Methylphenidate ER Capsules

Name: Methylphenidate ER Capsules

Methylphenidate ER Capsules - Clinical Pharmacology

Pharmacodynamics

Methylphenidate hydrochloride, USP, the active ingredient in methylphenidate hydrochloride extended-release capsules (LA), 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. 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.

Effects on QT Interval
The effect of dexmethylphenidate hydrochloride extended-release (dexmethylphenidate, the pharmacologically active d-enantiomer of methylphenidate hydrochloride) on the QT interval was evaluated in a double-blind, placebo- and open label active (moxifloxacin)-controlled study following single doses of dexmethylphenidate hydrochloride extended-release 40 mg in 75 healthy volunteers. ECGs were collected up to 12 hours postdose. Frederica’s method for heart rate correction was employed to derive the corrected QT interval (QTcF). The maximum mean prolongation of QTcF intervals was <5 ms, and the upper limit of the 90% confidence interval was below 10 ms for all time matched comparisons versus placebo. This was below the threshold of clinical concern and there was no evident-exposure response relationship.

Pharmacokinetics

Absorption
Methylphenidate hydrochloride extended-release capsules (LA) produce a bi-modal plasma concentration-time profile (i.e., 2 distinct peaks approximately 4 hours apart) when orally administered to children diagnosed with ADHD and to healthy 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 exhibit 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 1).

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 in adults.

Figure 1. Mean Plasma Concentration Time-Profile of Methylphenidate After a Single Dose of Methylphenidate Hydrochloride Extended-Release Capsules (LA) 40 mg Once a Day and Methylphenidate Hydrochloride Tablets 20 mg Given in Two Doses Four Hours Apart

Table 1. 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    Methylphenidate
   Methylphenidate  Hydrochloride  Methylphenidate  Hydrochloride
   Hydrochloride  Extended-Release  Hydrochloride  Extended-Release
   Tablets  Capsules (LA)  Tablets  Capsules (LA)
 Dose  10 mg & 10 mg  20 mg  10 mg & 10 mg  20 mg
 N  21  18  9  8
 a N = 15

 Tlag (h)

 0.24 ± 0.44

 0.28 ± 0.46

 1.0 ± 0.5

 0.7 ± 0.2

 

 0 to 1

 0 to 1

 0.7 to 1.3

 0.3 to 1.0

 Tmax1 (h)

 1.8 ± 0.6

 2.0 ± 0.8

 1.9 ± 0.4

 2.0 ± 0.9

 

 1 to 3

 1 to 3

 1.3 to 2.7

 1.3 to 4.0

 Cmax1 (ng/mL)

 10.2 ± 4.2

 10.3 ± 5.1

 4.3 ± 2.3

 5.3 ± 0.9

 

 4.2 to 20.2

 5.5 to 26.6

 1.8 to 7.5

 3.8 to 6.9

 Tminip (h)

 4.0 ± 0.2

 4.5 ± 1.2

 3.8 ± 0.4

 3.6 ± 0.6

 

 4 to 5

 2 to 6

 3.3 to 4.3

 2.7 to 4.3

 Cminip (ng/mL)

 5.8 ± 2.7

 6.1 ± 4.1

 1.2 ± 1.4

 3.0 ± 0.8

 

 3.1 to 14.4

 2.9 to 21.0

 0.0 to 3.7

 1.7 to 4.0

 Tmax2 (h)

 5.6 ± 0.7

 6.6 ± 1.5

 5.9 ± 0.5

 5.5 ± 0.8

 

 5 to 8

 5 to 11

 5.0 to 6.5

 4.3 to 6.5

 Cmax2 (ng/mL)

 15.3 ± 7.0

 10.2 ± 5.9

 5.3 ± 1.4

 6.2 ± 1.6

 

 6.2 to 32.8

 4.5 to 31.1

 3.6 to 7.2

 3.9 to 8.3

 AUC(0-∞)

 102.4 ± 54.6

 86.6 ± 64.0a

 37.8 ± 21.9

 45.8 ± 10.0

 (ng/mL x h-1)

 40.5 to 261.6

 43.3 to 301.44

 14.3 to 85.3

 34.0 to 61.6

 t1/2 (h)

 2.5 ± 0.8

 2.4 ± 0.7a

 3.5 ± 1.9

 3.3 ± 0.4

 

 1.8 to 5.3

 1.5 to 4.0

 1.3 to 7.7

 3.0 to 4.2

Dose Proportionality
After oral administration of methylphenidate hydrochloride extended-release capsules (LA) 20 mg and 40 mg capsules to adults there is a slight upward trend in the methylphenidate area under the curve (AUC) and peak plasma concentrations (Cmax1 and Cmax2).

Distribution
Binding to plasma proteins is low (10% to 33%). The volume of distribution was 2.65±1.11 L/kg for d-methylphenidate and 1.80±0.91 L/kg for l-methylphenidate.

Metabolism
The absolute oral bioavailability of methylphenidate in children was 22±8% for d-methylphenidate and 5±3% for l-methylphenidate, suggesting pronounced presystemic metabolism. Biotransformation of methylphenidate by the carboxylesterase CES1A1 is rapid and extensive leading to the main, de-esterified metabolite α-phenyl-2-piperidine acetic acid (ritalinic acid). Only small amounts of hydroxylated metabolites (e.g., hydroxymethylphenidate and hydroxyritalinic acid) are detectable in plasma. Therapeutic activity is principally due to the parent compound.

Elimination
In studies with methylphenidate hydrochloride extended-release capsules (LA) and methylphenidate hydrochloride tablets in adults, methylphenidate from methylphenidate hydrochloride tablets is eliminated from plasma with an average half-life of about 3.5 hours, (range 1.3 to 7.7 hours). In children the average half-life is about 2.5 hours, with a range of about 1.5 to 5.0 hours. The rapid half-life in both children and adults may result in unmeasurable concentrations between the morning and mid-day doses with methylphenidate hydrochloride tablets. No accumulation of methylphenidate is expected following multiple once a day oral dosing with methylphenidate hydrochloride extended-release capsules (LA). The half-life of ritalinic acid is about 3 to 4 hours.

The systemic clearance is 0.40±0.12 L/h/kg for d-methylphenidate and 0.73±0.28 L/h/kg for l-methylphenidate. After oral administration of an immediate release formulation of methylphenidate, 78% to 97% of the dose is excreted in the urine and 1% to 3% in the feces in the form of metabolites within 48 to 96 hours. Only small quantities (<1%) of unchanged methylphenidate appear in the urine. Most of the dose is excreted in the urine as ritalinic acid (60% to 86%), the remainder being accounted for by minor metabolites.

Food Effects
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.

For patients unable to swallow the capsule, the contents may be sprinkled on applesauce and administered (see DOSAGE AND ADMINISTRATION).

Alcohol Effect
Alcohol may exacerbate the adverse CNS effects of psychoactive drugs, including methylphenidate hydrochloride tablets. It is therefore advisable for patients to abstain from alcohol during treatment. An in vitro study was conducted to explore the effect of alcohol on the release characteristics of methylphenidate from the methylphenidate hydrochloride extended-release (LA) 40 mg capsule 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.

Special Populations
Age: The pharmacokinetics of methylphenidate hydrochloride extended-release capsules (LA) was examined in 18 children with ADHD between 7 and 12 years of age. Fifteen of these children were between 10 and 12 years of age. The time until the between peak minimum, and the time until the second peak were delayed and more variable in children compared to adults. After a 20-mg dose of methylphenidate hydrochloride extended-release capsules (LA), concentrations in children were approximately twice the concentrations observed in 18 to 35 year old adults. This higher exposure is almost completely due to the smaller body size and total volume of distribution in children, as apparent clearance normalized to body weight is independent of age.

Gender: There were no apparent gender differences in the pharmacokinetics of methylphenidate between healthy male and female adults when administered methylphenidate hydrochloride extended-release capsules (LA).

Renal Insufficiency: Methylphenidate hydrochloride extended-release capsules (LA) have not been studied in renally-impaired patients. Renal insufficiency is expected to have minimal effect on the pharmacokinetics of methylphenidate since less than 1% of a radiolabeled dose is excreted in the urine as unchanged compound, and the major metabolite (ritalinic acid), has little or no pharmacologic activity.

Hepatic Insufficiency: Methylphenidate hydrochloride extended-release capsules (LA) have not been studied in patients with hepatic insufficiency. Hepatic insufficiency is expected to have minimal effect on the pharmacokinetics of methylphenidate since it is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body.

CLINICAL STUDIES
Methylphenidate hydrochloride extended-release capsules (LA) were 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 Attention Deficit Hyperactivity Disorder (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 over patients who received placebo. (See Figure 2.) 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*

Precautions

Hematologic Monitoring
Periodic CBC, differential, and platelet counts are advised during prolonged therapy.

Information 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 methylphenidate hydrochloride extended-release capsules (LA). 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 advised 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.

Priapism

• Advise patients, caregivers, and family members of the possibility of painful or prolonged penile erections (priapism). Instruct the patient to seek immediate medical attention in the event of priapism.

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 in 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.

Drug Interactions

Methylphenidate is metabolized primarily by de-esterification (nonmicrosomal hydrolytic esterases) to ritalinic acid and not through oxidative pathways.

The effects of gastrointestinal pH alterations on the absorption of methylphenidate from methylphenidate hydrochloride extended-release capsules (LA) have not been studied. Since the modified release characteristics of methylphenidate hydrochloride extended-release capsules (LA) are pH dependent, the coadministration of antacids or acid suppressants could alter the release of methylphenidate.

Methylphenidate may decrease the effectiveness of drugs used to treat hypertension. Because of possible effects on blood pressure, methylphenidate should be used cautiously with pressor agents.

As an inhibitor of dopamine reuptake, methylphenidate may be associated with pharmacodynamic interactions when coadministered with direct and indirect dopamine agonists (including DOPA and tricyclic antidepressants) as well as dopamine antagonists (antipsychotics, e.g., haloperidol).

Case reports suggest a potential interaction of methylphenidate with coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and tricyclic drugs (e.g., imipramine, clomipramine, desipramine) but pharmacokinetic interactions were not confirmed when explored at higher sample sizes. 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.

Methylphenidate is not metabolized by cytochrome P450 to a clinically relevant extent. Inducers or inhibitors of cytochrome P450 are not expected to have any relevant impact on methylphenidate pharmacokinetics. Conversely, the d- and l-enantiomers of methylphenidate did not relevantly inhibit cytochrome P450 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A.

Methylphenidate coadministration did not increase plasma concentrations of the CYP2D6 substrate desipramine.

An interaction with the anticoagulant ethylbiscoumacetate in 4 subjects was not confirmed in a subsequent study with a higher sample size (n=12).

Other specific drug-drug interaction studies with methylphenidate have not been performed in vivo.

Carcinogenesis/Mutagenesis/Impairment of Fertility

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 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 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.

Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or in 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 (CHO) cells. Methylphenidate was negative in vivo in males and females in the mouse bone marrow micronucleus assay.

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 dose on a mg/kg and mg/m2 basis, respectively.

Pregnancy

Pregnancy Category C
In studies conducted in rats and rabbits, methylphenidate was administered orally at doses of up to 75 and 200 mg/kg/day, respectively, during the period of organogenesis. Teratogenic effects (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 40 times the maximum recommended human dose (MRHD) on a mg/m2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (11 times the MRHD on a mg/m2 basis). There was no evidence of specific teratogenic activity in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (7 times the MRHD on a mg/m2 basis), which was also maternally toxic. The no effect level for embryo-fetal development in rats was 25 mg/kg/day (2 times the MRHD on a mg/m2 basis). When methylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 45 mg/kg/day, offspring body weight gain was decreased at the highest dose (4 times the MRHD on a mg/m2 basis), but no other effects on postnatal development were observed. The no effect level for pre- and postnatal development in rats was 15 mg/kg/day (equal to the MRHD on a mg/m2 basis).

Adequate and well-controlled studies in pregnant women have not been conducted. Methylphenidate hydrochloride extended-release capsules (LA) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing 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 methylphenidate hydrochloride extended-release capsules (LA) are administered to a nursing woman.

Pediatric Use

Long-term effects of methylphenidate in children have not been well established. Methylphenidate hydrochloride extended-release capsules (LA) should not be used in children under 6 years of age (see WARNINGS).

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 6 times the maximum recommended human dose [MRHD] on a mg/m2 basis) or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose (12 times the MRHD on a mg/m2 basis). The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (half the MRHD on a mg/m2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.

Drug Abuse and Dependence

Methylphenidate hydrochloride extended-release capsules (LA), like other products containing methylphenidate, are a Schedule II controlled substance. (See WARNINGS  for boxed warning containing drug abuse and dependence information.)

Methylphenidate ER Capsules Dosage and Administration

Administration of Dose

Methylphenidate hydrochloride extended-release capsules (LA) are for oral administration once daily in the morning. Methylphenidate hydrochloride extended-release capsules (LA) may be swallowed as whole capsules or alternatively 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. Patients should be advised to avoid alcohol while taking methylphenidate hydrochloride extended-release capsules (LA).

Dosing Recommendations

Dosage should be individualized according to the needs and responses of the patients.

Initial Treatment
The recommended starting dose of methylphenidate hydrochloride extended-release capsules (LA) is 20 mg once daily. Dosage may be adjusted in weekly 10 mg increments to a maximum of 60 mg/day taken once daily in the morning, depending on tolerability and degree of efficacy observed. Daily dosage above 60 mg is not recommended. When in the judgement of the clinician a lower initial dose is appropriate, patients may begin treatment with methylphenidate hydrochloride extended-release capsules (LA) 10 mg.

Patients Currently Receiving Methylphenidate
The recommended dose of methylphenidate hydrochloride extended-release capsules (LA) for patients currently taking methylphenidate twice a day or sustained release (SR) is provided below.

Previous Methylphenidate Dose Recommended Methylphenidate Hydrochloride Extended-Release Capsule (LA) Dose

5 mg methylphenidate twice a day

10 mg once a day

10 mg methylphenidate twice a day or 20 mg methylphenidate-SR

20 mg once a day

15 mg methylphenidate twice a day

30 mg once a day

20 mg methylphenidate twice a day or 40 mg of    methylphenidate-SR 

40 mg once a day

30 mg methylphenidate twice a day or 60 mg methylphenidate-SR  

60 mg once a day

For other methylphenidate regimens, clinical judgment should be used when selecting the starting dose. Methylphenidate hydrochloride extended-release capsule (LA) dosage may be adjusted at weekly intervals in 10 mg increments. Daily dosage above 60 mg is not recommended.

Maintenance/Extended Treatment
There is no body of evidence available from controlled trials to indicate how long the patient with ADHD should be treated with methylphenidate hydrochloride extended-release capsules (LA). It is generally agreed, however, that pharmacological treatment of ADHD may be needed for extended periods. Nevertheless, the physician who elects to use methylphenidate hydrochloride extended-release capsules (LA) for extended periods in patients with ADHD should periodically re-evaluate the long-term usefulness of the drug for the individual patient with trials off medication to assess the patient’s functioning without pharmacotherapy. Improvement may be sustained when the drug is either temporarily or permanently discontinued.

Dose Reduction and Discontinuation
If paradoxical aggravation of symptoms or other adverse events occur, the dosage should be reduced, or, if necessary, the drug should be discontinued. If improvement is not observed after appropriate dosage adjustment over a 1-month period, the drug should be discontinued.

Reference

American Psychiatric Association. Diagnosis and Statistical Manual of Mental Disorders. 4th edition. Washington DC: American Psychiatric Association 1994.

Manufactured by:
Catalent Pharma Solutions
Winchester, KY 40391 USA

Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA 

Revised – May 2015
DP18598

Medication guide

METHYLPHENIDATE HYDROCHLORIDE (METH-il-FEN-i-date HYE-droe-KLOR-ide) EXTENDED-RELEASE CAPSULES (LA)        CII

Rx Only

Read the Medication Guide that comes with methylphenidate hydrochloride extended-release capsules (LA) 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 methylphenidate hydrochloride extended-release capsules (LA).                              

What is the most important information I should know about Methylphenidate Hydrochloride Extended-Release Capsules (LA)?

The following have been reported with use of methylphenidate hydrochloride 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 have 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 methylphenidate hydrochloride extended-release capsules (LA).

Your doctor should check your or your child’s blood pressure and heart rate regularly during treatment with methylphenidate hydrochloride extended-release capsules (LA).

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 methylphenidate hydrochloride extended-release capsules (LA).

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 have any new or worsening mental symptoms or problems while taking methylphenidate hydrochloride extended-release capsules (LA), especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.

3. Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’s phenomenon]: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.

• Tell your doctor if you have or your child has numbness, pain, skin color change, or sensitivity to temperature in the fingers or toes. • Call your doctor right away if you have or your child has any signs of unexplained wounds appearing on fingers or toes while taking methylphenidate hydrochloride extended-release capsules (LA).

What are Methylphenidate Hydrochloride Extended-Release Capsules (LA)?
Methylphenidate hydrochloride extended-release capsules (LA) are a central nervous system stimulant prescription medicine. It is used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Methylphenidate hydrochloride extended-release capsules (LA) may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.

Methylphenidate hydrochloride extended-release capsules (LA) should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.

Methylphenidate hydrochloride extended-release capsules (LA) are a federally controlled substance (CII) because they can be abused or lead to dependence. Keep methylphenidate hydrochloride extended-release capsules (LA) in a safe place to prevent misuse and abuse. Selling or giving away methylphenidate hydrochloride extended-release capsules (LA) 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 Methylphenidate Hydrochloride Extended-Release Capsules (LA)?
Methylphenidate hydrochloride extended-release capsules (LA) 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 anti-depression medicine called a monoamine oxidase inhibitor or MAOI. • are allergic to anything in methylphenidate hydrochloride extended-release capsules (LA). See the end of this Medication Guide for a complete list of ingredients.

Methylphenidate hydrochloride extended-release capsules (LA) should not be used in children less than 6 years old because it has not been studied in this age group.

Methylphenidate hydrochloride extended-release capsules (LA) may not be right for you or your child. Before starting methylphenidate hydrochloride extended-release capsules (LA) tell your or your child’s doctor about all health conditions (or a family history of) including:

• heart problems, heart defects, 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) • circulation problems in fingers or toes

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

Can Methylphenidate Hydrochloride Extended-Release Capsules (LA) 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. Methylphenidate hydrochloride extended-release capsules (LA) 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 methylphenidate hydrochloride extended-release capsules (LA).

Your doctor will decide whether methylphenidate hydrochloride extended-release capsules (LA) can be taken with other medicines.

Especially tell your doctor if you or your child takes:

• anti-depression medicines including MAOIs • seizure medicines • blood thinner medicines • blood pressure medicines • stomach acid medicines • cold or allergy medicines that contain decongestants

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

Do not start any new medicine while taking methylphenidate hydrochloride extended-release capsules (LA) without talking to your doctor first.

How should Methylphenidate Hydrochloride Extended-Release Capsules (LA) be taken?

• Take methylphenidate hydrochloride extended-release capsules (LA) exactly as prescribed. Your doctor may adjust the dose until it is right for you or your child. • Take methylphenidate hydrochloride extended-release capsules (LA) once a day in the morning. Methylphenidate hydrochloride extended-release capsules (LA) are an extended-release capsule. It releases medicine into your body throughout the day. • Swallow methylphenidate hydrochloride extended-release capsules (LA) whole with water or other liquids. If you cannot swallow the capsule, open it and sprinkle the medicine over a spoonful of applesauce. Swallow the applesauce and medicine mixture without chewing. Follow with a drink of water or other liquid. Never chew or crush the capsule or the medicine inside the capsule. • Methylphenidate hydrochloride extended-release capsules (LA) should not be taken with alcohol. This may result in a more rapid release of the dose of methylphenidate hydrochloride extended-release capsules (LA). • From time to time, your doctor may stop methylphenidate hydrochloride extended-release capsule (LA) treatment for a while to check ADHD symptoms. • Your doctor may do regular checks of the blood, heart, and blood pressure while taking methylphenidate hydrochloride extended-release capsules (LA). Children should have their height and weight checked often while taking methylphenidate hydrochloride extended-release capsules (LA). Methylphenidate hydrochloride extended-release capsule (LA) treatment may be stopped if a problem is found during these check-ups. • If you or your child takes too much methylphenidate hydrochloride extended-release capsules (LA) or overdoses, call your doctor or poison control center right away, or get emergency treatment.

What are possible side effects of Methylphenidate Hydrochloride Extended-Release Capsules (LA)?

See “What is the most important information I should know about Methylphenidate Hydrochloride Extended-Release Capsules (LA)” 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   painful and prolonged erections (priapism) have occurred with methylphenidate. If you or your child develop priapism, seek medical help right away. Because of the potential for lasting damage, priapism should be evaluated by a doctor immediately.

Common side effects include:

• headache • stomach ache • decreased appetite • trouble sleeping

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 list of possible side effects. Ask your doctor or pharmacist for more information.

How should I store Methylphenidate Hydrochloride Extended-Release Capsules (LA)?

• Store methylphenidate hydrochloride extended-release capsules (LA) in a safe place at room temperature, 59°F to 86°F (15°C to 30°C). • Keep methylphenidate hydrochloride extended-release capsules (LA) and all medicines out of the reach of children.

General information about Methylphenidate Hydrochloride Extended-Release Capsules (LA)
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use methylphenidate hydrochloride extended-release capsules (LA) for a condition for which it was not prescribed. Do not give methylphenidate hydrochloride extended-release capsules (LA) 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 methylphenidate hydrochloride extended-release capsules (LA). If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about methylphenidate hydrochloride extended-release capsules (LA) that was written for healthcare professionals. For more information about methylphenidate hydrochloride extended-release capsules (LA) call 1-800-432-8534.

What are the ingredients in Methylphenidate Hydrochloride Extended-Release Capsules (LA)?
Active Ingredient: methylphenidate hydrochloride, USP
Inactive Ingredients: sugar spheres (which contain sucrose and starch), hypromellose, cellulose acetate butyrate, hypromellose acetate succinate, acetyltributyl citrate, acetone, talc, and purified water. Opaque gelatin capsules contain: titanium dioxide and gelatin. The 30 and 40 mg capsules contain D&C Red #28 and FD&C Blue #1. The capsules are imprinted with black ink which contains black iron oxide, shellac and potassium hydroxide.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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

Manufactured by:
Catalent Pharma Solutions
Winchester, KY 40391 USA

Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA 

Revised – May 2015
DP18598

(web3)