Methylphenidate Hydrochloride 40 mg Capsule, Extended Release, 100-count — NDC 0115-1739-01 (Billing 00115-1739-01)
This is a package of 100 capsules of Methylphenidate Hydrochloride 40 mg Capsule, Extended Release from Amneal Pharmaceuticals of New York LLC, marketed since Sep 2016 and currently FDA-listed; retail pharmacies pay about $1.44 per capsule (NADAC). It is this product's only package size.
Other active recalls for Methylphenidate Hydrochloride (different manufacturers) — 1 · tap to view
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 060545
- GCN: 26734
- GPI-14 (Medi-Span): 61400020100240
- HICL (First Databank): 001682
- AHFS class code: 28:20.32.00
- RxCUI (RxNorm): 1806181
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Central Nervous System Stimulant class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
- It mainly treats ADHD, and some products are also used for narcolepsy. The exact approval depends on the product and the age group. Your prescriber chooses the right one for you.
- It depends on your product. Many extended-release forms are taken once daily in the morning, while Jornay PM is taken in the evening. Swallow extended-release tablets whole, and fo...
- The most common ones are decreased appetite, headache, dry mouth, nausea, trouble sleeping, anxiety and dizziness. Children and teens may get upper stomach pain. Call your doctor i...
- Call for chest pain, fainting, a racing heartbeat, hallucinations, seizures, painful erections that won’t go away, or color changes in your fingers or toes. Also call if you notice...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Methylphenidate Hydrochloride — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $1.441 | $144.14 / 100 capsules |
| Medicaid paysCMS SDUD · 12 mo | $1.74 | $174.47 / 100 capsules |
| Medicare drug plans payPart D · Q2 2026 | $1.80 | $180.26 / 100 capsules |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 00115-1739-01 You're viewing this Main listing | 100 CAPSULE, EXTENDED RELEASE in 1 BOTTLE | 2016-09-20 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Methylphenidate Hydrochloride 40 mgthis 00115-1739-01 | Amneal | 100 capsules | $1.441 | AB2 | Availability likely | — |
| Methylphenidate Hydrochloride Extended-Release 40 mg 00406-1840-01 | SpecGx | 100 capsules | $1.441 | AB2 | Availability likely | — |
| methylphenidate hydrochloride CD 40 mg 00527-4582-37 | Lannett | 100 capsules | $1.441 | AB2 | Availability likely | — |
| Methylphenidate Hydrochloride (LA) 40 mg 00093-5348-01 | Teva | 100 capsules | $1.854 | — | Discontinued | +29% |
| Methylphenidate Hydrochloride (LA) 40 mg 75907-0052-01 | Dr. | 100 capsules | $1.854 | AB1 | Availability likely | +29% |
| Methylphenidate Hydrochloride 40 mg 70010-0015-01 | Granules | 100 capsules | $1.854 | AB1 | Availability likely | +29% |
| Methylphenidate Hydrochloride (LA) 40 mg 51862-0612-01 | Mayne | 100 capsules | $2.078 | AB1 | Discontinued | +44% |
| Ritalin LA 40 mg 00078-0372-05 | Novartis | 100 capsules | $12.726 | AB1 | Availability likely | +783% |
| Metadate Cd 40 mg 69654-0582-30 | Aytu | 30 capsules | — | AB2 | FDA listed | — |
| Methylphenidate Hydrochloride 40 mg 42858-0079-45 | Rhodes | 90 capsules | — | AB3 | FDA listed | — |
| methylphenidate hydrochloride 40 mg 00591-3891-19 | Actavis | 90 capsules | — | AB3 | FDA listed | — |
| Metadate Cd 40 mg 00527-6582-30 | Lannett | 30 capsules | — | AB2 | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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Cetyl alcohol is a waxy, fatty substance derived from plant or animal sources. It acts as an emulsifier and thickener in medicines, helping blend oil and water components and giving products a smooth, creamy texture.
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Ethylcellulose is a plant-derived thickener and film-former made by chemically modifying cellulose. It's used as a binder to hold tablet ingredients together, a coating to control how quickly medicine is released, or a thickener in liquid formulations.
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19 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: ABUSE, MISUSE, AND ADDICTION Methylphenidate hydrochloride extended-release has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including methylphenidate hydrochloride extended-release, 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, assess each patient’s risk for abuse, misuse, and addiction.
Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout methylphenidate hydrochloride extended-release treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction [see Warnings and Precautions (5.1) and Drug Abuse and Dependence (9.2) ] . WARNING: ABUSE, MISUSE, AND ADDICTION See full prescribing information for complete boxed warning.
Methylphenidate hydrochloride extended-release has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including methylphenidate hydrochloride extended-release , can result in overdose and death (5.1 , 9.2 , 10) : Before prescribing methylphenidate hydrochloride extended-release , assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug.
Throughout treatment, reassess each patient’s risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Methylphenidate hydrochloride extended-release capsules are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 15 years of age. Limitations of Use The use of methylphenidate hydrochloride extended-release capsules is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g. weight loss) than patients 6 years and older at the same dosage [see Warnings and Precautions (5.7) .
Use in Specific Populations (8.4) ] . Methylphenidate hydrochloride extended-release capsules are a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 15 years of age. (1) Limitations of Use The use of methylphenidate hydrochloride extended-release capsules is not recommended in pediatric patients younger than 6 years of age because they had higher exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage.
(5.7 , 8.4)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Take orally once daily in the morning, before breakfast. Swallow whole with the aid of liquids, or sprinkle contents onto a small amount of applesauce and give immediately. Do not crush or chew the capsule or capsule contents. (2.1) Recommended starting dose is 20 mg once daily. Dosage may be increased 10 mg to 20 mg at weekly intervals; do not exceed 60 mg per day. (2.2)
2.1Pretreatment Screening Prior to treating patients with methylphenidate hydrochloride extended-release capsules, 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 (5.10) ] . the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating methylphenidate hydrochloride extended-release capsules [see Warnings and Precautions (5.10) ] .
2.2Dosage Recommendations The recommended starting dose of methylphenidate hydrochloride extended-release capsules is 20 mg once daily. Dosage may be adjusted in weekly 10 mg to 20 mg increments to the maximum recommended dose of 60 mg per day. Dosage should be individualized according to the needs and responses of the patient.
2.3Administration Instructions Administer methylphenidate hydrochloride extended-release capsules orally once daily in the morning, before breakfast. Swallow the capsule whole with the aid of liquids. Alternatively, open the capsule and sprinkle the contents onto a small amount (tablespoon) of applesauce and administer immediately.
Do not store for future use. Drink fluids following the intake of the sprinkled capsule contents with applesauce. The capsules and the capsule contents must not be crushed or chewed.
2.4Dosage Reduction and Discontinuation If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage or, if necessary, discontinue methylphenidate hydrochloride extended-release capsules. If improvement is not observed after appropriate dosage adjustment over a one-month period, discontinue methylphenidate hydrochloride extended-release capsules.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Methylphenidate hydrochloride extended-release capsules, 10 mg are green cap and white body, opaque capsules, imprinted with ‘CP’ over ‘401’ on the cap and ‘10 mg’ on the body. Methylphenidate hydrochloride extended-release capsules, 20 mg are blue cap and white body, opaque capsules, imprinted with ‘CP’ over ‘402’ on the cap and ‘20 mg’ on the body. Methylphenidate hydrochloride extended-release capsules, 30 mg are brown cap and white body, opaque capsules, imprinted with ‘CP’ over ‘403’ on the cap and ‘30 mg’ on the body.
Methylphenidate hydrochloride extended-release capsules, 40 mg are yellow cap and white body, opaque capsules, imprinted with ‘CP’ over ‘404’ on the cap and ‘40 mg’ on the body. Methylphenidate hydrochloride extended-release capsules, 50 mg are navy blue cap and white body, opaque capsules, imprinted with ‘CP’ over ‘405’ on the cap and ‘50 mg’ on the body. Methylphenidate hydrochloride extended-release capsules, 60 mg are white opaque capsule imprinted with ‘CP’ over ‘406’ on the cap and ‘60 mg’ on the body.
Extended-release capsules : 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Methylphenidate hydrochloride extended-release capsules are contraindicated in patients with: known hypersensitivity to methylphenidate or other component of methylphenidate hydrochloride extended-release capsules. Angioedema has been reported in patients treated with methylphenidate hydrochloride extended-release capsules. Anaphylactic reactions have been reported in patients treated with other methylphenidate products [see Adverse Reactions (6) ] .
Concomitant treatment with monoamine oxidase inhibitors (MAOIs), or within 14 days following discontinuation of treatment with an MAOI, because of the risk of hypertensive crisis [see Drug Interactions (7) ] . Methylphenidate hydrochloride extended-release capsules contain sucrose. Therefore, patients with hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicine.
Known hypersensitivity to methylphenidate or other components of methylphenidate hydrochloride extended-release capsules. ( 4 ) Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days. ( 4 ) Use in patients with patients with hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency.
( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease. (5.2) Increased Blood Pressure and Heart Rate: Monitor blood pressure and pulse. (5.3) Psychiatric Adverse Reactions: Prior to initiating methylphenidate hydrochloride extended-release, screen patients for risk factors for developing a manic episode.
If new psychotic or manic symptoms occur, consider discontinuing methylphenidate hydrochloride extended-release. (5.4) Priapism: If abnormally sustained or frequent and painful erections occur, patients should seek immediate medical attention. (5.5) Peripheral Vasculopathy, including Raynaud’s Phenomenon: Careful observation for digital changes is necessary during methylphenidate hydrochloride extended-release treatment.
Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy. (5.6) Long-Term Suppression of Growth in Pediatric Patients: Closely monitor growth (height and weight) in pediatric patients. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted.
(5.7) Acute Angle Closure Glaucoma: Methylphenidate hydrochloride extended-release-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist. (5.8) Increased Intraocular Pressure (IOP) and Glaucoma: Prescribe methylphenidate hydrochloride extended-release to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor patients with a history of increased IOP or open angle glaucoma.
(5.9) Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: Before initiating methylphenidate hydrochloride extended-release, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome. Discontinue treatment if clinically appropriate.
(5.10)
5.1Abuse, Misuse, and Addiction Methylphenidate hydrochloride extended-release has a high potential for abuse and misuse. The use of methylphenidate hydrochloride extended-release 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 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, 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, 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 in a safe place, preferably locked, and instruct patients to not give methylphenidate hydrochloride extended-release to anyone else. Throughout methylphenidate hydrochloride extended-release treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
5.2Risks to Patients with Serious Cardiac Disease Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended dosage. Avoid methylphenidate hydrochloride extended-release use in patients with known structural cardiac abnormalities, cardiomyopathy, se… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Warnings and Precautions (5.1) , Drug Abuse and Dependence (9.2, 9.3) ] Hypersensitivity to Methylphenidate and Other Component of Methylphenidate Hydrochloride Extended-Release Capsules [see Contraindications (4) ] Hypertensive Crisis when Used Concomitantly with MAOIs [see Contraindications (4) and Drug Interactions (7) ] Risks to Patients with Serious Cardiac Disease [see Warnings and Precautions (5.2) ] Increased Blood Pressure and Heart Rate [see Warnings and Precautions (5.3) ] Psychiatric Adverse Reactions [see Warnings and Precautions (5.4) ] Priapism [see Warnings and Precautions (5.5) ] Peripheral Vasculopathy, including Raynaud’s Phenomenon [see Warnings and Precautions (5.6) ] Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions (5.7) ] Acute Angle Closure Glaucoma [see Warnings and Precautions (5.8) ] Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions (5.9) ] Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions (5.10) ] The most common adverse reactions (≥ 5% and twice the rate of placebo) were anorexia and insomnia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials 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. Clinical trials experience with methylphenidate hydrochloride extended-release included 188 pediatric patients 6 to 15 years old with ADHD exposed to methylphenidate hydrochloride extended-release. Patients received methylphenidate hydrochloride extended-release 20 mg, 40 mg, and/or 60 mg per day.
The 188 patients were evaluated in the following studies: Study 1, a 3-week placebo-controlled clinical study consisting of a total of 314 pediatric patients (ages 6 to 15 years; methylphenidate hydrochloride extended-release n=155); Study 2, a placebo-controlled, crossover clinical study consisting of 25 pediatric patients (ages 7 to 12 years); and Study 3, an uncontrolled clinical study consisting of 8 pediatric patients (ages 6 to 10 years). Adverse Reactions Leading to Discontinuation of Treatment In the 3-week placebo-controlled, parallel-group trial, two methylphenidate hydrochloride extended-release-treated patients (1%) and no placebo-treated patients discontinued due to an adverse reaction (rash and pruritus; and headache, abdominal pain, and dizziness, respectively).
Most Common Adverse Reactions The most common adverse reactions that occurred in 5% or more of patients treated with methylphenidate hydrochloride extended-release in a pool of Studies 1, 2 and 3 (ages 6 to 15 years) where the incidence in patients treated with methylphenidate hydrochloride extended-release was at least twice the incidence in placebo-treated patients were anorexia and insomnia. Adverse reactions that occurred in ≥ 5% of patients treated with methylphenidate hydrochloride extended-release and greater than placebo in pooled Studies 1, 2, and 3 are presented in Table 2: Table 2: Adverse Reactions (≥ 5% and Greater than Placebo) in Pediatric Patients Ages 6 to 15 Years Receiving Methylphenidate Hydrochloride Extended-Release in Pooled Three to Four Week Trials Body System Preferred Term Methylphenidate Hydrochloride Extended-Release (n=188) % Placebo (n=190) % General Headache 12 8 Abdominal Pain (stomachache) 7 4 Digestive System Anorexia 9 2 Nervous System Insomnia 5 2
6.2Post-marketing Experience The following adverse reactions have been identified during post-marketing use of methylphenidate hydrochloride extended-release and other methylphenidate hydrochloride produ… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 3 presents clinically important drug interactions with methylphenidate hydrochloride extended-release. Table 3: Clinically Important Drug Interactions with Methylphenidate Hydrochloride Extended-Release Monoamine Oxidase Inhibitors (MAOI) Clinical Impact: Concomitant use of MAOIs and CNS stimulants, including methylphenidate hydrochloride extended-release, can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see Contraindications (4) ] .
Intervention: Concomitant use of methylphenidate hydrochloride extended-release with monoamine oxidase inhibitors (MAOIs) or within 14 days after discontinuing MAOI treatment is contraindicated. Antihypertensive Drugs Clinical Impact: Methylphenidate hydrochloride extended-release may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions (5.3) ] . Intervention: Adjust the dosage of the antihypertensive drug as needed.
Halogenated Anesthetics Clinical Impact: Concomitant use of halogenated anesthetics and methylphenidate hydrochloride extended-release may increase the risk of sudden blood pressure and heart rate increase during surgery. Intervention: Monitor blood pressure and avoid use of methylphenidate hydrochloride extended-release in patients being treated with anesthetics on the day of surgery. Risperidone Clinical Impact: Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS).
Intervention: Monitor for signs of EPS. Antihypertensive Drugs : Monitor blood pressure. Adjust dosage of antihypertensive drug as needed.
( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including methylphenidate hydrochloride extended-release, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388. Risk Summary Published studies and post-marketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
There may be risks to the fetus associated with the use of CNS stimulants use during pregnancy (see Clinical Considerations ) . No effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis at doses up to 10 and 15 times, respectively, the maximum recommended human dose (MRHD) of 60 mg/day given to adolescents on a mg/m 2 basis. However, spina bifida was observed in rabbits at a dose 53 times the MRHD given to adolescents.
A decrease in pup body weight was observed in a pre-and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 6 times the MRHD given to adolescents (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions CNS stimulants, such as methylphenidate hydrochloride extended-release, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers.
Animal Data In embryo-fetal development 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. Malformations (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 52 times the MRHD of 60 mg/day given to adolescents on a mg/m 2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (15 times the MRHD given to adolescents on a mg/m 2 basis).
There was no evidence of morphological development effects in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (10 times the MRHD of 60 mg/day given to adults on a mg/m 2 basis), which was also maternally toxic. The no effect level for embryo-fetal development in rats was 25 mg/kg/day (3 times the MRHD on a mg/m 2 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 (6 times the MRHD of 60 mg/day given to adults on a mg/m 2 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 (~2 times the MRHD given to adolescents on a mg/m 2 basis).
8.2Lactation Risk Summary Limited published literature, based on milk sampling from seven mothers reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7. There are no reports of adverse effects on the breastfed infant and no effects on milk production. Long-term neurodevelopmental effects on infants from stimul… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including methylphenidate hydrochloride extended-release, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388. Risk Summary Published studies and post-marketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
There may be risks to the fetus associated with the use of CNS stimulants use during pregnancy (see Clinical Considerations ) . No effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis at doses up to 10 and 15 times, respectively, the maximum recommended human dose (MRHD) of 60 mg/day given to adolescents on a mg/m 2 basis. However, spina bifida was observed in rabbits at a dose 53 times the MRHD given to adolescents.
A decrease in pup body weight was observed in a pre-and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 6 times the MRHD given to adolescents (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions CNS stimulants, such as methylphenidate hydrochloride extended-release, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers.
Animal Data In embryo-fetal development 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. Malformations (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 52 times the MRHD of 60 mg/day given to adolescents on a mg/m 2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (15 times the MRHD given to adolescents on a mg/m 2 basis).
There was no evidence of morphological development effects in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (10 times the MRHD of 60 mg/day given to adults on a mg/m 2 basis), which was also maternally toxic. The no effect level for embryo-fetal development in rats was 25 mg/kg/day (3 times the MRHD on a mg/m 2 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 (6 times the MRHD of 60 mg/day given to adults on a mg/m 2 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 (~2 times the MRHD given to adolescents on a mg/m 2 basis).
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of methylphenidate hydrochloride extended-release have not been established in pediatric patients below the age of 6 years. In studies evaluating extended-release methylphenidate products, patients 4 to <6 years of age had higher systemic methylphenidate exposures than those observed in older pediatric patients at the same dosage. Pediatric patients 4 to <6 years of age also had a higher incidence of adverse reactions, including weight loss.
The safety and effectiveness of methylphenidate hydrochloride extended-release for the treatment of ADHD have been established in pediatric patients 6 to 15 years of age. Long-Term Suppression of Growth Growth should be monitored during treatment with stimulants, including methylphenidate hydrochloride extended-release. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions (5.6) ] .
Juvenile Animal Toxicity Data 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 MRHD on a mg/m 2 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/m 2 basis).
The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (half the MRHD on a mg/m 2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.
🧓 Geriatric Use ▾
8.5Geriatric Use Methylphenidate hydrochloride extended-release has not been studied in patients over the age of 65 years.
🆘 Overdosage ▾
10 OVERDOSAGE Clinical Effects of Overdose Overdose of CNS stimulants is characterized by the following sympathomimetic effects: Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop.
CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur. Life-threatening hyperthermia (temperatures greater than 104ºF) and rhabdomyolysis may develop.
Overdose Management Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of methylphenidate hydrochloride extended-release 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Methylphenidate hydrochloride is a central nervous system (CNS) stimulant. The mode of therapeutic action in ADHD is not known.
12.2Pharmacodynamics 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.
12.3Pharmacokinetics Following one week of once-daily doses of 20 mg or 40 mg methylphenidate hydrochloride extended-release to children aged 7 to 12 years old with ADHD, C max and AUC of methylphenidate were approximately proportional to the administered doses. Absorption Following administration of methylphenidate hydrochloride extended-release in children aged 7 to 12 years old with ADHD, the plasma concentration time profile of methylphenidate showed two phases of drug release with a sharp, initial slope similar to a methylphenidate immediate-release tablet (median T max1 about 1.5 hours post dose), and a second rising portion approximately three hours later (median T max2 about 4.5 hours post dose)*, followed by a gradual decline (Figure 1).
The means for C max and area under the curve (AUC) following a dose of 20 mg were slightly lower than those seen with 10 mg of the immediate-release formulation, dosed at 0 and 4 hours. *25% to 30% of the subjects had only one observed peak (C max ) concentration of methylphenidate. Figure 1: Comparison of Immediate Release (IR) and Methylphenidate Hydrochloride Extended-Release Formulations After Repeated Doses of Methylphenidate Hydrochloride in Pediatric Patients 7 to 12 Years of Age with ADHD Effect of Food Ingestion of a high-fat meal with methylphenidate hydrochloride extended-release increased the mean C max and AUC of methylphenidate by about 30% and 17%, respectively.
The presence of food delayed the early peak by approximately 1 hour (range -2 to 5 hours delay) [see Dosage and Administration (2.1) ] . The bioavailability (C max and AUC) of methylphenidate was unaffected by sprinkling the methylphenidate hydrochloride extended-release capsule contents on applesauce as compared to the intact capsule. Effect of Alcohol At an alcohol concentration of 40%, there was an increase in the release rate of methylphenidate in the first hour, resulting in 84% of the methylphenidate being released.
The results with the 60 mg capsule are considered to be representative of the other available capsule strengths [see Drug Interactions (7) ] . Distribution Plasma protein binding is 10% to 33%. The volume of distribution was 2.65 ±
1.11L/kg for d- methylphenidate and 1.80 ±
0.91L/kg for l- methylphenidate. Elimination The mean terminal half-life (t1/2) of methylphenidate following administration of methylphenidate hydrochloride extended-release capsules (t1/2=6.8 hours) is longer than the mean terminal t1/2 following administration of methylphenidate hydrochloride immediate-release tablets (t1/2=2.9 hours) and methylphenidate hydrochloride extended-release tablets (t1/2=3.4 hours) in healthy adult volunteers. Metabolism In vitro studies showed that methylphenidate was not metabolized by cytochrome P450 isoenzymes.
Methylphenidate is metabolized primarily by deesterification to alpha-phenyl-piperidine acetic acid (ritalinic acid), which has little or no pharmacologic activity. Excretion After oral administration of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was ritalinic acid, accounting for approximately 80% of the dose.
Specific Populations Male and Female Patients The pharmacokinetics of methylphenidate after a single-dose of methylphenidate hydrochloride extended-release were similar between adult men and women. Racial or Ethnic Groups The influence of race on the pharmacokinetics o… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Methylphenidate hydrochloride is a central nervous system (CNS) stimulant. The mode of therapeutic action in ADHD is not known.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Methylphenidate hydrochloride extended-release capsules are available in six strengths: Methylphenidate hydrochloride extended-release capsules, 10 mg are green cap and white body, opaque capsules, imprinted with ‘CP’ over ‘401’ on the cap and ‘10 mg’ on the body. They are available as: Bottles of 100: NDC 0115-1736-01 Methylphenidate hydrochloride extended-release capsules, 20 mg are blue cap and white body, opaque capsules, imprinted with ‘CP’ over ‘402’ on the cap and ‘20 mg’ on the body.
They are available as: Bottles of 100: NDC 0115-1737-01 Methylphenidate hydrochloride extended-release capsules, 30 mg are brown cap and white body, opaque capsules, imprinted with ‘CP’ over ‘403’ on the cap and ‘30 mg’ on the body. They are available as: Bottles of 100: NDC 0115-1738-01 Methylphenidate hydrochloride extended-release capsules, 40 mg are yellow cap and white body, opaque capsules, imprinted with ‘CP’ over ‘404’ on the cap and ‘40 mg’ on the body. They are available as: Bottles of 100: NDC 0115-1739-01 Methylphenidate hydrochloride extended-release capsules, 50 mg are navy blue cap and white body, opaque capsules, imprinted with ‘CP’ over ‘405’ on the cap and ‘50 mg’ on the body.
They are available as: Bottles of 100: NDC 0115-1740-01 Methylphenidate hydrochloride extended-release capsules, 60 mg are white opaque capsule imprinted with ‘CP’ over ‘406’ on the cap and ‘60 mg’ on the body. They are available as: Bottles of 100: NDC 0115-1741-01 Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep out of the reach of children.
📋 Description ▾
11 DESCRIPTION Methylphenidate hydrochloride extended-release capsules contains methylphenidate hydrochloride, USP, a CNS stimulant. The extended-release capsules comprise both immediate-release (IR) and extended-release (ER) beads such that 30% of the dose is provided by the IR component and 70% of the dose is provided by the ER component. Methylphenidate hydrochloride extended-release capsules are available in six strengths containing 10 mg (3 mg IR; 7 mg ER), 20 mg (6 mg IR; 14 mg ER), 30 mg (9 mg IR; 21 mg ER), 40 mg (12 mg IR; 28 mg ER), 50 mg (15 mg IR; 35 mg ER), or 60 mg (18 mg IR; 42 mg ER) of methylphenidate hydrochloride, USP for oral administration.
Chemically, methylphenidate hydrochloride, USP is d , l (racemic)- threo -methyl α-phenyl-2-piperidineacetate hydrochloride. Its empirical formula is C 14 H 19 NO 2 •HCl. Its structural formula is: Methylphenidate hydrochloride, USP is a white, odorless, crystalline powder.
Its solutions are acid to litmus. It is freely soluble in water and in methanol, soluble in alcohol, and slightly soluble in chloroform and in acetone. Its molecular weight is 269.77 g/mol.
Methylphenidate hydrochloride extended-release capsules also contain the following inactive ingredients: Sugar spheres, povidone, hydroxypropylmethylcellulose and polyethylene glycol, ethyl cellulose, cetyl alcohol, sodium lauryl sulfate, dibutyl sebacate, gelatin and titanium dioxide. The imprinting ink for all strengths includes: D&C Yellow #10, ethanol, FD&C Blue #1, FD&C Blue #2, FD&C Red #40, iron oxide black, methanol, N-Butyl alcohol, propylene glycol, and shellac glaze. The individual capsules contain the following color agents: 10 mg capsules: FD&C Blue No.
2, FDA/E172 Yellow Iron Oxide 20 mg capsules: D&C Red No. 28, FD&C Blue No. 1, FD&C Green No.
3 30 mg capsules: FDA/E172 Black Iron Oxide, FDA/E172 Red Iron Oxide, FDA/E172 Yellow Iron Oxide 40 mg capsules: D&C Yellow No. 10, FD&C Red No. 40 50 mg capsules: D&C Red No.
28, FD&C Green No. 3, FDA/E172 Black Iron Oxide 5
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide) . Abuse, Misuse, and Addiction Educate patients and their families about the risks of abuse, misuse, and addiction of methylphenidate hydrochloride extended-release, 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 in a safe place, preferably locked, and instruct patients to not give methylphenidate hydrochloride extended-release to anyone else.
Administration Instructions Instruct patients and their caregivers that the methylphenidate hydrochloride extended-release capsules and the capsule contents must not be crushed or chewed. Instruct patients that the capsule may be swallowed whole, or alternatively, the capsule may be opened and the capsule contents sprinkled onto a small amount (tablespoon) of applesauce and given immediately, and not stored for future use [see Dosage and Administration (2.3) ] . 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 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 and their caregivers that methylphenidate hydrochloride extended-release can cause elevations of their blood pressure and pulse rate [see Warnings and Precautions (5.3) ]. Psychiatric Adverse Reactions Advise patients and their caregivers that methylphenidate hydrochloride extended-release, at recommended doses, can cause psychotic or manic symptoms, even in patients without a prior history of psychotic symptoms or mania [see Warnings and Precautions (5.4) ].
Priapism Advise patients and their caregivers of the possibility of painful or prolonged penile erections (priapism). Instruct the patient 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 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. 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 and their caregivers that methylphenidate hydrochloride extended-release can cause slowing of growth and weight loss [see Warnings and Precautions (5.7) ]. Increased Intraocular Pressure (IOP) and Glaucoma Advise patients that IOP and glaucoma may occur during treatment with methylphenidate hydrochloride extended-release [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.
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) ] . Pregnancy Registry Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women expo… [Excerpted — this section continues on DailyMed.]
💬 Medication Guide ▾
MEDICATION GUIDE Methylphenidate Hydrochloride (meth" il fen' i date hye" droe klor' ide) Extended-Release Capsules, CII What is the most important information I should know about methylphenidate hydrochloride extended-release capsules ? Methylphenidate hydrochloride extended-release capsules may cause serious side effects, including: Abuse, misuse, and addiction. Methylphenidate hydrochloride extended-release capsules, has a high chance for abuse and misuse and may lead to substance use problems, including addiction.
Misuse and abuse of methylphenidate hydrochloride extended-release capsules, other methylphenidate containing medicines, and amphetamine containing medicines, can lead to overdose and death. The risk of overdose and death is increased with higher doses of methylphenidate hydrochloride extended-release capsules or when it is used in ways that are not approved, such as snorting or injection. Your healthcare provider should check your child’s risk for abuse, misuse, and addiction before starting treatment with methylphenidate hydrochloride extended-release capsules and will monitor your child during treatment.
Methylphenidate hydrochloride extended-release capsules may lead to physical dependence after prolonged use, even if taken as directed by your healthcare provider. Do not give methylphenidate hydrochloride extended-release capsules to anyone else. See “What is methylphenidate hydrochloride extended-release capsules?” for more information.
Keep methylphenidate hydrochloride extended-release capsules in a safe place and properly dispose of any unused medicine. See “How should I store methylphenidate hydrochloride extended-release capsules?” for more information. Tell your healthcare provider if your child has ever abused or been dependent on alcohol, prescription medicines, or street drugs.
Risks for people with serious heart disease. Sudden death has happened in people who have heart defects or other serious heart disease. Your healthcare provider should check your child carefully for heart problems before starting treatment with methylphenidate hydrochloride extended-release capsules.
Tell your healthcare provider if your child has any heart problems, heart disease, or heart defects. Call your healthcare provider or go to the nearest hospital emergency room right away if your child has any signs of heart problems such as chest pain, shortness of breath, or fainting during treatment with methylphenidate hydrochloride extended-release capsules. Increased blood pressure and heart rate.
Your healthcare provider should check your child’s blood pressure and heart rate regularly during treatment with methylphenidate hydrochloride extended-release capsules. Mental (psychiatric) problems, including: new or worse behavior and thought problems new or worse bipolar illness new psychotic symptoms (such as hearing voices, or seeing or believing things that are not real) or new manic symptoms Tell your healthcare provider about any mental problems your child has, or about a family history of, suicide, bipolar illness, or depression.
Call your healthcare provider right away if your child has any new or worsening mental symptoms or problems during treatment with methylphenidate hydrochloride extended-release capsules, especially hearing voices, seeing or believing things that are not real, or new manic symptoms. What are methylphenidate hydrochloride extended-release capsules? Methylphenidate hydrochloride extended-release capsules are a prescription medicine used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children 6 to 15 years of age.
Methylphenidate hydrochloride extended-release capsules may help increase attention and decrease impulsiveness and hyperactivity in people with ADHD. Methylphenidate hydrochloride extended-release capsules is not recommended for use in children under 6 years of age with ADHD. Methylphenidate hydrochloride extended-release capsules are a federally controlled substanc… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Following one week of once-daily doses of 20 mg or 40 mg methylphenidate hydrochloride extended-release to children aged 7 to 12 years old with ADHD, C max and AUC of methylphenidate were approximately proportional to the administered doses. Absorption Following administration of methylphenidate hydrochloride extended-release in children aged 7 to 12 years old with ADHD, the plasma concentration time profile of methylphenidate showed two phases of drug release with a sharp, initial slope similar to a methylphenidate immediate-release tablet (median T max1 about 1.5 hours post dose), and a second rising portion approximately three hours later (median T max2 about 4.5 hours post dose)*, followed by a gradual decline (Figure 1).
The means for C max and area under the curve (AUC) following a dose of 20 mg were slightly lower than those seen with 10 mg of the immediate-release formulation, dosed at 0 and 4 hours. *25% to 30% of the subjects had only one observed peak (C max ) concentration of methylphenidate. Figure 1: Comparison of Immediate Release (IR) and Methylphenidate Hydrochloride Extended-Release Formulations After Repeated Doses of Methylphenidate Hydrochloride in Pediatric Patients 7 to 12 Years of Age with ADHD Effect of Food Ingestion of a high-fat meal with methylphenidate hydrochloride extended-release increased the mean C max and AUC of methylphenidate by about 30% and 17%, respectively.
The presence of food delayed the early peak by approximately 1 hour (range -2 to 5 hours delay) [see Dosage and Administration (2.1) ] . The bioavailability (C max and AUC) of methylphenidate was unaffected by sprinkling the methylphenidate hydrochloride extended-release capsule contents on applesauce as compared to the intact capsule. Effect of Alcohol At an alcohol concentration of 40%, there was an increase in the release rate of methylphenidate in the first hour, resulting in 84% of the methylphenidate being released.
The results with the 60 mg capsule are considered to be representative of the other available capsule strengths [see Drug Interactions (7) ] . Distribution Plasma protein binding is 10% to 33%. The volume of distribution was 2.65 ±
1.11L/kg for d- methylphenidate and 1.80 ±
0.91L/kg for l- methylphenidate. Elimination The mean terminal half-life (t1/2) of methylphenidate following administration of methylphenidate hydrochloride extended-release capsules (t1/2=6.8 hours) is longer than the mean terminal t1/2 following administration of methylphenidate hydrochloride immediate-release tablets (t1/2=2.9 hours) and methylphenidate hydrochloride extended-release tablets (t1/2=3.4 hours) in healthy adult volunteers. Metabolism In vitro studies showed that methylphenidate was not metabolized by cytochrome P450 isoenzymes.
Methylphenidate is metabolized primarily by deesterification to alpha-phenyl-piperidine acetic acid (ritalinic acid), which has little or no pharmacologic activity. Excretion After oral administration of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was ritalinic acid, accounting for approximately 80% of the dose.
Specific Populations Male and Female Patients The pharmacokinetics of methylphenidate after a single-dose of methylphenidate hydrochloride extended-release were similar between adult men and women. Racial or Ethnic Groups The influence of race on the pharmacokinetics of methylphenidate after methylphenidate hydrochloride extended-release administration has not been studied. Pediatric Patients The pharmacokinetics of methylphenidate after methylphenidate hydrochloride extended-release administration has not been studied in children less than 6 years of age.
Patients with Renal Impairment Methylphenidate hydrochloride extended-release has not been studied in patients with renal insufficiency. Since renal clearance is not an important route of methylphenidate clearance, and the major metabolite (rit… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics 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.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES Methylphenidate hydrochloride extended-release was evaluated in a double-blind, parallel-group, placebo-controlled trial in which 321 untreated or previously treated pediatric patients with a DSM-IV diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), 6 to 15 years of age, received a single morning dose for up to 3 weeks. Patients were required to have the combined or predominantly hyperactive-impulsive subtype of ADHD; patients with the predominantly inattentive subtype were excluded. Patients randomized to the methylphenidate hydrochloride extended-release group received 20 mg daily for the first week.
Their dosage could be increased weekly to a maximum of 60 mg by the third week, depending on individual response to treatment. The patient’s regular school teacher completed the teachers’ version of the Conners’ Global Index Scale (TCGIS), a scale for assessing ADHD symptoms, in the morning and again in the afternoon on three alternate days of each treatment week. The primary efficacy endpoint was determined by the average of the total scores for the 10-item TCGIS completed by the classroom teacher in the morning and again in the afternoon on the three observation days during the last week of double-blind therapy.
Patients treated with methylphenidate hydrochloride extended-release showed a statistically significant improvement in symptom scores from baseline over patients who received placebo (see Figure 2). Separate analyses of TCGIS scores in the morning and afternoon revealed superiority in improvement with methylphenidate hydrochloride extended-release over placebo during both time periods (see Figure 3). Figure 2: Least Squares Mean Change from Baseline in TCGIS Total Score in Pediatric Patients 6 to 15 years of Age with ADHD Figure 3: Least Squares Mean Change from Baseline in TCGIS Total Score in Pediatric Patients 6 to 15 years of Age with ADHD: Morning (AM) and Afternoon (PM) * FIGURES 2 & 3 : Last observation carried forward analysis at week 3.
Error bars represent the standard error of the mean. 2 3
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance Methylphenidate hydrochloride extended-release capsules contain methylphenidate hydrochloride, a Schedule II controlled substance.
9.2Abuse Methylphenidate hydrochloride extended-release 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 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 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, 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.
9.3Dependence Physical Dependence Methylphenidate hydrochloride extended-release may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal signs symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including methylphenidate hydrochloride extended-release include dysphoric mood; depression; fatigue; vivid; unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
Tolerance Methylphenidate hydrochloride extended-release may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, 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 per day. This dose is approximately 2 times the maximum recommended human dose (MRHD) of 60 mg/day given to children on a mg/m 2 basis. Hepatoblastoma is a relatively rare rodent malignant tumor type.
There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown. Methylphenidate did not cause any increases in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 4 times the MRHD (children) on a mg/m 2 basis.
In a 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 mg/kg to 74 mg/kg per day of methylphenidate. Mutagenesis Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay, in the in vitro mouse lymphoma cell forward mutation assay, or in the in vitro chromosomal aberration assay using human lymphocytes.
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 per day, approximately 10 times the maximum recommended human dose of 60 mg/day given to adolescents on a mg/m 2 basis.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, 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 per day. This dose is approximately 2 times the maximum recommended human dose (MRHD) of 60 mg/day given to children on a mg/m 2 basis. Hepatoblastoma is a relatively rare rodent malignant tumor type.
There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown. Methylphenidate did not cause any increases in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 4 times the MRHD (children) on a mg/m 2 basis.
In a 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 mg/kg to 74 mg/kg per day of methylphenidate. Mutagenesis Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay, in the in vitro mouse lymphoma cell forward mutation assay, or in the in vitro chromosomal aberration assay using human lymphocytes.
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 per day, approximately 10 times the maximum recommended human dose of 60 mg/day given to adolescents on a mg/m 2 basis.
📄 Recent Major Changes ▾
RECENT MAJOR CHANGES Indications and Usage (1) 09/2025 Warnings and Precautions (5.7) 09/2025
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL NDC 0115-1736-01 Methylphenidate Hydrochloride Extended-Release Capsules, 10 mg (CII) Rx only 100 Capsules NDC 0115-1737-01 Methylphenidate Hydrochloride Extended-Release Capsules, 20 mg (CII) Rx only 100 Capsules NDC 0115-1738-01 Methylphenidate Hydrochloride Extended-Release Capsules, 30 mg (CII) Rx only 100 Capsules NDC 0115-1739-01 Methylphenidate Hydrochloride Extended-Release Capsules, 40 mg (CII) Rx only 100 Capsules NDC 0115-1740-01 Methylphenidate Hydrochloride Extended-Release Capsules, 50 mg (CII) Rx only 100 Capsules NDC 0115-1741-01 Methylphenidate Hydrochloride Extended-Release Capsules, 60 mg (CII) Rx only 100 Capsules 1 2 3 4 5 6