Janssen Pharmaceuticals, Inc. AndersonBrecon Inc. Janssen Pharmaceuticals, Inc. Janssen Pharmaceuticals, Inc. Janssen Ortho LLC Janssen Pharmaceuticals, Inc. Janssen-Cilag Manufacturing, LLC

CONCERTA Methylphenidate hydrochloride METHYLPHENIDATE HYDROCHLORIDE METHYLPHENIDATE BUTYLATED HYDROXYTOLUENE CARNAUBA WAX HYPROMELLOSE, UNSPECIFIED LACTOSE, UNSPECIFIED FORM PHOSPHORIC ACID POLYETHYLENE GLYCOL, UNSPECIFIED POVIDONE, UNSPECIFIED PROPYLENE GLYCOL SODIUM CHLORIDE STEARIC ACID SUCCINIC ACID FERROSOFERRIC OXIDE TITANIUM DIOXIDE TRIACETIN CELLULOSE ACETATE Yellow capsule-shaped alza;18 CONCERTA Methylphenidate hydrochloride METHYLPHENIDATE HYDROCHLORIDE METHYLPHENIDATE BUTYLATED HYDROXYTOLUENE CARNAUBA WAX HYPROMELLOSE, UNSPECIFIED LACTOSE, UNSPECIFIED FORM PHOSPHORIC ACID POLYETHYLENE GLYCOL, UNSPECIFIED POVIDONE, UNSPECIFIED PROPYLENE GLYCOL SODIUM CHLORIDE STEARIC ACID SUCCINIC ACID FERROSOFERRIC OXIDE TITANIUM DIOXIDE TRIACETIN CELLULOSE ACETATE Gray capsule-shaped alza;27 CONCERTA Methylphenidate hydrochloride METHYLPHENIDATE HYDROCHLORIDE METHYLPHENIDATE STEARIC ACID SUCCINIC ACID FERROSOFERRIC OXIDE TITANIUM DIOXIDE TRIACETIN CELLULOSE ACETATE BUTYLATED HYDROXYTOLUENE CARNAUBA WAX HYPROMELLOSE, UNSPECIFIED LACTOSE, UNSPECIFIED FORM PHOSPHORIC ACID POLYETHYLENE GLYCOL, UNSPECIFIED POVIDONE, UNSPECIFIED PROPYLENE GLYCOL SODIUM CHLORIDE White capsule-shaped alza;36 CONCERTA Methylphenidate hydrochloride METHYLPHENIDATE HYDROCHLORIDE METHYLPHENIDATE TRIACETIN CELLULOSE ACETATE BUTYLATED HYDROXYTOLUENE CARNAUBA WAX HYPROMELLOSE, UNSPECIFIED LACTOSE, UNSPECIFIED FORM PHOSPHORIC ACID POLYETHYLENE GLYCOL, UNSPECIFIED POVIDONE, UNSPECIFIED PROPYLENE GLYCOL SODIUM CHLORIDE STEARIC ACID SUCCINIC ACID FERROSOFERRIC OXIDE TITANIUM DIOXIDE Red capsule-shaped alza;54

CONCERTA 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 CONCERTA, can result in overdose and death [see Overdosage (10)], and this risk is increased with a 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, proper storage of CONCERTA, and proper disposal of any unused drug. 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 [see Warnings and Precautions (5.1) and Drug Abuse and Dependence (9.1, 9.2)]. WARNING: ABUSE, MISUSE, AND ADDICTION See full prescribing information for complete boxed warning. CONCERTA 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 CONCERTA, can result in overdose and death (5.1, 9.2, 10): Before prescribing CONCERTA, assess each patient's risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of CONCERTA, and proper disposal of any unused drug. Throughout treatment, reassess each patient's risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

Indications and Usage (1)	9/2025
Dosage and Administration (2.3, 2.4)	2/2026
Warnings and Precautions: Long-Term Suppression of Growth in Pediatric Patients	9/2025
Warnings and Precautions: Removal Seizures and Hematologic Monitoring	2/2026

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).

Prior to initiating CONCERTA treatment assess for (2.1): the presence of cardiac disease for family history of tics or Tourette' syndrome and clinically evaluate patients for motor or verbal tics or Tourette's syndrome Administer once daily in the morning with or without food. Swallow whole with liquids; do not chew, divide, or crush. (2.2) Recommended dosage in pediatric patients 6 to 17 years of age new to methylphenidate: starting dosage is18 mg once daily. May be increased weekly in 18 mg increments.
Maximum dosage for pediatric patients (2.3): 6 to 12 years: 54 mg once daily 13 to 17 years: 72 mg once daily Recommended dosage in adults (up to 65 years of age) new to methylphenidate: starting dosage is 18 mg or 36 mg once daily. May be increased weekly in 18 mg increments, up to 72 mg once daily. (2.3) Patients currently using immediate-release methylphenidate: starting CONCERTA dosage is based on current dosage regimen. (2.4)

Prior to treating patients with CONCERTA, assess: For the presence of cardiac disease (e.g., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)]. The family history for tics or Tourette' syndrome and clinically evaluate patients for motor or verbal tics or Tourette's syndrome [see Warnings and Precautions (5.11)].

Administer CONCERTA orally once daily in the morning with or without food. Swallow CONCERTA whole with liquids. Do not split, crush, or chew the extended-release tablets because doing so will compromise the extended-release characteristics of CONCERTA and may compromise the effectiveness or safety of CONCERTA.

See Table 1 for the recommended once-daily dosage of CONCERTA in patients who were not taking a methylphenidate product. In patients who have not achieved an optimal response at a lower dosage, increase the CONCERTA dosage in 18 mg increments at weekly intervals. However, if a slower titration is recommended for patients who have not achieved an optimal response taking 18 mg of CONCERTA once daily, increase their daily dosage to 27 mg once per day.

Table 1: Recommended CONCERTA Dosage in Patients New to Methylphenidate

Patient Population	Recommended Starting Dosage	Dosage Range
Pediatric patients 6 to 12 years of age	18 mg once daily	18 mg to 54 mg once daily
Pediatric patients 13 to 17 years of age	18 mg once daily	18 mg to 72 mg once daily (not to exceed 2 mg/kg/day)
Adults 18 to 65 years of age	18 or 36 mg once daily	18 mg to 72 mg once daily

See Table 2 for the recommended starting dosage of CONCERTA in patients switching from an immediate-release methylphenidate product administered twice daily or three times daily (total daily dosage of 10 to 60 mg/day).

Table 2: Recommended Starting Dosage in Patients Switching from Another Methylphenidate Product

Previous Immediate-release Methylphenidate Daily Dosage	Recommended CONCERTA Starting Dosage
5 mg twice daily or three times daily	18 mg every morning
10 mg twice daily or three times daily	36 mg every morning
15 mg twice daily or three times daily	54 mg every morning
20 mg twice daily or three times daily	72 mg every morningOnly for patients 13–65 years of age.

In patients who have not achieved an optimal response at a lower dosage, increase the CONCERTA dosage in 18 mg increments at weekly intervals. The maximum recommended dosage in pediatric patients 6 to 12 years of age is 54 mg/day, and the maximum recommended dosage in patients 13–65 years old is 72 mg/day.

If paradoxical aggravation of ADHD symptoms or CONCERTA-associated adverse reactions occur, reduce the CONCERTA dosage or, if necessary, discontinue CONCERTA. If ADHD improvement is not observed after appropriate dosage modification over a one-month period, discontinue CONCERTA.

Extended-Release Tablets: 18 mg: yellow, imprinted with "alza 18" 27 mg: gray, imprinted with "alza 27" 36 mg: white, imprinted with "alza 36" 54 mg: brownish-red, imprinted with "alza 54" Extended-release tablets: 18, 27, 36, and 54 mg (3)

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)

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. 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)

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.

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.

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.

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.

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.

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.

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.

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 patients with pre-existing severe pathologic or iatrogenic GI narrowing. There have been rare reports of obstructive GI symptoms in patients with known strictures in association with the ingestion of drugs in nondeformable modified-release dosage forms. CONCERTA should be used only in patients who are able to swallow the extended-release tablets whole [see Dosage and Administration (2.2)].

There have been reports of angle closure glaucoma associated with methylphenidate treatment. Although the mechanism is not clear, CONCERTA-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.

There have been reports of an elevation of intraocular pressure (IOP) associated with methylphenidate treatment [see Adverse Reactions (6)]. 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 CONCERTA-treated patients with a history of abnormally increased IOP or open angle glaucoma.

CNS stimulants, including methylphenidate, have been associated with the onset or exacerbation of motor and verbal tics [see Adverse Reactions (6)]. Worsening of Tourette's syndrome has also been reported. Before initiating CONCERTA, assess the family history for tics or Tourette' syndrome and clinically evaluate patients for tics or Tourette's syndrome. Regularly monitor CONCERTA-treated patients for the emergence or worsening of tics or Tourette's syndrome, and discontinue CONCERTA treatment if clinically appropriate.

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.

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 ReactionsReported 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%
InsomniaInitial 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 ReactionsReported in ≥ 2% of CONCERTA-treated patients in Adults with ADHD in 2 Placebo-Controlled, Double-Blind Clinical Trials

	CONCERTAIncluded 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 study in adults 18 to 65 years of age with ADHD (Study 5) [see Clinical Studies (14.4)], mean changes from baseline in resting pulse rate were 3.6 in CONCERTA-treated patients and -1.6 for placebo-treated patients after 7 weeks of treatment. Mean changes from baseline in blood pressure after 7 weeks of treatment in CONCERTA-treated and placebo-treated patients were –1.2 and –0.5 mm Hg (systolic) and 1.1 and 0.4 mm Hg (diastolic), respectively [see Warnings and Precautions (5.3)]. In the 5-week fixed-dose, placebo-controlled trial in adults 18 to 65 years of age with ADHD (Study 5) [see Clinical Studies (14.4)], dose-dependent mean increases of 3.9 to 9.8 bpm from baseline in standing pulse rate were observed with CONCERTA-treated patients and 2.7 bpm with placebo-treated patients at the end of 5 weeks. Mean changes from baseline in standing blood pressure after 5 weeks of treatment ranged from 0.1 to 2.2 mm Hg (systolic) and -0.7 to 2.2 mm Hg (diastolic) for CONCERTA-treated patients and 1.1 mm Hg (systolic) and -1.8 mm Hg (diastolic) for placebo-treated patients.

The following adverse reactions have been identified during post-approval use of CONCERTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency: Blood and Lymphatic System Disorders: Pancytopenia, Thrombocytopenia, Thrombocytopenic purpura Cardiac Disorders: Angina pectoris, Bradycardia, Supraventricular tachycardia, Ventricular extrasystoles Eye Disorders: Diplopia, Increased intraocular pressure, Mydriasis General Disorders and Administration Site Conditions: Chest pain, Drug effect decreased, Hyperpyrexia Hepatobiliary Disorders: Hepatocellular injury, Acute hepatic failure, Blood bilirubin increased Immune System Disorders: Hypersensitivity reactions such as Angioedema, Anaphylactic reactions, Auricular swelling, Exanthemas NEC Investigations: Blood alkaline phosphatase increased, Platelet count decreased, Musculoskeletal and Connective Tissue Disorders: Arthralgia, Myalgia, Muscle twitching, Rhabdomyolysis Nervous System Disorders: Convulsion, Grand mal convulsion, Stroke in pediatric patients, Dyskinesia, Serotonin syndrome in combination with serotonergic drugs, Motor and Verbal Tics Psychiatric Disorders: Disorientation, Hallucination, Mania, Logorrhea Reproductive System and Breast Disorders: Priapism Skin and Subcutaneous Tissue Disorders: Alopecia, Bullous conditions, Erythema, Exfoliative conditions, Pruritus, Urticarias Vascular Disorders: Raynaud's phenomenon

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).

Caution should be exercised if administered to nursing mothers (8.3) Safety and efficacy has not been established in children less than six years old or elderly patients greater than 65 years of age (8.4 and 8.5)

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/m2 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/m2 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/m2 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/m2 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/m2 basis). The no effect level for maternal body weight in rats is 5 mg/day (equal to the MRHD for adults on a mg/m2 basis); and the no effect level for embryo-fetal development is 30 mg/kg/day (4 times the MRHD for adults on a mg/m2 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/m2 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/m2 basis).

Risk Summary Limited published literature, based on breast milk sampling from a small number of methylphenidate-treated lactating women, reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted methylphenidate dosage and a milk/plasma ratio ranging between 1.1 and 2.7. There are no reports of adverse effects on the breastfed infant or 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 CONCERTA and any potential adverse effects on the breastfed child from CONCERTA or from the underlying maternal condition. Clinical Considerations Monitor breastfeeding infants of CONCERTA-treated lactating women for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain.

The safety and effectiveness of CONCERTA for the treatment of ADHD have been established in pediatric patients 6 years of age and older. The safety and effectiveness of CONCERTA have not been established in pediatric patients below the age of 6 years. In studies evaluating extended-release methylphenidate products, patients 4 to <6 years of age had higher systemic methylphenidate 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. CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Growth (weight and height) should be monitored in pediatric patients during treatment with CNS stimulants, including CONCERTA. Pediatric patients who are not growing or gaining weight as expected may need to have their CONCERTA treatment interrupted [see Warnings and Precautions (5.7)]. Juvenile Animal Toxicity 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 4 times the MRHD of 54 mg/day given to pediatric patients 6 to 12 years of age on a mg/m2 basis. In a 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 to 14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 4 times the MRHD of 54 mg/day given to pediatric patients 6 to 12 years of age 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 (9 times the MRHD given to pediatric patients 6 to 12 years of age on a mg/m2 basis). The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (approximately 0.4 times the MRHD given to pediatric patients 6 to 12 years of age on a mg/m2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.

CONCERTA is not indicated for use in patients greater than 65 years of age.

CONCERTA contains methylphenidate, a Schedule II controlled substance.

CONCERTA has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see Warnings and Precautions (5.1)]. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of CONCERTA may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including CONCERTA, 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. Studies of Abuse Potential with CONCERTA In two placebo- and active-controlled, crossover human abuse potential (HAP) studies, the relative abuse potential of single oral doses of CONCERTA were compared to single oral doses of immediate-release methylphenidate (IR MPH) and placebo in subjects with a history of recreational CNS stimulant use. In these studies, the response for each of the abuse-related subjective measures was defined as the maximum effect within the first 8 hours after treatment administration. When evaluating these results, consider that 22% of the total methylphenidate amount in CONCERTA (methylphenidate hydrochloride) extended-release tablets is available for immediate release and the remaining 78% is available for extended-release over 24 hours. In the first HAP study (n=40), single dose administration of CONCERTA 108 mg (1.5 times the maximum recommended adult dose of CONCERTA), IR MPH 60 mg (2 times the maximum recommended adult dose of IR MPH), or placebo were administered to subjects in a cross-over design. CONCERTA 108 mg and IR MPH 60 mg produced responses on the subjective measures of Drug Liking and Abuse Potential that were statistically similar, and both were statistically significantly greater than the responses to placebo. However, on subjective measures of Euphoria, CONCERTA 108 mg produced responses that were statistically less than those produced by IR MPH 60 mg. In the second HAP study (n=49), a single dose of CONCERTA 108 mg (1.5 times the maximum recommended adult dose of CONCERTA), CONCERTA 54 mg (0.75 times the maximum recommended adult dose of CONCERTA), IR MPH 90 mg (3 times the maximum recommended adult dose of IR MPH), 50 mg (1.7 times the maximum recommended adult dose of IR MPH), or placebo were administered to subjects in a cross-over design. The three active treatments each produced responses on the subjective measure of Drug Liking that were statistically significantly greater than responses to placebo. IR MPH produced greater responses on Drug Liking compared to CONCERTA when similar doses were compared (50 mg vs. 54 mg, and 90 mg vs. 108 mg, respectively), consistent with the extended-release properties of CONCERTA. However, there were no significant differences in response between CONCERTA 108 mg and IR MPH 50 mg on the subjective measures of Drug Liking and Euphoria. The clinical significance of the differences in response between CONCERTA and IR MPH on subjective measures of abuse potential as reported in these HAP studies is unknown.

Physical Dependence CONCERTA may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal signs and symptoms after abrupt discontinuation or dosage reduction following prolonged use of CNS stimulants including CONCERTA included dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation. Tolerance CONCERTA may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

Overdose of CNS stimulants is characterized by the following sympathomimetic effects: Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop. CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur. Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop.

Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of CONCERTA should be considered when treating patients with overdose. Because methylphenidate has a large volume of distribution and is rapidly metabolized, dialysis is not useful. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

CONCERTA® is a central nervous system (CNS) stimulant. CONCERTA is available in four strengths. Each extended-release tablet for oral administration contains 18, 27, 36, or 54 mg of methylphenidate hydrochloride, USP. Chemically, methylphenidate hydrochloride is d,l (racemic) methyl α-phenyl-2-piperidineacetate hydrochloride, its empirical formula is C14H19NO2∙HCl, and its structural formula is: Methylphenidate hydrochloride, USP is a white, odorless crystalline powder. Its solutions are acid to litmus. It is freely soluble in water and in methanol, soluble in alcohol, and slightly soluble in chloroform and in acetone. Its molecular weight is 269.77. CONCERTA also contains the following inactive ingredients: butylated hydroxytoluene, carnauba wax, cellulose acetate, hypromellose, lactose, phosphoric acid, poloxamer, polyethylene glycol, polyethylene oxides, povidone, propylene glycol, sodium chloride, stearic acid, succinic acid, synthetic iron oxides, titanium dioxide, and triacetin. It is possible that CONCERTA extended-release tablets may be visible on abdominal x-rays under certain circumstances, especially when digital enhancing techniques are utilized. Chemical Structure

Methylphenidate is a central nervous system (CNS) stimulant. The mode of therapeutic action of methylphenidate in the treatment of ADHD is not known. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space.

Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more pharmacologically active than the l-isomer. The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of CONCERTA have not been fully characterized.

Absorption Following oral administration of CONCERTA, plasma methylphenidate concentrations reached an initial maximum concentration at about 1 hour, followed by gradual ascending concentrations over the next 5 to 9 hours, after which a gradual decrease begins. Mean times to reach peak plasma concentrations across all doses of CONCERTA occurred between 6 and 10 hours. CONCERTA once daily minimizes the fluctuations between peak and trough concentrations associated with immediate-release methylphenidate three times daily [see Figure 1 ]. No clinically significant difference in methylphenidate exposures was observed following the administration of either CONCERTA once daily and immediate-release methylphenidate three times daily in adults. Figure 1. Mean Methylphenidate Plasma Concentrations Following a Single 18 mg CONCERTA dose and Immediate-release Methylphenidate 5 mg Doses (Three Doses Administered Every 4 Hours) The mean single-dose pharmacokinetic parameters in 36 healthy adults following the administration of one 18 mg CONCERTA dose and three 5 mg methylphenidate doses every four hours are summarized in Table 7.

Table 7: Methylphenidate Pharmacokinetic Parameters (Mean ± SD) After CONCERTA and Immediate-release Methylphenidate Dosing in Healthy Adults

Parameters	CONCERTA (18 mg single dose) (n=36)	Immediate-release Methylphenidate (Three 5 mg doses every four hours) (n=35)
Cmax (ng/mL)	3.7 ± 1.0	4.2 ± 1.0
Tmax (h)	6.8 ± 1.8	6.5 ± 1.8
AUCinf (ng∙h/mL)	41.8 ± 13.9	38.0 ± 11.0
t½ (h)	3.5 ± 0.4	3.0 ± 0.5

The methylphenidate pharmacokinetics were evaluated in healthy adults following single- and multiple-doses (steady state) of CONCERTA (up to 144 mg/day (up to 2 times the maximum recommended dose)). The mean half-life was about 3.6 hours. No differences in the pharmacokinetics of CONCERTA were noted following single and repeated once-daily CONCERTA dosing, indicating no significant drug accumulation. The AUC and t_1/2 following repeated once-daily dosing are similar to those following a single 18 to 144 mg dose of CONCERTA. Dose Proportionality Following administration of CONCERTA in single doses of 18, 36, and 54 mg/day to healthy adults, C_max and AUC_(0–inf) of d-methylphenidate were dose proportional, whereas l-methylphenidate C_max and AUC_(0–inf) increased disproportionately with respect to dose. Following administration of CONCERTA, plasma concentrations of the l-isomer were approximately 1/40 the plasma concentrations of the d-isomer. In healthy adults, single and multiple doses (once-daily) CONCERTA doses from 54 to 144 mg/day resulted in linear and dose-proportional increases in C_max and AUC_inf for total methylphenidate (MPH) and its major metabolite, α-phenyl-piperidine acetic acid (PPAA). There was no time dependency in the pharmacokinetics of methylphenidate. The ratio of metabolite (PPAA) to parent drug (MPH) was constant across doses from 54 to 144 mg/day, both after single dose and upon multiple dosing. In a multiple-dose study, after patients aged 13 to 16 with ADHD were administered their prescribed CONCERTA dose (18 to 72 mg/day), mean C_max and AUC_TAU of d- and total methylphenidate increased proportionally with respect to dose. Food Effects: In patients, there were no differences in either the pharmacokinetics or the pharmacodynamic performance of CONCERTA when administered after a high-fat breakfast. Distribution Plasma methylphenidate concentrations in adults and adolescents decline biexponentially following oral CONCERTA administration. The half-life of methylphenidate in adults and adolescents following oral CONCERTA administration was approximately 3.5 hours. Elimination Metabolism: In humans, methylphenidate is metabolized primarily by de-esterification to PPAA, which has little or no pharmacologic activity. In adults the metabolism of CONCERTA once daily as evaluated by metabolism to PPAA was similar to that of immediate-release methylphenidate three times daily. The metabolism of single and repeated once-daily doses of CONCERTA was similar. Excretion: After oral dosing of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was PPAA, accounting for approximately 80% of the dose. Alcohol Effect on Methylphenidate Release in CONCERTA An in vitro study was conducted to explore the effect of alcohol on the release characteristics of methylphenidate from the CONCERTA 18 mg extended-release tablets. At an alcohol concentration up to 40% there was no increased release of methylphenidate in the first hour. The results with the 18 mg extended-release tablet strength are considered representative of the other available tablet strengths. Specific Populations Male and Female Patients: In healthy adults, the mean dose-adjusted AUC_(0–inf) values for CONCERTA were 36.7 ng∙h/mL in males and 37.1 ng∙h/mL in females, with no differences noted between the two groups. Ethnic Groups: In adults receiving CONCERTA, dose-adjusted AUC_(0–inf) was consistent across ethnic groups; however, the sample size was insufficient to detect ethnic variations in pharmacokinetics. Pediatric Patients: Increase in pediatric age was associated with increased apparent oral clearance (CL/F) (58% increase in adolescents compared to younger pediatric patients). Some of these differences could be explained by body-weight differences among these populations. This suggests that subjects with higher body weight may have a lower exposure of total methylphenidate at similar doses. Patients with Renal Impairment There is no pharmacokinetic information on the use of CONCERTA in patients with renal impairment. Patients with Hepatic Impairment There is no pharmacokinetic information on the use of CONCERTA in patients with hepatic impairment. Figure 1

Carcinogenesis 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 (MRHD) of CONCERTA given to adults 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 increases 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 6 times the MRHD (adults) on a mg/m2 basis. In a 24-week carcinogenicity study 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 concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 to 74 mg/kg/day of methylphenidate. Mutagenesis Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or 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 cells. Methylphenidate was negative in vivo in males and females in the 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 up to 160 mg/kg/day, approximately 11 times the MRHD of CONCERTA given to adults on a mg/m2 basis.

CONCERTA was demonstrated to be effective in the treatment of ADHD in patients who met the Diagnostic and Statistical Manual 4th edition (DSM-IV) criteria for ADHD in the following trials: Three trials in pediatric patients 6 to 12 years old (Studies 1, 2, and 3), One trial in adolescents (13 to 18 years old), Two trials in adults (18 to 65 years old).

Three double-blind, active- and placebo-controlled trials were conducted in 416 pediatric patients 6 to 12 years of age with ADHD: (1) two single-center, crossover trials (patients received each treatment for one week) (Studies 1 and 2) and (2) a multicenter, 4-week, parallel-group comparison trial (Study 3). In these trials, patients were randomized to receive: 18 mg, 36 mg, or 54 mg of oral CONCERTA given once daily, 5 mg, 10 mg, or 15 mg of oral immediate-release methylphenidate given three times daily (15, 30, or 45 mg total daily dosage) over 12 hours, and Placebo The primary comparison of interest in all three trials was the CONCERTA group versus the placebo group. ADHD symptoms were evaluated by community schoolteachers using the Inattention/Overactivity with Aggression (IOWA) Conners scale. A statistically significant reduction in the Inattention/Overactivity subscale (0 to 15) in the CONCERTA group versus the placebo group was shown in all three trials. The scores for CONCERTA and placebo for the three trials are presented in Figure 2. Figure 2. Mean Community School Teacher Inattention/Overactivity Subscores in the IOWA Conners Scale in Pediatric Patients 6 to 12 Years with ADHD Studies 1 and 2 involved a 3-way crossover of 1-week per treatment arm. Study 3 involved 4 weeks of parallel-group treatments with a Last Observation Carried Forward analysis at week 4. Error bars represent the mean plus standard error of the mean. In Studies 1 and 2, symptoms of ADHD including attentiveness were evaluated by schoolteachers using the Swanson, Kotkin, Agler, M-Fynn, and Pelham (SKAMP) laboratory school rating scale. The combined results from these two trials demonstrated statistically significant improvements in attention and behavior in the CONCERTA group compared to the placebo group. These results were maintained through 12 hours after dosing. Figure 3 presents the schoolteacher SKAMP ratings for the CONCERTA and placebo groups in Studies 1 and 2. Figure 3. School Teacher SKAMP Ratings (Mean (SEM) of Combined Attention) in Pediatric Patients 6 to 12 Years with ADHD (Studies 1 and 2) Figure 2 Figure 3

In a randomized-withdrawal, double-blind, multicenter, placebo-controlled trial (Study 4) with 177 pediatric patients 13 to 17 years of age with ADHD, CONCERTA demonstrated effectiveness with a dosage up to 72 mg/day (1.4 mg/kg/day): Of 220 patients who entered an open 4-week titration phase, 177 patients were titrated to an individualized CONCERTA dosage (maximum of 72 mg/day) based on meeting specific improvement criteria on the ADHD Rating Scale and the Global Assessment of Effectiveness with acceptable tolerability. Patients who met these criteria were then randomized to receive either their individualized dosage of CONCERTA (18 – 72 mg/day, n=87) or placebo (n=90) during a two-week double-blind phase. At the end of the double blind phase, mean scores for the investigator rating on the ADHD Rating Scale demonstrated that the CONCERTA group was statistically significantly superior to the placebo group.

Two randomized double-blind, placebo-controlled multicenter, parallel-group trials were conducted in 627 adults aged 18 to 65 years with ADHD who received CONCERTA or placebo once daily: Study 5 was a 7-week, dose-titration trial where patients were randomized to receive CONCERTA (n=110) or placebo (n=116) once daily. Patients treated with CONCERTA started at 36 mg/day and had incremental increases of 18 mg/day up to 108 mg/day of CONCERTA (titration was based on improvement criteria with acceptable tolerability). Study 6 was a 5-week, fixed-dose trial where patients were randomized to receive 18 mg (n=101), 36 mg (n=102), or 72 mg (n=102) of CONCERTA versus placebo (n=96) once daily. In Study 5, CONCERTA demonstrated efficacy based on the change from baseline to final study visit on the Adult ADHD Investigator Rating Scale (AISRS). At the final study visit, mean change scores (LS Mean, SEM) for the investigator rating on the AISRS demonstrated that the CONCERTA group was statistically significantly superior to the placebo group. In Study 6, all three CONCERTA dosages were statistically significantly more effective than placebo in improving Conners' Adult ADHD Rating Scale (CAARS) total scores after five weeks of treatment.

CONCERTA^® (methylphenidate hydrochloride) extended-release tablets are available in 18 mg, 27 mg, 36 mg, and 54 mg strengths: 18 mg: yellow and imprinted with "alza 18", 100-count bottle (NDC 50458-585-01) 27 mg: gray and imprinted with "alza 27", 100-count bottle (NDC 50458-588-01) 36 mg: white and imprinted with "alza 36", 100-count bottle (NDC 50458-586-01) 54 mg: brownish-red and imprinted with "alza 54", 100-count bottle (NDC 50458-587-01)

Storage and Handling Store at 25 °C (77 °F); excursions permitted to 15–30 °C (59–86 °F) [see USP Controlled Room Temperature]. Protect from humidity.

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Abuse, Misuse, and Addiction Educate patients and their families about the risks of abuse, misuse, and addiction of CONCERTA, which can lead to overdose and death, and proper disposal of any unused drug [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9.1, 9.2), Overdosage (10)]. Advise patients to store CONCERTA in a safe place, preferably locked, and instruct patients to not give CONCERTA to anyone else. Risks to Patients with Serious Cardiac Disease Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with CONCERTA 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 Precautions (5.2)]. Increased Blood Pressure and Heart Rate Advise patients and their caregivers that CONCERTA can cause elevations in blood pressure and heart rate [see Warnings and Precautions (5.3)]. Psychiatric Risks Advise patients and their caregivers that CONCERTA, 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 (5.4)]. Priapism Advise patients, caregivers, and family members of CONCERTA-treated males of the possibility of priapism. Instruct the patient to seek immediate medical attention in the event of priapism [see Warnings and Precautions (5.5)]. Peripheral Vasculopathy, including Raynaud's Phenomenon Instruct patients about the risk of peripheral vasculopathy, including Raynaud's phenomenon, and associated signs and symptoms; to report to their health care provider any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes; to call their health care provider immediately with any signs of unexplained wounds appearing on fingers or toes while taking CONCERTA [see Warnings and Precautions (5.6)]. Long-term Suppression of Growth in Pediatric Patients Advise patients, caregivers, and family members that CONCERTA may cause slowing of growth and weight loss in pediatric patients [see Warnings and Precautions (5.7)]. Glaucoma and Increased Intraocular Pressure Advise patients that increased intraocular pressure and glaucoma may occur during CONCERTA treatment [see Warnings and Precautions (5.10)]. 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 CONCERTA treatment. 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 (5.11)]. Administration Instructions Instruct patients to swallow CONCERTA whole with liquids, and not to split, crush, or chew, the extended-release tablets. Advise patients not to be concerned if they occasionally notice a tablet-appearing substance in their stool. Pregnancy Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to CONCERTA during pregnancy [see Use in Specific Populations (8.1)]. Lactation Advise CONCERTA-treated breastfeeding women to monitor their infants for agitation, poor sleeping patterns, changes in feeding, and reduced weight gain [see Use in Specific Populations (8.2)].

Manufactured for:
Janssen Pharmaceuticals, Inc.
Titusville, NJ 08560, USA For patent information: www.janssenpatents.com
© Johnson and Johnson and its affiliates 2026 For more information about CONCERTA call 1-800-526-7736.

MEDICATION GUIDE CONCERTA® (kon SER-ta) (methylphenidate hydrochloride) extended-release tablets for oral use, CII
This Medication Guide has been approved by the U.S. Food and Drug Administration.		Revised: 02/2026
What is the most important information I should know about CONCERTA? CONCERTA may cause serious side effects, including: Abuse, misuse, and addiction. CONCERTA has a high chance for abuse and misuse and may lead to substance use problems, including addiction. Misuse and abuse of CONCERTA, other methylphenidate containing medicines, and amphetamine containing medicines, can lead to overdose and death. The risk of overdose and death is increased with higher doses of CONCERTA or when it is used in ways that are not approved, such as snorting or injection. Your healthcare provider should check you or your child's risk for abuse, misuse, and addiction before starting treatment with CONCERTA and will monitor you or your child during treatment. CONCERTA may lead to physical dependence after prolonged use, even if taken as directed by your healthcare provider. Do not give CONCERTA to anyone else. See " What is CONCERTA?" for more information. Keep CONCERTA in a safe place and properly dispose of any unused medicine. See " How should I store CONCERTA? " for more information. Tell your healthcare provider if you or your child have ever abused or been dependent on alcohol, prescription medicines, or street drugs. Risks for people with serious heart disease. Sudden death has happened in people who have heart defects or other serious heart disease. Your healthcare provider should check you or your child carefully for heart problems before starting treatment with CONCERTA. Tell your healthcare provider if you or your child have any heart problems, heart disease, or heart defects. Call your healthcare provider or go to 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 during treatment with CONCERTA. Increased blood pressure and heart rate. Your healthcare provider should check your or your child's blood pressure and heart rate regularly during treatment with CONCERTA. Mental (psychiatric) problems, including: new or worse behavior or thought problems new or worse bipolar illness new psychotic symptoms (such as hearing voices, or seeing or believing things that are not real) or new manic symptoms Tell your healthcare provider about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression. Call your healthcare provider right away if you or your child have any new or worsening mental symptoms or problems during treatment with CONCERTA, especially hearing voices, seeing or believing things that are not real, or new manic symptoms. See "What are the possible side effects of CONCERTA?" for more information about side effects.
What is CONCERTA? CONCERTA is a central nervous system (CNS) stimulant prescription medicine used for the treatment of attention deficit hyperactivity disorder (ADHD) in people 6 to 65 years of age. CONCERTA may help increase attention and decrease impulsiveness and hyperactivity in people with ADHD. CONCERTA is not recommended for use in children under 6 years of age with ADHD. CONCERTA is a federally controlled substance (CII) because it contains methylphenidate that can be a target for people who abuse prescription medicines or street drugs. Keep CONCERTA in a safe place to protect it from theft. Never give your CONCERTA to anyone else because it may cause death or harm them. Selling or giving away CONCERTA may harm others and is against the law.
Who should not take CONCERTA? Do not take CONCERTA if you or your child are: allergic to methylphenidate or any of the ingredients in CONCERTA. See the end of this Medication Guide for a complete list of ingredients in CONCERTA. taking, or have stopped taking within the past 14 days, a medicine called a monoamine oxidase inhibitor (MAOI)
Before taking CONCERTA, tell your healthcare provider about all of your or your child's medical conditions, including if you or your child: have heart problems, heart disease, heart defects, or high blood pressure have mental problems including psychosis, mania, bipolar illness, or depression, or have a family history of suicide, bipolar illness, or depression have circulation problems in fingers and toes have had a blockage or narrowing of the intestines have eye problems, including increased pressure in your eye, glaucoma, or problems with your close-up vision (farsightedness) have or had repeated movements or sounds (tics) or Tourette's syndrome, or have a family history of tics or Tourette's syndrome are pregnant or plan to become pregnant. It is not known if CONCERTA will harm the unborn baby. There is a pregnancy exposure registry for women are exposed to CONCERTA during pregnancy. The purpose of the registry is to collect information about the health of women exposed to CONCERTA and their baby. If you or your child becomes pregnant during treatment with CONCERTA, talk to your healthcare provider about registering with the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visit online at https://womensmentalhealth.org/adhd-medications/. are breastfeeding or plan to breastfeed. CONCERTA passes into the breast milk. Talk to your healthcare provider about the best way to feed the baby during treatment with CONCERTA. If you breastfeed during treatment with CONCERTA, monitor your baby for agitation, poor sleeping patterns, changes in feeding, and reduced weight gain. Tell your healthcare provider about all of the medicines that you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. CONCERTA and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be changed during treatment with CONCERTA. Your healthcare provider will decide whether CONCERTA can be taken with other medicines. Especially tell your healthcare provider if you or your child take: a medicine to treat blood pressure (anti-hypertensive) risperidone Know the medicines that you or your child take. Keep a list of your or your child's medicines with you to show your healthcare provider and pharmacist when you or your child get a new medicine. Do not start any new medicine during treatment with CONCERTA without first talking to your healthcare provider.
How should I take CONCERTA? Take CONCERTA exactly as prescribed by your or your child's healthcare provider. Your healthcare provider may change the dose or tell you to stop taking CONCERTA if needed. Take CONCERTA 1 time each day in the morning with or without food. Swallow CONCERTA tablets whole with water or other liquids. Do not split, crush, or chew the tablets. Tell your healthcare provider if you or your child cannot swallow CONCERTA tablets whole. A different medicine will need to be prescribed. CONCERTA does not dissolve completely in the body after all the medicine has been released. You or your child may sometimes notice the empty tablet in a bowel movement. This is normal. If you or your child take too much CONCERTA, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.
What are the possible side effects of CONCERTA? CONCERTA may cause serious side effects, including: See "What is the most important information I should know about CONCERTA?" Painful and prolonged erections (priapism). Priapism that may require surgery has happened in males who take products that contain methylphenidate. If you or your child develop priapism, get medical help right away. 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 any 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 during treatment with CONCERTA. Slowing of growth (height and weight) in children. Children should have their height and weight checked often during treatment with CONCERTA. CONCERTA treatment may be stopped if your child is not growing or gaining weight as expected. Risk of intestinal blockage in people with narrowed digestive tract (gastrointestinal narrowing). Because the CONCERTA tablet does not change in shape in the intestines (GI tract), CONCERTA should not be taken by people with severe intestinal problems (pre-existing severe gastrointestinal narrowing). Eye problems (increased pressure in the eye and glaucoma). Call your healthcare provider right away if you or your child develop changes in your vision or eye pain, swelling, or redness. New or worsening tics or worsening Tourette's syndrome. Tell your healthcare provider if you or your child get any new or worsening tics or worsening Tourette's syndrome during treatment with CONCERTA. The most common side effect of CONCERTA in children 6 to 17 years of age is upper stomach-area (abdominal) pain. The most common side effects of CONCERTA in adults up to 65 years of age include:
decreased appetite headache dry mouth nausea trouble sleeping anxiety	dizziness weight loss irritability fast heart beat increased sweating
These are not all the possible side effects of CONCERTA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Janssen Pharmaceuticals, Inc. at 1-800-JANSSEN (1-800-526-7736).
How should I store CONCERTA? Store CONCERTA at room temperature between 59 °F to 86 °F (15 °C to 30 °C). Protect from moisture. Store CONCERTA in a safe place, like a locked cabinet. Dispose of remaining, unused, or expired CONCERTA by a medicine take-back program at a U.S. Drug Enforcement Administration (DEA) authorized collection site. If no take-back program or DEA authorized collector is available, mix CONCERTA with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and throw away CONCERTA in the household trash. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines. Keep CONCERTA and all medicines out of the reach of children.
General information about the safe and effective use of CONCERTA. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use CONCERTA for a condition for which it was not prescribed. Do not give CONCERTA to other people, even if they have the same condition. It may harm them and it is against the law. You can ask your pharmacist or healthcare provider for information about CONCERTA that is written for health professionals.
What are the ingredients in CONCERTA? Active ingredient: methylphenidate hydrochloride Inactive ingredients: butylated hydroxytoluene, carnauba wax, cellulose acetate, hypromellose, lactose, phosphoric acid, poloxamer, polyethylene glycol, polyethylene oxides, povidone, propylene glycol, sodium chloride, stearic acid, succinic acid, synthetic iron oxides, titanium dioxide, and triacetin. Manufactured for: Janssen Pharmaceuticals, Inc., Titusville, NJ 08560, USA For patent information: www.janssenpatents.com © Johnson and Johnson and its affiliates 2026 For more information, go to www.concerta.net or call 1-800-JANSSEN (1-800-526-7736).

NDC 50458-585-01 CONCERTA®
(methylphenidate HCl)
CII Extended-release tablets 18 mg Each tablet contains 18 mg
methylphenidate hydrochloride
in a controlled-release formulation. Please see the Medication Guide
provided by your pharmacist. Rx only
100 Tablets janssen PRINCIPAL DISPLAY PANEL - 18 mg Tablet Bottle Label

NDC 50458-588-01 CONCERTA®
(methylphenidate HCl)
CII Extended-release tablets 27 mg Each tablet contains 27 mg
methylphenidate hydrochloride
in a controlled-release formulation. Please see the Medication Guide
provided by your pharmacist. Rx only
100 Tablets janssen PRINCIPAL DISPLAY PANEL - 27 mg Tablet Bottle Label

NDC 50458-586-01 CONCERTA ®
(methylphenidate HCl)
CII Extended-release tablets 36 mg Each tablet contains 36 mg
methylphenidate hydrochloride
in a controlled-release formulation. Please see the Medication Guide
provided by your pharmacist. Rx only
100 Tablets janssen PRINCIPAL DISPLAY PANEL - 36 mg Tablet Bottle Label

NDC 50458-587-01 CONCERTA®
(methylphenidate HCl)
CII Extended-release tablets 54 mg Each tablet contains 54 mg
methylphenidate hydrochloride
in a controlled-release formulation. Please see the Medication Guide
provided by your pharmacist. Rx only
100 Tablets janssen PRINCIPAL DISPLAY PANEL - 54 mg Tablet Bottle Label