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ONSTRYV is a brand name for Safinamide, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: ONSTRYV (Safinamide tablets) is indicated as an add-on therapy to a regimen that includes levodopa for the treatment of the signs and symptoms of idiopathic Parkinson’s disease (PD) in patients experiencing “off” episodes while on a stable dose of levodopa (see Clinical Trials). ONSTRYV has not been shown to be…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations The efficacy and safety of ONSTRYV (safinamide tablets) for treatment of patients with PD who are experiencing “off” episodes have only been demonstrated when used adjunctively with a stable dose of levodopa alone or levodopa in combination with other antiparkinson medications (see Clinical Trials).
Hepatic impairment For patients with moderate hepatic impairment (Child-Pugh B, 7-9), the maximum recommended dose is 50 mg administered orally once daily (see Action and Clinical Pharmacology, Special Populations and Conditions). If a patient progresses from moderate to severe hepatic impairment, treatment with ONSTRYV should be discontinued (see Warnings Serious Warnings and Precautions Sudden Onset of Sleep Patients receiving treatment with ONSTRYV and other dopaminergic agents have reported suddenly falling asleep while engaged in activities of daily living, including driving a car, which has sometimes resulted in accidents.
Although some of the patients reported somnolence while on ONSTRYV, others perceived that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Physicians should alert patients of the reported cases of sudden onset of sleep, bearing in mind that these events are not limited to initiation of therapy.
Patients should also be advised that sudden onset of sleep has occurred without warning signs and should be specifically asked about factors that may increase the risk with ONSTRYV, such as concomitant medications or the presence of sleep disorders.
Given the reported cases of somnolence and sudden onset of sleep (not necessarily preceded by somnolence), physicians should caution patients about the risk of operating hazardous machinery, including driving motor vehicles, while taking ONSTRYV.
If drowsiness or sudden onset of sleep should occur, patients should be informed to refrain from driving or operating machines and to immediately contact their physician. Episodes of falling asleep while engaged in activities of daily living have also been reported in patients taking other dopaminergic agents, therefore, symptoms may not be alleviated by substituting these products.
While dose reduction clearly reduces the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. Currently, the precise cause of this event is unknown.
1 Adverse Reaction Overview The safety of ONSTRYV (safinamide tablets) was evaluated in placebo controlled clinical trials that included 1218 patients with mid- to late stage idiopathic Parkinson’s disease who received at least one dose of ONSTRYV 50 mg/day, ONSTRYV 100 mg/day or placebo, administered as adjunctive therapy to a stable dose of levodopa, with or without other antiparkinson medications.
Serious adverse reactions can occur with the concomitant use of SSRIs, SNRIs, tricyclic/tetracyclic antidepressants and MAO inhibitors, including hypertensive crisis (high blood pressure, collapse), neuroleptic malignant syndrome (confusion, sweating, muscle rigidity, hyperthermia, CPK increase), serotonin toxicity (spontaneous, inducible or ocular clonus, diaphoresis, agitation, restlessness, tachycardia) and hypotension.
Hypertensive crisis has been reported when MAO inhibitors were used concomitantly with sympathomimetic medications (see Contraindications, Warnings and Precautions, and Drug Interactions). Patients treated with dopaminergic agents, including ONSTRYV, have reported suddenly falling asleep while engaged in activities of daily living.
Sudden daytime sleepiness or episodes of falling asleep during activities that require full attention, such as driving a motor vehicle, could put patients and others at risk of serious injury or death (see Serious Warnings and Precautions).
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, including ONSTRYV (see Warnings and Precautions, Psychiatric).
Dyskinesia was the most common treatment emergent adverse event reported in patients using safinamide in combination with levodopa alone or levodopa in combination with other antiparkinson medications. Dyskinesia adverse events were non-serious in most patients and led to discontinuation of few patients (see Warnings and Precautions, Neurologic; Adverse Reactions, Clinical Trial Adverse Reactions).
Cardiovascular Hypertension Hypertension or exacerbation of existing hypertension may occur during treatment with ONSTRYV (Safinamide tablets). Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting ONSTRYV.
Medication adjustment may be necessary if elevation of blood pressure is sustained. In clinical trials, the incidence of hypertension/increased blood pressure was 6% for ONSTRYV 50 mg/day, 3% for ONSTRYV 100 mg/day, and 3% for placebo.
Monitor for hypertension if ONSTRYV is prescribed concomitantly with sympathomimetic medications, including prescription or non-prescription nasal, oral, and ophthalmic decongestants and cold medications (see Drug Interactions). At the recommended doses of 50 mg/day or 100 mg/day safinamide is a selective inhibitor of MAO-B.
Selectivity for MAO-B inhibition decreases in a dose-related manner as the dose increases above the maximum recommended daily dose (see Action and Clinical Pharmacology). Therefore, the daily dose of ONSTRYV should not exceed the recommended doses because of the risks of hypertension, exacerbation of existing hypertension, or hypertensive crisis.
Dietary tyramine restriction is not ordinarily required with ingestion of most foods and beverages that may contain tyramine, during treatment with recommended doses of ONSTRYV. , > 150 mg) of Product Monograph ONSTRYV® tablets Page 8 of 38 tyramine could potentially cause a hypertensive reaction in patients taking ONSTRYV, even at the recommended doses, due to increased sensitivity to tyramine.
Patients should be advised to avoid such foods while taking recommended doses of ONSTRYV. Isoniazid has some monoamine oxidase inhibiting activity. Monitor for hypertension and reaction to dietary tyramine in patients treated concomitantly with isoniazid and ONSTRYV.
QTc Interval Shortening ONSTRYV causes a shortening of the QTc interval (see Action and Clinical Pharmacology, Cardiac Electrophysiology). Caution is recommended for patients with congenital Short QT Syndrome. Hepatic/Biliary/Pancreatic Moderate hepatic impairment increases exposure to safinamide.
ONSTRYV (Safinamide tablets) is contraindicated in patients with hypersensitivity to this drug or to any ingredient in the formulation, including any non- medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.
concomitant use of other drugs in the monoamine oxidase (MAO) inhibitor class, or other drugs that are potent inhibitors of monoamine oxidase (including the antibiotic linezolid and the dye methylene blue) due to the risk of non-selective MAO inhibition, which may lead to hypertensive crisis (see Warnings and Precautions, Cardiovascular; Drug Interactions).
At least 14 days should elapse between discontinuation of ONSTRYV and initiation of treatment with other MAO inhibitors. , meperidine and its derivatives, methadone, propoxyphene, tramadol, tapentadol); serotonin-norepinephrine reuptake inhibitors (SNRIs); tricyclic, tetracyclic or triazolopyridine antidepressants; cyclobenzaprine; or St John’s wort due to the risk of life-threatening serotonin toxicity; (see Warnings and Precautions; Drug Interactions).
At least 14 days should elapse between discontinuation of ONSTRYV and initiation of treatment with these drugs. concomitant use of the antitussive dextromethorphan. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or abnormal behaviour.
severe hepatic impairment (Child-Pugh C, 10-15) (see Warnings and Precautions; Action and Clinical Pharmacology). albinism, retinal degeneration, uveitis, inherited retinopathy or any active retinopathy such as severe progressive diabetic retinopathy (see Warnings and Precautions, Ophthalmologic; Non-Clinical Toxicology).
Product Monograph ONSTRYV® tablets Page 5 of 38
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It is known that many Parkinson’s disease patients experience alterations in sleep architecture, which results in excessive daytime sleepiness or spontaneous dozing, and that dopaminergic agents can also induce sleepiness. Product Monograph ONSTRYV® tablets Page 6 of 38 and Precautions).
Use in patients with severe hepatic impairment is contraindicated (see Contraindications). No dose adjustment is required for patients with mild hepatic impairment. 2 Recommended Dose and Dosage Adjustment Treatment with safinamide should be started with a dose of 50 mg once per day, administered orally.
After two weeks the dose may be increased to 100 mg once per day based on individual clinical need and tolerability. When discontinuing treatment, ONSTRYV 100 mg/day should be tapered by decreasing the dose to 50 mg/day for one week prior to stopping (see Warnings and Precautions, Neurologic).
Doses of ONSTRYV above 100 mg/day have not been shown to provide additional benefit and may increase the risk of adverse events (see Warnings and Precautions, Cardiovascular). 3 Administration ONSTRYV is administered orally and should be taken with water at the same time each day.
ONSTRYV may be taken with or without food, without regard to meals. 4 Missed Dose If a dose is missed, the next dose should be taken the next day, at the same time that it is normally taken.
2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. In two 24-week, randomized, double-blind placebo-controlled clinical trials, patients with mid-to late stage Parkinson’s disease (LSPD) who experienced “off” episodes received at least one dose of ONSTRYV 50 mg/day or 100 mg/day (N=721) or placebo (N=497) as an adjunct to a stable dose of levodopa alone or levodopa in combination with other antiparkinson medications.
Patients in Study 1 were randomized to placebo (N=222), ONSTRYV 50 mg/day (N=223) or ONSTRYV 100 mg/day (N=224) and patients in Study 2 were randomized to placebo (N=275) or ONSTRYV 50 mg/day to 100 mg/day (N=274) (see Clinical Trials).
The most commonly observed treatment emergent adverse events (incidence > 5%) that were reported more frequently with ONSTRYV 50 mg/day or ONSTRYV 100 mg/day than with placebo were dyskinesia, headache, nausea, urinary tract infection, cataract, fall, and hypertension/increased blood pressure.
Several of the reported adverse events did not suggest a relationship to safinamide dose. 5% of patients that received placebo experienced serious adverse events during the clinical trials. Serious adverse events that were reported in 2 or more patients treated with safinamide and more frequently than in the placebo group were Parkinson’s disease worsening, femur fracture, breast cancer, dyspnea, visual hallucination and death.
Approximately 5% and 6% of patients treated with ONSTRYV 50 mg/day and ONSTRYV 100 mg/day, respectively, compared to 4% of patients in the placebo group discontinued treatment due to adverse events. 4% placebo). Table 2 lists treatment emergent adverse events that were reported in at least 2% of patients treated with ONSTRYV 50 mg/day or 100 mg/day and more frequently than in patients that received placebo.
4) 0 (0) Infections and infestations Urinary tract infection 68 (14) 18 (4) 20 (9) 6 (3) 81 (16) 24 (5) General disorders and administration site conditions Pyrexia Chest pain 69 (14) 13 (3) 4 (1) 34 (15) 8 (4) 7 (3) 62 (12) 7 […]
Caution should be exercised when initiating treatment with ONSTRYV in patients with moderate hepatic impairment and the maximum recommended dose for these patients is 50 mg administered once daily (see Dosage and Administration; Action and Clinical Pharmacology, Special Populations and Conditions).
ONSTRYV is contraindicated in patients with severe hepatic impairment (see Contraindications). In case a patient progresses from moderate to severe hepatic impairment, treatment with ONSTRYV should be discontinued (see Dosage and Administration, Recommended Dose and Dosage Adjustment, Contraindications, Action and Clinical Pharmacology, Special Populations and Conditions).
Neurologic Serotonin Toxicity/Serotonin Syndrome Serotonin toxicity, also known as serotonin syndrome, is a potentially life-threatening condition and has been reported with MAO inhibitors (including selective MAO-B inhibitors), including ONSTRYV, particularly during combined use with other serotonergic drugs (see Drug Interactions).
g. g. anxiety, agitation, hypomania). In accordance with the Hunter Criteria, serotonin toxicity diagnosis is likely when, in the presence of at least one serotonergic agent, one of the following is observed: Spontaneous clonus Inducible clonus or ocular clonus with agitation or diaphoresis Tremor and hyperreflexia Hypertonia and body temperature >38°C and ocular clonus or inducible clonus.
, meperidine and meperidine derivatives, propoxyphene, tramadol, tapentadol) is contraindicated due to the risk of serotonin toxicity (see Contraindications, Drug Interactions). At least 14 days should elapse between discontinuation of ONSTRYV and initiation of treatment with these drugs.
In clinical trials, serotonin toxicity was reported in a patient treated with ONSTRYV and a selective serotonin reuptake inhibitor (SSRI). If concomitant treatment with ONSTRYV and an SSRI is clinically warranted, the lowest effective dose of the SSRI should be used and careful observation of the patient is advised, particularly during treatment initiation and dose increases Product Monograph ONSTRYV® tablets Page 9 of 38 (see Drug Interactions).
The concomitant use of ONSTRYV with fluoxetine or fluvoxamine should be avoided. A washout period corresponding to 5 half-lives of the SSRI should be considered prior to initiating treatment with ONSTRYV. If serotonin toxicity is suspected, discontinuation of the serotonergic agents should be considered.
Neuroleptic Malignant Syndrome A symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious aetiology, has been reported in association with rapid dose reduction, abrupt withdrawal of, or changes in dopaminergic therapy.
Tapering treatment is recommended during treatment discontinuation (see Dosage and Administration, Recommended Dose and Dosage Adjustment). Dyskinesia Safinamide may cause dyskinesia and when used as an adjunct to levodopa may potentiate dopaminergic side effects and exacerbate pre-existing dyskinesia.
In clinical trials, when used as adjunct to levodopa, treatment emergent adverse events of dyskinesia were reported in 21% of patients treated with ONSTRYV 50 mg/day, 18% of patients treated with ONSTRYV 100 mg/day and 9% of patients that received placebo (see Adverse Reactions).
Decreasing the […]