TUZULBY

Treatment must be initiated under the supervision of a specialist in childhood and/or adolescent behavioural disorders. Posology Tuzulby prolonged-release chewable tablets consists of an immediate release component (30% of the dose, which ensures rapid onset of action) and a prolonged- release component (70% of the dose, which is designed to maintain therapeutic plasma levels over an extended period).

2). Dose titration Careful dose titration is necessary at the start of treatment with methylphenidate. Dose titration should be started at the lowest possible dose. Other methylphenidate-containing medicinal products with different strengths may be available.

Switching from immediate-release methylphenidate-containing medicinal products to Tuzulby prolonged-release chewable tablets, administered as a single dose, provides comparable overall exposure of methylphenidate compared to the same total dose of the immediate release formulation administered twice daily.

The recommended dose of Tuzulby should be equal to the total daily dose of the immediate-release methylphenidate-containing formulation not exceeding a total dose of 60 mg. Examples are provided in the table below. Immediate-release methylphenidate dose Tuzulby dose 10 mg methylphenidate twice daily 20 mg once daily 15 mg methylphenidate twice daily 30 mg once daily 20 mg methylphenidate twice daily 40 mg once daily 30 mg methylphenidate twice daily 60 mg once daily Treatment of hyperkinetic disorders/ADHD in children and adolescents (from 6 years to less than 18 years of age) For patients from 6 years to less than 18 years of age, the recommended starting dose is 20 mg given orally once daily in the morning.

The dose may be titrated up or down weekly in increments of 10 mg, 15 mg or 20 mg. The 10 mg and 15 mg doses can each be achieved by breaking in half the functionally scored 20 mg and 30 mg tablets, respectively. The dose should be individualised according to the treatment needs and responses of the patient.

The maximum daily dose of methylphenidate is 60 mg for treatment of children and adolescents (from 6 years to less than 18 years of age) with ADHD. Long term (more than 12 months) use in children and adolescents (from 6 years to less than 18 years of age) The safety and efficacy of long-term use of methylphenidate has not been systematically evaluated in controlled trials.

Methylphenidate treatment should not and need not, be indefinite. Methylphenidate treatment is usually discontinued during or after puberty. The physician who elects to use methylphenidate for extended periods (more than 12 months) in children and adolescents (from 6 years to less than 18 years of age) with ADHD should periodically re-evaluate the long-term usefulness of the medicinal product for the individual patient with trial periods off medication to assess the patient’s functioning without pharmacotherapy.

It is recommended that methylphenidate is de-challenged at least once yearly to assess the child’s condition (preferable during school holidays). Improvement may be sustained when the medicinal product is either temporarily or permanently discontinued.

Dose reduction and discontinuation Treatment must be stopped if the symptoms do not improve after appropriate dose adjustment over a one-month period. If paradoxical aggravation of symptoms or other serious adverse reactions occur, the dosage should be reduced or discontinued.

Special populations Adults Methylphenidate is not indicated for use in adults in ADHD. Safety and efficacy have not been established in this age group. Elderly Methylphenidate should not be used in the elderly. Safety and efficacy have not been established in this age group.

Hepatic impairment Methylphenidate has not been studied in patients with hepatic impairment. Caution should be exercised in these patients. Renal impairment Methylphenidate has not been studied in patients with renal impairment. Caution should be exercised in these patients.

Paediatric population Methylphenidate should not be used in children under the age of 6 years. The safety and efficacy of methylphenidate in this age group have not been established. Method of administration Tuzulby is for oral use. 2).

Tuzulby must be chewed and not swallowed whole or crushed.

Summary of the safety profile In general, the most common adverse reactions associated with methylphenidate treatment have been reported with a very common frequency are decreased appetite, insomnia, nervousness, headache, nausea and dry mouth.

Tabulated list of adverse reactions Table 1 below shows all adverse reactions reported during clinical trials and post-marketing experience with methylphenidate, as well as those adverse reactions which have been reported with other methylphenidate hydrochloride formulations.

If adverse reactions frequencies reported with methylphenidate and other methylphenidate hydrochloride formulations were different, the highest frequency from the safety databases was used. Adverse reactions are listed by MedDRA system organ class and frequency convention as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Table 1. 4 “Special warnings and precautions for use” ** Adverse reactions from clinical trials in adult patients that were reported with a higher frequency than in children and adolescents.

*** Reports were poorly documented and in most cases, patients were also receiving other medicinal products, so the role of methylphenidate is unclear **** These usually occur at the beginning of treatment and may be alleviated by concomitant food intake ***** Cases of abuse and dependence have been described, more often with immediate release formulations.

****** Frequency derived from adult clinical trials and not on data from trials in children and adolescents; may also be relevant for children and adolescents Description of selected adverse reactions Very rare cases of sudden death have been also reported in association with the use of stimulants of the CNS at usual doses in children, some of […]

The decision to use the medicinal product must be based on a very thorough assessment of the severity and chronicity of the child’s/adolescent’s symptoms in relation to the child’s/adolescent’s age. Pre-treatment screening Prior to prescribing, it is necessary to conduct a baseline evaluation of the patient’s cardiovascular status, including blood pressure and heart rate.

3). Long term use (more than 12 months) in children and adolescents The safety and efficacy of long term use of methylphenidate has not been systematically evaluated in controlled trials. Methylphenidate treatment should not and need not be indefinite.

Methylphenidate treatment is usually discontinued during or after puberty. e. 4 for cardiovascular status, growth, appetite, development of de novo or worsening of pre-existing psychiatric disorders. Psychiatric disorders to be monitored are described below, and include (but are not limited to) motor or vocal tics, aggressive or hostile behaviour, agitation, anxiety, depression, psychosis, mania, delusions, irritability, lack of spontaneity, withdrawal and excessive perseveration.

The physician who elects to use methylphenidate for extended periods (over 12 months) in children and adolescents with ADHD should periodically re- evaluate the long term usefulness of the medicinal product for the individual patient with trial periods off medication to assess the patient’s functioning without pharmacotherapy.

It is recommended that methylphenidate is de- challenged at least once yearly to assess the child’s/adolescent’s condition (preferably during times of school holidays). Improvement may be sustained when the medicinal product is either temporary or permanently discontinued.

Cardiovascular status Patients who are being considered for treatment with stimulant medicinal products should have a careful history (including assessment for a family history of sudden cardiac or unexplained death or malignant arrhythmia) and physical examination to assess for the presence of cardiac disease, and should receive further specialist cardiac evaluation if initial findings suggest such history or disease.

Patients who develop symptoms, such as palpitations, exertional chest pain, unexplained syncope, dyspnoea or other symptoms suggestive of cardiac disease during methylphenidate treatment should undergo a prompt specialist cardiac evaluation.

Analyses of data from clinical trials of methylphenidate in children and adolescents with ADHD showed that patients using methylphenidate may commonly experience changes in diastolic and systolic blood pressure of over 10 mmHg relative to controls.

The short- and long- term clinical consequences of these cardiovascular effects in children and adolescents are not known, but the possibility of clinical complications cannot be excluded as a result of the effects observed in the clinical trial data.

Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate. 3 for conditions in which methylphenidate treatment is contraindicated. Cardiovascular status should be carefully monitored.

Blood pressure and pulse should be recorded on centile chart at each adjustment of dose and then at least every 6 months. Sudden death and pre-existing cardiac structural abnormalities or other serious cardiac disorders Sudden death has been reported in association with the use of stimulants of the central nervous system (CNS) at usual doses in children and adolescents, some of whom had structural cardiac abnormalities or other serious heart problems.

Although some serious heart problems alone may carry an increased risk of sudden death, stimulant medicinal products are not recommended in children or adolescents with known cardiac structural abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant medicinal product.

Misuse and cardiovascular events Misuse of stimulants of the CNS may be associated with sudden death and other serious cardiovascular adverse reactions. 3 for cerebrovascular conditions in which methylphenidate treatment is contraindicated.

Patients with additional risk factors (such as a history of cardiovascular disease, concomitant medications that elevate blood pressure) should be assessed at every visit for neurological signs and symptoms after initiating treatment with methylphenidate.

Cerebral vasculitis appears to be very rare idiosyncratic reaction to methylphenidate exposure. There is little evidence to suggest that patients at higher risk can be identified and the initial onset of symptoms may be the first indication of an underlying clinical problem.

Early diagnosis, based on a high index of suspicion, may allow the prompt withdrawal of methylphenidate and early treatment. The diagnosis should therefore be considered in any patient who develops new neurological symptoms that are consistent with cerebral ischemia during methylphenidate therapy.

These symptoms could include severe headache, numbness, weakness, paralysis, and impairment of coordination, vision, speech, language or memory. Psychiatric disorders Co-morbidity of psychiatric disorders in ADHD is common and should be taken into account when prescribing stimulant products.

In the case of emergent psychiatric symptoms or exacerbation of pre-existing psychiatric disorders, […]

4) - Pre-existing cerebrovascular disorders cerebral aneurysm, vascular abnormalities including vasculitis or stroke or known risk factors for cerebrovascular disorders