SAFINAMIDE AMAROX

Posology Treatment with safinamide should be started at 50 mg per day. This daily dose may be increased to 100 mg/day on the basis of individual clinical need. If a dose is missed the next dose should be taken at the usual time the next day.

Elderly No change in dose is required for elderly patients. Experience of use of safinamide in patients over 75 years of age is limited. 3). No dose adjustment is required in patients with mild hepatic impairment. The lower dose of 50 mg/day is recommended for patients with moderate hepatic impairment.

4). Renal impairment No change in dose is required for patients with renal impairment. Paediatric population The safety and efficacy of safinamide in children and adolescents under 18 years of age have not been established. No data are available.

Method of administration For oral use. Safinamide should be taken with water. Safinamide may be taken with or without food.

Summary of the safety profile Dyskinesia was the most common adverse reaction reported in safinamide patients when used in combination with L-dopa alone or in combination with other PD treatments. Serious adverse reactions are known to occur with the concomitant use of SSRIs, SNRIs, tricyclic/tetracyclic antidepressants and MAO inhibitors, such as hypertensive crisis (high blood pressure, collapse), neuroleptic malignant syndrome (confusion, sweating, muscle rigidity, hyperthermia, CPK increase), serotonin syndrome (confusion, hypertension, muscle stiffness, hallucinations), and hypotension.

With MAO-inhibitors there have been reports of drug interactions with concomitant use of sympathomimetic medicinal products. Impulse control disorders; pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments.

Tabulated list of adverse reactions The tabulation below includes all adverse reactions in clinical trials where adverse reactions were considered related. Adverse reactions are ranked under headings of frequency using the following conventions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

System Organ Class Very common Common Uncommon Rare Infections and infestations Urinary tract infection Bronchopneumonia, furuncle, nasopharyngitis, pyoderma, rhinitis, tooth infection, viral infection Neoplasms benign, malignant and unspecified (inclcysts and polyps) Basal cell carcinoma Acrochordon, melanocytic naevus, seborrhoeic keratosis, skin papilloma Blood and lymphatic system disorders Anaemia, leukopenia, red blood cell abnormality Eosinophilia, lymphopenia Metabolism and nutrition disorders Decreased appetite, hypertriglyceridaemia, increased appetite, hypercholesterolaemia, hyperglycaemia, Cachexia, hyperkalaemia Psychiatric disorders Insomnia Hallucination, depression, abnormal dreams, anxiety, confusional state, affect lability, Compulsions, delirium, disorientation, illusion, impulsive behaviour, loss of libido, libido increased, psychotic disorder, restlessness, sleep disorder obsessive thoughts, paranoia, premature ejaculation, sleep attacks, social phobia, suicidal ideation Nervous system disorders Dyskinesia somnolenc e, dizziness, headache, Parkinson' s disease Paraesthesia, balance disorder, hypoaesthesia, dystonia, head discomfort, dysarthria, syncope, cognitive disorder Coordination abnormal, disturbance in attention, dysgeusia, hyporeflexia, radicular pain, Restless Legs Syndrome, sedation Eye disorders Cataract Vision blurred, scotoma, diplopia, photophobia, retinal disorder, conjunctivitis, glaucoma Amblyopia, chromatopsia, diabetic retinopathy, erythropsia, eye haemorrhage, eye pain, eyelid oedema, hypermetropia, keratitis, lacrimation increased, night blindness, papilloedema, presbyopia, strabismus Ear and labyrinth disorders Vertigo Cardiac disorders Palpitations, tachycardia, sinus bradycardia, arrhythmia Myocardial infarction Vascular disorders Orthostatic hypotensio n Hypertension, hypotension, varicose vein Arterial spasm, arteriosclerosis, hypertensive crisis Respiratory, thoracic and mediastinal disorders Cough, dyspnoea, rhinorrhoea Bronchospasm, dysphonia, oropharyngeal pain, oropharyngeal spasm Gastrointestinal disorders Nausea Constipation, dyspepsia, vomiting, dry mouth, diarrhoea, Peptic ulcer, retching, upper gastrointestinal haemorrhage abdominal pain, gastritis, flatulence, abdominal distension, salivary hypersecretion, gastrooesophageal reflux disease, aphthous stomatitis Hepatobiliary disorders Hyperbilirubinaemia Skin and subcutaneous tissue disorders Hyperhidrosis, pruritus generalised, photosensitivity reaction, erythema Alopecia, blister, dermatitis contact, dermatosis, ecchymosis, lichenoid keratosis, night sweats, pain of skin, pigmentation disorder, psoriasis, seborrhoeic dermatitis Musculoskeletal and connective tissue disorders Back pain, arthralgia, muscle spasms, muscle rigidity, pain in extremity, muscular weakness, sensation of heaviness Ankylosing spondylitis, flank pain, joint swelling, musculoskeletal pain, myalgia, neck pain, osteoarthritis, synovial cyst Renal and urinary disorders Nocturia, dysuria Micturition urgency, polyuria, pyuria, urinary hesitation Reproductive system and breast disorders Erectile dysfunction Benign prostatic hyperplasia, breast disorder, breast pain General disorders and administration site conditions Fatigue, asthenia, gait disturbance, oedema peripheral, pain, feeling hot Drug effect decreased, drug intolerance, feeling cold, malaise, pyrexia, xerosis Investigations Weight decreased, weight increased, blood creatine Blood calcium decreased, blood potassium phosphokinase increased, blood triglycerides increased, blood glucose increased, blood urea increased, blood alkaline phosphatase increased, blood bicarbonate increased, blood creatinine increased, electrocardiogram QT prolonged, liver function test abnormal, urine analysis abnormal, blood pressure increased, blood pressure decreased, ophthalmic diagnostic procedures abnormal decreased, blood cholesterol decreased, body temperature increased, cardiac murmur, cardiac stress test abnormal, haematocrit decreased, haemoglobin decreased, international normalised ratio decreased, lymphocyte count decreased, platelet count decreased, very low density lipoprotein increased Injury, poisoning and procedural complications Fall Foot fracture Contusion, fat embolism, head injury, mouth injury, skeletal injury Social circumstances Gambling Description of selected adverse reactions Dyskinesia occurred early in treatment, was rated “severe”, led to discontinuation in very few patients (approx.

General warning In general, safinamide may be used with selective serotonin re-uptake inhibitors (SSRIs) at the lowest effective dose, with caution for serotoninergic symptoms. 5). A washout period corresponding to 5 half-lives of the SSRI used previously should be considered prior to initiating treatment with safinamide.

5). When safinamide is co-administered with products that are BCRP substrates, please refer to the SmPC for that particular medicinal product. Hepatic impairment Caution should be exercised when initiating treatment with safinamide in patients with moderate hepatic impairment.

2). 3. Impulse control disorders (ICDs) Impulse control disorders can occur in patients treated with dopamine agonists and/or dopaminergic treatments. Some reports of ICDs have also been observed with other MAO-inhibitors. Safinamide treatment has not been associated with any increase in the appearance of ICDs.

Patients and carers should be made aware of the behavioural symptoms of ICDs that were observed in patients treated with MAO-inhibitors, including cases of compulsions, obsessive thoughts, pathological gambling, increased libido, hypersexuality, impulsive behaviour and compulsive spending or buying.

Dopaminergic side effects Safinamide used as an adjunct to levodopa may potentiate the side effects of levodopa, and pre-existing dyskinesia may be exacerbated, requiring a decrease of levodopa. This effect was not seen when safinamide was used as an adjunct to dopamine agonists in early-stage PD patients.

1). 5). 5). 2). 3).