Ritalin 10 mg/20 mg/30 mg/40 mg Tablets

RITALIN u00ae 10 mg tablets Attention deficit hyperactivity disorder (ADHD) in children aged 6 years or older. Narcolepsy in adults.

RITALIN u00ae LA capsules Attention deficit hyperactivity disorder (ADHD) in children aged 6 years or older, and in adults with ADHD onset in childhood. The diagnosis should be made according to current DSM criteria or the guidance from International Classification of Diseases (ICD).

Posology: The dosage of RITALIN u00ae should be individualised according to the patientu2019s clinical needs and responses. RITALIN u00ae should be started at a low dose, with increments at weekly intervals. Daily doses above 60 mg are not recommended for the treatment of narcolepsy in adults, or for the treatment of ADHD in children. Effective doses in adults may vary and range from 40 to 80 mg per day. Daily doses above 80 mg are not recommended for the treatment of ADHD in adults (RITALIN u00ae LA only). If improvement is not observed after appropriate dosage adjustment over a one-month period, RITALIN u00ae should be discontinued. If paradoxical aggravation of symptoms or other adverse effects occur, RITALIN u00ae should be discontinued.

Pre-treatment screening Before initiating RITALIN u00ae treatment, patients should be assessed for pre-existing cardiovascular and psychiatric disorders and a family history of sudden death, ventricular dysrhythmia and psychiatric disorders (see section 4.3 and 4.4).

NARCOLEPSY: Only the RITALIN u00ae 10 mg formulation is approved in the treatment of narcolepsy in adults. The average dosage is 20 to 30 mg daily, given in 2 to 3 divided doses. Some patients may require 40 to 60 mg daily. In others, 10 to 15 mg daily will be adequate. Patients who are unable to sleep if medication is taken late in the day should take the last dose before 6 p.m. A total daily dose of 60 mg should not be exceeded.

Periodic assessment of the treatment in ADHD Medicine treatment should not and need not be indefinite. RITALIN u00ae should be periodically discontinued to assess the patientu2019s condition. Improvement may be sustained when the medicine is either temporarily or permanently discontinued. When used in children with ADHD, RITALIN u00ae can usually be discontinued after puberty.

ADHD: Children and adolescents (6 years and over): Tablets: Start with 5 mg once or twice daily (before breakfast and lunch) with gradual increments of 5 to 10 mg weekly. The total daily dose should be administered in divided doses. RITALIN u00ae LA capsules: RITALIN u00ae LA (methylphenidate hydrochloride modified-release capsules) is for oral administration once daily in the morning. The recommended starting dose of RITALIN u00ae LA is 20 mg. When in the judgement of the clinician a lower initial dose is appropriate, patients may begin treatment with RITALIN u00ae LA 10. Daily dosage above 60 mg is not recommended.

Adults: Only the RITALIN u00ae LA formulation should be used for the treatment of ADHD in adults. RITALIN u00ae LA is administered once daily in the morning. Patients new to methylphenidate: The recommended starting dose of RITALIN u00ae LA in patients who are not currently taking methylphenidate is 20 mg once daily. Patients currently using methylphenidate: Treatment may be continued with the same daily dose. If the patient was previously treated with an immediate release formulation, a conversion to an appropriate recommended dose of RITALIN u00ae LA should be made (see below subsection u201cSwitching patients to RITALIN u00ae LAu201d). A maximum daily dose of 80 mg should not be exceeded.

Switching patients to RITALIN u00ae LA: The recommended dose of RITALIN u00ae LA should be equal to the total daily dose of the immediate release formulation, not exceeding a total of 60 mg in children and 80 mg in adults. An example in patients being switched from the immediate-released formulation is provided below. Recommended daily dose when switching patients to RITALIN LA Previous RITALIN u00ae dose Recommended RITALIN u00ae LA dose 5 mg RITALIN u00ae twice daily 10 mg once daily 10 mg RITALIN u00ae twice daily 20 mg once daily 15 mg RITALIN u00ae twice daily 30 mg once daily 20 mg RITALIN u00ae twice daily 40 mg once daily For other RITALIN u00ae regimens, clinical judgment should be used when selecting the starting dose. RITALIN u00ae LA dosage may be adjusted at weekly intervals in 10 mg increments for children and in 20 mg increments for adults.

Special populations Renal impairment No studies have been performed in renally impaired patients. Hepatic impairment No studies have been performed in hepatically impaired patients. Geriatric patients No studies have been performed in patients over 60 years of age.

Method of administration: General recommendations RITALIN u00ae 10 mg tablets can be taken with or without food. RITALIN u00ae LA capsules may be administered with or without food. They may be swallowed as whole capsules or alternatively may be administered by sprinkling the contents over a small amount of food (see specific instructions below). The granules must be swallowed whole and not chewed or crushed. RITALIN u00ae LA capsules and/or their contents should not be crushed or chewed. RITALIN u00ae LA administration by sprinkling capsule contents on food: The capsules may be carefully opened, and the beads sprinkled over soft food. The food should not be warm because this could affect the modified-release properties of this formulation. The mixture of medicine and food should be consumed immediately in its entirety. This soft food mixture should not be chewed but swallowed only. The medicine and food mixture should not be stored for future use.

Anxiety, tension, agitation, a family history or diagnosis of Touretteu2019s syndrome, hyperthyroidism, glaucoma, phaeochromocytoma. Pre-existing cardiovascular disorders, including hypertension, angina, arterial occlusive disease; heart failure, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening dysrhythmias, channelopathies (disorders caused by the dysfunction of ion channels) and QT prolongation either congenital, familial or caused by medication (see section 4.4). During treatment with monoamine oxidase (MAO) inhibitors, or within a minimum of 2 weeks of discontinuing those medicines, due to risk of hypertensive crisis (see section 4.5). Known hypersensitivity to methylphenidate or to any of the excipients of RITALIN u00ae. Pregnancy and Lactation (see section 4.6).

General: RITALIN u00ae should not be used for the prevention or treatment of normal fatigue states. Treatment with RITALIN u00ae is not indicated in all cases of Attention-deficit/Hyperactivity disorder and should be considered only after detailed history-taking and evaluation. The decision to prescribe RITALIN u00ae should depend on an assessment of the severity of symptoms and, in paediatric patients, their appropriateness to the childu2019s age and not simply on the presence of one or more abnormal behavioural characteristics.

RITALIN u00ae should not be used for the treatment of attention-deficit or hyperactivity secondary to amenable causes, including acute stress reactions. Chronic abuse of RITALIN u00ae can lead to marked tolerance and psychological dependence with varying degrees of abnormal behaviour. Frank psychotic episodes may occur. Abuse of RITALIN u00ae may prove a problem in predisposed patients e.g. in emotionally unstable individuals or those with a history of drug dependence or alcoholism. RITALIN u00ae should therefore be used only under medical supervision. Clinical data indicate that children given RITALIN u00ae are not more likely to abuse drugs than adolescents or adults.

Cardiovascular: Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems: Sudden death has been reported in association with the use of RITALIN u00ae at usual doses in patients with pre-existing structural cardiac abnormalities or other serious heart problems. A causal relationship with RITALIN u00ae has not been established since some of these conditions alone may carry an increased risk of sudden death. RITALIN u00ae generally should not be used in patients with known structural cardiac abnormalities or other serious cardiac disorders that may increase the risk of sudden death due to its sympathomimetic effects. Before initiating RITALIN u00ae treatment, patients should be assessed for pre-existing cardiovascular disorders such as a congenital long QT syndrome, or a family history of sudden death and ventricular dysrhythmia (see section 4.2).

Misuse and Cardiovascular Events: Misuse of RITALIN u00ae, may be associated with sudden death and other serious cardiovascular adverse events. Cardiovascular conditions: RITALIN is contraindicated in patients with hypertension. RITALIN u00ae increases heart rate and systolic and diastolic blood pressure. Therefore, caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g. those with pre-existing hypertension and severe cardiovascular disorders (see section 4.3). Blood pressure should be monitored at appropriate intervals in all patients taking RITALIN u00ae. Patients who develop symptoms suggestive of cardiac disease during RITALIN u00ae treatment should undergo a prompt cardiac evaluation.

Cerebrovascular: Cerebrovascular conditions: Patients with pre-existing central nervous system (CNS) abnormalities, e.g. cerebral aneurysm and/or other vascular abnormalities such as vasculitis or pre-existing stroke should not be treated with RITALIN u00ae. Patients with additional risk factors (history of cardiovascular disease, concomitant medications that elevate blood pressure) should be assessed regularly for neurological/psychiatric signs and symptoms after initiating treatment with RITALIN u00ae (see above, paragraph on Cardiovascular Conditions and section 4.5).

Psychiatric: Co-morbidity of psychiatric disorders in ADHD is common and should be taken into account when prescribing RITALIN u00ae. Prior to initiating treatment with RITALIN u00ae, patients should be assessed for pre-existing psychiatric disorders and a family history of psychiatric disorders (see section 4.2). Treatment of ADHD with RITALIN u00ae should not be initiated in patients with acute psychosis, acute mania or acute suicidality. These acute conditions should be treated and controlled before ADHD treatment is considered. In the case of emergent psychiatric symptoms or exacerbation of pre-existing psychiatric symptoms, RITALIN u00ae should not be given to patients unless the benefit outweighs the potential risk.

Psychotic symptoms: Psychotic symptoms, including visual and tactile hallucinations or mania have been reported in patients administered recommended therapeutic doses of RITALIN (see section 4.8). Medical practitioners should consider treatment discontinuation.

Aggressive behaviour: Emergent aggressive behaviour or an exacerbation of baseline aggressive behaviour has been reported during RITALIN u00ae therapy. Medical practitioners should evaluate the need for adjustment of treatment regimen in patients experiencing these behavioural changes, bearing in mind that upwards or downwards titration may be appropriate. Treatment interruption can be considered.

Suicidal tendency: Patients and caregivers of patients should be alerted about the need to monitor for clinical worsening, suicidal behaviour or thoughts or unusual changes in behaviour and to seek medical advice immediately if these symptoms appear. The medical practitioner should initiate appropriate treatment of any underlying psychiatric condition and consider a possible discontinuation or change in the ADHD treatment regimen.

Tics: RITALIN u00ae is associated with the onset or exacerbation of motor and verbal tics. Worsening of Touretteu2019s syndrome has also been reported (see section 4.8). Family history should be assessed and clinical evaluation for tics or Touretteu2019s syndrome in patients should precede use of RITALIN u00ae for ADHD treatment. RITALIN u00ae is contraindicated in case of diagnosis or family history of Touretteu2019s syndrome (see section 4.3). Patients should be regularly monitored for the emergence or worsening of tics during treatment with RITALIN u00ae.

Serotonin syndrome: Serotonin syndrome has been reported following co-administration of methylphenidate with serotonergic medicines such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). The concomitant use of RITALIN u00ae and serotonergic medicines is not recommended as this may lead to the development of serotonin syndrome. The symptoms of serotonin syndrome may include mental status changes (e.g. agitation, hallucinations, delirium, and coma), autonomic instability (e.g. tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g. tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). Prompt recognition of these symptoms is important so that treatment with RITALIN u00ae and serotonergic medicines can be immediately discontinued and appropriate treatment instituted (see section 4.5).

Acute Angle Closure Glaucoma: There have been reports of acute angle closure glaucoma associated with methylphenidate treatment. Although the mechanism is not clear, Ritalin-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.

Increased Intraocular Pressure and Glaucoma: There have been reports of an elevation of intraocular pressure (IOP) and glaucoma (including open angle glaucoma and angle closure glaucoma) associated with methylphenidate treatment (see section 4.8). Close monitoring of Ritalin-treated patients with a history of abnormally increased IOP or glaucoma is recommended.

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

Growth retardation: Reduced weight gain and slight growth retardation have been reported with the long-term use of RITALIN u00ae (see section 4.8). Growth and weight should be monitored during treatment with RITALIN, and patients who are not growing or gaining height or weight as expected or are losing weight may need to have their treatment interrupted and adjusted.

Haematological effects: The long-term safety and efficacy profiles of RITALIN u00ae are not fully known. Patients requiring long-term therapy should therefore be carefully monitored and complete and differential blood counts and a platelet count performed periodically. In the event of haematological disorders appropriate medical intervention should be considered (see section 4.8).

Seizures: RITALIN u00ae should be used with caution in patients with epilepsy as clinical experience has shown that it can cause an increase in seizure frequency. If seizure frequency increases, RITALIN u00ae should be discontinued.

Drug abuse and dependence: Chronic abuse of RITALIN u00ae can lead to marked tolerance and psychological dependence with varying degrees of abnormal behaviour. Frank psychotic episodes may occur, especially with parenteral abuse. Caution is called for in emotionally unstable patients, such as those with a history of drug dependence or alcoholism, because they may increase the dosage on their own initiative.

Withdrawal: Careful supervision is required during RITALIN u00ae withdrawal, since this may unmask depression as well as the effects of chronic overactivity. Some patients may require long-term follow-up.

Paediatric patients under 6 years of age: RITALIN u00ae is not indicated in children less than six years of age.

Treatment with RITALIN u00ae is not indicated in all cases of Attention-Deficit/Hyperactivity disorder and should be considered only after detailed history-taking and evaluation. The decision to prescribe RITALIN u00ae should depend on the medical practitioner assessment of the chronicity and severity of the childu2019s symptoms and, their appropriateness to the childu2019s age. Prescription should not depend solely on the presence of one or more abnormal behavioural characteristics. Where these symptoms are associated with acute stress reactions, treatment with RITALIN u00ae is not indicated.

Lactose intolerance: RITALIN u00ae 10 tablets contain lactose. Patients with rare hereditary problems of lactose intolerance e.g. galactosaemia or severe lactase deficiency should not use RITALIN u00ae 10 tablets. RITALIN u00ae LA capsules contains sucrose. Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take RITALIN u00ae LA capsules. RITALIN u00ae 10 (containing lactose) and RITALIN u00ae LA (containing sucrose) may have an effect on the glycaemic control of patients with diabetes mellitus.

Medicine/Laboratory test: RITALIN u00ae may induce false positive laboratory tests for amphetamines, particularly with immunoassays screen test.

Pharmacokinetic interactions RITALIN u00ae is not metabolised by cytochrome P450 to a clinically relevant extent. Inducers or inhibitors of cytochrome P450 are not expected to have any relevant impact on RITALIN u00ae pharmacokinetics. Conversely, the d- and l- enantiomers of methylphenidate in RITALIN u00ae did not relevantly inhibit cytochrome P450 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A. RITALIN u00ae co-administration did not increase plasma concentrations of the CYP2D6 substrate desipramine. Case reports suggested a potential interaction of RITALIN u00ae with warfarin, some anticonvulsants (e.g. phenobarbital, phenytoin, primidone) and tricyclic antidepressants but pharmacokinetic interactions were not confirmed when explored at higher sample sizes. The dosage of these medicines might have to be reduced.

Other specific medicine-medicine interaction studies with RITALIN u00ae have not been performed in vivo.

Pharmacodynamic interactions Anti-hypertensive medicines RITALIN u00ae may decrease the effectiveness of medicines used to treat hypertension. Use with medicines that elevate blood pressure RITALIN u00ae should be used with caution in patients being treated with medicines that elevate blood pressure (see paragraph on Cerebrovascular Conditions under section 4.4). Because of possible hypertensive crisis, RITALIN u00ae is contraindicated in patients being treated (currently or within the preceding 2 weeks) with MAO-inhibitors (see section 4.3).

Use with alcohol Alcohol may exacerbate the central nervous system adverse reactions of RITALIN u00ae. It is advisable for patients to abstain from alcohol during treatment.

Use with dopaminergic medicines As an inhibitor of dopamine reuptake, RITALIN u00ae may be associated with pharmacodynamic interactions when co-administered with direct and indirect dopamine agonists (including DOPA and tricyclic antidepressants) as well as dopamine antagonists (antipsychotics, e.g. haloperidol). Concomitant use of RITALIN u00ae with antipsychotics is not recommended due to its counteracting mechanism of action. If upon medical assessment the combination is deemed necessary, monitoring for extrapyramidal symptoms (EPS) is recommended, as the concomitant use of methylphenidate with antipsychotics may increase the risk of EPS when there is a change (increase or decrease) in dosage of either or both medications.

Use with anaesthetics There is a risk of sudden blood pressure and heart rate increase during surgery. If surgery is planned, RITALIN u00ae should not be taken on the day of surgery.

Use with centrally acting alpha-2 agonists (e.g. clonidine or dexmedetomidine) Serious adverse events including sudden death may occur in concomitant use with clonidine or dexmedetomidine, although no causality for the combination has been established.

Use with serotonergic medicines The concomitant use of RITALIN u00ae and serotonergic medicines is not recommended as this may lead to the development of serotonin syndrome (see section 4.4). Methylphenidate has been shown to increase extracellular serotonin and norepinephrine and appears to have weak potency in binding serotonin transporter.

Pregnancy RITALIN u00ae is contraindicated in pregnancy and lactation as safety has not been demonstrated (see section 4.3).

Lactation Mothers on RITALIN u00ae should not breastfeed their infants.

RITALIN u00ae may cause dizziness, drowsiness, blurred vision, hallucinations or other CNS side-effects (see section 4.8). Patients experiencing such side-effects should refrain from driving, operating machines or engaging in other potentially hazardous activities.

Nervousness and insomnia are very common adverse reactions. These usually occur at the beginning of RITALIN u00ae treatment and may be reduced by decreasing the dose and omitting the medicine in the afternoon or evening. Decreased appetite is very common. Abdominal pain, nausea and vomiting are common to very common. Reports of neuroleptic malignant syndrome (NMS) have been received. In most of these reports patients were also receiving other medications. It is uncertain what role RITALIN u00ae played in these cases.

Tabulated summary of adverse reactions Adverse reactions are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Infections and infestations: Very common: Nasopharyngitis* Blood and the lymphatic system disorders: Very rare: Leucopenia, thrombocytopenia, anaemia Immune system disorders: Very rare: Hypersensitivity reactions Metabolism and nutrition disorders: Very Common: Decreased appetite** Rare: Reduced weight gain during prolonged use in children Psychiatric disorders: Very Common: Nervousness, insomnia Common: Anxiety*, restlessness*, sleep disorder*, agitation* depression, aggression, bruxism* Very rare: Hyperactivity, psychosis (sometimes with visual and tactile hallucinations), transient depressed mood Nervous system disorders: Common: Dyskinesia, tremor*, headache, drowsiness, dizziness Very rare: Convulsions, choreo-athetoid movements, tics or exacerbation of existing tics and Touretteu2019s syndrome, cerebrovascular disorders including vasculitis, cerebral haemorrhages and cerebrovascular accidents Skin and subcutaneous tissue disorders: Common: Rash, pruritus, urticaria, fever, scalp hair loss, hyperhidrosis* Very rare: Thrombocytopenic purpura, exfoliative dermatitis, erythema multiforme Musculoskeletal and connective tissue disorders: Common: Arthralgia Uncommon: Trismus Very rare: Muscle cramps General disorders and administration site conditions: Common: Feeling jittery* Rare: Growth retardation during prolonged use in children Investigations: Common: Weight decreased* Vascular disorders: Common: Raynaud's phenomenon**, peripheral coldness** * ADRs reported from clinical trials performed in adult ADHD patients **The reported frequency of ADRs was based on the frequency observed in the adult ADHD clinical studies, which was higher than that previously reported for children.

The list below shows reported post-marketing adverse reactions Blood and lymphatic disorders: Pancytopenia Immune system disorders: Hypersensitivity reactions, including angioedema and anaphylaxis Psychiatric disorders: Irritability, affect lability, abnormal behaviour or thinking abnormal, anger, mood altered, mood swings, hypervigilance, mania, disorientation, libido disorder 1 , apathy, stereotypy 2 , change in sustained attention 3 , confusional state, drug abuse 4 and drug dependence 4 . Nervous system disorders: Reversible ischaemic neurological deficit, migraine Eye disorders: Diplopia, mydriasis, visual impairment 5 Ear and labyrinth disorders Auricular swelling 6 Cardiac disorders: Cardiac arrest, myocardial infarction Respiratory, thoracic and mediastinal disorders: Laryngeal pain 7 , dyspnoea, epistaxis Gastrointestinal disorders: Diarrhoea, constipation Skin and subcutaneous tissue disorders: Angioedema, erythema, fixed eruption 8 Musculoskeletal, connective tissue and bone disorders: Myalgia, muscle twitching Renal and urinary disorders: Haematuria Reproductive system and breast disorders: Gynaecomastia, erectile dysfunction General disorders and administration site conditions: Chest pain, fatigue, sudden cardiac death Investigations: Cardiac murmur, increased intraocular pressure 1 Includes libido decreased 2 Includes repetitive behaviours 3 Includes overfocusing and hyperfocusing 4 Cases of abuse and dependence have been described, more often with immediate-release formulations 5 Includes visual disturbance 6 Related to hypersensitivity reactions 7 Includes pharyngolaryngeal pain 8 Includes fixed drug eruption

Adverse reactions from spontaneous reports and literature cases (frequency not known) The following adverse reactions have been derived from post-marketing experience with RITALIN u00ae via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. Adverse reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness. Reproductive system and breast disorders Priapism Psychiatric disorders Dysphemia, suicidal ideation or attempt (including completed suicide) Renal and urinary disorders Enuresis Reporting of suspected adverse reactions 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 requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Signs and symptoms: Vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitation, cardiac dysrhythmias, hypertension, mydriasis, dryness of mucous membranes and rhabdomyolysis.

Treatment: When treating overdose practitioners should bear in mind that a second release of methylphenidate from RITALIN u00ae LA (methylphenidate hydrochloride modified-release capsules) occurs at approximately four hours after administration. Treatment consists of appropriate supportive measures and symptomatic treatment of life-threatening events e.g. hypertensive crisis, cardiac dysrhythmias, convulsions. For the most current guidance for treatment of symptoms of overdose, the practitioner should consult a certified Poison Control Centre or current toxicological publication. Supportive measures include protection of the patient against self-injury and against external stimuli that would exacerbate the overstimulation already present. If the overdose is oral and the patient is conscious, administration of activated charcoal is recommended. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required to reduce hyperpyrexia. Efficacy of peritoneal dialysis or extracorporeal haemodialysis for overdosage of RITALIN u00ae has not been established.