Methylphenidate hydrochloride extended-release tablets have 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 tablets, can result in overdose and death [see Overdosage ( 10 )] , and this risk is increased with higher doses or unapproved methods of adm...
Methylphenidate hydrochloride extended-release tablets are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children 6 years of age and older, adolescents, and adults up to the age of 65 [see Clinical Studies ( 14 )] .
Prior to treating patients with methylphenidate hydrochloride extended-release tablets, assess: for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions ( 5.2 )]. the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating methylphenidat...
Strength Color Tablet Description Bottle Count NDC 27 mg Gray capsule shaped, imprinted with “M” in a box and “27” on one side in black ink 100 0406-0127-01 36 mg White capsule shaped, imprinted with “M” in a box and “36” on one side in black ink 100 0406-0136-01 54 mg Red capsule shaped, imprinted with “M” in a box and “54” on one side in black ink 100 0406-0154-01 Storage ...
www.fda.gov/medwatch
www.mallinckrodt.com/Medguide/L20M49.pdfwww.fda.gov/drugdisposalwww.mallinckrodt.comMethylphenidate hydrochloride extended-release tablets have 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 tablets, 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 tablets, 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 tablets 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)].
Methylphenidate hydrochloride extended-release tablets are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children 6 years of age and older, adolescents, and adults up to the age of 65 [see Clinical Studies (14)].
Prior to treating patients with methylphenidate hydrochloride extended-release tablets, assess:
Methylphenidate hydrochloride extended-release tablets should be administered orally once daily in the morning with or without food.
Methylphenidate hydrochloride extended-release tablets must be swallowed whole with the aid of liquids, and must not be chewed, divided, or crushed [see Patient Counseling Information (17)].
The recommended starting dose of methylphenidate hydrochloride extended-release tablets for patients who are not currently taking methylphenidate or stimulants other than methylphenidate is 18 mg once daily for children and adolescents and 18 or 36 mg once daily for adults (see Table 1).
| Patient Age | Recommended Starting Dose | Dose Range |
| Children | 18 mg/day | 18 mg - 54 mg/day |
| Adolescents | 18 mg/day | 18 mg - 72 mg/day not to exceed |
| Adults | 18 or 36 mg/day | 18 mg - 72 mg/day |
The recommended dose of methylphenidate hydrochloride extended-release tablets for patients who are currently taking methylphenidate twice daily or three times daily at doses of 10 to 60 mg/day is provided in Table 2. Dosing recommendations are based on current dose regimen and clinical judgment. Conversion dosage should not exceed 72 mg daily.
| Previous Methylphenidate Daily Dose | Recommended Methylphenidate Hydrochloride Extended-Release Tablets Starting Dose |
| 5 mg Methylphenidate twice daily or three times daily | 18 mg every morning |
| 10 mg Methylphenidate twice daily or three times daily | 36 mg every morning |
| 15 mg Methylphenidate twice daily or three times daily | 54 mg every morning |
| 20 mg Methylphenidate twice daily or three times daily | 72 mg every morning |
Other methylphenidate regimens: Clinical judgment should be used when selecting the starting dose.
Doses may be increased in 18 mg increments at weekly intervals for patients who have not achieved an optimal response at a lower dose. Daily dosages above 54 mg in children and 72 mg in adolescents have not been studied and are not recommended. Daily dosages above 72 mg in adults are not recommended.
A 27 mg dosage strength is available for physicians who wish to prescribe between the 18 mg and 36 mg dosages.
If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage or, if necessary, discontinue methylphenidate hydrochloride extended-release tablets.
If improvement is not observed after appropriate dosage adjustment over a one-month period, discontinue methylphenidate hydrochloride extended-release tablets.
| Strength | Color | Tablet Description |
| 27 mg | Gray | capsule shaped, imprinted with “M” in a box and “27” on one side in black ink |
| 36 mg | White | capsule shaped, imprinted with “M” in a box and “36” on one side in black ink |
| 54 mg | Red | capsule shaped, imprinted with “M” in a box and “54” on one side in black ink |
Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been observed in patients treated with methylphenidate hydrochloride extended-release tablets. Therefore, methylphenidate hydrochloride extended-release tablets are contraindicated in patients known to be hypersensitive to methylphenidate or other components of the product [see Adverse Reactions (6.5)].
Methylphenidate hydrochloride extended-release tablets are contraindicated during treatment with monoamine oxidase (MAO) inhibitors, and also within a minimum of 14 days following discontinuation of a MAO inhibitor (hypertensive crises may result) [see Drug Interactions (7.1)].
Methylphenidate hydrochloride extended-release tablets have a high potential for abuse and misuse. The use of methylphenidate hydrochloride extended-release tablets 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 tablets 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 tablets, 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 tablets, 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 tablets in a safe place, preferably locked, and instruct patients to not give methylphenidate hydrochloride extended-release tablets to anyone else. Throughout methylphenidate hydrochloride extended-release tablets treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage.
Avoid methylphenidate hydrochloride extended-release tablets use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
CNS stimulants may cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm). Some patients may have larger increases.
Monitor all methylphenidate hydrochloride extended-release tablets-treated patients for hypertension and tachycardia.
Exacerbation of Pre-Existing Psychosis
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.
Induction of a Manic Episode in Patients with Bipolar Disorder
CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating methylphenidate hydrochloride extended-release tablets treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).
New Psychotic or Manic Symptoms
CNS stimulants, at the recommended dosage, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared with 0% of placebo-treated patients. If such symptoms occur, consider discontinuing methylphenidate hydrochloride extended-release tablets.
There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.
Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate use in both adult and pediatric male patients [see Adverse Reactions (6.5)]. Although priapism was not reported with methylphenidate initiation, it developed after some time on methylphenidate, often subsequent to an increase in dosage. Priapism also occurred during methylphenidate withdrawal (drug holidays or during discontinuation).
Methylphenidate hydrochloride extended-release tablets-treated patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.
CNS stimulants, including methylphenidate hydrochloride extended-release tablets, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in postmarketing reports and at the therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant.
Careful observation for digital changes is necessary during methylphenidate hydrochloride extended-release tablets treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for methylphenidate hydrochloride extended-release tablets-treated patients who develop signs or symptoms of peripheral vasculopathy.
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.
Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or nonmedication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and nonmedication-treated children over 36 months (to the ages of 10 to 13 years), suggests that pediatric patients who received methylphenidate for 7 days per week throughout the year had a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this development period. Closely monitor growth (weight and height) in methylphenidate hydrochloride extended-release tablets-treated pediatric patients. Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
Because the methylphenidate hydrochloride extended-release tablets are nondeformable and do not appreciably change in shape in the GI tract, methylphenidate hydrochloride extended-release tablets should not ordinarily be administered to patients with pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic, for example: esophageal motility disorders, small bowel inflammatory disease, “short gut” syndrome due to adhesions or decreased transit time, past history of peritonitis, cystic fibrosis, chronic intestinal pseudo-obstruction, or Meckel’s diverticulum). There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of drugs in nondeformable controlled-release formulations. Due to the controlled-release design of the tablet, methylphenidate hydrochloride extended-release tablets should be used only in patients who are able to swallow the tablet whole [see Patient Counseling Information (17)].
Periodic CBC, differential, and platelet counts are advised during prolonged therapy.
There have been rare reports of angle closure glaucoma associated with methylphenidate treatment.
Although the mechanism is not clear, methylphenidate hydrochloride extended-release tablets-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.
There have been reports of an elevation of intraocular pressure (IOP) associated with methylphenidate treatment [see Adverse Reactions (6.5)].
Prescribe methylphenidate hydrochloride extended-release tablets to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor methylphenidate hydrochloride extended-release tablets-treated patients with a history of abnormally increased IOP or open-angle glaucoma.
CNS stimulants, including methylphenidate, have been associated with the onset or exacerbation of motor and verbal tics [see Adverse Reactions (6.2, 6.5)]. Worsening of Tourette’s syndrome has also been reported.
Before initiating methylphenidate hydrochloride extended-release tablets, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor methylphenidate hydrochloride extended-release tablets-treated patients for the emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically appropriate.
The following are discussed in more detail in other sections of the labeling:
Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions (5.1)]
Hypersensitivity to Methylphenidate [see Contraindications (4.1)]
Monoamine Oxidase Inhibitors [see Contraindications (4.2) and Drug Interactions (7.1)]
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)]
Seizures [see Warnings and Precautions (5.5)]
Priapism [see Warnings and Precautions (5.6)]
Peripheral Vasculopathy, including Raynaud’s Phenomenon [see Warnings and Precautions (5.7)]
Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions (5.8)]
Potential for Gastrointestinal Obstruction [see Warnings and Precautions (5.9)]
Hematologic Monitoring [see Warnings and Precautions (5.10)]
Acute Angle Closure Glaucoma [see Warnings and Precautions (5.11)]
Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions (5.12)]
Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions (5.13)]
The most common adverse reaction in double-blind clinical trials (>5%) in pediatric patients (children and adolescents) was abdominal pain upper. The most common adverse reactions in double-blind clinical trials (>5%) in adult patients were decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis [see Adverse Reactions (6.1)].
The most common adverse reactions associated with discontinuation (≥1%) from either pediatric or adult clinical trials were anxiety, irritability, insomnia, and blood pressure increased [see Adverse Reactions (6.3)].
The development program for methylphenidate hydrochloride extended-release tablets included exposures in a total of 3906 participants in clinical trials. Children, adolescents, and adults with ADHD were evaluated in 6 controlled clinical studies and 11 open-label clinical studies (see Table 3). Safety was assessed by collecting adverse events, vital signs, weights, and ECGs, and by performing physical examinations and laboratory analyses.
| Patient Population | N | Dose Range |
| Children | 2216 | 18 to 54 mg once daily |
| Adolescents | 502 | 18 to 72 mg once daily |
| Adults | 1188 | 18 to 108 mg once daily |
Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using their own terminology. Consequently, to provide a meaningful estimate of the proportion of individuals experiencing adverse events, events were grouped in standardized categories using MedDRA terminology.
The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.
Throughout this section, adverse reactions are reported. Adverse reactions are adverse events that were considered to be reasonably associated with the use of methylphenidate hydrochloride extended-release tablets based on the comprehensive assessment of the available adverse event information. A causal association for methylphenidate hydrochloride extended-release tablets often cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice.
The majority of adverse reactions were mild to moderate in severity.
Adverse reactions in either the pediatric or adult double-blind adverse reactions tables may be relevant for both patient populations.
Children and Adolescents
Table 4 lists the adverse reactions reported in 1% or more of methylphenidate hydrochloride extended-release tablets-treated children and adolescent subjects in 4 placebo-controlled, double-blind clinical trials.
| System/Organ Class | Methylphenidate Hydrochloride Extended-Release Tablets (n=321) % | Placebo (n=318) % |
| Gastrointestinal Disorders | ||
| Abdominal pain upper | 6.2 | 3.8 |
| Vomiting General Disorders and Administration Site Conditions | 2.8 | 1.6 |
| Pyrexia Infections and Infestations | 2.2 | 0.9 |
| Nasopharyngitis Nervous System Disorders | 2.8 | 2.2 |
| Dizziness Psychiatric Disorders | 1.9 | 0 |
| Insomnia* Respiratory, Thoracic and Mediastinal Disorders | 2.8 | 0.3 |
| Cough | 1.9 | 0.9 |
| Oropharyngeal pain | 1.2 | 0.9 |
* Terms of Initial insomnia (methylphenidate hydrochloride extended-release tablets=0.6%) and Insomnia (methylphenidate hydrochloride extended-release tablets=2.2%) are combined into Insomnia.
The majority of adverse reactions were mild to moderate in severity.
Adults
Table 5 lists the adverse reactions reported in 1% or more of methylphenidate hydrochloride extended-release tablets-treated adults in 2 placebo-controlled, double-blind clinical trials.
| System/Organ Class | Methylphenidate Hydrochloride Extended-Release Tablets (n=415) % | Placebo (n=212) % |
| Cardiac Disorders | ||
| Tachycardia | 4.8 | 0 |
| Palpitations Ear and Labyrinth Disorders | 3.1 | 0.9 |
| Vertigo Eye Disorders | 1.7 | 0 |
| Vision blurred Gastrointestinal Disorders | 1.7 | 0.5 |
| Dry mouth | 14.0 | 3.8 |
| Nausea | 12.8 | 3.3 |
| Dyspepsia | 2.2 | 0.9 |
| Vomiting | 1.7 | 0.5 |
| Constipation General Disorders and Administration Site Conditions | 1.4 | 0.9 |
| Irritability Infections and Infestations | 5.8 | 1.4 |
| Upper respiratory tract infection Investigations Weight decreased | 2.2 6.5 | 0.9 3.3 |
| Metabolism and Nutrition Disorders | ||
| Decreased appetite | 25.3 | 6.6 |
| Anorexia Musculoskeletal and Connective Tissue Disorders | 1.7 | 0 |
| Muscle tightness Nervous System Disorders | 1.9 | 0 |
| Headache | 22.2 | 15.6 |
| Dizziness | 6.7 | 5.2 |
| Tremor | 2.7 | 0.5 |
| Paresthesia | 1.2 | 0 |
| Sedation | 1.2 | 0 |
| Tension headache Psychiatric Disorders | 1.2 | 0.5 |
| Insomnia | 12.3 | 6.1 |
| Anxiety | 8.2 | 2.4 |
| Initial insomnia | 4.3 | 2.8 |
| Depressed mood | 3.9 | 1.4 |
| Nervousness | 3.1 | 0.5 |
| Restlessness | 3.1 | 0 |
| Agitation | 2.2 | 0.5 |
| Aggression | 1.7 | 0.5 |
| Bruxism | 1.7 | 0.5 |
| Depression | 1.7 | 0.9 |
| Libido decreased | 1.7 | 0.5 |
| Affect lability | 1.4 | 0.9 |
| Confusional state | 1.2 | 0.5 |
| Tension Respiratory, Thoracic and Mediastinal Disorders | 1.2 | 0.5 |
| Oropharyngeal pain Skin and Subcutaneous Tissue Disorders | 1.7 | 1.4 |
| Hyperhidrosis | 5.1 | 0.9 |
* Included doses up to 108 mg.
The majority of ADRs were mild to moderate in severity.
This section includes adverse reactions reported by methylphenidate hydrochloride extended-release tablets-treated subjects in double-blind trials that do not meet the criteria specified for Table 4 or Table 5 and all adverse reactions reported by methylphenidate hydrochloride extended-release tablets-treated subjects who participated in open-label and postmarketing clinical trials.
Blood and Lymphatic System Disorders: Leukopenia
Eye Disorders: Accommodation disorder, Dry eye
Vascular Disorders: Hot flush
Gastrointestinal Disorders: Abdominal discomfort, Abdominal pain, Diarrhea
General Disorders and Administrative Site Conditions: Asthenia, Fatigue, Feeling jittery, Thirst
Infections and Infestations: Sinusitis
Investigations: Alanine aminotransferase increased, Blood pressure increased, Cardiac murmur, Heart rate increased
Musculoskeletal and Connective Tissue Disorders: Muscle spasms
Nervous System Disorders: Lethargy, Psychomotor hyperactivity, Somnolence
Psychiatric Disorders: Anger, Hypervigilance, Mood altered, Mood swings, Panic attack, Sleep disorder, Tearfulness, Tic
Reproductive System and Breast Disorders: Erectile dysfunction
Respiratory, Thoracic and Mediastinal Disorders: Dyspnea
Skin and Subcutaneous Tissue Disorders: Rash, Rash macular
Vascular Disorders: Hypertension
Adverse reactions in the 4 placebo-controlled studies of children and adolescents leading to discontinuation occurred in 2 methylphenidate hydrochloride extended-release tablets patients (0.6%) including depressed mood (1, 0.3%) and headache and insomnia (1, 0.3%), and 6 placebo patients (1.9%) including headache and insomnia (1, 0.3%), irritability (2, 0.6%), headache (1, 0.3%), psychomotor hyperactivity (1, 0.3%), and tic (1, 0.3%).
In the 2 placebo-controlled studies of adults, 25 methylphenidate hydrochloride extended-release tablets patients (6.0%) and 6 placebo patients (2.8%) discontinued due to an adverse reaction. Those events with an incidence of >0.5% in the methylphenidate hydrochloride extended-release tablets patients included anxiety (1.7%), irritability (1.4%), blood pressure increased (1.0%), and nervousness (0.7%). In placebo patients, blood pressure increased and depressed mood had an incidence of >0.5% (0.9%).
In the 11 open-label studies of children, adolescents, and adults, 266 methylphenidate hydrochloride extended-release tablets patients (7.0%) discontinued due to an adverse reaction. Those events with an incidence of >0.5% included insomnia (1.2%), irritability (0.8%), anxiety (0.7%), decreased appetite (0.7%), and tic (0.6%).
In the laboratory classroom clinical trials in children (Studies 1 and 2), both methylphenidate hydrochloride extended-release tablets once daily and methylphenidate three times daily increased resting pulse by an average of 2 to 6 bpm and produced average increases of systolic and diastolic blood pressure of roughly 1 to 4 mm Hg during the day, relative to placebo. In the placebo-controlled adolescent trial (Study 4), mean increases from baseline in resting pulse rate were observed with methylphenidate hydrochloride extended-release tablets and placebo at the end of the double-blind phase (5 and 3 beats/minute, respectively). Mean increases from baseline in blood pressure at the end of the double-blind phase for methylphenidate hydrochloride extended-release tablets and placebo-treated patients were 0.7 and 0.7 mm Hg (systolic) and 2.6 and 1.4 mm Hg (diastolic), respectively. In one placebo-controlled study in adults (Study 6), dose-dependent mean increases of 3.9 to 9.8 bpm from baseline in standing pulse rate were observed with methylphenidate hydrochloride extended-release tablets at the end of the double-blind treatment vs. an increase of 2.7 beats/minute with placebo. Mean changes from baseline in standing blood pressure at the end of double-blind treatment ranged from 0.1 to 2.2 mm Hg (systolic) and -0.7 to 2.2 mm Hg (diastolic) for methylphenidate hydrochloride extended-release tablets and was 1.1 mm Hg (systolic) and -1.8 mm Hg (diastolic) for placebo. In a second placebo-controlled study in adults (Study 5), mean changes from baseline in resting pulse rate were observed for methylphenidate hydrochloride extended-release tablets and placebo at the end of the double-blind treatment (3.6 and -1.6 beats/minute, respectively). Mean changes from baseline in blood pressure at the end of the double-blind treatment for methylphenidate hydrochloride extended-release tablets and placebo-treated patients were -1.2 and -0.5 mm Hg (systolic) and 1.1 and 0.4 mm Hg (diastolic), respectively [see Warnings and Precautions (5.3)].
The following additional adverse reactions have been identified during postapproval use of methylphenidate hydrochloride extended-release tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency:
Blood and Lymphatic System Disorders: Pancytopenia, Thrombocytopenia, Thrombocytopenic purpura
Cardiac Disorders: Angina pectoris, Bradycardia, Extrasystoles, Supraventricular tachycardia, Ventricular extrasystoles
Eye Disorders: Diplopia, Increased intraocular pressure, Mydriasis, Visual impairment
General Disorders: Chest pain, Chest discomfort, Drug effect decreased, Hyperpyrexia, Therapeutic response decreased
Hepatobiliary Disorders: Hepatocellular injury, Acute hepatic failure
Immune System Disorders: Hypersensitivity reactions such as Angioedema, Anaphylactic reactions, Auricular swelling, Bullous conditions, Exfoliative conditions, Urticarias, Pruritus NEC, Rashes, Eruptions, and Exanthemas NEC
Investigations: Blood alkaline phosphatase increased, Blood bilirubin increased, Hepatic enzyme increased, Platelet count decreased, White blood cell count abnormal
Musculoskeletal, Connective Tissue and Bone Disorders: Arthralgia, Myalgia, Muscle twitching, Rhabdomyolysis
Nervous System Disorders: Convulsion, Grand mal convulsion, Dyskinesia, Serotonin syndrome in combination with serotonergic drugs, Motor and verbal tics
Psychiatric Disorders: Disorientation, Hallucination, Hallucination auditory, Hallucination visual, Mania, Logorrhea, Libido changes
Reproductive System and Breast Disorders: Priapism
Skin and Subcutaneous Tissue Disorders: Alopecia, Erythema
Vascular Disorders: Raynaud’s phenomenon
Methylphenidate hydrochloride extended-release tablets should not be used in patients being treated (currently or within the preceding 2 weeks) with MAO inhibitors [see Contraindications (4.2)].
Because of possible increases in blood pressure, methylphenidate hydrochloride extended-release tablets should be used cautiously with vasopressor agents [see Warnings and Precautions (5.3)].
Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). Downward dose adjustment of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentrations (or, in the case of coumarin, coagulation times), when initiating or discontinuing concomitant methylphenidate.
Concomitant use of halogenated anesthetics and methylphenidate hydrochloride extended-release tablets may increase the risk of sudden blood pressure and heart rate increase during surgery. Monitor blood pressure and avoid use of methylphenidate hydrochloride extended-release tablets in patients being treated with anesthetics on the day of surgery.
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). Monitor for signs of EPS.
Pregnancy Category C
Methylphenidate has been shown to have teratogenic effects in rabbits when given in doses of 200 mg/kg/day, which is approximately 100 times and 40 times the maximum recommended human dose on a mg/kg and mg/m2 basis, respectively.
A reproduction study in rats revealed no evidence of harm to the fetus at oral doses up to 30 mg/kg/day, approximately 15-fold and 3-fold the maximum recommended human dose of methylphenidate hydrochloride extended-release tablets on a mg/kg and mg/m2 basis, respectively. The approximate plasma exposure to methylphenidate plus its main metabolite PPAA in pregnant rats was 1 to 2 times that seen in trials in volunteers and patients with the maximum recommended dose of methylphenidate hydrochloride extended-release tablets based on the AUC.
The safety of methylphenidate for use during human pregnancy has not been established. There are no adequate and well-controlled studies in pregnant women. Methylphenidate hydrochloride extended-release tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
The effect of methylphenidate hydrochloride extended-release tablets on labor and delivery in humans is unknown.
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 tablets are administered to a nursing woman.
In lactating female rats treated with a single oral dose of 5 mg/kg radiolabeled methylphenidate, radioactivity (representing methylphenidate and/or its metabolites) was observed in milk and levels were generally similar to those in plasma.
Methylphenidate hydrochloride extended-release tablets should not be used in children under six years, since safety and efficacy in this age group have not been established. Long-term effects of methylphenidate in children have not been well established.
Methylphenidate hydrochloride extended-release tablets have not been studied in patients greater than 65 years of age.
Methylphenidate hydrochloride extended-release tablets contain methylphenidate, a Schedule II controlled substance.
Methylphenidate hydrochloride extended-release tablets have 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 tablets 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 healthcare 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 tablets, 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.
In two placebo-controlled human abuse potential studies, single oral doses of methylphenidate hydrochloride extended-release tablets were compared to single oral doses of immediate-release methylphenidate (IR MPH) and placebo in subjects with a history of recreational stimulant use to assess relative abuse potential. For the purpose of this assessment, the response for each of the subjective measures was defined as the maximum effect within the first 8 hours after dose administration.
In one study (n=40), both methylphenidate hydrochloride extended-release tablets (108 mg) and 60 mg IR MPH compared to placebo produced statistically significantly greater responses on the five subjective measures suggestive of abuse potential. In comparisons between the two active treatments, however, methylphenidate hydrochloride extended-release tablets (108 mg) produced variable responses on positive subjective measures that were either statistically indistinguishable from (Abuse Potential, Drug Liking, Amphetamine, and Morphine Benzedrine Group [Euphoria]) or statistically less than (Stimulation – Euphoria) responses produced by 60 mg IR MPH.
In another study (n=49), both doses of methylphenidate hydrochloride extended-release tablets (54 mg and 108 mg) and both doses of IR MPH (50 mg and 90 mg) produced statistically significantly greater responses compared to placebo on the two primary scales used in the study (Drug Liking, Euphoria). When doses of methylphenidate hydrochloride extended-release tablets (54 mg and 108 mg) were compared to IR MPH (50 mg and 90 mg), respectively, methylphenidate hydrochloride extended-release tablets produced statistically significantly lower subjective responses on these two scales than IR MPH. Methylphenidate hydrochloride extended-release tablets (108 mg) produced responses that were statistically indistinguishable from the responses on these two scales produced by IR MPH (50 mg). Differences in subjective responses to the respective doses should be considered in the context that only 22% of the total amount of methylphenidate in methylphenidate hydrochloride extended-release tablets is available for immediate release from the drug overcoat [see System Components and Performance (11.1)].
Although these findings reveal a relatively lower response to methylphenidate hydrochloride extended-release tablets on subjective measures suggestive of abuse potential compared to IR MPH at roughly equivalent total MPH doses, the relevance of these findings to the abuse potential of methylphenidate hydrochloride extended-release tablets in the community is unknown.
Physical Dependence
Methylphenidate hydrochloride extended-release tablets may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including methylphenidate hydrochloride extended-release tablets include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
Tolerance
Methylphenidate hydrochloride extended-release tablets may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Overdose of CNS stimulants is characterized by the following sympathomimetic effects:
Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop.
CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur.
Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop.
Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of methylphenidate hydrochloride extended-release tablets 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.
Methylphenidate Hydrochloride Extended-Release Tablets USP are a central nervous system (CNS) stimulant. Methylphenidate hydrochloride extended-release tablets are available in four tablet strengths. Each extended-release tablet for once-a-day oral administration contains 27, 36, or 54 mg of methylphenidate HCl USP and is designed to have a 12-hour duration of effect. Chemically, methylphenidate HCl is d,l (racemic) methyl α-phenyl-2-piperidineacetate hydrochloride.
Its structural formula is:
Methylphenidate HCl USP is a white, odorless crystalline powder. Its solutions are acid to litmus. It is freely soluble in water and in methanol, soluble in alcohol, and slightly soluble in chloroform and in acetone.
Methylphenidate hydrochloride extended-release tablets also contain the following inert ingredients: silicified microcrystalline cellulose, ethylcellulose, hydroxypropyl cellulose, hypromellose, magnesium stearate, medium-chain triglycerides, oleic acid, polyethylene glycol, polyvinyl alcohol, propylene glycol, talc, titanium dioxide, triacetin, shellac.
Each tablet also contains the following additional inert ingredients: 27 mg : yellow iron oxide, red iron oxide, black iron oxide; 36 mg : red iron oxide, black iron oxide; 54 mg : red iron oxide, black iron oxide.
Methylphenidate hydrochloride extended-release tablets use a precisely designed diffusion process to deliver methylphenidate hydrochloride at a controlled rate. The system comprises a polymeric core surrounded by a diffusion controlling membrane with an immediate release drug overcoat. In an aqueous environment, such as the gastrointestinal tract, the drug overcoat dissolves within one hour, providing an initial dose of methylphenidate. Water enters the tablet core through the diffusion controlling membrane, and methylphenidate is released in a controlled fashion resulting in Cmax at 6 to 7 hours. The non-absorbed components of the tablet pass through the gastrointestinal tract and are eliminated in the stool. It is possible that methylphenidate hydrochloride extended-release tablets may be visible on abdominal x-rays under certain circumstances, especially when digital enhancing techniques are utilized.
Meets USP Dissolution Test 4.
Methylphenidate HCl is a central nervous system (CNS) stimulant. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.
Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more pharmacologically active than the l-isomer.
Absorption
Methylphenidate is readily absorbed. Following oral administration of methylphenidate hydrochloride extended-release tablets, plasma methylphenidate concentrations increase rapidly, reaching an initial maximum at about 1 hour, followed by gradual ascending concentrations over the next 5 to 9 hours, after which a gradual decrease begins. Mean times to reach peak plasma concentrations across all doses of methylphenidate hydrochloride extended-release tablets occurred between 6 and 10 hours.
Methylphenidate hydrochloride extended-release tablets once daily minimizes the fluctuations between peak and trough concentrations associated with immediate-release methylphenidate three times daily (see Figure 1). The relative bioavailability of methylphenidate hydrochloride extended-release tablets once daily and methylphenidate three times daily in adults is comparable.
Figure 1. Mean methylphenidate plasma concentrations in 36 adults, following a single dose of methylphenidate hydrochloride extended-release tablets 18 mg once daily and immediate-release methylphenidate 5 mg three times daily administered every 4 hours.
The mean single-dose pharmacokinetic parameters in 36 healthy adults following the administration of methylphenidate hydrochloride extended-release tablets 18 mg once daily and methylphenidate 5 mg three times daily are summarized in Table 6.
Table 6. Pharmacokinetic Parameters (Mean ± SD) After Single Dose in Healthy Adults
| Parameters | Methylphenidate Hydrochloride Extended-Release Tablets (18 mg once daily) (n=36) | Methylphenidate |
| Cmax (ng/mL) | 3.7 ± 1.0 | 4.2 ± 1.0 |
| Tmax (h) | 6.8 ± 1.8 | 6.5 ± 1.8 |
| AUCinf (ng•h/mL) | 41.8 ± 13.9 | 38.0 ± 11.0 |
| t½ (h) | 3.5 ± 0.4 | 3.0 ± 0.5 |
The pharmacokinetics of methylphenidate hydrochloride extended-release tablets were evaluated in healthy adults following single- and multiple-dose administration (steady state) of doses up to 144 mg/day. The mean half-life was about 3.6 hours. No differences in the pharmacokinetics of methylphenidate hydrochloride extended-release tablets were noted following single and repeated once-daily dosing, indicating no significant drug accumulation. The AUC and t½ following repeated once-daily dosing are similar to those following the first dose of methylphenidate hydrochloride extended-release tablets in a dose range of 18 to 144 mg.
Dose Proportionality
Following administration of methylphenidate hydrochloride extended-release tablets in single doses of 18, 36, and 54 mg/day to healthy adults, Cmax and AUC(0-inf) of d-methylphenidate were proportional to dose, whereas l-methylphenidate Cmax and AUC(0-inf) increased disproportionately with respect to dose. Following administration of methylphenidate hydrochloride extended-release tablets, plasma concentrations of the l-isomer were approximately 1/40th the plasma concentrations of the d-isomer.
In healthy adults, single and multiple dosing of once-daily methylphenidate hydrochloride extended-release tablets doses from 54 to 144 mg/day resulted in linear and dose-proportional increases in Cmax and AUCinf for total methylphenidate (MPH) and its major metabolite, α-phenyl-piperidine acetic acid (PPAA). There was no time dependency in the pharmacokinetics of methylphenidate. The ratio of metabolite (PPAA) to parent drug (MPH) was constant across doses from 54 to 144 mg/day, both after single dose and upon multiple dosing.
In a multiple-dose study in adolescent ADHD patients aged 13 to 16 administered their prescribed dose (18 to 72 mg/day) of methylphenidate hydrochloride extended-release tablets, mean Cmax and AUCTAU of d- and total methylphenidate increased proportionally with respect to dose.
Distribution
Plasma methylphenidate concentrations in adults and adolescents decline biexponentially following oral administration. The half-life of methylphenidate in adults and adolescents following oral administration of methylphenidate hydrochloride extended-release tablets was approximately
3.5 hours.
Metabolism and Excretion
In humans, methylphenidate is metabolized primarily by de-esterification to PPAA, which has little or no pharmacologic activity. In adults the metabolism of methylphenidate hydrochloride extended-release tablets once daily as evaluated by metabolism to PPAA is similar to that of methylphenidate three times daily. The metabolism of single and repeated once-daily doses of methylphenidate hydrochloride extended-release tablets is similar.
After oral dosing of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was PPAA, accounting for approximately 80% of the dose.
Food Effects
In patients, there were no differences in either the pharmacokinetics or the pharmacodynamic performance of methylphenidate hydrochloride extended-release tablets when administered after a high-fat breakfast. There is no evidence of dose dumping in the presence or absence of food.
Alcohol Effect
An in vitro study was conducted to explore the effect of alcohol on the release characteristics of methylphenidate from the methylphenidate hydrochloride extended-release tablets 18 mg tablet dosage form. At an alcohol concentration up to 40% there was no increased release of methylphenidate in the first hour. The results with the 18 mg tablet strength are considered representative of the other available tablet strengths.
Special Populations
Gender
In healthy adults, the mean dose-adjusted AUC(0-inf) values for methylphenidate hydrochloride extended-release tablets were 36.7 ng•h/mL in men and 37.1 ng•h/mL in women, with no differences noted between the two groups.
Race
In adults receiving methylphenidate hydrochloride extended-release tablets, dose-adjusted AUC(0-inf) was consistent across ethnic groups; however, the sample size may have been insufficient to detect ethnic variations in pharmacokinetics.
Age
Increase in age resulted in increased apparent oral clearance (CL/F) (58% increase in adolescents compared to children). Some of these differences could be explained by body-weight differences among these populations. This suggests that subjects with higher body weight may have lower exposures of total methylphenidate at similar doses.
The pharmacokinetics of methylphenidate hydrochloride extended-release tablets has not been studied in children less than 6 years of age.
Renal Insufficiency
There is no experience with the use of methylphenidate hydrochloride extended-release tablets in patients with renal insufficiency. After oral administration of radiolabeled methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of PPAA. Since renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of methylphenidate hydrochloride extended-release tablets.
Hepatic Insufficiency
There is no experience with the use of methylphenidate hydrochloride extended-release tablets in patients with hepatic insufficiency.
Carcinogenesis
In a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas and, in males only, an increase in hepatoblastomas at a daily dose of approximately 60 mg/kg/day. This dose is approximately 30 times and 4 times the maximum recommended human dose of methylphenidate hydrochloride extended-release tablets on a mg/kg and mg/m2 basis, respectively. Hepatoblastoma is a relatively rare rodent malignant tumor type. There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown.
Methylphenidate did not cause any increases in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 22 times and 5 times the maximum recommended human dose of methylphenidate hydrochloride extended-release tablets on a mg/kg and mg/m2 basis, respectively.
In a 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 to 74 mg/kg/day of methylphenidate.
Mutagenesis
Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or the in vitro mouse lymphoma cell forward mutation assay. Sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay in cultured Chinese Hamster Ovary cells. Methylphenidate was negative in vivo in males and females in the mouse bone marrow micronucleus assay.
Impairment of Fertility
Methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week Continuous Breeding study. The study was conducted at doses up to 160 mg/kg/day, approximately 80-fold and 8-fold the highest recommended human dose of methylphenidate hydrochloride extended-release tablets on a mg/kg and mg/m2 basis, respectively.
Methylphenidate hydrochloride extended-release tablets were demonstrated to be effective in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in 4 randomized, double-blind, placebo-controlled studies in children and adolescents and 2 double-blind placebo-controlled studies in adults who met the Diagnostic and Statistical Manual 4th edition (DSM-IV) criteria for ADHD.
Three double-blind, active- and placebo-controlled studies were conducted in 416 children aged 6 to 12 years. The controlled studies compared methylphenidate hydrochloride extended-release tablets given once daily (18, 36, or 54 mg), methylphenidate given three times daily over 12 hours (15, 30, or 45 mg total daily dose), and placebo in two single-center, 3-week crossover studies (Studies 1 and 2) and in a multicenter, 4-week, parallel-group comparison (Study 3). The primary comparison of interest in all three trials was methylphenidate hydrochloride extended-release tablets versus placebo.
Symptoms of ADHD were evaluated by community schoolteachers using the Inattention/Overactivity with Aggression (IOWA) Conners scale. Statistically significant reduction in the Inattention/Overactivity subscale versus placebo was shown consistently across all three controlled studies for methylphenidate hydrochloride extended-release tablets. The scores for methylphenidate hydrochloride extended-release tablets and placebo for the three studies are presented in Figure 2.
Figure 2. Mean Community School Teacher IOWA Conners Inattention/Overactivity Scores with methylphenidate hydrochloride extended-release tablets once-daily (18, 36, or 54 mg) and placebo. Studies 1 and 2 involved a 3-way crossover of 1 week per treatment arm. Study 3 involved 4 weeks of parallel-group treatments with a Last Observation Carried Forward analysis at week 4. Error bars represent the mean plus standard error of the mean.
In Studies 1 and 2, symptoms of ADHD were evaluated by laboratory schoolteachers using the SKAMP* laboratory school rating scale. The combined results from these two studies demonstrated statistically significant improvements in attention and behavior in patients treated with methylphenidate hydrochloride extended-release tablets versus placebo that were maintained through 12 hours after dosing. Figure 3 presents the laboratory schoolteacher SKAMP ratings for methylphenidate hydrochloride extended-release tablets and placebo.
*Swanson, Kotkin, Agler, M-Fynn and Pelham
Figure 3. Laboratory School Teacher SKAMP Ratings: Mean (SEM) of Combined Attention (Studies 1 and 2)
In a randomized, double-blind, multicenter, placebo-controlled trial (Study 4) involving 177 patients, methylphenidate hydrochloride extended-release tablets were demonstrated to be effective in the treatment of ADHD in adolescents aged 13 to 18 years at doses up to 72 mg/day (1.4 mg/kg/day). Of 220 patients who entered an open 4-week titration phase, 177 were titrated to an individualized dose (maximum of 72 mg/day) based on meeting specific improvement criteria on the ADHD Rating Scale and the Global Assessment of Effectiveness with acceptable tolerability. Patients who met these criteria were then randomized to receive either their individualized dose of methylphenidate hydrochloride extended-release tablets (18 to 72 mg/day, n=87) or placebo (n=90) during a two-week double-blind phase. At the end of this phase, mean scores for the investigator rating on the ADHD Rating Scale demonstrated that methylphenidate hydrochloride extended-release tablets were statistically significantly superior to placebo.
Two double-blind, placebo-controlled studies were conducted in 627 adults aged 18 to 65 years. The controlled studies compared methylphenidate hydrochloride extended-release tablets administered once daily and placebo in a multicenter, parallel-group, 7-week dose-titration study (Study 5) (36 to 108 mg/day) and in a multicenter, parallel-group, 5-week, fixed-dose study (Study 6) (18, 36, and 72 mg/day).
Study 5 demonstrated the effectiveness of methylphenidate hydrochloride extended-release tablets in the treatment of ADHD in adults aged 18 to 65 years at doses from 36 mg/day to 108 mg/day based on the change from baseline to final study visit on the Adult ADHD Investigator Symptom Rating Scale (AISRS). Of 226 patients who entered the 7-week trial, 110 were randomized to methylphenidate hydrochloride extended-release tablets and 116 were randomized to placebo. Treatment was initiated at 36 mg/day and patients continued with incremental increases of 18 mg/day (36 to 108 mg/day) based on meeting specific improvement criteria with acceptable tolerability. At the final study visit, mean change scores (LS Mean, SEM) for the investigator rating on the AISRS demonstrated that methylphenidate hydrochloride extended-release tablets were statistically significantly superior to placebo.
Study 6 was a multicenter, double-blind, randomized, placebo-controlled, parallel-group, dose-response study (5-week duration) with 3 fixed-dose groups (18, 36, and 72 mg). Patients were randomized to receive methylphenidate hydrochloride extended-release tablets administered at doses of 18 mg (n=101), 36 mg (n=102), 72 mg/day (n=102), or placebo (n=96). All three doses of methylphenidate hydrochloride extended-release tablets were statistically significantly more effective than placebo in improving CAARS (Conners’ Adult ADHD Rating Scale) total scores at double-blind end point in adult subjects with ADHD.
| Strength | Color | Tablet Description | Bottle Count | NDC |
| 27 mg | Gray | capsule shaped, imprinted with | 100 | 0406-0127-01 |
| 36 mg | White | capsule shaped, imprinted with | 100 | 0406-0136-01 |
| 54 mg | Red | capsule shaped, imprinted with | 100 | 0406-0154-01 |
Storage and Handling
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from humidity. Dispense in tight, light-resistant container with child-resistant closure.
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 tablets, 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 tablets in a safe place, preferably locked, and instruct patients to not give methylphenidate hydrochloride extended-release tablets to anyone else.
Risks to Patients with Serious Cardiac Disease
Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with methylphenidate hydrochloride extended-release tablets use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see Warnings and Precautions (5.2)].
Increased Blood Pressure and Heart Rate
Advise patients that methylphenidate hydrochloride extended-release tablets can cause elevations in blood pressure and heart rate [see Warnings and Precautions (5.3)].
Psychiatric Risks
Advise patients that methylphenidate hydrochloride extended-release tablets, at recommended doses, can cause psychotic or manic symptoms, even in patients without a prior history of psychotic symptoms or mania [see Warnings and Precautions (5.4)].
Priapism
Advise patients, caregivers, and family members of 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 (5.6)].
Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, including Raynaud’s Phenomenon]
Instruct patients beginning treatment with methylphenidate hydrochloride extended-release tablets about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.
Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.
Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking methylphenidate hydrochloride extended-release tablets.
Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
Suppression of Growth
Advise patients, caregivers, and family members that methylphenidate hydrochloride extended-release tablets may cause slowing of growth and weight loss [see Warnings and Precautions (5.8)].
Increased Intraocular Pressure (IOP) and Glaucoma
Advise patients that IOP and glaucoma may occur during treatment with methylphenidate hydrochloride extended-release tablets [see Warnings and Precautions (5.12)].
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 tablets. 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 (5.13)].
Administration Instructions
Patients should be informed that methylphenidate hydrochloride extended-release tablets should be swallowed whole with the aid of liquids. Tablets should not be chewed, divided, or crushed. The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The tablet shell, along with insoluble core components, is eliminated from the body; patients should not be concerned if they occasionally notice in their stool something that looks like a tablet.
For more information call 1-800-778-7898.
Issued: 09/2024
An electronic copy of this medication guide can be obtained from www.mallinckrodt.com/Medguide/L20M49.pdf or by calling 1-800-778-7898 for alternate delivery options.
MEDICATION GUIDE Methylphenidate Hydrochloride Extended-Release Tablets USP, CII (METH il FEN i date) |
|
What is the most important information I should know about methylphenidate hydrochloride extended-release tablets? Methylphenidate hydrochloride extended-release tablets may cause serious side effects, including:
Your healthcare provider should check you or your child carefully for heart problems before starting treatment with methylphenidate hydrochloride extended-release tablets. Tell your healthcare provider if you or your child have any heart problems, heart disease, or heart defects. Call your healthcare provider or go to the nearest hospital emergency room right away if you or your child have any signs of heart problems such as chest pain, shortness of breath, or fainting during treatment with methylphenidate hydrochloride extended-release tablets.
Call your healthcare provider right away if you or your child have any new or worsening mental symptoms or problems during treatment with methylphenidate hydrochloride extended-release tablets, especially hearing voices, seeing or believing things that are not real, or new manic symptoms. |
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What are methylphenidate hydrochloride extended-release tablets? Methylphenidate hydrochloride extended-release tablets are a central nervous system (CNS) stimulant prescription medicine used for the treatment of Attention Deficit and Hyperactivity Disorder (ADHD) in children 6 years of age and older and adults up to 65 years of age. Methylphenidate hydrochloride extended-release tablets may help increase attention and decrease impulsiveness and hyperactivity in people with ADHD. It is not known if methylphenidate hydrochloride extended-release tablets is safe and effective in children under 6 years of age. Methylphenidate hydrochloride extended-release tablets have not been studied in adults older than 65 years of age. Methylphenidate hydrochloride extended-release tablets are a federally controlled substance (CII) because they contain methylphenidate that can be a target for people who abuse prescription medicines or street drugs. Keep methylphenidate hydrochloride extended-release tablets in a safe place to protect them from theft. Never give your methylphenidate hydrochloride extended-release tablets to anyone else because they may cause death or harm them. Selling or giving away methylphenidate hydrochloride extended-release tablets may harm others and is against the law. |
Do not take methylphenidate hydrochloride extended-release tablets if you or your child:
|
Before taking methylphenidate hydrochloride extended-release tablets, tell your healthcare provider about all of your or your child’s medical conditions, including if you or your child:
Tell your healthcare provider about all of the medicines that you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Methylphenidate hydrochloride extended-release tablets and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be changed during treatment with methylphenidate hydrochloride extended-release tablets. Your healthcare provider will decide whether methylphenidate hydrochloride extended-release tablets can be taken with other medicines. Especially tell your healthcare provider if you or your child take:
Know the medicines that you or your child take. Keep a list of your or your child’s medicines with you to show your healthcare provider and pharmacist when you or your child get a new medicine. Do not start any new medicine during treatment with methylphenidate hydrochloride extended-release tablets without first talking to your healthcare provider. |
How should methylphenidate hydrochloride extended-release tablets be taken?
If you or your child take too many methylphenidate hydrochloride extended-release tablets, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away. |
What are the possible side effects of methylphenidate hydrochloride extended-release tablets? Methylphenidate hydrochloride extended-release tablets may cause serious side effects, including:
The most common side effect of methylphenidate hydrochloride extended-release tablets in children is upper stomach-area (abdominal) pain. The most common side effects of methylphenidate hydrochloride extended-release tablets in adults include:
These are not all the possible side effects of methylphenidate hydrochloride extended-release tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Mallinckrodt at 1-800-778-7898. |
How should I store methylphenidate hydrochloride extended-release tablets?
Keep methylphenidate hydrochloride extended-release tablets and all medicines out of the reach of children. |
General information about the safe and effective use of methylphenidate hydrochloride extended-release tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use methylphenidate hydrochloride extended-release tablets for a condition for which they were not prescribed. Do not give methylphenidate hydrochloride extended-release tablets to other people, even if they have the same condition. They may harm them and it is against the law. You can ask your healthcare provider or pharmacist for information about methylphenidate hydrochloride extended-release tablets that is written for healthcare professionals. |
What are the ingredients in methylphenidate hydrochloride extended-release tablets? Active ingredient: methylphenidate HCl USP Inactive ingredients: silicified microcrystalline cellulose, ethylcellulose, hydroxypropyl cellulose, hypromellose, magnesium stearate, medium-chain triglycerides, oleic acid, polyethylene glycol, polyvinyl alcohol, propylene glycol, talc, titanium dioxide, triacetin, shellac. Additional inactive ingredients: 27 mg: yellow iron oxide, red iron oxide, black iron oxide; 36 mg: red iron oxide, black iron oxide; 54 mg : red iron oxide, black iron oxide. Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. © 2024 Mallinckrodt. Manufactured by Mallinckrodt™ |
| This Medication Guide has been approved by the U.S. Food and Drug Administration | Revised: 09/2024 L20M49 |
NDC 0406-0127-01
100 TABLETS
Methylphenidate Hydrochloride
Extended-Release Tablets USP
CII
27 mg
Rx only
PHARMACIST: Dispense the Medication Guide provided separately to each patient.
Mallinckrodt™
L0M122
Rev 08/2017
NDC 0406-0136-01
100 TABLETS
Methylphenidate Hydrochloride
Extended-Release Tablets USP
CII
36 mg
Rx only
PHARMACIST: Dispense the Medication Guide provided separately to each patient.
Mallinckrodt™
L0M123
Rev 08/2017
NDC 0406-0154-01
100 TABLETS
Methylphenidate Hydrochloride
Extended-Release Tablets USP
CII
54 mg
Rx only
PHARMACIST: Dispense the Medication Guide provided separately to each patient.
Mallinckrodt™
L0M124
Rev 08/2017
| Resource | Code type | Value | Equivalent identifiers | Source image |
|---|---|---|---|---|
| Barcode | EAN-13 | 0304060127012 | GTIN-13: 0304060127012 EAN-13: 0304060127012 GTIN-12: 304060127012 UPC-A: 304060127012 GTIN storage (14 digits): 00304060127012 | methylphenidate-hydrochloride-er-tablets-5.jpg |
| Barcode | EAN-13 | 0304060136014 | GTIN-13: 0304060136014 EAN-13: 0304060136014 GTIN-12: 304060136014 UPC-A: 304060136014 GTIN storage (14 digits): 00304060136014 | methylphenidate-hydrochloride-er-tablets-6.jpg |
| Barcode | EAN-13 | 0304060154018 | GTIN-13: 0304060154018 EAN-13: 0304060154018 GTIN-12: 304060154018 UPC-A: 304060154018 GTIN storage (14 digits): 00304060154018 | methylphenidate-hydrochloride-er-tablets-7.jpg |
| Data code | Data Matrix | (10)0000000000(17)000000(21)000000000000 | methylphenidate-hydrochloride-er-tablets-7.jpg, methylphenidate-hydrochloride-er-tablets-5.jpg, methylphenidate-hydrochloride-er-tablets-6.jpg |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 0406-0127-01 | EA - Each | 0406-0127 | f3e8a39a-f662-46c4-9550-4e5607b388cf | 1 | 2013-02-13 |
| 0406-0136-01 | EA - Each | 0406-0136 | 51b951fd-3e49-497e-bd17-f4c61aa358a8 | 1 | 2013-02-13 |
| 0406-0154-01 | EA - Each | 0406-0154 | dd82257d-79e4-4f35-bd86-7e5c08e27464 | 1 | 2013-02-13 |
| Ingredient | Type | UNII | SPL version | Uploaded |
|---|---|---|---|---|
| METHYLPHENIDATE HYDROCHLORIDE | ACTIVE INGREDIENT | 4B3SC438HI | 18 | |
| METHYLPHENIDATE | ACTIVE MOIETY | 207ZZ9QZ49 | 18 | |
| CELLULOSE, MICROCRYSTALLINE | INACTIVE INGREDIENT | OP1R32D61U | 18 | |
| ETHYLCELLULOSES | INACTIVE INGREDIENT | 7Z8S9VYZ4B | 18 | |
| FERRIC OXIDE RED | INACTIVE INGREDIENT | 1K09F3G675 | 18 | |
| FERRIC OXIDE YELLOW | INACTIVE INGREDIENT | EX438O2MRT | 18 | |
| FERROSOFERRIC OXIDE | INACTIVE INGREDIENT | XM0M87F357 | 18 | |
| HYDROXYPROPYL CELLULOSE (TYPE H) | INACTIVE INGREDIENT | RFW2ET671P | 18 | |
| HYPROMELLOSE 2910 (6 MPA.S) | INACTIVE INGREDIENT | 0WZ8WG20P6 | 18 | |
| MAGNESIUM STEARATE | INACTIVE INGREDIENT | 70097M6I30 | 18 | |
| MEDIUM-CHAIN TRIGLYCERIDES | INACTIVE INGREDIENT | C9H2L21V7U | 18 | |
| OLEIC ACID | INACTIVE INGREDIENT | 2UMI9U37CP | 18 | |
| POLYETHYLENE GLYCOLS | INACTIVE INGREDIENT | 3WJQ0SDW1A | 18 | |
| POLYVINYL ALCOHOL | INACTIVE INGREDIENT | 532B59J990 | 18 | |
| PROPYLENE GLYCOL | INACTIVE INGREDIENT | 6DC9Q167V3 | 18 | |
| SHELLAC | INACTIVE INGREDIENT | 46N107B71O | 18 | |
| SILICON DIOXIDE | INACTIVE INGREDIENT | ETJ7Z6XBU4 | 18 | |
| TALC | INACTIVE INGREDIENT | 7SEV7J4R1U | 18 | |
| TITANIUM DIOXIDE | INACTIVE INGREDIENT | 15FIX9V2JP | 18 | |
| TRIACETIN | INACTIVE INGREDIENT | XHX3C3X673 | 18 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 0406-0127 | 0406-0127-01 |
| 0406-0136 | 0406-0136-01 |
| 0406-0154 | 0406-0154-01 |
Every source-derived ingredient row is available through these pages.
| Version | Effective date | Source | Hydrated |
|---|---|---|---|
| 34 | 2024-09-01 | full-release | 2026-05-31 21:16:18 |
Inactive Ingredient Database values describe FDA-listed use contexts. The match method and ambiguity count are shown because ingredient names, routes, and dosage forms are not always unique. Browse recovered IID releases and source provenance.
| DailyMed ingredient | IID ingredient | UNII | Dosage form / route | Potency | Maximum daily exposure | Match |
|---|---|---|---|---|---|---|
| SHELLAC | SHELLAC | 46N107B71O | TABLET, EXTENDED RELEASE / ORAL | 213.24 mg | ||
| ETHYLCELLULOSES | ETHYLCELLULOSE | 7Z8S9VYZ4B | TABLET, EXTENDED RELEASE / ORAL | 1120 mg | ||
| POLYVINYL ALCOHOL | POLYVINYL ALCOHOL | 532B59J990 | TABLET, EXTENDED RELEASE / ORAL | 96 mg | ||
| HYDROXYPROPYL CELLULOSE (TYPE H) | HYDROXYPROPYL CELLULOSE (1600000 WAMW) | RFW2ET671P | TABLET, EXTENDED RELEASE / ORAL | 864 mg | ||
| FERRIC OXIDE YELLOW | FERRIC OXIDE YELLOW | EX438O2MRT | TABLET, EXTENDED RELEASE / ORAL | 15 mg | ||
| CELLULOSE, MICROCRYSTALLINE | MICROCRYSTALLINE CELLULOSE | OP1R32D61U | TABLET, EXTENDED RELEASE / ORAL | 5119 mg | ||
| HYPROMELLOSE 2910 (6 MPA.S) | HYPROMELLOSE 2910 (6 MPA.S) | 0WZ8WG20P6 | TABLET, EXTENDED RELEASE / ORAL | 85 mg | ||
| PROPYLENE GLYCOL | PROPYLENE GLYCOL | 6DC9Q167V3 | TABLET, EXTENDED RELEASE / ORAL | 9 mg | ||
| POLYVINYL ALCOHOL | POLYVINYL ALCOHOL | 532B59J990 | TABLET, EXTENDED RELEASE / ORAL | 96 mg | ||
| FERROSOFERRIC OXIDE | FERROSOFERRIC OXIDE | XM0M87F357 | TABLET, EXTENDED RELEASE / ORAL | 8 mg | ||
| TITANIUM DIOXIDE | TITANIUM DIOXIDE | 15FIX9V2JP | TABLET, EXTENDED RELEASE / ORAL | 90 mg | ||
| PROPYLENE GLYCOL | PROPYLENE GLYCOL | 6DC9Q167V3 | TABLET, EXTENDED RELEASE / ORAL | 9 mg | ||
| TALC | TALC | 7SEV7J4R1U | TABLET, EXTENDED RELEASE / ORAL | 300 mg | ||
| MEDIUM-CHAIN TRIGLYCERIDES | MEDIUM-CHAIN TRIGLYCERIDES | C9H2L21V7U | TABLET, EXTENDED RELEASE / ORAL | 0.37 mg | ||
| POLYVINYL ALCOHOL | POLYVINYL ALCOHOL | 532B59J990 | TABLET, EXTENDED RELEASE / ORAL | 96 mg | ||
| FERROSOFERRIC OXIDE | FERROSOFERRIC OXIDE | XM0M87F357 | TABLET, EXTENDED RELEASE / ORAL | 8 mg | ||
| FERRIC OXIDE YELLOW | FERRIC OXIDE YELLOW | EX438O2MRT | TABLET, EXTENDED RELEASE / ORAL | 15 mg | ||
| TITANIUM DIOXIDE | TITANIUM DIOXIDE | 15FIX9V2JP | TABLET, EXTENDED RELEASE / ORAL | 90 mg | ||
| MEDIUM-CHAIN TRIGLYCERIDES | MEDIUM-CHAIN TRIGLYCERIDES | C9H2L21V7U | TABLET, EXTENDED RELEASE / ORAL | 0.37 mg | ||
| OLEIC ACID | OLEIC ACID | 2UMI9U37CP | TABLET, EXTENDED RELEASE / ORAL | 3 mg | ||
| FERROSOFERRIC OXIDE | FERROSOFERRIC OXIDE | XM0M87F357 | TABLET, EXTENDED RELEASE / ORAL | 8 mg | ||
| TITANIUM DIOXIDE | TITANIUM DIOXIDE | 15FIX9V2JP | TABLET, EXTENDED RELEASE / ORAL | 90 mg | ||
| FERRIC OXIDE YELLOW | FERRIC OXIDE YELLOW | EX438O2MRT | TABLET, EXTENDED RELEASE / ORAL | 15 mg | ||
| TRIACETIN | TRIACETIN | XHX3C3X673 | TABLET, EXTENDED RELEASE / ORAL | 26 mg | ||
| FERROSOFERRIC OXIDE | FERROSOFERRIC OXIDE | XM0M87F357 | TABLET, EXTENDED RELEASE / ORAL | 8 mg | ||
| SILICON DIOXIDE | SILICON DIOXIDE | ETJ7Z6XBU4 | TABLET, EXTENDED RELEASE / ORAL | 450 mg | ||
| TALC | TALC | 7SEV7J4R1U | TABLET, EXTENDED RELEASE / ORAL | 300 mg | ||
| HYDROXYPROPYL CELLULOSE (TYPE H) | HYDROXYPROPYL CELLULOSE (1600000 WAMW) | RFW2ET671P | TABLET, EXTENDED RELEASE / ORAL | 864 mg | ||
| HYPROMELLOSE 2910 (6 MPA.S) | HYPROMELLOSE 2910 (6 MPA.S) | 0WZ8WG20P6 | TABLET, EXTENDED RELEASE / ORAL | 85 mg | ||
| TALC | TALC | 7SEV7J4R1U | TABLET, EXTENDED RELEASE / ORAL | 300 mg | ||
| FERROSOFERRIC OXIDE | FERROSOFERRIC OXIDE | XM0M87F357 | TABLET, EXTENDED RELEASE / ORAL | 8 mg | ||
| PROPYLENE GLYCOL | PROPYLENE GLYCOL | 6DC9Q167V3 | TABLET, EXTENDED RELEASE / ORAL | 9 mg | ||
| SHELLAC | SHELLAC | 46N107B71O | TABLET, EXTENDED RELEASE / ORAL | 213.24 mg | ||
| SILICON DIOXIDE | SILICON DIOXIDE | ETJ7Z6XBU4 | TABLET, EXTENDED RELEASE / ORAL | 450 mg | ||
| ETHYLCELLULOSES | ETHYLCELLULOSE | 7Z8S9VYZ4B | TABLET, EXTENDED RELEASE / ORAL | 1120 mg | ||
| FERRIC OXIDE YELLOW | FERRIC OXIDE YELLOW | EX438O2MRT | TABLET, EXTENDED RELEASE / ORAL | 15 mg | ||
| HYDROXYPROPYL CELLULOSE (TYPE H) | HYDROXYPROPYL CELLULOSE (1600000 WAMW) | RFW2ET671P | TABLET, EXTENDED RELEASE / ORAL | 864 mg | ||
| FERRIC OXIDE RED | FERRIC OXIDE RED | 1K09F3G675 | TABLET, EXTENDED RELEASE / ORAL | 7 mg | ||
| FERRIC OXIDE RED | FERRIC OXIDE RED | 1K09F3G675 | TABLET, EXTENDED RELEASE / ORAL | 7 mg | ||
| MAGNESIUM STEARATE | MAGNESIUM STEARATE | 70097M6I30 | TABLET, EXTENDED RELEASE / ORAL | 173 mg | ||
| CELLULOSE, MICROCRYSTALLINE | MICROCRYSTALLINE CELLULOSE | OP1R32D61U | TABLET, EXTENDED RELEASE / ORAL | 5119 mg | ||
| TITANIUM DIOXIDE | TITANIUM DIOXIDE | 15FIX9V2JP | TABLET, EXTENDED RELEASE / ORAL | 90 mg | ||
| MAGNESIUM STEARATE | MAGNESIUM STEARATE | 70097M6I30 | TABLET, EXTENDED RELEASE / ORAL | 173 mg | ||
| OLEIC ACID | OLEIC ACID | 2UMI9U37CP | TABLET, EXTENDED RELEASE / ORAL | 3 mg | ||
| CELLULOSE, MICROCRYSTALLINE | MICROCRYSTALLINE CELLULOSE | OP1R32D61U | TABLET, EXTENDED RELEASE / ORAL | 5119 mg | ||
| FERRIC OXIDE RED | FERRIC OXIDE RED | 1K09F3G675 | TABLET, EXTENDED RELEASE / ORAL | 7 mg | ||
| FERROSOFERRIC OXIDE | FERROSOFERRIC OXIDE | XM0M87F357 | TABLET, EXTENDED RELEASE / ORAL | 8 mg | ||
| TALC | TALC | 7SEV7J4R1U | TABLET, EXTENDED RELEASE / ORAL | 300 mg | ||
| TRIACETIN | TRIACETIN | XHX3C3X673 | TABLET, EXTENDED RELEASE / ORAL | 26 mg | ||
| HYDROXYPROPYL CELLULOSE (TYPE H) | HYDROXYPROPYL CELLULOSE (1600000 WAMW) | RFW2ET671P | TABLET, EXTENDED RELEASE / ORAL | 864 mg | ||
| CELLULOSE, MICROCRYSTALLINE | MICROCRYSTALLINE CELLULOSE | OP1R32D61U | TABLET, EXTENDED RELEASE / ORAL | 5119 mg | ||
| TALC | TALC | 7SEV7J4R1U | TABLET, EXTENDED RELEASE / ORAL | 300 mg | ||
| POLYVINYL ALCOHOL | POLYVINYL ALCOHOL | 532B59J990 | TABLET, EXTENDED RELEASE / ORAL | 96 mg | ||
| PROPYLENE GLYCOL | PROPYLENE GLYCOL | 6DC9Q167V3 | TABLET, EXTENDED RELEASE / ORAL | 9 mg | ||
| HYPROMELLOSE 2910 (6 MPA.S) | HYPROMELLOSE 2910 (6 MPA.S) | 0WZ8WG20P6 | TABLET, EXTENDED RELEASE / ORAL | 85 mg | ||
| ETHYLCELLULOSES | ETHYLCELLULOSE | 7Z8S9VYZ4B | TABLET, EXTENDED RELEASE / ORAL | 1120 mg | ||
| FERRIC OXIDE RED | FERRIC OXIDE RED | 1K09F3G675 | TABLET, EXTENDED RELEASE / ORAL | 7 mg | ||
| HYPROMELLOSE 2910 (6 MPA.S) | HYPROMELLOSE 2910 (6 MPA.S) | 0WZ8WG20P6 | TABLET, EXTENDED RELEASE / ORAL | 85 mg | ||
| HYPROMELLOSE 2910 (6 MPA.S) | HYPROMELLOSE 2910 (6 MPA.S) | 0WZ8WG20P6 | TABLET, EXTENDED RELEASE / ORAL | 85 mg | ||
| TALC | TALC | 7SEV7J4R1U | TABLET, EXTENDED RELEASE / ORAL | 300 mg |
All distinct exact application/product contexts derived from this label’s complete NDC list are paginated below.
| Application-product | Trade name | Ingredient | Strength | Dosage form / route | TE codes | RLD / RS | Approval date |
|---|---|---|---|---|---|---|---|
| A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | 2012-12-28 | ||
| A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | 2012-12-28 | ||
| A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | 2012-12-28 |
Observed FDA ZIP history: Each table is queried independently by exact application/product key from successfully parsed Orange Book snapshots. Capture times identify archived source observations; absence or a change between snapshots is not inferred. FDA publication files that were not recoverable as structured ZIP data are not represented as states.
| Captured | Edition | Application-product | Trade name | Strength | Dosage form / route | Product TE source text | RLD / RS | Approval date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | 2012-12-28 | 84e616aacf4f… | ||
| 2026-09-14 22:38:34 | 2026-08 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | 2012-12-28 | 84e616aacf4f… | ||
| 2026-09-14 22:38:34 | 2026-08 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | 2012-12-28 | 84e616aacf4f… | ||
| 2026-08-18 06:07:40 | 2026-07 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | 2012-12-28 | caaa826d4ba7… | ||
| 2026-08-18 06:07:40 | 2026-07 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | 2012-12-28 | caaa826d4ba7… | ||
| 2026-08-18 06:07:40 | 2026-07 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | 2012-12-28 | caaa826d4ba7… | ||
| 2026-02-19 14:30 UTC | 2026-02 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 011fe1cb6892… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 31067a03dcf5… | |
| 2025-08-23 18:47 UTC | 2025-08 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 6a471c1ec25d… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | fd3edfee7708… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | b8a1b40f171c… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 03ed91905a0d… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 03ed91905a0d… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 03ed91905a0d… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 2680178bc6a6… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 2680178bc6a6… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 2680178bc6a6… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 5bbf6a4d5a75… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 5bbf6a4d5a75… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 5bbf6a4d5a75… | |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | d8e5a09893c0… | |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | d8e5a09893c0… | |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | d8e5a09893c0… | |
| 2024-10-29 15:01 UTC | 2024-10 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | d06236e962d9… | |
| 2024-10-29 15:01 UTC | 2024-10 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | d06236e962d9… | |
| 2024-10-29 15:01 UTC | 2024-10 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | d06236e962d9… | |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 79d66fd596c7… | |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A202608-002 | METHYLPHENIDATE HYDROCHLORIDE | 36MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 79d66fd596c7… | |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A202608-003 | METHYLPHENIDATE HYDROCHLORIDE | 54MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 79d66fd596c7… | |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | A202608-001 | METHYLPHENIDATE HYDROCHLORIDE | 27MG | TABLET, EXTENDED RELEASE / ORAL | BX | 2012-12-28 | 301d65b070ca… |
| Captured | Edition | Application-product | TE code | Order | Source SHA-256 |
|---|---|---|---|---|---|
| 2026-02-19 14:30 UTC | 2026-02 | A202608-001 | BX | 1 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | A202608-002 | BX | 1 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | A202608-003 | BX | 1 | 011fe1cb6892… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A202608-001 | BX | 1 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A202608-002 | BX | 1 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A202608-003 | BX | 1 | 31067a03dcf5… |
| 2025-08-23 18:47 UTC | 2025-08 | A202608-001 | BX | 1 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | A202608-002 | BX | 1 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | A202608-003 | BX | 1 | 6a471c1ec25d… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A202608-001 | BX | 1 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A202608-002 | BX | 1 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A202608-003 | BX | 1 | fd3edfee7708… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A202608-001 | BX | 1 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A202608-002 | BX | 1 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A202608-003 | BX | 1 | b8a1b40f171c… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A202608-001 | BX | 1 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A202608-002 | BX | 1 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A202608-003 | BX | 1 | 03ed91905a0d… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A202608-001 | BX | 1 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A202608-002 | BX | 1 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A202608-003 | BX | 1 | 2680178bc6a6… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A202608-001 | BX | 1 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A202608-002 | BX | 1 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A202608-003 | BX | 1 | 5bbf6a4d5a75… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A202608-001 | BX | 1 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A202608-002 | BX | 1 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A202608-003 | BX | 1 | d8e5a09893c0… |
| 2024-10-29 15:01 UTC | 2024-10 | A202608-001 | BX | 1 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | A202608-002 | BX | 1 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | A202608-003 | BX | 1 | d06236e962d9… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A202608-001 | BX | 1 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A202608-002 | BX | 1 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A202608-003 | BX | 1 | 79d66fd596c7… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | A202608-001 | BX | 1 | 301d65b070ca… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | A202608-002 | BX | 1 | 301d65b070ca… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | A202608-003 | BX | 1 | 301d65b070ca… |
| 2024-06-18 03:08 UTC · 5 captures of this ZIP | 2024-06 | A202608-001 | BX | 1 | 1e350fbaab3a… |
| 2024-06-18 03:08 UTC · 5 captures of this ZIP | 2024-06 | A202608-002 | BX | 1 | 1e350fbaab3a… |
| 2024-06-18 03:08 UTC · 5 captures of this ZIP | 2024-06 | A202608-003 | BX | 1 | 1e350fbaab3a… |
| 2024-05-31 18:47 UTC | 2024-05 | A202608-001 | BX | 1 | 8072bd15b7f6… |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| Methylphenidate Hydrochloride Extended-Release | METHYLPHENIDATE HYDROCHLORIDE | SpecGx LLC | b1b0f2ff-d9df-42ab-b471-226ecf97e075 | 2024-09-01 | Boxed warning, Warnings, Adverse reactions | 0406-0127-01 0406-0136-01 0406-0154-01 0406-0154 0406-0127 0406-0136 00406015401 00406013601 00406012701 24d8e2c3-6e4d-44b8-aafe-7c713b11af5a b1b0f2ff-d9df-42ab-b471-226ecf97e075 |
Adverse event summaries are temporarily unavailable. Other product information remains available.