PROVIGIL

1). A diagnosis of narcolepsy should be made according to the International Classification of Sleep Disorders (ICSD2) guideline. Patient monitoring and clinical assessment of the need for treatment should be performed on a periodic basis.

Posology The recommended starting dose is 200 mg daily. The total daily dose may be taken as a single dose in the morning or as two doses, one in the morning and one at noon, according to physician assessment of the patient and the patient's response.

Doses of up to 400 mg in one or two divided doses can be used in patients with insufficient response to the initial 200 mg modafinil dose. Long-term use Physicians prescribing modafinil for an extended time should periodically re-evaluate the long-term use for the individual patients as the long-term efficacy of modafinil has not been evaluated (> 9 weeks).

2). 2). Elderly There are limited data available on the use of modafinil in elderly patients. In view of the potential for lower clearance and increased systemic exposure, it is recommended that patients over 65 years of age commence treatment at 100 mg daily.

4). Method of administration For oral use. Tablets should be swallowed whole.

Summary of the safety profile The most commonly reported adverse drug reaction is headache, affecting approximately 21 % of patients. This is usually mild or moderate, dose-dependent and disappears within a few days. Tabulated list of adverse reactions The following adverse reactions have been reported in clinical trials (involving 1,561 patients taking modafinil) and/or post-marketing experience.

, hay fever symptoms) Angioedema Urticaria (hives) Hypersensitivi ty reactions (characterised by features such as fever, rash, lymphadenopa thy and evidence of other concurrent organ involvement) Anaphylaxis Metabolism and nutrition disorders Decreased appetite Hypercholeste rolaemia Hyperglycaem ia Diabetes mellitus Increased appetite Psychiatric disorders Nervousness Insomnia Anxiety Depression Abnormal thinking Confusion Irritability Sleep disorder Emotional lability Decreased libido Hostility Depersonalisat ion Personality disorder Abnormal dreams Hallucination Mania Psychosis Delusions System Organ Class Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1000 to <1/100) Rare (≥1/10000 to <1/1000) Frequency not known (cannot be estimated from the available data) Agitation Aggression Suicidal ideation Psychomotor hyperactivity Nervous system disorders Headache Dizziness Somnolence Paraesthesia Dyskinesia Hypertonia Hyperkinesia Amnesia Migraine Tremor Vertigo CNS stimulation Hypoaesthesia Incoordination Movement disorder Speech disorder Taste perversion Eye disorders Blurred vision Abnormal vision Dry eye Cardiac disorders Tachycardia Palpitation Extrasystoles Arrhythmia Bradycardia Vascular disorders Vasodilatation Hypertension Hypotension Respiratory, thoracic and mediastinal disorders Dyspnoea Increased cough Asthma Epistaxis Rhinitis Gastrointesti nal disorders Abdominal pain Nausea Dry mouth Diarrhoea Dyspepsia Constipation Flatulence Reflux Vomiting Dysphagia Glossitis Mouth ulcers System Organ Class Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1000 to <1/100) Rare (≥1/10000 to <1/1000) Frequency not known (cannot be estimated from the available data) Skin and subcutaneou s tissue disorders Sweating Rash Acne Pruritus Serious skin reactions, including erythema multiforme, Stevens- Johnson Syndrome, Toxic Epidermal Necrolysis, and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Musculoskel etal and connective tissue disorders Back pain Neck pain Myalgia Myasthenia Leg cramps Arthralgia Twitch Renal and urinary disorders Abnormal urine Urinary frequency Reproductiv e system and breast disorders Menstrual disorder General disorders and administrati on site conditions Asthenia Chest pain Peripheral oedema Thirst Investigation s Abnormal liver function tests Dose related increases in alkaline Abnormal ECG Weight increase Weight decrease System Organ Class Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1000 to <1/100) Rare (≥1/10000 to <1/1000) Frequency not known (cannot be estimated from the available data) phosphatase and gamma- glutamyl transferase Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Diagnosis of sleep disorders Modafinil should be used only in patients who have had a complete evaluation of their excessive sleepiness, and in whom a diagnosis of narcolepsy, has been made in accordance with ICSD diagnostic criteria.

Such an evaluation usually consists, in addition to the patient’s history, sleep measurements testing in a laboratory setting and exclusion of other possible causes of the observed hypersomnia. Serious rash, including Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis and Drug Rash with Eosinophilia and Systemic Symptoms Serious rash requiring hospitalisation and discontinuation of treatment has been reported with the use of modafinil occurring within 1 to 5 weeks after treatment initiation.

, 3 months). 8 % (13 per 1,585) in paediatric patients (age < 17 years); this includes serious rash. No serious skin rashes have been reported in adult clinical trials (0 per 4,264) of modafinil. 8). Rare cases of serious or life-threatening rash, including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been reported in adults and children in worldwide post-marketing experience.

Paediatric population Because safety and effectiveness in controlled studies in children have not been established and because of the risk of serious cutaneous hypersensitivity and psychiatric adverse reactions, the use of modafinil is not recommended in the paediatric population (below 18 years).

Multi-organ hypersensitivity reaction Multi-organ hypersensitivity reactions, including at least one fatality in post- marketing experience, have occurred in close temporal association to the initiation of modafinil. Although there have been a limited number of reports, multi-organ hypersensitivity reactions may result in hospitalization or be life-threatening.

There are no factors that are known to predict the risk of occurrence or the severity of multi-organ hypersensitivity reactions associated with modafinil. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement.

1. Uncontrolled moderate to severe hypertension. Cardiac arrhythmias.