CONCERTA is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in patients aged 6 to 65 years old. Limitations of Use The use of CONCERTA is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage [see Warnings and Precautions (5.7) and Use in Specific Populations (8.4) ].
CONCERTA is a CNS stimulant indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in patients aged 6 to 65 years old. ( 1 ) Limitations of Use The use of CONCERTA is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage ( 5.7 , 8.4 ).
Contraindications
CONCERTA is contraindicated in patients: Known to be hypersensitive to methylphenidate or other components of CONCERTA. Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been reported in patients treated with CONCERTA. [see Adverse Reactions (6) ] . Receiving concomitant monoamine oxidase inhibitors (MAOIs), and within 14 days following discontinuation of treatment with a MAO inhibitor because of the risk of a hypertensive crisis [see Drug Interactions (7) ] .
Known hypersensitivity to methylphenidate or other components of CONCERTA ( 4 ) Receiving concomitant monoamine oxidase inhibitors and within 14 days following discontinuation of treatment with a MAO inhibitor ( 4 )
Warnings and precautions
Risks to Patients with Serious Cardiac Disease : Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease ( 5.2 ). Increased Blood Pressure and Heart Rate : Monitor blood pressure and pulse ( 5.3 ). Psychiatric Adverse Reactions : Prior to initiating CONCERTA, screen patients for risk factors for developing a manic episode.
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If new psychotic or manic symptoms occur, consider discontinuing CONCERTA. ( 5.4 ) Priapism : If abnormally sustained or frequent and painful erections occur, patients should seek immediate medical attention ( 5.5 ) Peripheral Vasculopathy, including Raynaud's Phenomenon : Carefully assess for digital changes during CONCERTA treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy ( 5.6 ) Long-Term Suppression of Growth in Pediatric Patients : Closely monitor growth (height and weight) in pediatric patients.
Pediatric patients not growing or gaining height or weight as expected may need to have their CONCERTA treatment interrupted. ( 5.7 ) Risk of Gastrointestinal (GI) Obstruction in Patients with GI Narrowing: Only use in patients able to swallow the extended-release tablet whole, and should not ordinarily be used in patients with pre-existing severe GI narrowing. ( 5.8 ) Acute Angle Closure Glaucoma: CONCERTA-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.
( 5.9 ) Increased Intraocular Pressure (IOP) and Glaucoma : Prescribe CONCERTA to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor patients with a history of increased IOP or open angle glaucoma. ( 5.10 ) Motor and Verbal Tics, and Worsening of Tourette's Syndrome : Before initiating CONCERTA, assess the family history and clinically evaluate patients for tics or Tourette's syndrome.
Regularly monitor patients for the emergence or worsening of tics or Tourette's syndrome. Discontinue CONCERTA treatment if clinically appropriate. ( 5.11 )
5.1Abuse, Misuse, and Addiction
CONCERTA has a high potential for abuse and misuse. The use of CONCERTA exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction [see Drug Abuse and Dependence (9.1 , 9.2) ] . Misuse and abuse of CNS stimulants, including CONCERTA, can result in overdose and death [see Overdosage (10) ] , and this risk is increased with higher dosage or unapproved methods of administration, such as snorting or injection.
Before prescribing CONCERTA, 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 CONCERTA in a safe place, preferably locked, and instruct patients to not give CONCERTA to anyone else. Throughout CONCERTA treatment, reassess each patient's risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
5.2Risks to Patients with Serious Cardiac Disease
Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage. Avoid CONCERTA use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
5.3Increased Blood Pressure and Heart Rate
CNS stimulants may cause an increase in blood pressure (mean increase approximately 2 to 4 mm Hg) and heart rate (mean increase approximately 3 to 6 beats per minute) [see Adverse Reactions (6) ] . Some patients may have larger increases. Monitor all CONCERTA-treated patients for hypertension and tachycardia.
5.4Psychiatric Adverse Reactions Exacerbation of Psychosis in Patients with a Psychotic Disorder
CNS stimulants, including CONCERTA, may exacerbate behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder CNS stimulants, including CONCERTA, may induce a manic or mixed episode in patients with bipolar disorder. Prior to initiating CONCERTA treatment, screen patients for risk factors for developing a manic episode (e.g., history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).
New Psychotic or Manic Symptoms in Patients without a History of a Bipolar or Psychotic Disorder CNS stimulants (including CONCERTA), at the recommended dosage, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. 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 with 0% of placebo-treated patients.
If such symptoms occur, consider discontinuing CONCERTA.
5.5Priapism Prolonged
and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate use in adult and pediatric male patients [see Adverse Reactions (6) ] . Although priapism was not reported with methylphenidate initiation, priapism occurred in patients treated with methylphenidate after some time, often subsequent to an increase in dosage. Priapism also occurred during methylphenidate withdrawal (drug holidays or during discontinuation).
CONCERTA-treated patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.
5.6Peripheral
Vasculopathy, including Raynaud's Phenomenon CNS stimulants, including CONCERTA, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon [see Adverse Reactions (6.2) ] . Signs and symptoms of these cases of peripheral vasculopathy were usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports and at the therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment.
Signs and symptoms of peripheral vasculopathy generally improved after CNS stimulant dosage reduction or discontinuation. During CONCERTA treatment, carefully assess for digital changes. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for CONCERTA-treated patients who develop signs or symptoms of peripheral vasculopathy.
5.7Long-Term Suppression of Growth in Pediatric Patients
CONCERTA is not approved for use and is not recommended in pediatric patients below 6 years of age [see Use in Specific Populations (8.4) ] . CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Pediatric patients 7 to 13 years of age who received methylphenidate for 7 days per week for over 14 months to over 36 months had 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 development period.
Closely monitor growth (weight and height) in CONCERTA-treated pediatric patients. Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
5.8Risk of Gastrointestinal Obstruction in Patients with Gastrointestinal Narrowing Because
CONCERTA extended-release tablets are nondeformable and do not appreciably change in shape in the gastrointestinal (GI) tract, CONCERTA should not ordinarily be administered to pat
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Interactions
Table 6 describes clinically significant drug interactions with CONCERTA. Table 6: Clinically Significant Drug Interactions Monoamine Oxidase Inhibitors Prevention or Management Concomitant use of CNS stimulants, including CONCERTA, with MAOIs or within 14 days after discontinuing an MAOI is contraindicated [ see Contraindications (4) ]. Mechanism and Clinical Effect(s) Concomitant use of MAOIs and CNS stimulants, including CONCERTA, can cause hypertensive crisis.
Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Antihypertensive Drugs Prevention or Management Increase monitoring for blood pressure and adjust the dosage of the antihypertensive drug, as needed. Mechanism and Clinical Effect(s) CONCERTA may decrease effectiveness of drugs used to treat hypertension [see Warnings and Precautions 5.3 ].
Halogenated Anesthetics Prevention or Management Avoid use of CONCERTA in patients being treated with anesthetics on the day of surgery. Mechanism and Clinical Effect(s) Concomitant use of halogenated anesthetics and CONCERTA may increase the risk of sudden blood pressure and heart rate increase during surgery. Risperidone Prevention or Management Monitor for signs of extrapyramidal symptoms. Mechanism and Clinical Effect(s) The risk of risperidone-associated extrapyramidal symptoms may increase in patients taking concomitant CONCERTA when there is a change in the CONCERTA or risperidone dosage.
Antihypertensive drugs : Monitor blood pressure. Adjust dosage of antihypertensive drug as needed. ( 7 ) See additional clinically significant drug interactions, in the DRUG INTERACTIONS section ( 7 ).
Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD drugs, including CONCERTA, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/ . Risk Summary Published studies and post-marketing reports on methylphenidate use during pregnancy have inconsistent findings about a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
There are risks to the fetus associated with the use of central nervous system (CNS) stimulants during pregnancy ( see Clinical Considerations ) . No effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits throughout organogenesis at doses up to 4 and 16 times, respectively, the maximum recommended human dose (MRHD) of 72 mg/day given to adults on a mg/m 2 basis.
However, spina bifida was observed in rabbits at a dose 54 times the MRHD given to adults. A slight decrease in body weight was observed in pregnant rats at the highest dose of 30 mg/kg/day (4 times the MRHD given to adults). In a pre- and postnatal development study in which rats were treated with oral administration of methylphenidate throughout pregnancy and lactation, a decrease in pup body weight, alterations in sensory and neuromotor performance, and deficits in learning and memory were observed in both sexes at the highest dose (4 times the MRHD given to adults on a mg/m 2 basis) (see Data ) .
The background risk of major birth defects and miscarriage in those with ADHD is unknown. All pregnancies have a background risk of birth defects, 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% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions: CNS stimulants, such as CONCERTA, can cause vasoconstriction and thereby decrease placental perfusion.
No fetal and/or neonatal adverse reactions have been reported with the use of a therapeutic dosage of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine dependent mothers. Data Animal Data: In embryo-fetal development studies conducted in rats and rabbits, methylphenidate was administered orally at doses up to 30 and 200 mg/kg/day, respectively, during the period of organogenesis.
Malformations (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 54 times the maximum recommended human dose (MRHD) of 72 mg/day given to adults on a mg/m 2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (16 times the MRHD given to adults on a mg/m 2 basis). There was no evidence of changes in morphological development in rats, although a reduction in maternal body weight was observed at the highest dose of 30 mg/kg/day (4 times the MRHD of 72 mg/day given to adults (on a mg/m 2 basis).
The no effect level for maternal body weight in rats is 5 mg/day (equal to the MRHD for adults on a mg/m 2 basis); and the no effect level for embryo-fetal development is 30 mg/kg/day (4 times the MRHD for adults on a mg/m 2 basis). When methylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 30 mg/kg/day, decreases in offspring body weight, alterations in sensory and neuromotor performance, and deficits in learning and memory were observed in both sexes at the highest dose (4 times the MRHD of 72 mg/day, given to adults on a mg/m 2 basis).
The no effect level for pre- and post-natal development in rats was 12.5 mg/kg/day (2 times the MRHD given to adults on a mg/m 2 basis).
Adverse reactions
The following are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions (5.1) , Drug Abuse and Dependence (9.2) ] Hypersensitivity Reactions [see Contraindications (4) ] Monoamine Oxidase Inhibitors [see Contraindications (4) , Drug Interactions (7) ] Risks to Patients with Serious Cardiac Disease [see Warnings and Precautions (5.2) ] Increased Blood Pressure and Heart Rate [see Warnings and Precautions (5.3) ] Psychiatric Adverse Reactions [see Warnings and Precautions (5.4) ] Priapism [see Warnings and Precautions (5.5) ] Peripheral Vasculopathy, including Raynaud's Phenomenon [see Warnings and Precautions (5.6) ] Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions (5.7) ] Risks of Gastrointestinal Obstruction in Patients with Gastrointestinal Narrowing [see Warnings and Precautions (5.8) ] Acute Angle Closure Glaucoma [see Warnings and Precautions (5.9) ] Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions (5.10) ] Motor and Verbal Tics, and Worsening of Tourette's Syndrome [see Warnings and Precautions (5.11) ] The most common adverse reactions (≥5%) in double-blind clinical trials were: Pediatric patients 6 to 17 years: upper abdominal pain.
( 6.1 ) Adults up to 65 years of age: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, tachycardia, and hyperhidrosis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice. The data below is based on a total of 3,906 patients in clinical studies who received CONCERTA. Patients aged 6 up to 65 years old with ADHD were evaluated in 6 controlled clinical studies and 11 open-label clinical studies [see Table 3 ].
Table 3: CONCERTA-treated Patients in Double-Blind and Open-Label Clinical Studies Patient Population N Dosage Range Pediatric patients 6 to 12 years of age 2,216 18 to 54 mg once daily Adolescents 502 18 to 72 mg once daily Adults up to 65 years of age 1,188 18 to 108 mg once daily The most common adverse reactions (≥5%) in double-blind clinical trials were: Pediatric patients: upper abdominal pain [see Table 4 ] . Adults: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, tachycardia, and hyperhidrosis [see Table 5 ] .
The most common adverse reactions associated with CONCERTA discontinuation (≥1%) from the pediatric and adult clinical trials were anxiety, irritability, insomnia, and increased blood pressure . Most Common Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials: Adverse reactions in either the pediatric or adult double-blind adverse reactions tables may be relevant for both patient populations. Adverse Reactions in Pediatric Patients Aged 6 years and Older Table 4 displays adverse reactions reported in 2% or more of CONCERTA-treated pediatric patients ages 6 and older with ADHD in 4 placebo-controlled, double-blind clinical trials.
Table 4: Most Common Adverse Reactions Reported in ≥ 2% of CONCERTA-treated patients in Pediatric Patients 6 Years of Age and Older with ADHD in 4 Placebo-Controlled, Double-Blind Clinical Trials CONCERTA (n=321) Placebo (n=318) Upper abdominal pain 6% 4% Insomnia Initial insomnia (CONCERTA=0.6%) and insomnia (CONCERTA=2.2%) terms were combined into Insomnia. 3% 1% Nasopharyngitis 3% 2% Vomiting 3% 2% Pyrexia 2% 1% Adverse Reactions in Adults Table 5 lists the adverse reactions reported in 2% or more of CONCERTA-treated adults with ADHD in 2 placebo-controlled, double-blind clinical trials.
Table 5: Most Common Adverse Reactions Reported in ≥ 2% of CONCERTA-treated patients in Adults with ADHD in 2 Placebo-Controlled, Double-Blind Clinical Trials CONCERTA Included dosages up to 108 mg/day (1.5 times the maximum recommended dosage). (n=415) Placebo (n=212) Decreased appetite 25% 7% Headache 22% 16% Dry mouth 14% 4% Nausea 13% 3% Insomnia 12% 6% Anxiety 8% 2% Decreased weight 7% 3% Dizziness 7% 5% Irritability 6% 1% Tachycardia 5% 0% Hyperhidrosis 5% 1% Depressed mood 4% 1% Initial insomnia 4% 3% Restlessness 3% 0% Palpitations 3% 1% Nervousness 3% 1% Tremor 3% 1% Upper respiratory tract infection 2% 1% Agitation 2% 1% Dyspepsia 2% 1% Other Adverse Reactions Observed in Clinical Trials of CONCERTA The following adverse reactions occurred in less than 2% of CONCERTA-treated patients ages 6 to 65 years of age in the double-blind and open-label clinical ADHD trials.
Blood and Lymphatic System Disorders : Leukopenia Cardiac Disorders : Cardiac murmur, Hypertension, Heart rate increased Ear and Labyrinth Disorders : Vertigo Eye Disorders : Accommodation disorder, Dry eye, Vision blurred Gastrointestinal Disorders : Abdominal discomfort/pain, Constipation, Diarrhea, Vomiting General Disorders and Administration Site Conditions : Asthenia, Fatigue, Feeling jittery, Thirst Hepatobiliary Disorders : Hepatic enzymes increased Infections and Infestations : Sinusitis Metabolism and Nutrition Disorders : Anorexia Musculoskeletal and Connective Tissue Disorders: Muscle spasms, Muscle tightness Nervous System Disorders : Lethargy, Paresthesia, Psychomotor hyperactivity, Sedation, Somnolence, Tension headache Psychiatric Disorders : Affect lability, Aggression, Anger, Bruxism, Confusional state, Depression, Hypervigilance, decreased libido, Mood swings, Panic attack, Sleep disorder, Tearfulness, Tension, Tic Reproductive System and Breast Disorders : Erectile dysfunction Respiratory, Thoracic and Mediastinal Disorders : Cough, Dyspnea, Oropharyngeal pain Skin and Subcutaneous Tissue Disorders : Rash Vascular Disorders : Hot flush Discontinuation Due to Adverse Reactions In the 2 placebo-controlled studies in adults with ADHD, 25 (6%) CONCERTA-treated patients and 6 (3%) placebo-treated patients discontinued due to an adverse reaction.
In the CONCERTA group, adverse reactions leading to discontinuation with an incidence of >0.5% were anxiety (1.7%), irritability (1.4%), increased blood pressure (1%), and nervousness (0.7%). In the placebo group, adverse reactions leading to discontinuation with an incidence of >0.5% were increased blood pressure (0.9%) and depressed mood (0.9%). In the 11 open-label studies in patients 6 to 65 years of age with ADHD, 266 (7%) CONCERTA-treated patients discontinued due to an adverse reaction including insomnia (1.2%), irritability (0.8%), anxiety (0.7%), decreased appetite (0.7%), and tic (0.6%).
Blood Pressure and Heart Rate Increases In the 1-week treatment, controlled trials in pediatric patients 6 to 12 years of age with ADHD (Studies 1 and 2) [see Clinical Studies (14.2) ] , both the CONCERTA once daily group and the methylphenidate three times daily group increased resting pulse by an average of 2 to 6 beats per minute (bpm) and increased the average systolic and diastolic blood pressure roughly 1 to 4 mm Hg during the day, relative to placebo.
In the randomized withdrawal portion of the double-blind, placebo-controlled trial with pediatric patients 13 to 17 years of age with ADHD (Study 4) [see Clinical Studies (14.3) ] , mean increases from baseline in resting pulse rate were observed with CONCERTA and placebo at the end of the double-blind phase (5 and 3 beats/minute (bpm), respectively). At the end of four weeks of treatment, mean increases from baseline in blood pressure for CONCERTA and placebo-treated patients were 0.7 and 0.7 mm Hg (systolic) and 2.6 and 1.4 mm Hg (diastolic), respectively.
In the 7-week dose-titration, placebo-controlled
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Composition
Active ingredients
METHYLPHENIDATE HYDROCHLORIDE 36MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
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