Included as part of the PRECAUTIONS section.
Potential For Abuse And Dependence
CNS stimulants, including Focalin, 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 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 taking CNS stimulants at
recommended doses for ADHD. Avoid use in patients with known serious structural
cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities,
coronary artery disease, and other serious heart problems. Further evaluate
patients who develop exertional chest pain, unexplained syncope, or arrhythmias
during Focalin treatment.
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 Preexisting Psychosis
CNS stimulants may exacerbate symptoms of behavior
disturbance and thought disorder in patients with a preexisting psychotic
Induction Of A Manic Episode In Patients With Bipolar
CNS stimulants may induce a manic or mixed mood 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 Focalin. In a pooled analysis of
multiple short-term, placebo-controlled studies of CNS Â timulants, 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 Focalin, 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
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 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 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 development.
Closely monitor growth (weight and height) in pediatric
patients treated with CNS stimulants, including Focalin, and patients who are
not growing or gaining height or weight as expected may need to have their
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (Medication Guide).
Controlled Substance Status/High Potential For Abuse And Dependence
Advise patients that Focalin is a controlled substance,
and it can be abused and lead to dependence. Instruct patients that they should
not give Focalin to anyone else. Advise patients to store Focalin 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 Focalin by a medicine take-back program if available [see BOXED
WARNING, WARNINGS AND PRECAUTIONS, Drug Abuse And Dependence,
HOW SUPPLIED/Storage And Handling].
Serious Cardiovascular Risks
Advise patients that there is a potential serious
cardiovascular risk including sudden death, myocardial infarction, stroke, and
hypertension with Focalin 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
Blood Pressure And Heart Rate Increases
Instruct patients that Focalin can cause elevations of
their blood pressure and pulse rate [see WARNINGS AND PRECAUTIONS].
Advise patients that Focalin, at recommended doses, can
cause psychotic or manic symptoms, even in patients without prior history of
psychotic symptoms or mania [see WARNINGS AND PRECAUTIONS].
Advise patients of the possibility of painful or
prolonged penile erections (priapism). Instruct them 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 Focalin 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 toes.
Instruct patients to call their physician immediately
with any signs of unexplained wounds appearing on fingers or toes while taking
Focalin. Further clinical evaluation (e.g., rheumatology referral) may be appropriate
for certain patients [see WARNINGS AND PRECAUTIONS].
Suppression Of Growth
Advise patients that Focalin may cause slowing of growth
and weight loss [see WARNINGS AND PRECAUTIONS].
Carcinogenesis, Mutagenesis, And Impairment Of Fertility
Lifetime carcinogenicity studies have not been carried
out with dexmethylphenidate. In a lifetime carcinogenicity study carried out in
B6C3F1 mice, racemic methylphenidate caused an increase in hepatocellular
adenomas, and in males only, an increase in hepatoblastomas was seen at a daily
dose of approximately 60 mg/kg/day. This dose is approximately 2 times the MRHD
of 60 mg of racemic methylphenidate in pediatric patients 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.
Racemic 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 4
times the MRHD of 60 mg of racemic methylphenidate in pediatric patients on a
In a 24-week carcinogenicity study with racemic
methylphenidate in the transgenic mouse strain p53+/-, which is sensitive to
genotoxic carcinogens, there was no evidence of carcinogenicity. Male and
female mice were fed diets containing the same concentrations as in the
lifetime carcinogenicity study; the high-dose group was exposed to 60-74
mg/kg/day of racemic methylphenidate.
Dexmethylphenidate was not mutagenic in the in vitro Ames
reverse mutation assay, in the in vitro mouse lymphoma cell forward mutation
assay, or in the in vivo mouse bone marrow micronucleus test. In an in vitro assay
using cultured Chinese Hamster Ovary (CHO) cells treated with racemic
methylphenidate, sister chromatid exchanges and chromosome aberrations were
increased, indicative of a weak clastogenic response.
Impairment Of Fertility
No human data on the effect of methylphenidate on
fertility are available.
Fertility studies have not been conducted with
dexmethylphenidate. Racemic 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 10-fold the maximum recommended dose of 60 mg of racemic methylphenidate
in adolescents on a mg/m² basis.
Use In Specific Populations
Pregnancy Category C
In studies conducted in rats and rabbits,
dexmethylphenidate was administered orally at doses of up to 20 and 100 mg/kg/day,
respectively, during the period of organogenesis. No evidence of teratogenic
activity was found in either the rat or rabbit study; however, delayed fetal
skeletal ossification was observed at the highest dose level in rats. When dexmethylphenidate
was administered to rats throughout pregnancy and lactation at doses of up to
20 mg/kg/day, postweaning body weight gain was decreased in male offspring at
the highest dose, but no other effects on postnatal development were observed.
At the highest doses tested, plasma levels (AUCs) of dexmethylphenidate in
pregnant rats and rabbits were approximately 5 and 1 times, respectively, those
in adults dosed with the maximum recommended human dose (MRHD) of 20 mg/day.
Racemic methylphenidate has been shown to have
teratogenic effects in rabbits when given in doses of 200 mg/kg/day throughout
Adequate and well-controlled studies in pregnant women
have not been conducted. Focalin should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
It is not known whether dexmethylphenidate is excreted in
human milk. Because many drugs are excreted in human milk, caution should be
exercised if Focalin is administered to a nursing woman.
The safety and effectiveness of Focalin have been
established in pediatric patients ages 6 to 17 years in two adequate and well-controlled
clinical trials [see Clinical Studies].
The safety and effectiveness of Focalin in pediatric
patients less than 6 years have not been established.
The long-term efficacy of Focalin in pediatric patients
has not been established.
Long Term Suppression Of Growth
Growth should be monitored during treatment with
stimulants, including Focalin. Pediatric patients who are not growing or
gaining weight as expected may need to have their treatment interrupted [see WARNINGS
Juvenile Animal Toxicity Data
In a study conducted in young rats, racemic
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 to 14), decreased spontaneous locomotor activity was
observed in males and females previously treated with 50 mg/kg/day
(approximately 6 times the MRHD of 60 mg of racemic methylphenidate on a mg/m²
basis) or greater, and a deficit in the acquisition of a specific learning task
was seen in females exposed to the highest dose (12 times the MRHD of 60 mg of
racemic methylphenidate on a mg/m² basis). The no effect level for juvenile
neurobehavioral development in rats was 5 mg/kg/day (half the MRHD of 60 mg of
racemic methylphenidate on a mg/m² basis). The clinical significance of the
long-term behavioral effects observed in rats is unknown.
Focalin has not been studied in the geriatric population.