Hospital Pharmacy - September 2017 - 541
541
Baker and Kim
Hg with safinamide plus tyramine).14 Exercise-induced systolic blood pressure changes (range, 20-52 mm Hg) were
greater than the increases in systolic blood pressure observed
after concomitant exposure to safinamide and tyramine.14 A
randomized, double-blind, positive-controlled (phenelzine),
comparator-controlled (selegiline), and double-dummy placebo-controlled study confirmed that oral exposure to tyramine while taking safinamide (100 mg or a supratherapeutic
dose of 350 mg) did not produce a clinically significant
increase in blood pressure.26 However, the safinamide prescribing information recommends caution because the selectivity of safinamide is dose related above the highest
recommended daily dosage; patients should be advised to
avoid foods containing large amounts of tyramine (eg, aged,
fermented, cured, smoked, and pickled foods containing
large amounts of exogenous amines), even if they are receiving the recommended doses of safinamide.2
Serious, sometimes fatal reactions have been precipitated
with concomitant use of safinamide with opioid drugs (eg,
meperidine and its derivatives, methadone, propoxyphene,
tramadol) and MAOIs, including selective MAO-B inhibitors. Concomitant use of safinamide with these drugs is contraindicated. At least 14 days should elapse between
discontinuation of safinamide and initiation of treatment
with these drugs.2
The use of some serotonergic drugs (ie, SNRIs; triazolopyridine, tricyclic, or tetracyclic antidepressants; cyclobenzaprine; St. John's wort) with safinamide is
contraindicated. At least 14 days should elapse between discontinuation of safinamide and initiation of treatment with
these drugs.2 Patients requiring treatment with SSRIs may be
at risk of developing serotonin syndrome and should be
closely monitored.2
The combination of MAOIs and dextromethorphan has
been reported to cause episodes of psychosis or bizarre
behavior. Due to safinamide's MAO inhibitory activity, concomitant use with dextromethorphan is contraindicated.2
Sympathomimetic medications used in combination with
nonselective or selective MAOIs may cause severe hypertensive reactions, including hypertensive crisis. Concomitant use
of safinamide with methylphenidate, amphetamine, and their
derivatives is contraindicated. Caution is recommended if
safinamide is prescribed concomitantly with prescription or
nonprescription sympathomimetic medications, including
nasal, oral, or ophthalmic decongestants and cold remedies.2
Safinamide and its major metabolite may inhibit intestinal
breast cancer resistance protein (BCRP). Inhibition of BCRP
could increase plasma concentrations of BCRP substrates
(eg, methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan). Monitor
patients for increased pharmacologic or adverse effects of
BCRP substrates if safinamide is used concomitantly.2
Dopamine antagonists (eg, antipsychotics, metoclopramide) may decrease the effectiveness of safinamide and
exacerbate the symptoms of Parkinson disease.2
The metabolism of safinamide is minimally affected by
strong CYP-450 inhibitors.15 In a randomized, open-label,
single-center, crossover study, 7 male and 7 female subjects
were exposed to a single dose of safinamide 100 mg alone
and a single dose of safinamide 100 mg on day 3 of a 6-day
regimen of ketoconazole 200 mg twice daily. Treatments
were separated by a washout period of at least 21 days.
Plasma levels (Cmax and AUC) of safinamide and its metabolites were not significantly different after taking safinamide
alone compared with taking safinamide with ketoconazole, a
strong CYP-450 inhibitor.15
Recommended Monitoring
Monitor for signs of worsening Parkinson disease symptoms
and/or signs of dyskinesia; blood pressure; signs and symptoms of serotonin syndrome; and visual changes.2,6
Dosing
The recommended starting dosage is safinamide 50 mg
orally once daily at the same time of day and without regard
to meals. After 2 weeks, the dosage may be increased to 100
mg once daily based on individual need and tolerability.2 In
patients with moderate hepatic impairment (Child-Pugh
class B), the maximum recommended dose is 50 mg once
daily. Use in patients with severe hepatic impairment (ChildPugh class C) is contraindicated.2
Daily doses of safinamide above 100 mg have not been
shown to provide additional benefit, and higher doses
increase the risk for adverse reactions. Safinamide has been
shown to be effective only in combination with carbidopa/
levodopa.2
If safinamide therapy needs to be discontinued and the
safinamide dosage is 100 mg/d, the dosage should be
decreased to 50 mg/d for 1 week before discontinuation.2
Table 3 provides a comparison of dosing recommendations for the MAO-B inhibitors approved for the treatment of
Parkinson disease.2-4
Product Availability
A New Drug Application was submitted to the FDA on May
29, 2014. The Prescription Drug User Fee Act date was originally set for May 2015.27 Safinamide was approved by the
FDA on March 21, 2017.1
Safinamide is available as 50-mg and 100-mg round,
film-coated, biconcave shaped tablets in bottles of 30 and 90.
It should be stored at 25°C (77°F), with excursions permitted
between 15°C and 30°C (59°F and 86°F).2
Drug Safety/Risk Evaluation and
Mitigation Strategy (REMS)
No REMS is required for safinamide.1
Table of Contents for the Digital Edition of Hospital Pharmacy - September 2017
Pharmacy Transitions of Care and Culture
Bivalirudin Medication Use Evaluation and Cost Savings Initiative
Navigating the New Antimicrobial Stewardship Regulations
Safinamide
Biosimilar Substitution Laws
Evaluation of Corticosteroid Dose in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Hazardous Drug Contamination of Drug Preparation Devices and Staff: A Contamination Study Simulating the Use of Chemotherapy Drugs in a Clinical Setting
A Case of Metronidazole Injection Infiltration Without Sequelae
Doubling Pharmacist Coverage in the Intensive Care Unit: Impact on the Pharmacists’ Clinical Activities and Team Members’ Satisfaction
Extended Stability of Epinephrine Hydrochloride Injection in Polyvinyl Chloride Bags Stored in Amber Ultraviolet Light–Blocking Bags
Formation of a Citywide Pharmacy Residents’ Collaborative Committee
Hospital Pharmacy - September 2017 - 513
Hospital Pharmacy - September 2017 - 514
Hospital Pharmacy - September 2017 - 515
Hospital Pharmacy - September 2017 - 516
Hospital Pharmacy - September 2017 - 517
Hospital Pharmacy - September 2017 - 518
Hospital Pharmacy - September 2017 - 519
Hospital Pharmacy - September 2017 - Pharmacy Transitions of Care and Culture
Hospital Pharmacy - September 2017 - 521
Hospital Pharmacy - September 2017 - Bivalirudin Medication Use Evaluation and Cost Savings Initiative
Hospital Pharmacy - September 2017 - 523
Hospital Pharmacy - September 2017 - 524
Hospital Pharmacy - September 2017 - 525
Hospital Pharmacy - September 2017 - 526
Hospital Pharmacy - September 2017 - Navigating the New Antimicrobial Stewardship Regulations
Hospital Pharmacy - September 2017 - 528
Hospital Pharmacy - September 2017 - 529
Hospital Pharmacy - September 2017 - 530
Hospital Pharmacy - September 2017 - 531
Hospital Pharmacy - September 2017 - Safinamide
Hospital Pharmacy - September 2017 - 533
Hospital Pharmacy - September 2017 - 534
Hospital Pharmacy - September 2017 - 535
Hospital Pharmacy - September 2017 - 536
Hospital Pharmacy - September 2017 - 537
Hospital Pharmacy - September 2017 - 538
Hospital Pharmacy - September 2017 - 539
Hospital Pharmacy - September 2017 - 540
Hospital Pharmacy - September 2017 - 541
Hospital Pharmacy - September 2017 - 542
Hospital Pharmacy - September 2017 - 543
Hospital Pharmacy - September 2017 - Biosimilar Substitution Laws
Hospital Pharmacy - September 2017 - 545
Hospital Pharmacy - September 2017 - Evaluation of Corticosteroid Dose in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Hospital Pharmacy - September 2017 - 547
Hospital Pharmacy - September 2017 - 548
Hospital Pharmacy - September 2017 - 549
Hospital Pharmacy - September 2017 - 550
Hospital Pharmacy - September 2017 - Hazardous Drug Contamination of Drug Preparation Devices and Staff: A Contamination Study Simulating the Use of Chemotherapy Drugs in a Clinical Setting
Hospital Pharmacy - September 2017 - 552
Hospital Pharmacy - September 2017 - 553
Hospital Pharmacy - September 2017 - 554
Hospital Pharmacy - September 2017 - 555
Hospital Pharmacy - September 2017 - 556
Hospital Pharmacy - September 2017 - 557
Hospital Pharmacy - September 2017 - 558
Hospital Pharmacy - September 2017 - A Case of Metronidazole Injection Infiltration Without Sequelae
Hospital Pharmacy - September 2017 - 560
Hospital Pharmacy - September 2017 - 561
Hospital Pharmacy - September 2017 - 562
Hospital Pharmacy - September 2017 - 563
Hospital Pharmacy - September 2017 - Doubling Pharmacist Coverage in the Intensive Care Unit: Impact on the Pharmacists’ Clinical Activities and Team Members’ Satisfaction
Hospital Pharmacy - September 2017 - 565
Hospital Pharmacy - September 2017 - 566
Hospital Pharmacy - September 2017 - 567
Hospital Pharmacy - September 2017 - 568
Hospital Pharmacy - September 2017 - 569
Hospital Pharmacy - September 2017 - Extended Stability of Epinephrine Hydrochloride Injection in Polyvinyl Chloride Bags Stored in Amber Ultraviolet Light–Blocking Bags
Hospital Pharmacy - September 2017 - 571
Hospital Pharmacy - September 2017 - 572
Hospital Pharmacy - September 2017 - 573
Hospital Pharmacy - September 2017 - Formation of a Citywide Pharmacy Residents’ Collaborative Committee
Hospital Pharmacy - September 2017 - 575
Hospital Pharmacy - September 2017 - 576
Hospital Pharmacy - September 2017 - 577
Hospital Pharmacy - September 2017 - 578
Hospital Pharmacy - September 2017 - 579
Hospital Pharmacy - September 2017 - 580
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2020
https://www.nxtbook.com/nxtbooks/sage/psychologicalscience_demo
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2020
https://www.nxtbook.com/nxtbooks/sage/fai_202009
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_august2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2019
https://www.nxtbook.com/nxtbooks/sage/fai_201909
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_july2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2019
https://www.nxtbook.com/nxtbooks/sage/canadianpharmacistsjournal_05062019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2019
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201903
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2018
https://www.nxtbook.com/nxtbooks/sage/tec_20180810
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2018
https://www.nxtbook.com/nxtbooks/sage/fai_201807
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2018
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201803
https://www.nxtbook.com/nxtbooks/sage/slas_discovery_201712
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_november2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_september2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2017
https://www.nxtbook.com/nxtbooks/sage/fai_supplement_201709
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_may2017
https://www.nxtbook.com/nxtbooks/sage/fai_201706
https://www.nxtbook.com/nxtbooks/sage/fai_201607
https://www.nxtbookmedia.com