CONCERTA® (methylphenidate HCl) Extended-Release Tablets CII

CONCERTA® (methylphenidate HCl) Extended-Release Tablets CII

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CONCERTA® (methylphenidate HCl) Extended-Release Tablets CII

CONCERTA is a central nervous system (CNS) stimulant. CONCERTA is available in four tablet strengths. Each extended-release tablet for once-a-day oral administration contains 18, 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 empirical formula is C14H19NO2•HCl.

CONCERTA also contains the following inert ingredients: butylated hydroxytoluene, carnauba wax, cellulose acetate, hypromellose, lactose, phosphoric acid, poloxamer, polyethylene glycol, polyethylene oxides, povidone, propylene glycol, sodium chloride, stearic acid, succinic acid, synthetic iron oxides, titanium dioxide, and triacetin.

Indications and usage

CONCERTA® is a CNS stimulant 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.

Mechanism of Action

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.

Dosage and administration

CONCERTA® should be taken once daily in the morning and swallowed whole with the aid of liquids. CONCERTA® should not be chewed or crushed. CONCERTA® may be taken with or without food.

For children and adolescents new to methylphenidate, the recommended starting dosage is 18 mg once daily. Dosage may be increased by 18 mg/day at weekly intervals and should not exceed 54 mg/day in children and 72 mg/day in adolescents.

For adult patients new to methylphenidate, the recommended starting dose is 18 or 36 mg/day. Dosage may be increased by 18 mg/day at weekly intervals and should not exceed 72 mg/day for adults.

For patients currently using methylphenidate, dosing is based on current dose regimen and clinical judgment

Contraindications

Hypersensitivity to Methylphenidate: Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been observed in patients treated with CONCERTA. Therefore, CONCERTA is contraindicated in patients known to be hypersensitive to methylphenidate or other components of the product

Agitation: CONCERTA is contraindicated in patients with marked anxiety, tension, and agitation, since the drug may aggravate these symptoms.

Glaucoma: CONCERTA is contraindicated in patients with glaucoma.

Tics: CONCERTA is contraindicated in patients with motor tics or with a family history or diagnosis of Tourette’s syndrome

Monoamine Oxidase Inhibitors: CONCERTA is 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)

Warnings and precautions

Serious Cardiovascular Events

Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems.

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD.

Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mm Hg) and average heart rate (about 3 to 6 bpm), and individuals may have larger increases.

Preexisting Psychosis: Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder.

Bipolar Illness: Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

Emergence of New Psychotic or Manic Symptoms: Treatment-emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in patients without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate.

Seizures: 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.

Priapism: Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products, including CONCERTA, in both pediatric and adult patients

Peripheral Vasculopathy, including Raynaud’s Phenomenon: Stimulants, including CONCERTA, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown.

Long-Term Suppression of Growth: Published data are inadequate to determine whether chronic use of amphetamines may cause similar suppression of growth; however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

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Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

Potential for Gastrointestinal Obstruction: Because the CONCERTA tablet is nondeformable and does not appreciably change in shape in the GI tract, CONCERTA should not ordinarily be administered to patients with preexisting 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).

Side effects

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

Drug interactions

MAO Inhibitors: CONCERTA should not be used in patients being treated (currently or within the preceding 2 weeks) with MAO inhibitors

Vasopressor Agents: Because of possible increases in blood pressure, CONCERTA should be used cautiously with vasopressor agents

Coumarin Anticoagulants, Antidepressants, and Selective Serotonin Reuptake Inhibitors: Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (eg, 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.

Risperidone: 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.

Use in specific populations

Pregnancy: Pregnancy Category C

The safety of methylphenidate for use during human pregnancy has not been established. There are no adequate and well-controlled studies in pregnant women.

Nursing Mothers: It is not known whether methylphenidate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if CONCERTA is administered to a nursing woman.

Pediatric Use: CONCERTA 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.

Geriatric Use: CONCERTA has not been studied in patients greater than 65 years of age.

Drug abuse and dependence

Controlled Substance: Methylphenidate is a Schedule II controlled substance under the Controlled Substances Act.

Abuse: CONCERTA® should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse.

Dependence: As noted in the Box Warning, careful supervision is required during withdrawal from abusive use since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.

Overdosage

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.

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