NEUCON Extended-release tablet Ref.[115224] Active ingredients: Methylphenidate

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 Tourette’s syndrome

NEUCON has been associated with the onset or exacerbation of motor and verbal tics. Worsening of verbal Tourette’s syndrome has also been reported. It is recommended that the family history be assessed, and that the patient is clinically evaluated for tics or Tourettes’s syndrome before initiating methylphenidate. Regular monitoring for the emergence or worsening of tics or Tourette’s 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).

Dose administration

NEUCON must be swallowed whole with the aid of liquids. Tablets should not be chewed, divided or crushed. Methylphenidate is contained within a non-absorbable 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 NEUCON tablet is non-deformable and does not appreciably change in shape in the GI tract, NEUCON should not be administered to patients with pre-existing 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, NEUCON should only be used in patients who are able to swallow the tablet whole.

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). 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 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:

• Psychotic patients: Administration of NEUCON may exacerbate symptoms of behaviour disturbances and thought disorder in psychotic patients.
• 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 –1 to 1 mm Hg (systolic) and 0 to 1 mm Hg (diastolic) for NEUCON and from –1 to 1 mm Hg (systolic) and –2 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: NEUCON 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.

Haematologic monitoring

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

Lactose

Contains lactose which may have 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 NEUCON.

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 (≥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 the available data).

Table 2:

^* 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:

Reporting of side effects

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8.

Not applicable.