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

NEUCON 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 NEUCON: The recommended starting dose of NEUCON 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 NEUCON: The recommended dose of NEUCON 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 NEUCON
Previous Methylphenidate Daily Dose Recommended NEUCON Dose
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 NEUCON has not been systematically evaluated in controlled clinical trials. The medical practitioner who elects to use NEUCON 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 NEUCON 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, NEUCON should be discontinued.

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

Method of administration
NEUCON must be swallowed whole with adequate amounts of liquids, and must not be chewed, divided, or crushed. NEUCON may be administered with or without food.

Dosage should be individualised according to the need and response of each individual patient. NEUCON should not be used in patients under six years old. NEUCON 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.

NEUCON is contraindicated:
u2022 in patients known to be hypersensitive to methylphenidate or other components of NEUCON;
u2022 in patients with poorly controlled open-angle or angle-closure glaucoma;
u2022 during treatment with monoamine oxidase inhibitors, and also within a minimum of 14 days following discontinuation of a monoamine oxidase inhibitor (as hypertensive crises may result);
u2022 in patients with hyperthyroidism, cardiac dysrhythmias, ischaemic heart disease, uncontrolled hypertension;
u2022 in pregnancy and lactation. (see section 4.6)

NEUCON increases heart rate, systolic and diastolic blood pressure, therefore caution is advised when NEUCON 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 NEUCON 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 NEUCON used, at usual doses. Although the data are inconclusive regarding causal relationship between treatment with NEUCON and sudden death, caution is advised when NEUCON 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 NEUCON.

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

Motor and verbal tics, and worsening of Touretteu2019s syndrome
NEUCON 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 NEUCON 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 NEUCON 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. NEUCON is not recommended in patients with acute angle glaucoma. NEUCON is contraindicated in all patients with poorly controlled glaucoma (See section 4.3).

Use in other indications
NEUCON 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 NEUCON at usual doses. If such symptoms occur, consideration should be given to a possible causal role of NEUCON, 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 NEUCON (see section 4.8). Anxiety led to discontinuation of NEUCON is some patients. It is recommended to monitor patients beginning treatment with NEUCON 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 NEUCON, 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).

Cerebrovascular disorders
Cerebrovascular disorders (including cerebral vasculitis and cerebral haemorrhage) have been reported with the use of NEUCON (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 NEUCON 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 NEUCON immediately. Early diagnosis may guide subsequent treatment.

Conditions requiring caution
NEUCON should be given with caution in the following conditions:
u2022 Psychotic patients: Administration of NEUCON may exacerbate symptoms of behaviour disturbances and thought disorder in psychotic patients.
u2022 Underlying medical conditions that may be compromised by increases in blood pressure or heart rate: In clinical trials in children, NEUCON 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 NEUCON 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 NEUCON and from u20131 to 1 mm Hg (systolic) and u20132 to 0 mm Hg (diastolic) for placebo.

Because of the effects on blood pressure, NEUCON should be used cautiously with pressor agents. NEUCON should not be used in patients being treated (currently or within the preceding 2 weeks) with MAO inhibitors (See section 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 NEUCON. 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 NEUCON.

There have been reports of serotonin syndrome following coadministration of methylphenidate with serotonergic medicines. If concomitant use of NEUCON with a serotonergic medicine is warranted, prompt recognition of the symptoms of serotonin syndrome is important NEUCON 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 NEUCON in combination with clonidine or other centrally acting alpha-2 agonists has not been systematically evaluated. Alcohol may exacerbate the adverse CNS effects of NEUCON. It is therefore desirable for patients to abstain from alcohol during treatment.

Pregnancy
NEUCON 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 NEUCON.

NEUCON 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 NEUCON 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 NEUCON and those, which have been reported with other methylphenidate hydrochloride formulations. If the ADRs with NEUCON 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
Infections and infestations Nasopharyngitis, upper respiratory tract infection*, sinusitis *
Blood and lymphatic system disorders Anaemia** , Leukopaenia **
Metabolism and nutritional disorders Anorexia, decreased appetite**, moderately reduced weight and height gain during prolonged use in children
Psychiatric disorders Insomnia, nervousness Anorexia, affect lability, aggression, agitation, anxiety**, depression*, Psychotic disorders, anger, suicidal ideation, altered mood, restlessness**, Libido disorder, confusional state** Suicidal attempt (including completed suicide)**, transient Delusions **, thought disturbances, dependence irritability, abnormal behaviour, mood swings, tics, initial insomnia*, depressed mood*, depression**, decreased libido*, tension *, bruxism*, panic attack* tearfulness, worsening of pre-existing tics of Touretteu2019s syndrome, hypervigilance, sleep disorder depressed mood, abnormal thinking, apathy**, repetitive behaviours, over-focusing
Nervous system disorders Headache Dizziness, psychomotor hyperactivity, somnolence, paraesthesia*, tension headache* Sedation, tremor**, lethargy* Choreo-athetoid movements , reversible ischaemic neurological deficit, neuroleptic malignant syndrome (NMS; reports were poorly documented and in most cases, patients were also receiving other medicines, so the role of methylphenidate is unclear)
Cerebrovascular disorders* * (including vasculitis, cerebral haemorrhages, cerebrovascular accidents, cerebral arteritis, cerebral occlusion) , migraine* *
Eye disorder Accommodation disorder* Blurred vision**, Dry eye * Difficulties in visual accommodation
Ear and labyrinth disorders Vertigo* Cardiac disorders Dysrhythmia, tachycardia, palpitations Chest pain Cardiac arrest, myocardial infarction Vascular disorders Hypertension Hot flushes* Cerebral arteritis and/or occlusion, peripheral coldness** Respiratory, thoracic and mediastinal disorders Cough, oropharyngeal pain Dyspnoea**
Gastrointestinal disorders Upper abdominal pain, diarrhoea, nausea**, abdominal discomfort, vomiting, dry mouth **, dyspepsia* Constipation** Hepatobiliary disorders Hepatic enzyme elevations Abnormal liver function, including hepatic coma Skin and subcutaneous tissue disorders Pruritis, rash, urticaria Angioneurotic oedema, bullous conditions, exfoliative conditions Hyperhidrosis**, Macular rash Erythema multiforme, exfoliative dermatitis, fixed medicine eruption Musculoskeletal and connective tissue disorders Muscle tightness*, muscle spasms* Muscle cramps
Renal and urinary disorders Haematuria, pollakiura Reproductive system and breast disorders Erectile dysfunction* Gynaecomastia Priapism, Erection increased *,Prolonged erection* General disorders and administration site conditions Pyrexia, growth retardation during prolonged use in children, fatigue**, irritability *, feeling jittery*, asthenia*, thirst* Sudden cardiac death Investigations Changes in blood pressure and heart rate (usually an increase), decreased weight, increased alanine aminotransferase * Cardiac murmur *Frequency derived from adult clinical trials and not on data from trials in children and adolescents; may also be relevant for children and adolescents. **Frequency derived from clinical trials in children and adolescent and reported at a higher frequency in clinical trials in adult patients.

Post-Marketing experience
Postmarketing data ADRs identified during post-marketing experience with NEUCON are included in Table 3

Table 3. Adverse Drug Reactions Identified During Post-Marketing Experience with NEUCON
Blood and Lymphatic System Disorders Pancytopenia, thrombocytopenia, thrombocytopenic purpura
Immune System Disorders Hypersensitivity reactions such as angioedema, anaphylactic reactions, auricular swelling, bullous conditions, exfoliative conditions, urticaria, pruritus, rashes, eruptions and exanthemas
Psychiatric Disorders Disorientation, hallucination, auditory hallucination, visual hallucination, mania, logorrhea, libido disorder
Nervous System Disorders Convulsion, grand mal convulsion, dyskinesia , Cerebrovascular disorder (including cerebral vasculitis, cerebral haemorrhage, cerebral arteritis, cerebral occlusion)
Eye Disorders Diplopia, mydriasis, visual impairment
Cardiac Disorders Angina pectoris, bradycardia, extrasystoles, supraventricular tachycardia, ventricular extrasystoles
Vascular Disorders Raynaudu2019s phenomenon
Respiratory and Thoracic and Mediastinal Disorders Epistaxis
Hepato-biliary disorders Hepatocellular injury Acute hepatic failure
Skin and Subcutaneous Tissue Disorders Alopecia, erythema
Musculoskeletal and Connective Tissue Disorders Arthralgia, myalgia, muscle twitching
Reproductive System and Breast Disorders Priapism
General Disorders and Administration Site Conditions Decreased therapeutic response chest pain, chest discomfort, decreased drug effect, hyperpyrexia
Investigations

Signs and symptoms of NEUCON in overdosage, resulting 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 dysrhythmias, 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 haemodialysis for NEUCON overdosage has not been established. The prolonged release of methylphenidate from NEUCON should be considered when treating patients with overdose.