Concerta (methylphenidate hydrochloride 36 mg) Dailymed

7drug Interactions

• Do not use CONCERTA^® in patients currently using or within 2 weeks of using an MAO inhibitor (7.1)
• CONCERTA^® may increase blood pressure; use cautiously with vasopressors (7.2)
• Inhibition of metabolism of coumarin anticoagulants, anticonvulsants, and some antidepressants (7.3)

7.1MAO Inhibitors

CONCERTA^® should not be used in patients being treated (currently or within the preceding 2 weeks) with MAO inhibitors [see Contraindications (4.5)].

7.2Vasopressor Agents

Because of possible increases in blood pressure, CONCERTA^® should be used cautiously with vasopressor agents [see Warnings and Precautions (5.1)].

7.3Coumarin Anticoagulants, Antidepressants, and Selective Serotonin Reuptake Inhibitors

Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (eg, phenobarbital, phenytoin, primidone), and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). Downward dose adjustment of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentrations (or, in the case of coumarin, coagulation times), when initiating or discontinuing concomitant methylphenidate.

8use In Specific Populations

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)

8.1 Pregnancy

TERATOGENIC EFFECTS SECTION

Pregnancy Category C

Methylphenidate has been shown to have teratogenic effects in rabbits when given in doses of 200 mg/kg/day, which is approximately 100 times and 40 times the maximum recommended human dose on a mg/kg and mg/m² basis, respectively.

A reproduction study in rats revealed no evidence of harm to the fetus at oral doses up to 30 mg/kg/day, approximately 15-fold and 3-fold the maximum recommended human dose of CONCERTA^® on a mg/kg and mg/m² basis, respectively. The approximate plasma exposure to methylphenidate plus its main metabolite PPAA in pregnant rats was 1–2 times that seen in trials in volunteers and patients with the maximum recommended dose of CONCERTA^® based on the AUC.

The safety of methylphenidate for use during human pregnancy has not been established. There are no adequate and well-controlled studies in pregnant women. CONCERTA^® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.2Labor and Delivery

The effect of CONCERTA^® on labor and delivery in humans is unknown.

8.3Nursing Mothers

It is not known whether methylphenidate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if CONCERTA^® is administered to a nursing woman.

In lactating female rats treated with a single oral dose of 5 mg/kg radiolabeled methylphenidate, radioactivity (representing methylphenidate and/or its metabolites) was observed in milk and levels were generally similar to those in plasma.

8.4Pediatric Use

CONCERTA^® should not be used in children under six years, since safety and efficacy in this age group have not been established. Long-term effects of methylphenidate in children have not been well established.

8.5Geriatric Use

CONCERTA^® has not been studied in patients greater than 65 years of age.

9drug Abuse And Dependence

9.1Controlled Substance

Methylphenidate is a Schedule II controlled substance under the Controlled Substances Act.

9.2Abuse

As noted in the Box Warning, CONCERTA^® should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse.

In two placebo-controlled human abuse potential studies, 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 stimulant use to assess relative abuse potential. For the purpose of this assessment, the response for each of the subjective measures was defined as the maximum effect within the first 8 hours after dose administration.

In one study (n=40), both CONCERTA^® (108 mg) and 60 mg IR MPH compared to placebo produced statistically significantly greater responses on the five subjective measures suggestive of abuse potential. In comparisons between the two active treatments, however, CONCERTA^® (108 mg) produced variable responses on positive subjective measures that were either statistically indistinguishable from (Abuse Potential, Drug Liking, Amphetamine, and Morphine Benzedrine Group [Euphoria]) or statistically less than (Stimulation – Euphoria) responses produced by 60 mg IR MPH.

In another study (n=49), both doses of CONCERTA^® (54 mg and 108 mg) and both doses of IR MPH (50 mg and 90 mg) produced statistically significantly greater responses compared to placebo on the two primary scales used in the study (Drug Liking, Euphoria). When doses of CONCERTA^® (54 mg and 108 mg) were compared to IR MPH (50 mg and 90 mg), respectively, CONCERTA^® produced statistically significantly lower subjective responses on these two scales than IR MPH. CONCERTA^® (108 mg) produced responses that were statistically indistinguishable from the responses on these two scales produced by IR MPH (50 mg). Differences in subjective responses to the respective doses should be considered in the context that only 22% of the total amount of methylphenidate in CONCERTA^® tablets is available for immediate release from the drug overcoat [see System Components and Performance (11.1) ].

Although these findings reveal a relatively lower response to CONCERTA^® on subjective measures suggestive of abuse potential compared to IR MPH at roughly equivalent total MPH doses, the relevance of these findings to the abuse potential of CONCERTA^® in the community is unknown.

9.3Dependence

As noted in the Box Warning, careful supervision is required during withdrawal from abusive use since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.

10overdosage

10.1Signs and Symptoms

Signs and symptoms of CONCERTA^® overdosage, resulting principally from overstimulation of the CNS and from excessive sympathomimetic effects, may include the following: vomiting, agitation, muscle twitching, convulsion, grand mal convulsion, confusional state, hallucinations (auditory and/or visual), hyperhidrosis, headache, pyrexia, tachycardia, palpitations, heart rate increased, sinus arrhythmia, hypertension, mydriasis, and dry mouth.

10.2Recommended Treatment

Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Gastric contents may be evacuated by gastric lavage as indicated. Before performing gastric lavage, control agitation and seizures if present and protect the airway. Other measures to detoxify the gut include administration of activated charcoal and a cathartic. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for pyrexia.

Efficacy of peritoneal dialysis or extracorporeal hemodialysis for CONCERTA^® overdosage has not been established.

The prolonged release of methylphenidate from CONCERTA^® should be considered when treating patients with overdose.

10.3Poison Control Center

As with the management of all overdosage, the possibility of multiple-drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-to-date information on the management of overdosage with methylphenidate.

11description

CONCERTA^® is a central nervous system (CNS) stimulant. CONCERTA^® is available in four tablet strengths. Each extended-release tablet for once-a-day oral administration contains 18, 27, 36, or 54 mg of methylphenidate HCl USP and is designed to have a 12-hour duration of effect. Chemically, methylphenidate HCl is d,l (racemic) methyl α-phenyl-2-piperidineacetate hydrochloride. Its empirical formula is C₁₄H₁₉NO₂•HCl. Its structural formula is:

Methylphenidate HCl 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 inert 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.

11.1System Components and Performance

CONCERTA^® uses osmotic pressure to deliver methylphenidate HCl at a controlled rate. The system, which resembles a conventional tablet in appearance, comprises an osmotically active trilayer core surrounded by a semipermeable membrane with an immediate-release drug overcoat. The trilayer core is composed of two drug layers containing the drug and excipients, and a push layer containing osmotically active components. There is a precision-laser drilled orifice on the drug-layer end of the tablet. In an aqueous environment, such as the gastrointestinal tract, the drug overcoat dissolves within one hour, providing an initial dose of methylphenidate. Water permeates through the membrane into the tablet core. As the osmotically active polymer excipients expand, methylphenidate is released through the orifice. The membrane controls the rate at which water enters the tablet core, which in turn controls drug delivery. Furthermore, the drug release rate from the system increases with time over a period of 6 to 7 hours due to the drug-concentration gradient incorporated into the two drug layers of CONCERTA^®. The biologically inert components of the tablet remain intact during gastrointestinal transit and are eliminated in the stool as a tablet shell along with insoluble core components. 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.

12clinical Pharmacology

12.1Mechanism of Action

Methylphenidate HCl is a central nervous system (CNS) stimulant. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

12.2Pharmacodynamics

Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more pharmacologically active than the l-isomer.

12.3Pharmacokinetics

Absorption

Methylphenidate is readily absorbed. Following oral administration of CONCERTA^®, plasma methylphenidate concentrations increase rapidly, reaching an initial maximum 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). The relative bioavailability of CONCERTA^® once daily and methylphenidate three times daily in adults is comparable.

Figure 1. Mean methylphenidate plasma concentrations in 36 adults, following a single dose of CONCERTA^® 18 mg once daily and immediate-release methylphenidate 5 mg three times daily administered every 4 hours.

The mean single-dose pharmacokinetic parameters in 36 healthy adults following the administration of CONCERTA^® 18 mg once daily and methylphenidate 5 mg three times daily are summarized in Table 6.

TABLE 6. Pharmacokinetic Parameters (Mean ± SD) After Single Dose in Healthy Adults

Parameters	CONCERTA® (18 mg once daily)(n=36)	Methylphenidate(5 mg three times daily)(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 pharmacokinetics of CONCERTA^® were evaluated in healthy adults following single- and multiple-dose administration (steady state) of doses up to 144 mg/day. The mean half-life was about 3.6 hours. No differences in the pharmacokinetics of CONCERTA^® were noted following single and repeated once-daily dosing, indicating no significant drug accumulation. The AUC and t_1/2 following repeated once-daily dosing are similar to those following the first dose of CONCERTA^® in a dose range of 18 to 144 mg.

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 proportional to dose, 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 dosing of 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 in adolescent ADHD patients aged 13 to 16 administered their prescribed dose (18 to 72 mg/day) of CONCERTA^®, mean C_max and AUC_TAU of d- and total methylphenidate increased proportionally with respect to dose.

Distribution

Plasma methylphenidate concentrations in adults and adolescents decline biexponentially following oral administration. The half-life of methylphenidate in adults and adolescents following oral administration of CONCERTA^® was approximately 3.5 hours.

Metabolism and Excretion

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 is similar to that of methylphenidate three times daily. The metabolism of single and repeated once-daily doses of CONCERTA^® is similar.

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.

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. There is no evidence of dose dumping in the presence or absence of food.

Special Populations

Gender

In healthy adults, the mean dose-adjusted AUC _{(0–inf)} values for CONCERTA^® were 36.7 ng∙h/mL in men and 37.1 ng∙h/mL in women, with no differences noted between the two groups.

Race

In adults receiving CONCERTA^®, dose-adjusted AUC _{(0–inf)} was consistent across ethnic groups; however, the sample size may have been insufficient to detect ethnic variations in pharmacokinetics.

Age

Increase in age resulted in increased apparent oral clearance (CL/F) (58% increase in adolescents compared to children). Some of these differences could be explained by body-weight differences among these populations. This suggests that subjects with higher body weight may have lower exposures of total methylphenidate at similar doses.

The pharmacokinetics of CONCERTA^® have not been studied in children less than 6 years of age.

Renal Insufficiency

There is no experience with the use of CONCERTA^® in patients with renal insufficiency. After oral administration of radiolabeled methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of PPAA. Since renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of CONCERTA^®.

Hepatic Insufficiency

There is no experience with the use of CONCERTA^® in patients with hepatic insufficiency.

13nonclinical Toxicology

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

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 30 times and 4 times the maximum recommended human dose of CONCERTA^® on a mg/kg and mg/m² basis, respectively. 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 22 times and 5 times the maximum recommended human dose of CONCERTA^® on a mg/kg and mg/m² basis, respectively.

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 80-fold and 8-fold the highest recommended human dose of CONCERTA^® on a mg/kg and mg/m² basis, respectively.

14clinical Studies

CONCERTA^® was demonstrated to be effective in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in 4 randomized, double-blind, placebo-controlled studies in children and adolescents and 2 double-blind placebo-controlled studies in adults who met the Diagnostic and Statistical Manual 4^th edition (DSM-IV) criteria for ADHD.

14.1Children

Three double-blind, active- and placebo-controlled studies were conducted in 416 children aged 6 to 12 years. The controlled studies compared CONCERTA^® given once daily (18, 36, or 54 mg), methylphenidate given three times daily over 12 hours (15, 30, or 45 mg total daily dose), and placebo in two single-center, 3-week crossover studies (Studies 1 and 2) and in a multicenter, 4-week, parallel-group comparison (Study 3). The primary comparison of interest in all three trials was CONCERTA^® versus placebo.

Symptoms of ADHD were evaluated by community schoolteachers using the Inattention / Overactivity with Aggression (IOWA) Conners scale. Statistically significant reduction in the Inattention / Overactivity subscale versus placebo was shown consistently across all three controlled studies for CONCERTA^®. The scores for CONCERTA^® and placebo for the three studies are presented in Figure 2.

Figure 2: Mean Community School Teacher IOWA Conners Inattention/Overactivity Scores with CONCERTA^® once daily (18, 36, or 54 mg) and placebo. 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 were evaluated by laboratory schoolteachers using the SKAMPSwanson, Kotkin, Agler, M-Fynn, and Pelham laboratory school rating scale. The combined results from these two studies demonstrated statistically significant improvements in attention and behavior in patients treated with CONCERTA^® versus placebo that were maintained through 12 hours after dosing. Figure 3 presents the laboratory schoolteacher SKAMP ratings for CONCERTA^® and placebo.

Figure 3: Laboratory School Teacher SKAMP Ratings: Mean (SEM) of Combined Attention (Studies 1 and 2)

14.2Adolescents

In a randomized, double-blind, multicenter, placebo-controlled trial (Study 4) involving 177 patients, CONCERTA^® was demonstrated to be effective in the treatment of ADHD in adolescents aged 13 to 18 years at doses up to 72 mg/day (1.4 mg/kg/day). Of 220 patients who entered an open 4-week titration phase, 177 were titrated to an individualized dose (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 dose of CONCERTA^® (18 – 72 mg/day, n=87) or placebo (n=90) during a two-week double-blind phase. At the end of this phase, mean scores for the investigator rating on the ADHD Rating Scale demonstrated that CONCERTA^® was statistically significantly superior to placebo.

14.3Adults

Two double-blind, placebo-controlled studies were conducted in 627 adults aged 18 to 65 years. The controlled studies compared CONCERTA^® administered once daily and placebo in a multicenter, parallel-group, 7-week dose-titration study (Study 5) (36 to 108 mg/day) and in a multicenter, parallel-group, 5-week, fixed-dose study (Study 6) (18, 36, and 72 mg/day).

Study 5 demonstrated the effectiveness of CONCERTA^® in the treatment of ADHD in adults aged 18 to 65 years at doses from 36 mg/day to 108 mg/day based on the change from baseline to final study visit on the Adult ADHD Investigator Rating Scale (AISRS). Of 226 patients who entered the 7-week trial, 110 were randomized to CONCERTA^® and 116 were randomized to placebo. Treatment was initiated at 36 mg/day and patients continued with incremental increases of 18 mg/day (36 to 108 mg/day) based on meeting specific improvement criteria with acceptable tolerability. At the final study visit, mean change scores (LS Mean, SEM) for the investigator rating on the AISRS demonstrated that CONCERTA^® was statistically significantly superior to placebo.

Study 6 was a multicenter, double-blind, randomized, placebo-controlled, parallel-group, dose-response study (5-week duration) with 3 fixed-dose groups (18, 36, and 72 mg). Patients were randomized to receive CONCERTA^® administered at doses of 18 mg (n=101), 36 mg (n=102), 72 mg/day (n=102), or placebo (n=96). All three doses of CONCERTA^® were statistically significantly more effective than placebo in improving CAARS (Conners' Adult ADHD Rating Scale) total scores at double-blind end point in adult subjects with ADHD.

15references

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994.

16how Supplied/storage And Handling

CONCERTA^® (methylphenidate HCl) Extended-release Tablets are available in 18-mg, 27-mg, 36-mg, and 54-mg dosage strengths. The 18-mg tablets are yellow and imprinted with "alza 18." The 27-mg tablets are gray and imprinted with "alza 27." The 36-mg tablets are white and imprinted with "alza 36." The 54-mg tablets are brownish-red and imprinted with "alza 54." All four dosage strengths are supplied in

18 mg
Bottles of 10	NDC 54868-4489-0
Bottles of 30	NDC 54868-4489-2
Bottles of 60	NDC 54868-4489-3
Bottles of 90	NDC 54868-4489-1

27 mg
Bottles of 10	NDC 54868-4957-0
Bottles of 30	NDC 54868-4957-1

36 mg
Bottles of 10	NDC 54868-4759-3
Bottles of 20	NDC 54868-4759-1
Bottles of 30	NDC 54868-4759-2
Bottles of 60	NDC 54868-4759-0

54 mg
Bottles of 10	NDC 54868-4789-1
Bottles of 30	NDC 54868-4789-0

STORAGE AND HANDLING SECTION

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.

17patient Counseling Information

See Medication Guide

17.1Information for Patients

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with methylphenidate and should counsel them in its appropriate use. A patient Medication Guide is available for CONCERTA^®. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be informed that CONCERTA^® should be swallowed whole with the aid of liquids. Tablets should not be chewed, divided, or crushed. The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The tablet shell, along with insoluble core components, is eliminated from the body; patients should not be concerned if they occasionally notice in their stool something that looks like a tablet.

Stimulants may impair the ability of the patient to operate potentially hazardous machinery or vehicles. Patients should be cautioned accordingly until they are reasonably certain that CONCERTA^® does not adversely affect their ability to engage in such activities.

For more information call 1-888-440-7903.

Manufactured for:McNeil Pediatrics, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.Titusville, NJ 08560

10180604

Revised: November 2010



Relabeling and Repackaging by: Physicians Total Care, Inc.Tulsa, OK        74146

Spl Medguide Section

MEDICATION GUIDECONCERTA^® (kon SER-ta)(methylphenidate HCl) Extended-release Tablets CII

Read the Medication Guide that comes with CONCERTA^® before you or your child starts taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your or your child's treatment with CONCERTA^®.

BOXED WARNING SECTION

What is the most important information I should know about CONCERTA^®?

The following have been reported with use of methylphenidate HCl and other stimulant medicines:

1. Heart-related problems:

• sudden death in patients who have heart problems or heart defects
• stroke and heart attack in adults
• increased blood pressure and heart rate

Tell your doctor if you or your child has any heart problems, heart defects, high blood pressure, or a family history of these problems.

Your doctor should check you or your child carefully for heart problems before starting CONCERTA^®.

Your doctor should check you or your child's blood pressure and heart rate regularly during treatment with CONCERTA^®.

Call your doctor right away if you or your child has any signs of heart problems such as chest pain, shortness of breath, or fainting while taking CONCERTA^®.

2. Mental (Psychiatric) problems:

All Patients

• new or worse behavior and thought problems
• new or worse bipolar illness
• new or worse aggressive behavior or hostility

Children and Teenagers

• new psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms

Tell your doctor about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression.

Call your doctor right away if you or your child has any new or worsening mental symptoms or problems while taking CONCERTA^®, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.

What Is CONCERTA^®?

CONCERTA^® is a central nervous system stimulant prescription medicine. It is used for the treatment of attention deficit and hyperactivity disorder (ADHD). CONCERTA^® may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.

CONCERTA^® should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.

BOXED WARNING SECTION

CONCERTA^® is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep CONCERTA^® in a safe place to prevent misuse and abuse. Selling or giving away CONCERTA^® may harm others, and is against the law.

Tell your doctor if you or your child have (or have a family history of) ever abused or been dependent on alcohol, prescription medicines, or street drugs.

Who should not take CONCERTA^®?

CONCERTA^® should not be taken if you or your child:

• are very anxious, tense, or agitated
• have an eye problem called glaucoma
• have tics or Tourette's syndrome, or a family history of Tourette's syndrome. Tics are hard-to-control repeated movements or sounds.
• are taking or have taken within the past 14 days an antidepression medicine called a monoamine oxidase inhibitor or MAOI.
• are allergic to anything in CONCERTA^®. See the end of this Medication Guide for a complete ul of ingredients.

CONCERTA^® should not be used in children less than 6 years old because it has not been studied in this age group.

CONCERTA^® may not be right for you or your child. Before starting CONCERTA^®, tell your or your child's doctor about all health conditions (or a family history of) including:

• heart problems, heart defects, or high blood pressure
• mental problems including psychosis, mania, bipolar illness, or depression
• tics or Tourette's syndrome
• seizures or have had an abnormal brain wave test (EEG)
• esophagus, stomach, or small or large intestine problems

Tell your doctor if you or your child is pregnant, planning to become pregnant, or breastfeeding.

Can CONCERTA^® be taken with other medicines?

Tell your doctor about all of the medicines that you or your child take including prescription and nonprescription 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 adjusted while taking CONCERTA^®.

Your doctor will decide whether CONCERTA^® can be taken with other medicines.

Especially tell your doctor if you or your child takes:

• antidepression medicines including MAOIs
• seizure medicines
• blood thinner medicines
• blood pressure medicines
• cold or allergy medicines that contain decongestants

Know the medicines that you or your child takes. Keep a ul of your medicines with you to show your doctor and pharmacist.

Do not start any new medicine while taking CONCERTA^® without talking to your doctor first.

How should CONCERTA^® be taken?

• Take CONCERTA^® exactly as prescribed. Your doctor may adjust the dose until it is right for you or your child.
• Do not chew, crush, or divide the tablets. Swallow CONCERTA^® tablets whole with water or other liquids. Tell your doctor if you or your child cannot swallow CONCERTA^® whole. A different medicine may need to be prescribed.
• CONCERTA^® can be taken with or without food.
• Take CONCERTA^® once each day in the morning. CONCERTA^® is an extended-release tablet. It releases medication into your/your child's body throughout the day.
• The CONCERTA^® tablet 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.
• From time to time, your doctor may stop CONCERTA^® treatment for a while to check ADHD symptoms.
• Your doctor may do regular checks of the blood, heart, and blood pressure while taking CONCERTA^®. Children should have their height and weight checked often while taking CONCERTA^®. CONCERTA^® treatment may be stopped if a problem is found during these check-ups.
• If you or your child takes too much CONCERTA^® or overdoses, call your doctor or poison control center right away, or get emergency treatment.

What are possible side effects of CONCERTA^®?

See "What is the most important information I should know about CONCERTA ^®?" for information on reported heart and mental problems.

Other serious side effects include:

• slowing of growth (height and weight) in children
• seizures, mainly in patients with a history of seizures
• eyesight changes or blurred vision
• blockage of the esophagus, stomach, small or large intestine in patients who already have a narrowing in any of these organs

Common side effects include:

decreased appetite dry mouth trouble sleeping dizziness stomach ache increased sweating

headache nausea anxiety weight loss irritability

Stimulants may impair the ability of you or your child to operate potentially hazardous machinery or vehicles. You or your child should exercise caution until you/your child is reasonably certain that CONCERTA^® does not adversely affect your/your child's ability to engage in such activities.

Talk to your doctor if you or your child has side effects that are bothersome or do not go away.

This is not a complete ul of possible side effects. Ask your doctor or pharmacist for more information.

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 McNeil Pediatrics at 1-888-440-7903.

How should I store CONCERTA^®?

• Store CONCERTA^® in a safe place at room temperature, 59 to 86° F (15 to 30° C). Protect from moisture.
• Keep CONCERTA^® and all medicines out of the reach of children.

General information about CONCERTA^®

Medicines are sometimes prescribed for purposes other than those uled 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.

This Medication Guide summarizes the most important information about CONCERTA^®. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about CONCERTA^® that was written for healthcare professionals. For more information about CONCERTA^® call 1-888-440-7903.

What are the ingredients in CONCERTA^®?

Active Ingredient: methylphenidate HCl

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.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:McNeil PediatricsDivision of Ortho-McNeil-Janssen Pharmaceuticals, Inc., Titusville, NJ 08560

10180602Revised: November 2010