Ritalin/Ritalin LA Adverse Reactions

Adverse effects reported during clinical trials: Children: A randomised, double-blind, placebo-controlled parallel group clinical study (Protocol 07) was conducted to evaluate the efficacy and safety of Ritalin LA in children aged 6-12 years with ADHD. In the double-blind treatment phase of this study, Ritalin LA was administered once daily for up to two weeks at individually titrated doses in the 10-40 mg range. The incidence of treatment-emergent adverse events reported during the double-blind treatment phase is summarised in Table 6. (see Table 6). Adverse events reported with an incidence ≥2% in all treated subjects in Protocol 07 (including adverse events during the titration period and placebo-washout period) are included in Table 7 (see Table 7).

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Adults: Ritalin LA was evaluated in a randomized, double-blind, placebo-controlled, multicentre core study (D2302) in the treatment of 725 adult patients (395 male and 330 female) diagnosed with ADHD. Maintenance of effect of Ritalin LA was evaluated in a 6-month maintenance study (D2302E1) in 298 patients. The incidence of adverse events reported during the core study and extension studies are summarised in Table 8 and Table 9 respectively. (See Table 8 and 9.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

The AE profile seen in the maintenance period was similar to that observed in the core study. No unexpected SAEs or AEs were observed in this extension study and the commonly observed AEs were expected and driven by the pharmacologic activity.
The most frequently affected primary SOCs (≥10% in all extension patients) starting in the extension study were infections and infestations, nervous system disorders, psychiatric disorders, and gastrointestinal disorders. There was no evidence of toxicity to any organ system. The most commonly reported individual AEs (≥5.0% in any dose group) during the extension study were nasopharyngitis (19.1%), headache (14.1%), decreased appetite (7.7%), dry mouth (6.7%) and nausea (5.0%).
Post-marketing Experience: Nervousness and insomnia are very common adverse reactions which occur at the beginning of Ritalin/Ritalin LA treatment and are usually controlled by reducing the dosage and omitting the drug in the afternoon or evening.
Loss of appetite is very common but usually transient. Abdominal pain, insomnia and tachycardia are common, usually at the beginning of treatment and may be alleviated by concomitant food intake.
Tabulated summary of adverse reactions: Adverse drug reactions listed in Table 10 are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): Very common ≥10%; common ≥1% to <10%; uncommon ≥0.1% to <1%; rare ≥0.01% to <0.1%; very rare <0.01%. (See Table 10.)

Click on icon to see table/diagram/image

Very rare reports of poorly documented neuroleptic malignant syndrome (NMS) have been received. In most of these reports, patients were also receiving other medications. It is uncertain what role Ritalin played in these cases.
Adverse events reported since market introduction in patients taking methylphenidate include suicide, suicide attempt and suicidal ideation. No causal relationship between methylphenidate and these events has been established.
Adverse drug reactions from spontaneous reports and literature cases (frequency not known): The following adverse drug reactions have been derived from post-marketing experience with Ritalin 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 drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness. (See Table 11.)

Click on icon to see table/diagram/image

Additional adverse reactions reported with other methylphenidate-containing products: The list as follows shows adverse reactions not listed for Ritalin that have been reported with other methylphenidate-containing products based on clinical trials data and post-market spontaneous reports.
Blood and lymphatic disorders: Pancytopenia.
Immune system disorders: Hypersensitivity reactions such as auricular swelling.
Psychiatric disorders: Irritability, affect lability, abnormal thinking or behaviour, anger, mood altered, mood swings, hypervigilance, mania, disorientation, libido disorder, apathy, repetitive behaviours, over-focussing, confusional state, dependence. Cases of abuse and dependence have been described, more often with immediate-release formulations.
Nervous system disorders: Reversible ischaemic neurological deficit, migraine.
Eye disorders: Diplopia, mydriasis, visual disturbance.
Cardiac disorders: Cardiac arrest, myocardial infarction.
Respiratory, thoracic and mediastinal disorders: Pharyngolaryngeal pain, dyspnoea.
Gastrointestinal disorders: Diarrhoea, constipation.
Skin and subcutaneous tissue disorders: Angioneurotic oedema, erythema, fixed drug eruption.
Musculoskeletal, connective tissue and bone disorders: Myalgia, muscle twitching.
Renal and urinary disorders: Haematuria, incontinence.
Reproductive system and breast disorders: Gynaecomastia.
General disorders and administration site conditions: Chest pain, fatigue, sudden cardiac death.
Investigations: Cardiac murmur.