and Dependence]. Instruct patients that they should not
give QUILLIVANT XR to anyone else. Advise patients to store QUILLIVANT XR 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 QUILLIVANT XR through a medicine take-back program if
available [see WARNINGS AND PRECAUTIONS, Abuse and Dependence].
Instructions For Using The Enclosed Oral Dosing Dispenser
Provide the following instructions on administration to
the patient or caregiver:
- The pharmacist should provide this medicine in its
original packaging (bottle within carton) with the bottle adapter fully inserted
and the accompanying oral dosing dispenser. Use only with the oral dosing
dispenser provided with this product.
- Check and make sure that the QUILLIVANT XR bottle
contains liquid medicine. If QUILLIVANT XR is in powder form, do not use it.
Return it to your pharmacist.
- VIGOROUSLY SHAKE the bottle of QUILLIVANT XR for at least
10 seconds before each dose, to ensure that the proper dose is administered.
- Remove the bottle cap. Confirm that the bottle adapter
has been inserted into top of the bottle.
- Insert the tip of the oral dosing dispenser provided with
this product into the bottle adapter.
- Turn bottle upside down and withdraw prescribed amount of
QUILLIVANT XR into the oral dosing dispenser.
- Remove filled oral dosing dispenser from bottle and
dispense QUILLIVANT XR directly into mouth.
- Replace bottle cap and store bottle as directed.
- Wash oral dosing dispenser after each use (components are
Serious Cardiovascular Risks
Advise patients, caregivers, and family members that
there is a potential for serious cardiovascular risks including sudden death,
myocardial infarction, and stroke with QUILLIVANT XR use. Instruct patients to
contact a health care provider immediately if they develop symptoms such as
exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac
disease [see WARNINGS AND PRECAUTIONS].
Blood Pressure And Heart Rate Increases
Advise patients that QUILLIVANT XR can elevate blood
pressure and heart rate [see WARNINGS AND PRECAUTIONS].
Advise patients that QUILLIVANT XR, at recommended doses,
can cause psychotic or manic symptoms, even in patients without a prior history
of psychotic symptoms or mania [see WARNINGS AND PRECAUTIONS].
Advise patients, caregivers, and family members of the
possibility of painful or prolonged penile erections (priapism). Instruct the
patient to seek immediate medical attention in the event of priapism [see
WARNINGS AND PRECAUTIONS].
Circulation Problems In Fingers And Toes [Peripheral
Vasculopathy, Including Raynaud's Phenomenon]
- Instruct patients beginning treatment with QUILLIVANT XR
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 color 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
- Instruct patients to call their physician immediately
with any signs of unexplained wounds appearing on fingers or toes while taking
- Further clinical evaluation (e.g., rheumatology referral)
may be appropriate for certain patients.
Suppression Of Growth
Advise patients, families, and caregivers that QUILLIVANT
XR can cause slowing of growth and weight loss[ see WARNINGS AND PRECAUTIONS].
Patients should be advised to avoid alcohol while taking
QUILLIVANT XR Oral Suspension. Consumption of alcohol while taking QUILLIVANT
XR may result in a more rapid release of the dose of methylphenidate [see CLINICAL
This product's label may have been updated. For current
full prescribing information, please visit www.pfizer.com.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In a lifetime carcinogenicity study carried out in B6C3F1
mice, methylphenidate caused an increase in hepatocellular adenomas and, in
males only, an increase in hepatoblastomas, at a daily dose of approximately 60
mg/kg/day. This dose is approximately 4 times the maximum recommended human
dose on a mg/m² basis. Hepatoblastoma is a relatively rare rodent malignant
tumor type. There was no increase in total malignant hepatic tumors. The mouse
strain used is sensitive to the development of hepatic tumors, and the
significance of these results to humans is unknown.
Methylphenidate did not cause any increase in tumors in a
lifetime carcinogenicity study carried out in F344 rats; the highest dose used
was approximately 45 mg/kg/day, which is approximately 5 times the maximum
recommended human dose on a mg/m² basis.
Methylphenidate was not mutagenic in the in vitro Ames
reverse mutation assay or in the in vitro mouse lymphoma cell forward mutation
assay. Sister chromatid exchanges and chromosome aberrations were increased,
indicative of a weak clastogenic response, in an in vitro assay in cultured
Chinese Hamster Ovary (CHO) cells. Methylphenidate was negative in an in vivo mouse
bone marrow micronucleus assay.
Impairment Of Fertility
Methylphenidate did not impair fertility in male or
female mice that were fed diets containing the drug in an 18-week Continuous Breeding
study. The study was conducted at doses of up to 160 mg/kg/day, approximately
8-fold the maximum recommended human dose on a mg/m² basis.
Use In Specific Populations
There are limited published studies and small case series
that report on the use of methylphenidate in pregnant women; however, the data
are insufficient to inform any drug-associated risks. There are clinical
considerations [see Clinical Considerations]. No teratogenic effects
were observed in embryo-fetal development studies with oral administration of methylphenidate
to pregnant rats and rabbits during organogenesis at doses 2 and 11 times,
respectively, the maximum recommended human dose (MRHD). However, spina bifida
was observed in rabbits at a dose 40 times the MRHD [see Data].
In the U.S. general population, the estimated background
risk of major birth defects and miscarriage in clinically recognized pregnancies
is 2–4% and 15–20%, respectively.
Fetal/Neonatal Adverse Reactions
CNS stimulant medications, such as QUILLIVANT XR, can
cause vasoconstriction and thereby decrease placental perfusion. No fetal
and/or neonatal adverse reactions have been reported with the use of
therapeutic doses of methylphenidate during pregnancy; however, premature
delivery and low birth weight infants have been reported in
In studies conducted in rats and rabbits, methylphenidate
was administered orally at doses of up to 75 and 200 mg/kg/day, respectively,
during the period of organogenesis. Teratogenic effects (increased incidence of
fetal spina bifida) were observed in rabbits at the highest dose, which is
approximately 40 times the maximum recommended human dose (MRHD) on a mg/m² basis.
The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day
(11 times the MRHD on a mg/m² basis). There was no evidence of specific
teratogenic activity in rats, although increased incidences of fetal skeletal
variations were seen at the highest dose level (7 times the MRHD on a mg/m²
basis), which was also maternally toxic. The no effect level for embryo-fetal
development in rats was 25 mg/kg/day (2 times the MRHD on a mg/m² basis).
Limited published literature reports that methylphenidate
is present in human milk, which resulted in infant doses of 0.16% to 0.7% of
the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1
and 2.7. There are no reports of adverse effects on the breastfed infant and no
effects on milk production. Long-term neurodevelopmental effects on infants from
CNS stimulant exposure are unknown. The developmental and health benefits of
breastfeeding should be considered along with the mother's clinical need for
QUILLIVANT XR and any potential adverse effects on the breastfed infant from QUILLIVANT
XR or from the underlying maternal condition.
Monitor breastfeeding infants for adverse reactions, such
as agitation, insomnia, anorexia, and reduced weight gain.
The safety and effectiveness of QUILLIVANT XR have been
established in pediatric patients ages 6 to 17 years. Use of QUILLIVANT XR in
pediatric patients 6 to 12 years of age is supported by one adequate and
well-controlled study [see Clinical Studies]. Use in 12 to 17 year olds
is supported by the adequate and well-controlled studies of QUILLIVANT XR in
younger pediatric patients and additional pharmacokinetic data in adolescents,
along with safety information from other methylphenidate-containing products.
The long-term efficacy of methylphenidate in pediatric patients has not been
established. Safety and efficacy in pediatric patients below the age of 6 years
have not been established.
Long Term Suppression Of Growth
Growth should be monitored during treatment with CNS
stimulants, including QUILLIVANT XR. Children who are not growing or gaining
weight as expected may need to have their treatment interrupted [see WARNINGS
Juvenile Animal Data
Rats treated with methylphenidate early in the postnatal
period through sexual maturation demonstrated a decrease in spontaneous
locomotor activity in adulthood. A deficit in acquisition of a specific
learning task was observed in females only. The doses at which these findings
were observed are at least 6 times the maximum recommended human dose (MRHD) on
a mg/m² basis.
In the study conducted in young rats, methylphenidate was
administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early
in the postnatal period (postnatal day 7) and continuing through sexual
maturity (postnatal week 10). When these animals were tested as adults
(postnatal weeks 13–14), decreased spontaneous locomotor activity was observed
in males and females previously treated with 50 mg/kg/day (approximately 6 times
the maximum recommended human dose [MRHD] on a mg/m² basis) or greater, and a
deficit in the acquisition of a specific learning task was observed in females
exposed to the highest dose (12 times the MRHD on a mg/m² basis). The no effect
level for juvenile neurobehavioral development in rats was 5 mg/kg/day (half
the MRHD on a mg/m² basis). The clinical significance of the long-term
behavioral effects observed in rats is unknown.
QUILLIVANT XR has not been studied in patients over the
age of 65 years.