Concerta 18 mg, 27 mg, 36 mg, 54 mg XR tablets

CONCERTA is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents aged 6-17 and adults aged 18 to 65 who meet DSM-IV criteria for ADHD.

Posology

Patients new to methylphenidate: The recommended starting dose of CONCERTA for patients who are not currently taking methylphenidate, or for patients who are on stimulants other than methylphenidate, is 18 mg once daily for children and adolescents and 18 or 36 mg once daily for adults.

Patients currently using methylphenidate: The recommended dose of CONCERTA for patients who are currently taking methylphenidate three times daily at doses of 15 to 60 mg/day is provided in Table 1. Dosing recommendations are based on current dose regimen and clinical judgement.

Table 1. Recommended Dose Conversion from Other Methylphenidate Regimens to CONCERTA

• 5 mg Methylphenidate hydrochloride twice daily or three times daily. 18 mg once daily
• 10 mg Methylphenidate hydrochloride twice daily or three times daily 36 mg once daily
• 15 mg Methylphenidate hydrochloride twice daily or three times daily. 54 mg once daily
• 20 mg Methylphenidate hydrochloride twice daily or three times daily 72 mg once daily

Clinical judgment should be used when selecting the dose for patients currently taking methylphenidate in other regimens. Dosage may be adjusted in 18 mg increments to a maximum of 54 mg/day for children aged between 6 u2013 12 years and to a maximum of 72 mg for adolescents aged between 13 u2013 18 years and 108 mg in adults. In general, dosage adjustment may proceed at approximately weekly intervals.

Daily dosage above 54 mg is not recommended for children aged between 6 u2013 12 years. Daily dosage above 72 mg is not recommended for adolescents aged between 13 u2013 18 years. Daily dosage above 108 mg is not recommended in adults.

Maintenance/Extended Treatment: The long-term use of CONCERTA has not been systematically evaluated in controlled clinical trials. The physician who elects to use CONCERTA for extended periods in patients with ADHD should periodically re-evaluate the long-term usefulness of the medicine for the individual patient with trials off medication to assess the patientu2019s functioning without pharmacotherapy.

Changing from one extended-release methylphenidate product to another: The efficacy and tolerability profile of CONCERTA over the dosing period is determined by the specific release profile of the product. Other extended-release methylphenidate formulations with different release profiles may have different efficacy and tolerability profiles. If changing from one extended-release methylphenidate product to another, it is recommended that this be carried out only with additional medical supervision.

Dose reduction and discontinuation: If paradoxical aggravation of symptoms or other adverse events occur, the dosage should be reduced, or, if necessary, CONCERTA should be discontinued.

Special populations

Elderly: Use of CONCERTA in elderly patients over 65 years has not been studied in controlled trials.

Method of administration: CONCERTA must be swallowed whole with adequate amounts of liquids, and must not be chewed, divided, or crushed. CONCERTA may be administered with or without food. Dosage should be individualized according to the need and response of each individual patient. CONCERTA should not be used in patients under six years old. CONCERTA is administered orally once daily. As the effect has been shown to be present 12 hours after dosing, the product should be taken in the morning.

CONCERTA is contraindicated:

• in patients known to be hypersensitive to methylphenidate or other components of CONCERTA;
• in patients with poorly controlled open-angle or angle-closure glaucoma;
• during treatment with monoamine oxidase inhibitors, and within a minimum of 14 days following discontinuation of a monoamine oxidase inhibitor (as hypertensive crises may result);
• in patients with hyperthyroidism, cardiac dysrrhythmias, ischaemic heart disease, uncontrolled hypertension;
• in pregnancy and lactation. (see section 4.6)

CONCERTA increases heart rate, systolic and diastolic blood pressure, therefore caution is advised when CONCERTA is prescribed for ADHD patients whose underlying medical conditions might be compromised by increases in heart rate and/or blood pressure e.g. heart failure and hypertension. Blood pressure should be monitored in patients treated with CONCERTA especially those with hypertension (see section 4.3).

Structural cardiac abnormalities: Cases of sudden death have been reported in ADHD patients with structural cardiac abnormalities treated with CONCERTA used, at usual doses. Although the data are inconclusive regarding causal relationship between treatment with CONCERTA and sudden death, caution is advised when CONCERTA, is prescribed for ADHD patients with structural cardiac abnormalities.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency of glucose-galactose malabsorption should not take CONCERTA.

Patients under 6 years old: CONCERTA should not be used in patients under six years old. Sufficient data on the safety of long-term use of CONCERTA is not yet available.

Motor and verbal tics, and worsening of Tourettesu2019s syndrome: CONCERTA has been associated with the onset or exacerbation of motor and verbal tics. Worsening of verbal Touretteu2019s syndrome has also been reported. It is recommended that the family history be assessed, and that the patient is clinically evaluated for tics or Tourettesu2019s syndrome before initiating methylphenidate. Regular monitoring for the emergence or worsening of tics or Touretteu2019s syndrome before initiating methylphenidate is recommended at every dose adjustment and every visit, and treatment discontinued if clinically appropriate.

Long-term use: Although a causal relationship has not been established, suppression of growth (i.e. weight gain, and/or height) has been reported with the long-term use of CONCERTA in children. Therefore, patients requiring long-term therapy should be carefully monitored. Patients who are not growing or gaining weight as expected should have their treatment interrupted.

Increased intraocular pressure and glaucoma: There have been reports of a transient elevation of intraocular pressure (IOP) associated with methylphenidate treatment. It is recommended to prescribe CONCERTA to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Patients with a history of abnormally increased IOP or open-angle glaucoma, and patients at risk for acute angle-closure glaucoma (e.g. patients with significant hyperopia) must be closely monitored. CONCERTA is not recommended in patients with acute angle glaucoma. CONCERTA is contraindicated in all patients with poorly controlled glaucoma (see section 4.3).

Dose administration: CONCERTA must be swallowed whole with the aid of liquids. Tablets should not be chewed, divided or crushed. Methylphenidate is contained within a nonabsorbable shell designed to release the medicine at an extended 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 stools something that looks like a tablet. Because the CONCERTA tablet is non-deformable and does not appreciably change in shape in the GI tract, CONCERTA should not be administered to patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic) or in patients with dysphagia or significant difficulty in swallowing tablets. There have been reports of obstructive symptoms in patients with known strictures. Due to the extended-release design of the tablet, CONCERTA should only be used in patients who are able to swallow the tablet whole.

Use in other indications: CONCERTA should not be used to treat depression and/or for the prevention of treatment of normal fatigue states.

Psychotic or manic symptoms: Psychotic (e.g., hallucinations) or manic symptoms have been reported in patients without a prior history of psychotic illness or mania during treatment with CONCERTA at usual doses. If such symptoms occur, consideration should be given to a possible causal role of CONCERTA and discontinuation of treatment may be appropriate.

Aggression, anxiety and agitation: Aggressive behaviour, marked anxiety, or agitation are often observed with patients with ADHD, and have been reported in patients treated with CONCERTA (see section 4.8). Anxiety led to discontinuation of CONCERTA is some patients. It is recommended to monitor patients beginning treatment with CONCERTA for appearance of, or worsening of, aggressive behaviour, marked anxiety, or agitation and at every adjustment of dose and then at least every 6 months or every visit.

Priapism: Prolonged and painful erections requiring immediate medical attention (sometimes including surgical intervention), have been reported with methylphenidate products, including CONCERTA, in both paediatric and adult patients (see section 4.8). Priapism can develop after some time on methylphenidate, often subsequent to an increase in dose. Priapism has also appeared during a period of methylphenidate withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained erections or frequent and painful erections should seek immediate medical attention.

Cerebrovascular disorders: Cerebrovascular disorders (including cerebral vasculitis and cerebral haemorrhage) have been reported with the use of CONCERTA (see section 4.8). Consider cerebrovascular disorders as a possible diagnosis in any patient who develops new neurological symptoms that are consistent with cerebral ischemia during CONCERTA therapy. These symptoms could include severe headache, unilateral weakness or paralysis, and impairment of coordination, vision, speech, language, or memory. If a cerebrovascular disorder is suspected during treatment, discontinue CONCERTA immediately. Early diagnosis may guide subsequent treatment.

Conditions requiring caution: CONCERTA should be given with caution in the following conditions:

• Psychotic patients: Administration of CONCERTA may exacerbate symptoms of behaviour disturbances and thought disorder in psychotic patients.
• Underlying medical conditions that might be compromised by increases in blood pressure or heart rate: In clinical trials in children, CONCERTA increased resting pulse by an average of 2-6 bpm and produced average increases of systolic and diastolic blood pressure of roughly 1-4 mm Hg during the day, relative to placebo. In placebo-controlled studies in adults, mean increases in resting pulse rate of approximately 4 to 6 bpm were observed with CONCERTA at endpoint vs. a mean change of roughly -2 to 3 bpm with placebo. Mean changes in blood pressure at endpoint ranged from about u20131 to 1 mm Hg (systolic) and 0 to 1 mm Hg (diastolic) for CONCERTA and from u20131 to 1 mm Hg (systolic) and u20132 to 0 mm Hg (diastolic) for placebo. Therefore, caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate. (see section 4.4)
• History of drug dependence or alcoholism: 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 behaviour. Frank psychotic episodes can occur, especially with parenteral abuse. 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.

Hematologic monitoring: Periodic haematologic monitoring (Complete blood count, differential, and platelet counts) is advised during prolonged therapy.

Lactose: Contains lactose which may an effect on the glycaemic control of patients with diabetes mellitus. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency of glucose-galactose malabsorption should not take CONCERTA.

Because of the effects on blood pressure, CONCERTA should be used cautiously with pressor agents. CONCERTA should not be used in patients being treated (currently or within the preceding 2 weeks) with MAO inhibitors (see 4.3). Human pharmacological studies have shown that methylphenidate may inhibit the metabolism of warfarin anticoagulants, anticonvulsants (e.g. phenobarbital, phenytoin, primidone), and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). Downward dose adjustment of these medicines may be required when given concomitantly with CONCERTA. It may be necessary to adjust the dosage and monitor plasma medicines concentrations (or, in the case of coumarin, coagulation times), when initiating or discontinuing concomitant use of CONCERTA.

There have been reports of serotonin syndrome following coadministration of methylphenidate with serotonergic medicines. If concomitant use of CONCERTA with a serotonergic medicine is warranted, prompt recognition of the symptoms of serotonin syndrome is important. CONCERTA must be discontinued as soon as possible is serotonin syndrome is suspected.

Serious adverse events have been reported in concomitant use with clonidine, although no causality for the combination has been established. The safety of using CONCERTA in combination with clonidine or other centrally acting alpha-2 agonists has not been systematically evaluated. Alcohol may exacerbate the adverse CNS effects of CONCERTA. It is therefore desirable for patients to abstain from alcohol during treatment.

Pregnancy: CONCERTA should not be used in pregnancy as safety has not been established. Teratogenicity has been shown in laboratory animals.

Lactation: Methylphenidate has been detected in human milk. Based on breast milk sampling from five mothers, methylphenidate concentrations in human milk resulted in infant doses of 0,16 % to 0,7 % of the maternal weight - adjusted dosage, and a milk to maternal plasma ratio ranging between 1.1 and 2.7. Mothers breastfeeding their infants should not be treated with CONCERTA.

CONCERTA may impair the ability of the patient to operate potentially hazardous machinery or vehicles. Patients should be cautioned accordingly until they are reasonably certain that CONCERTA does not adversely affect their ability to engage in such activities.

Clinical Trial Data: The table below shows all the adverse drug reactions (ADRs) observed during clinical trials of children, adolescents and adults with CONCERTA and those, which have been reported with other methylphenidate hydrochloride formulations. If the ADRs with CONCERTA and the methylphenidate formulation frequencies were different, the highest frequency of both databases was used.

Frequency estimate: Very common (u2265 1/10), Common (u2265 1/100 to < 1/10), Uncommon (u2265 1/1 000 to < 1/100), Rare (u2265 1/10 000 to < 1/1 000), Very rare ( < 1/10 000), Not known (cannot be estimated from the available data)

Table 2

System Organ Class Adverse Drug Reaction Frequency

Signs and symptoms of CONCERTA, in overdosage, result principally from overstimulation of the CNS and excessive sympathomimetic stimulations. They may include the following: vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions, coma, grand mal convulsion, euphoria, confusional state, confusion, hallucinations (auditory and/or visual), hyperhidrosis, flushing, headache, pyrexia, tachycardia, palpitations, heart rate increased, sinus dysrrhythmias, hypertension, mydriasis, and dry mouth.

Treatment consists of appropriate supportive measures. The patients must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. The efficacy of activated charcoal has not been established. 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.