Adverse reactions : תופעות לוואי

4.8   Undesirable effects

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          Very   Common            Uncommon                       Rare Class                 common
Infections and                                 Urinary tract infection        Bronchopneumonia, infestations                                                                  furuncle, nasopharyngitis,
pyoderma,
rhinitis,
tooth infection,
viral infection
Neoplasms                                      Basal cell carcinoma           Acrochordon, benign, malignant                                                             melanocytic naevus, and unspecified                                                               seborrhoeic keratosis, (incl cysts and                                                               skin papilloma polyps)
Blood and                                      Anaemia,                       Eosinophilia, lymphatic system                               leukopenia,                    lymphopenia disorders                                      red blood cell abnormality
Metabolism and                                 Decreased appetite,            Cachexia, nutrition disorders                            hypertriglyceridaemia,         hyperkalaemia increased appetite,
hypercholesterolaemia,
hyperglycaemia,
Psychiatric                     Insomnia       Hallucination,                 Compulsions, XADAGO-SPC-0820-V1                                 Page 5 of 14
System Organ         Very   Common         Uncommon                   Rare Class                common disorders                                  depression,                delirium, abnormal dreams,           disorientation,
anxiety,                   illusion,
confusional state,         impulsive behaviour,
affect lability,           loss of libido,
libido increased,          obsessive thoughts,
psychotic disorder,        paranoia,
restlessness,              premature ejaculation,
sleep disorder             sleep attacks,
social phobia,
suicidal ideation
Nervous system               Dyskinesia    Paraesthesia,              Coordination abnormal, disorders                    somnolence,   balance disorder,          disturbance in attention, dizziness,    hypoaesthesia,             dysgeusia,
headache,     dystonia,                  hyporeflexia,
Parkinson's   head discomfort,           radicular pain,
disease       dysarthria,                Restless Legs Syndrome,
syncope,                   sedation cognitive disorder
Eye disorders                Cataract      Vision blurred,            Amblyopia, scotoma,                   chromatopsia,
diplopia,                  diabetic retinopathy,
photophobia,               erythropsia,
retinal disorder,          eye haemorrhage,
conjunctivitis,            eye pain,
glaucoma                   eyelid oedema,
hypermetropia,
keratitis,
lacrimation increased,
night blindness,
papilloedema,
presbyopia,
strabismus
Ear and labyrinth                          Vertigo disorders
Cardiac disorders                        Palpitations,                Myocardial infarction tachycardia,
sinus bradycardia,
arrhythmia
Vascular disorders           Orthostatic Hypertension,                Arterial spasm, hypotension hypotension,                 arteriosclerosis,
varicose vein                hypertensive crisis
Respiratory,                             Cough,                       Bronchospasm, thoracic and                             dyspnoea,                    dysphonia, mediastinal                              rhinorrhoea                  oropharyngeal pain, disorders                                                             oropharyngeal spasm Gastrointestinal             Nausea        Constipation,              Peptic ulcer, disorders                                  dyspepsia,                 retching, vomiting,                  upper gastrointestinal dry mouth,                 haemorrhage
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System Organ        Very   Common        Uncommon                     Rare Class               common diarrhoea,
abdominal pain,
gastritis,
flatulence,
abdominal distension,
salivary hypersecretion,
gastrooesophageal reflux disease,
aphthous stomatitis
Hepatobiliary                                                         Hyperbilirubinaemia disorders
Skin and                                 Hyperhidrosis,               Alopecia, subcutaneous                             pruritus generalised,        blister, tissue disorders                         photosensitivity reaction,   dermatitis contact, erythema                     dermatosis,
ecchymosis,
lichenoid keratosis,
night sweats,
pain of skin,
pigmentation disorder,
psoriasis,
seborrhoeic dermatitis
Musculoskeletal                          Back pain,                   Ankylosing spondylitis, and connective                           arthralgia,                  flank pain, tissue disorders                         muscle spasms,               joint swelling, muscle rigidity,             musculoskeletal pain,
pain in extremity,           myalgia,
muscular weakness,           neck pain,
sensation of heaviness       osteoarthritis,
synovial cyst
Renal and urinary                        Nocturia,                    Micturition urgency, disorders                                dysuria                      polyuria, pyuria, urinary hesitation
Reproductive                             Erectile dysfunction         Benign prostatic system and breast                                                     hyperplasia, disorders                                                             breast disorder, breast pain
General disorders                        Fatigue,                     Drug effect decreased, and                                      asthenia,                    drug intolerance, administration                           gait disturbance,            feeling cold, site conditions                          oedema peripheral,           malaise, pain,                        pyrexia,
feeling hot                  xerosis
Investigations                           Weight decreased,            Blood calcium decreased, weight increased,            blood potassium blood creatine               decreased,
phosphokinase                blood cholesterol increased,                   decreased,
blood triglycerides          body temperature increased,                   increased,
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System Organ         Very   Common             Uncommon                    Rare Class                common blood glucose increased,    cardiac murmur,
blood urea increased,       cardiac stress test blood alkaline              abnormal,
phosphatase increased,      haematocrit decreased,
blood bicarbonate           haemoglobin decreased,
increased,                  international normalised blood creatinine            ratio decreased,
increased,                  lymphocyte count electrocardiogram QT        decreased,
prolonged,                  platelet count decreased,
liver function test         very low density abnormal,                   lipoprotein increased urine analysis abnormal,
blood pressure increased,
blood pressure decreased,
ophthalmic diagnostic procedures abnormal
Injury, poisoning               Fall           Foot fracture               Contusion, and procedural                                                             fat embolism, complications                                                              head injury, mouth injury,
skeletal injury
Social                                                                     Gambling circumstances

Description of selected adverse reactions
Dyskinesia occurred early in treatment, was rated “severe”, led to discontinuation in very few patients (approx. 1.5%), and did not require reduction of dose in any patient.

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