Methylphenidate Extended-Release Tablets

Name: Methylphenidate Extended-Release Tablets

Overdose

Signs And Symptoms

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

Recommended Treatment

Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Gastric contents may be evacuated by gastric lavage as indicated. Before performing gastric lavage, control agitation and seizures if present and protect the airway.

Other measures to detoxify the gut include administration of activated charcoal and a cathartic. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for pyrexia.

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

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

Poison Control Center

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

What is methylphenidate (concerta, metadate cd, metadate er, methylin, methylin er, ritalin, ritalin la, ritalin-sr)?

Methylphenidate is a central nervous system stimulant. It affects chemicals in the brain and nerves that contribute to hyperactivity and impulse control.

Methylphenidate is used to treat attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and narcolepsy.

Methylphenidate may also be used for purposes not listed in this medication guide.

Side effects

The following are discussed in more detail in other sections of the labeling:

  • Drug Dependence [see BOX WARNING]
  • Hypersensitivity to Methylphenidate [see CONTRAINDICATIONS]
  • Agitation [see CONTRAINDICATIONS]
  • Glaucoma [see CONTRAINDICATIONS]
  • Tics [see CONTRAINDICATIONS]
  • Monoamine Oxidase Inhibitors [see CONTRAINDICATIONS and DRUG INTERACTIONS]
  • Serious Cardiovascular Events [see WARNINGS AND PRECAUTIONS]
  • Psychiatric Adverse Events [see WARNINGS AND PRECAUTIONS]
  • Seizures [see WARNINGS AND PRECAUTIONS]
  • Priapism [see WARNINGS AND PRECAUTIONS]
  • Long-Term Suppression of Growth [see WARNINGS AND PRECAUTIONS]
  • Visual Disturbance [see WARNINGS AND PRECAUTIONS]
  • Potential for Gastrointestinal Obstruction [see WARNINGS AND PRECAUTIONS]
  • Hematologic Monitoring [see WARNINGS AND PRECAUTIONS]

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].

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].

The development program for CONCERTA® 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.

Table 3: CONCERTA® Exposure in Double-Blind and Open-Label Clinical Studies

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 CONCERTA® based on the comprehensive assessment of the available adverse event information. A causal association for CONCERTA® 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.

Commonly Observed Adverse Reactions In Double-Blind, Placebo-Controlled Clinical Trials

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 CONCERTA®-treated children and adolescent subjects in 4 placebo-controlled, double-blind clinical trials.

Table 4: Adverse Reactions Reported by ≥ 1% of CONCERTA®-Treated Children and Adolescent Subjects in 4 Placebo-Controlled, Double-Blind Clinical Trials of CONCERTA®

System/Organ Class
Adverse Reaction
CONCERTA®
(n=321) %
Placebo
(n=318) %
Gastrointestinal Disorders
  Abdominal pain upper 6.2 3.8
  Vomiting 2.8 1.6
General Disorders and Administration Site Conditions
  Pyrexia 2.2 0.9
Infections and Infestations
  Nasopharyngitis 2.8 2.2
Nervous System Disorders
  Dizziness 1.9 0
Psychiatric Disorders
  Insomnia* 2.8 0.3
Respiratory, Thoracic and Mediastinal Disorders
  Cough 1.9 0.9
  Oropharyngeal pain 1.2 0.9
*Terms of Initial insomnia (CONCERTA®=0.6%) and Insomnia (CONCERTA®=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 CONCERTA®-treated adults in 2 placebo-controlled, double-blind clinical trials.

Table 5: Adverse Reactions Reported by ≥ 1% of CONCERTA®-Treated Adult Subjects in 2 Placebo-Controlled, Double-Blind Clinical Trials*

System/Organ Class
Adverse Reaction
CONCERTA®
(n=415) %
Placebo
(n=212) %
Cardiac Disorders
  Tachycardia 4.8 0
  Palpitations 3.1 0.9
Ear and Labyrinth Disorders
  Vertigo 1.7 0
Eye Disorders
  Vision blurred 1.7 0.5
Gastrointestinal Disorders
  Dry mouth 14.0 3.8
  Nausea 12.8 3.3
  Dyspepsia 2.2 0.9
  Vomiting 1.7 0.5
  Constipation 1.4 0.9
General Disorders and Administration Site Conditions
  Irritability 5.8 1.4
Infections and Infestations
  Upper respiratory tract infection 2.2 0.9
Investigations
  Weight decreased 6.5 3.3
Metabolism and Nutrition Disorders
  Decreased appetite 25.3 6.6
  Anorexia 1.7 0
Musculoskeletal and Connective Tissue Disorders
  Muscle tightness 1.9 0
Nervous System Disorders
  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 1.2 0.5
Psychiatric Disorders
  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 1.2 0.5
Respiratory, Thoracic and Mediastinal Disorders
  Oropharyngeal pain 1.7 1.4
Skin and Subcutaneous Tissue Disorders
  Hyperhidrosis 5.1 0.9
* Included doses up to 108 mg.

The majority of ADRs were mild to moderate in severity.

Other Adverse Reactions Observed In CONCERTA® Clinical Trials

This section includes adverse reactions reported by CONCERTA®-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 CONCERTA®-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

Discontinuation Due To Adverse Reactions

Adverse reactions in the 4 placebo-controlled studies of children and adolescents leading to discontinuation occurred in 2 CONCERTA® 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 CONCERTA® 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 CONCERTA® 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 CONCERTA® 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%).

Tics

In a long-term uncontrolled study (n=432 children), the cumulative incidence of new onset of tics was 9% after 27 months of treatment with CONCERTA®.

In a second uncontrolled study (n=682 children) the cumulative incidence of new-onset tics was 1% (9/682 children). The treatment period was up to 9 months with mean treatment duration of 7.2 months.

Blood Pressure And Heart Rate Increases

In the laboratory classroom clinical trials in children (Studies 1 and 2), both CONCERTA® 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 CONCERTA® 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 CONCERTA® 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 CONCERTA® 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 CONCERTA® 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 CONCERTA® 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 CONCERTA® 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].

Postmarketing Experience

The following additional adverse reactions have been identified during postapproval use of CONCERTA®. 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, 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

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

Read the entire FDA prescribing information for Concerta (Methylphenidate Extended-Release Tablets)

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How is this medicine (Methylphenidate Extended-Release Tablets) best taken?

Use this medicine (methylphenidate extended-release tablets) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take in the morning.
  • Some drugs may need to be taken with food or on an empty stomach. For some drugs it does not matter. Check with your pharmacist about how to take this medicine.
  • Swallow whole. Do not chew, break, or crush.
  • To gain the most benefit, do not miss doses.
  • If you have been taking this medicine (methylphenidate extended-release tablets) for a long time or at high doses, it may not work as well and you may need higher doses to get the same effect. This is known as tolerance. Call your doctor if this medicine stops working well. Do not take more than ordered.
  • Do not switch between different forms of this medicine (methylphenidate extended-release tablets) without first talking with the doctor.
  • Limit your use of caffeine (for example, tea, coffee, cola) and chocolate. Use with this medicine may cause nervousness, shakiness, and a fast heartbeat.
  • If you are taking this medicine (methylphenidate extended-release tablets) and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.

What do I do if I miss a dose?

  • Use a missed dose as soon as you think about it. Do not take this medicine after 6 PM.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

What are some other side effects of Methylphenidate Extended-Release Tablets?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Dizziness.
  • Feeling sleepy.
  • Dry mouth.
  • Headache.
  • Upset stomach or throwing up.
  • Weight loss.
  • Feeling nervous and excitable.
  • Not hungry.
  • Not able to sleep.
  • Belly pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about this medicine (methylphenidate extended-release tablets), please talk with the doctor, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine (methylphenidate extended-release tablets). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine (methylphenidate extended-release tablets).

Review Date: October 4, 2017

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