Adverse reactions : תופעות לוואי

4.8. Undesirable effects
Nervousness and insomnia are very common adverse reactions which occur at the beginning of Ritalin treatment but can usually be controlled by reducing the dosage and/or omitting the afternoon or evening dose.

RIT API 11APR24 V14           Page 13 of 23          reference: New Zealand Data Sheet Jan.2024 Decreased appetite is also very common but usually transient. Abdominal pain, nausea and vomiting are common to very common, usually occur at the beginning of treatment and may be alleviated by concomitant food intake.

Tabulated summary of adverse drug reactions
The adverse reactions listed in Table 2 are listed by MedDRA (v15.1) system organ class.
Within each organ class, the adverse drug reactions are ranked by frequency, using the following convention: very common  10%, common  1% to < 10%; uncommon  0.1% to < 1%; rare  0.01% to < 0.1%; very rare < 0.01%.

Table 2 Adverse reactions reported with Ritalin use from clinical studies, spontaneous reports and literature
Infections and infestations
Nasopharyngitis*
Very common:
Blood and the lymphatic system disorders
Very rare:                        Leucopenia, thrombocytopenia, anaemia 
Immune system disorders
Very rare:                           Hypersensitivity reactions, including angioedema*** and anaphylaxis

Metabolism and nutrition disorders
Very common:                     Decreased appetite**
Rare:                            Moderately 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, choreoathetoid movements, tics or exacerbation of existing tics and Tourette’s syndrome,
cerebrovascular disorders including vasculitis, cerebral haemorrhages and cerebrovascular accidents

Eye disorders
Rare:                                Difficulties in visual accommodation, blurred vision 
Cardiac disorders
Common:                              Tachycardia, palpitation, arrhythmias, changes in blood pressure and heart rate (usually an increase)
Rare:                                Angina pectoris

Respiratory, Thoracic and mediastinal disorders
Common:                          Cough*

RIT API 11APR24 V14          Page 14 of 23          reference: New Zealand Data Sheet Jan.2024 Gastrointestinal disorders
Very common:                         Nausea**, dry mouth**
Common:                              Abdominal pain, vomiting, dyspepsia*, toothache* 
Hepatobiliary disorders
Very rare:                           Abnormal liver function, ranging from transaminase elevation to hepatic coma

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:                            Slight growth retardation during prolonged use in children

Investigations
Common:                              Weight decreased*

Vascular disorders
Common:                              Raynaud’s phenomenon**, peripheral coldness** *        ADRs reported from the clinical trials performed in adult ADHD patients **       The reported frequency of ADRs was based on the frequency observed higher in the adult ADHD clinical study which was higher than that previously reported for children.
***      includes angioneurotic oedema

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 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.

Table 3 Adverse drug reactions from spontaneous reports and literature (frequency not known)
Blood and lymphatic disorders
Pancytopenia

RIT API 11APR24 V14             Page 15 of 23           reference: New Zealand Data Sheet Jan.2024 Psychiatric disorders
Dysphemia, suicidal ideation or attempt (including completed suicide), irritability, affect lability, abnormal behaviour or thinking abnormal, anger, mood altered, mood swings, hypervigilance, mania, disorientation, libido disorder1, apathy, stereotypy2, change in sustained attention3, confusional state, drug abuse4 and drug dependence4
Nervous system disorders
Reversible ischemic neurological deficit, migraine
Eye disorders
Diplopia, mydriasis, visual impairment5
Ear and labyrinth disorders
Auricular swelling6
Cardiac disorders
Cardiac arrest, myocardial infarction
Respiratory, thoracic and mediastinal disorders
Laryngeal pain7, dyspnoea
Gastrointestinal disorders
Diarrhoea, constipation
Skin and subcutaneous tissue disorders
Erythema, fixed eruption8
Musculoskeletal, connective tissue and bone disorders
Myalgia, muscle twitching
Renal and urinary disorders
Enuresis
Reproductive system and breast disorders
Priapism, erectile dysfunction, gynaecomastia
General disorders and administration site conditions
Chest pain, fatigue
Investigations
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.

Table 4           Additional adverse reactions reported with other methylphenidate- containing products
The list below shows adverse reactions not listed for Ritalin (see Table 2) that have been reported with other methylphenidate-containing products based on clinical studies data and post-market spontaneous reports.

RIT API 11APR24 V14               Page 16 of 23           reference: New Zealand Data Sheet Jan.2024 Renal and urinary disorders           Haematuria

General disorders and                 Sudden cardiac death administration site conditions

Investigations                        Cardiac murmur
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il