2.1 Pretreatment Screening

Prior to treating patients with methylphenidate hydrochloride extended release capsules (LA), assess:

• for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)].
• the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating methylphenidate hydrochloride extended release capsules (LA) [see Warnings and Precautions (5.10)].

2.2 General Dosing Information

The recommended starting dose for methylphenidate hydrochloride extended-release capsules (LA) is 20 mg once daily. Increase dosage gradually, in increments of 10 mg weekly. Daily dosage above 60 mg is not recommended. When a lower initial dose is appropriate, patients may begin treatment with 10 mg.

Administer methylphenidate hydrochloride extended-release capsules (LA) orally once daily in the morning. Methylphenidate hydrochloride extended-release capsules (LA) may be swallowed as whole capsules or may be administered by sprinkling the capsule contents on a small amount of applesauce (see specific instructions below). Methylphenidate hydrochloride extended-release capsules (LA) and/or their contents should not be crushed, chewed, or divided.

The capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The applesauce should not be warm because it could affect the modified release properties of this formulation. The mixture of drug and applesauce should be consumed immediately in its entirety. The drug and applesauce mixture should not be stored for future use.

2.3 Patients Currently Using Methylphenidate Hydrochloride Tablets

The recommended dose of methylphenidate hydrochloride extended-release capsules (LA) for patients currently taking methylphenidate hydrochloride tablets twice daily is provided in table 1.

2.4 Switching From Other Methylphenidate Products

If switching from other methylphenidate products, discontinue that treatment, and titrate with methylphenidate hydrochloride extended-release capsules (LA) using the titration schedule.

Do not substitute for other methylphenidate products on a milligram-per-milligram basis, because different methylphenidate base compositions and differing pharmacokinetic profiles [see Description (11), Clinical Pharmacology (12.3)].

Clinical judgment should be used when selecting the starting dose. Daily dosage above 60 mg is not recommended.

2.5 Dosage Reduction and Discontinuation

If paradoxical worsening of symptoms or other adverse reactions occur, reduce the dosage, or, if necessary, discontinue methylphenidate hydrochloride extended-release capsules (LA). If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.

5.1Abuse, Misuse and Addiction

Methylphenidate hydrochloride extended release capsules (LA) has a high potential for abuse and misuse. The use of methylphenidate hydrochloride extended release capsules (LA) exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Methylphenidate hydrochloride extended release capsules (LA) can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence (9.2)]. Misuse and abuse of CNS stimulants, including methylphenidate hydrochloride extended release capsules (LA), 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.

Before prescribing methylphenidate hydrochloride extended release capsules (LA), 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 methylphenidate hydrochloride extended release capsules (LA) in a safe place, preferably locked, and instruct patients to not give methylphenidate hydrochloride extended release capsules (LA) to anyone else. Throughout methylphenidate hydrochloride extended release capsules (LA) treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

5.2 Risks to Patients with Serious Cardiac Disease

Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended ADHD dosage.

Avoid methylphenidate hydrochloride extended release capsules (LA) use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.

5.3 Increased Blood Pressure and Heart Rate

CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 beats per minute). Some patients may have larger increases. Monitor all methylphenidate hydrochloride extended release capsules (LA) patients for hypertension and tachycardia.

5.4 Psychiatric Adverse Reactions

5.5 Priapism

Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate use in both adult and pediatric male patients. Although priapism was not reported with methylphenidate initiation, it developed after some time on methylphenidate, often subsequent to an increase in dosage. Priapism also occurred during methylphenidate withdrawal (drug holidays or during discontinuation).

Methylphenidate hydrochloride extended release capsules (LA)-treated patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.

5.6 Peripheral Vasculopathy, Including Raynaud's Phenomenon

CNS stimulants, including methylphenidate hydrochloride extended release capsules (LA), used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are 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 dosage of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or the CNS stimulant.

Careful observation for digital changes is necessary during methylphenidate hydrochloride extended release capsules (LA) treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for methylphenidate hydrochloride extended release capsules (LA)-treated patients who develop signs or symptoms of peripheral vasculopathy.

5.7 Long-Term Suppression of Growth in Pediatric Patients

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.

Careful follow-up of weight and height in pediatric patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated patients over 36 months (to the ages of 10 to13 years), suggests that pediatric patients who received methylphenidate for 7 days per week throughout the year 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 of period.

Closely monitor growth (weight and height) in methylphenidate hydrochloride extended release capsules (LA)-treated pediatric patients. Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

5.8 Acute Angle Closure Glaucoma

There have been reports of angle closure glaucoma associated with methylphenidate treatment.

Although the mechanism is not clear, methylphenidate hydrochloride extended release capsules (LA)-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 and Glaucoma

There have been reports of an elevation of intraocular pressure (IOP) associated with methylphenidate treatment [see Adverse Reactions (6.2)].

Prescribe methylphenidate hydrochloride extended release capsules (LA) to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor methylphenidate hydrochloride extended release capsules (LA)-treated patients with a history of abnormally increased IOP or open angle glaucoma.

5.10 Motor and Verbal Tics, and Worsening of Tourette’s Syndrome

CNS stimulants, including methylphenidate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported [see Adverse Reactions (6.2)].

Before initiating methylphenidate hydrochloride extended release capsules (LA), assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor methylphenidate hydrochloride extended release capsules (LA)-treated patients for the emergence or worsening of tics or Tourette’s syndrome and discontinue treatment if clinically appropriate.

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The clinical program for methylphenidate hydrochloride extended-release capsules (LA) consisted of 6 studies: 2 controlled clinical studies conducted in children with ADHD aged 6 to 12 years and 4 clinical pharmacology studies conducted in healthy adult volunteers. These studies included a total of 256 subjects; 195 children with ADHD and 61 healthy adult volunteers. The subjects received methylphenidate hydrochloride extended-release capsules (LA) in doses of 10 to 40 mg per day. Safety of methylphenidate hydrochloride extended-release capsules (LA) was assessed by evaluating frequency and nature of adverse events, routine laboratory tests, vital signs, and body weight. A placebo-controlled, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of methylphenidate hydrochloride extended-release capsules (LA) in children with ADHD aged 6 to 12 years. All subjects received methylphenidate hydrochloride extended-release capsules (LA) for up to 4 weeks, and had their dose optimally adjusted, prior to entering the double-blind phase of the trial. In the 2-week double-blind treatment phase of this study, patients received either placebo or methylphenidate hydrochloride extended-release capsules (LA) at their individually-titrated dose (range, 10 to 40 mg).

Adverse reactions with an incidence greater than 5% during the initial 4-week single-blind methylphenidate hydrochloride extended-release capsules (LA) titration period of this study were headache, insomnia, upper abdominal pain, appetite decreased, and anorexia.

Adverse reactions with an incidence greater than 2% among methylphenidate hydrochloride extended-release capsules (LA) -treated subjects, during the 2-week double-blind phase of the clinical study, are shown in Table 2:

6.2 Postmarketing Experience

The following adverse reactions have been identified during the post approval use of methylphenidate products. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

7.1 Clinically Important Drug Interactions with Methylphenidate Hydrochloride Extended-Release Capsules (LA)

Table 3 presents clinically important drug interactions with methylphenidate hydrochloride extended-release capsules (LA)

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The safety and effectiveness of methylphenidate hydrochloride extended-release capsules (LA) for the treatment of ADHD have been established in pediatric patients age 6 to 12 years.

The safety and effectiveness of methylphenidate hydrochloride extended-release capsules (LA) in pediatric patients age less than 6 years have not been established. The long-term efficacy of methylphenidate hydrochloride in pediatric patients has not been established.

8.5 Geriatric Use

Methylphenidate hydrochloride extended-release capsules (LA) has not been studied in the geriatric population.

9.1 Controlled Substance

Methylphenidate hydrochloride extended-release capsules (LA) contains methylphenidate hydrochloride, a Schedule II controlled substance.

9.2 Abuse

Methylphenidate hydrochloride extended release capsules (LA) 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)]. Methylphenidate hydrochloride extended release capsules (LA) can be diverted for non-medical use into illicit channels or distribution.

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 methylphenidate hydrochloride 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 methylphenidate hydrochloride extended release capsules (LA)-, 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.

9.3 Dependence

Clinical Effects of Overdose 

Overdose of CNS stimulants is characterized by the followingsympathomimetic 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.

Overdose Management

Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of methylphenidate hydrochloride extended release capsules (LA) 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.

12.1 Mechanism of Action

Methylphenidate hydrochloride is a CNS stimulant. The mode of therapeutic action in ADHD is not known.

12.2 Pharmacodynamics

Methylphenidate is a racemic mixture comprised of the d- and l-threo enantiomers. The d-threo enantiomer is more pharmacologically active than the l-threo enantiomer. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space.

12.3 Pharmacokinetics

Methylphenidate hydrochloride extended-release capsules (LA) produces a bi-modal plasma concentration-time profile (i.e., 2 distinct peaks approximately 4 hours apart) when administered orally to children diagnosed with ADHD and healthy adults.

No accumulation of methylphenidate is expected following multiple once daily oral dosing with methylphenidate hydrochloride extended-release capsules (LA), however, there is a slight upward trend in the methylphenidate area under the curve and peak plasma concentrations (Cmax1 and Cmax2) after oral administration of methylphenidate hydrochloride extended-release capsules (LA) 20 mg and 40 mg to adults.

Absorption

The absolute oral bioavailability of methylphenidate in children was 22 ± 8% for d-methylphenidate and 5 ± 3% for l- methylphenidate. The relative bioavailability of methylphenidate hydrochloride extended-release capsules (LA) given once daily is comparable to the same total dose of methylphenidate hydrochloride tablets given in 2 doses 4 hours apart in both children and adults.

The initial rate of absorption for methylphenidate hydrochloride extended-release capsules (LA) is similar to that of methylphenidate hydrochloride tablets as shown by the similar rate parameters between the 2 formulations, i.e., initial lag time (Tlag), first peak concentration (Cmax1), and time to the first peak (Tmax1), which is reached in 1 to 3 hours. The mean time to the interpeak minimum (Tminip), and time to the second peak (Tmax2) are also similar for methylphenidate hydrochloride extended-release capsules (LA) given once daily and methylphenidate hydrochloride tablets given in 2 doses 4 hours apart (see Figure 1 and Table 1), although the ranges observed are greater for methylphenidate hydrochloride extended-release capsules (LA).

Methylphenidate hydrochloride extended-release capsules (LA) given once daily exhibits a lower second peak concentration (Cmax2), higher interpeak minimum concentrations (Cminip), and less peak and trough fluctuations than methylphenidate hydrochloride tablets given in 2 doses given 4 hours apart. This is due to an earlier onset and more prolonged absorption from the delayed-release beads (see Figure 1 and Table 4).

Figure 1: Mean Plasma Concentration Time-profile of Methylphenidate After a Single Dose of Methylphenidate Hydrochloride Extended-Release Capsule (LA) 40 mg and Methylphenidate Hydrochloride Tablets 20 mg Given in Two Doses 4 Hours Apart

Table 4: Mean ± SD and Range of Pharmacokinetic Parameters of Methylphenidate After a Single Dose of Methylphenidate Hydrochloride Extended-Release Capsules (LA) and Methylphenidate Hydrochloride Tablets Given in Two Doses 4 Hours Apart

Population	Children		Adult Males
Formulation	Methylphenidate Hydrochloride Tablets	Methylphenidate Hydrochloride Extended-Release Capsules (LA)	Methylphenidate Hydrochloride Tablets	Methylphenidate Hydrochloride Extended-Release Capsules (LA)
Dose N	10 mg & 10 mg 21	20 mg 18	10 mg & 10 mg 9	20 mg 8
* N = 15
Tlag (h)	0.24 ± 0.44 0 – 1	0.28 ± 0.46 0 - 1	1.0 ± 0.5 0.7 - 1.3	0.7 ± 0.2 0.3 - 1.0
Tmax1 (h)	1.8 ± 0.6 1 – 3	2.0 ± 0.8 1 - 3	1.9 ± 0.4 1.3 - 2.7	2.0 ± 0.9 1.3 - 4.0
Cmax1 (ng/mL)	10.2 ± 4.2 4.2 - 20.2	10.3 ± 5.1 5.5 - 26.6	4.3 ± 2.3 1.8 - 7.5	5.3 ± 0.9 3.8 - 6.9
Tminip (h)	4.0 ± 0.2 4 – 5	4.5 ± 1.2 2 - 6	3.8 ± 0.4 3.3 - 4.3	3.6 ± 0.6 2.7 - 4.3
Cminip (ng/mL)	5.8 ± 2.7 3.1 - 14.4	6.1 ± 4.1 2.9 - 21.0	1.2 ± 1.4 0.0 - 3.7	3.0 ± 0.8 1.7 - 4.0
Tmax2 (h)	5.6 ± 0.7 5 – 8	6.6 ± 1.5 5 - 11	5.9 ± 0.5 5.0 - 6.5	5.5 ± 0.8 4.3 - 6.5
Cmax2 (ng/mL)	15.3 ± 7.0 6.2 - 32.8	10.2 ± 5.9 4.5 - 31.1	5.3 ± 1.4 3.6 - 7.2	6.2 ± 1.6 3.9 - 8.3
AUC(0-∞) (ng/mL × h-1)	102.4 ± 54.6 40.5 - 261.6	86.6 ± 64.0* 43.3 - 301.44	37.8 ± 21.9 14.3 - 85.3	45.8 ± 10.0 34.0 - 61.6
t1/2 (h)	2.5 ± 0.8 1.8 - 5.3	2.4 ± 0.7 1.5 - 4.0	3.5 ± 1.9 1.3 - 7.7	3.3 ± 0.4 3.0 - 4.2

Effect of Food

Administration times relative to meals and meal composition may need to be individually titrated.

When methylphenidate hydrochloride extended-release capsules (LA) was administered with a high fat breakfast to adults, methylphenidate hydrochloride extended-release capsules (LA) had a longer lag time until absorption began and variable delays in the time until the first peak concentration, the time until the interpeak minimum, and the time until the second peak. The first peak concentration and the extent of absorption were unchanged after food relative to the fasting state, although the second peak was approximately 25% lower. The effect of a high fat lunch was not examined.

There were no differences in the pharmacokinetics of methylphenidate hydrochloride extended-release capsules (LA) when administered with applesauce, compared to administration in the fasting condition. There is no evidence of dose dumping in the presence or absence of food.

Effect of Alcohol

An in vitro study was conducted to explore the effect of alcohol on the release characteristics of methylphenidate from the methylphenidate hydrochloride extended-release capsules (LA) 40 mg dosage form. At an alcohol concentration of 40% there was a 98% release of methylphenidate in the first hour. The results with the 40 mg capsule are considered to be representative of the other available capsule strengths.

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

14.1 Children and Adolescents

Methylphenidate hydrochloride extended-release capsules (LA) was evaluated in a randomized, double-blind, placebo-controlled, parallel group clinical study in which 134 children, ages 6 to 12, with DSM-IV diagnoses of ADHD received a single morning dose of methylphenidate hydrochloride extended-release capsules (LA)in the range of 10 to 40 mg/day, or placebo, for up to 2 weeks. The doses used were the optimal doses established in a previous individual dose titration phase. In that titration phase, 53 of 164 patients (32%) started on a daily dose of 10 mg and 111 of 164 patients (68%) started on a daily dose of 20 mg or higher. The patient's regular schoolteacher completed the Conners ADHD/DSM-IV Scale for Teachers (CADS-T) at baseline and the end of each week. The CADS-T assesses symptoms of hyperactivity and inattention. The change from baseline of the (CADS-T) scores during the last week of treatment was analyzed as the primary efficacy parameter. Patients treated with methylphenidate hydrochloride extended-release capsules (LA) showed a statistically significant improvement in symptom scores from baseline [Mean (final score - baseline) = -10.7 points)] over patients who received placebo [Mean (final score - baseline) = +2.8 points ]. The lower the final score on the CADS-T scale from baseline, the less severe the disease is. This demonstrates that a single morning dose of methylphenidate hydrochloride extended-release capsules (LA) exerts a treatment effect in ADHD.

Figure 2: CADS-T Total Subscale - Mean Change From Baseline*

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F and 86°F). [See USP controlled room temperature].

Dispense in tight container (USP).

Abuse, Misuse, and Addiction 

Educate patients and their families about the risks of abuse, misuse, and addiction of methylphenidate hydrochloride extended release capsules (LA), which can lead to overdose and death, and proper disposal of any unused drug [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2), Overdosage (10)]. Advise patients to store methylphenidate hydrochloride extended release capsules (LA) in a safe place, preferably locked, and instruct patients to not give methylphenidate hydrochloride extended release capsules (LA) 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 methylphenidate hydrochloride extended release capsules (LA) 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

Instruct patients that methylphenidate hydrochloride extended-release capsules (LA) can cause elevations of their blood pressure and pulse rate [see Warnings and Precautions (5.3)].

Psychiatric Adverse Reaction

Advise patients that methylphenidate hydrochloride extended-release capsules (LA), at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania [see Warnings and Precautions (5.4)].

Priapism

Advise patients of the possibility of painful or prolonged penile erections (priapism). Instruct them to seek immediate medical attention in the event of priapism [see Warnings and Precautions (5.5)].

Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, Including Raynaud's Phenomenon]

Instruct patients beginning treatment with methylphenidate hydrochloride extended-release capsules (LA) about the risk of peripheral vasculopathy, including Raynaud's phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red. Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.

Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking methylphenidate hydrochloride extended-release capsules (LA). Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients [see Warnings and Precautions (5.6)].

Long-term Suppression of Growth in Pediatric Patients

Advise patients that methylphenidate hydrochloride extended-release capsules (LA) may cause slowing of growth and weight loss [see Warnings and Precautions (5.7)].

Increased Intraocular Pressure (IOP) and Glaucoma

dvise patients that IOP and glaucoma may occur during treatment with methylphenidate hydrochloride extended release capsules (LA) [see Warnings and Precautions (5.9)].

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 treatment with methylphenidate hydrochloride extended release capsules (LA). 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 (5.10)].

Alcohol Effect

Advise patients to avoid alcohol while taking methylphenidate hydrochloride extended-release capsules (LA). Consumption of alcohol while taking methylphenidate hydrochloride extended-release capsules (LA) may result in a more rapid release of the dose of methylphenidate [see Clinical Pharmacology (12.3)].

Pregnancy Registry

Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to methylphenidate hydrochloride extended-release capsules (LA) during pregnancy [see Use in Specific Populations (8.1)].