Chemical formula: C₁₇H₁₉FN₂O₂ Molecular mass: 302.349 g/mol PubChem compound: 131682
Safinamide interacts in the following cases:
Safinamide inhibits OCT1 in vitro at clinically relevant portal vein concentrations. Therefore, caution is necessary when safinamide is taken concomitantly with medicinal products that are OCT1 substrates and have a tmax similar to safinamide (2 hours) (e.g. metformin, aciclovir, ganciclovir) as exposure to these substrates might be increased as a consequence.
Safinamide may transiently inhibit BCRP in vitro. In drug-drug-interaction studies in human, a weak interaction was observed with rosuvastatin (AUC increase between 1.25 and 2.00 fold) but no significant interaction was found with diclofenac.
It is recommended to monitor patients when safinamide is taken with medicinal products that are BCRP substrates (e.g., rosuvastatin, pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan, diclofenac or glyburide) and to refer to their SmPCs to determine if a dose adjustment is needed.
The concomitant use of safinamide and fluoxetine or fluvoxamine should be avoided, this precaution is based on the occurrence of serious adverse reactions (e.g. serotonin syndrome), although rare, that have occurred when SSRIs and dextromethorphan have been used with MAO inhibitors. If necessary, the concomitant use of these medicinal products should be at the lowest effective dose. A washout period corresponding to 5 half-lives of the SSRI used previously should be considered prior to initiating treatment with safinamide.
Serious adverse reactions have been reported with the concomitant use of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic/tetracyclic antidepressants and MAO inhibitors. In view of the selective and reversible MAO-B inhibitory activity of safinamide, antidepressants may be administered but used at the lowest doses necessary.
The lower dose of 50 mg/day is recommended for patients with moderate hepatic impairment. If patients progress from moderate to severe hepatic impairment safinamide should be stopped.
Animal studies indicate that safinamide treatment is associated with adverse reactions on female rat reproductive performance and sperm quality. Male rat fertility is not affected.
There have been reports of medicinal product interactions with the concomitant use of dextromethorphan and non-selective MAO inhibitors. In view of the MAO inhibitory activity of safinamide, the concomitant administration of safinamide and dextromethorphan is not recommended, or if concomitant treatment is necessary, it should be used with caution.
There are no or limited amount of data from the use of safinamide in pregnant women. Studies in animals have shown reproductive toxicity. Safinamide is not recommended during pregnancy and in women of childbearing potential not using contraception.
Available pharmacodynamic/toxicological data in animals have shown excretion of safinamide in milk. A risk for the breast-fed child cannot be excluded. Safinamide should not be used during breast-feeding.
Safinamide should not be given to women of childbearing potential unless adequate contraception is practiced.
Animal studies indicate that safinamide treatment is associated with adverse reactions on female rat reproductive performance and sperm quality. Male rat fertility is not affected.
Somnolence and dizziness may occur during safinamide treatment, therefore patients should be cautioned about using hazardous machines, including motor vehicles, until they are reasonably certain that safinamide does not affect them adversely.
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.
The list 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 (incl cysts 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, libido increased, psychotic disorder, restlessness, sleep disorder | Compulsions, delirium, disorientation, illusion, impulsive behaviour, loss of libido, obsessive thoughts, paranoia, premature ejaculation, sleep attacks, social phobia, suicidal ideation | |
| Nervous system disorders | Dyskinesia somnolence, 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 hypotension | 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, abdominal pain, gastritis, flatulence, abdominal distension, salivary hypersecretion, gastrooesophageal reflux disease, aphthous stomatitis | Peptic ulcer, retching, upper gastrointestinal haemorrhage | |
| 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 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 | Blood calcium decreased, blood potassium 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 |
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.
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