Hospital Pharmacy - September 2017 - 533
533
Baker and Kim
Table 1. Comparison of the Selective, Reversible MAO-B Inhibitors Approved for the Treatment of Parkinson Disease.2-4
Rasagiline
Safinamide
Trade name (manufacturer)
Generic available
FDA approval year
Dosage forms available
Azilect (Teva Pharmaceuticals)
Yes
2006
Tablets
Xadago (US WorldMeds)
No
2017
Tablets
Indication
Treatment of Parkinson
disease as monotherapy or
as adjunct therapy with or
without levodopa
MAO-B inhibitor
Treatment of Parkinson disease
in patients experiencing "off"
episodes, as adjunctive therapy
to carbidopa/levodopa
MAO-B inhibitor; sodium/calcium/
glutamate inhibitor
Mechanism of action
Selegiline
Eldepryl, Zelapar (Various)
Yes
1996
Capsules, tablets, orally
disintegrating tablets
Treatment of Parkinson
disease as adjunct therapy
to carbidopa/levodopa
MAO-B inhibitor
Note. MAO-B = monoamine oxidase type B; FDA = Food and Drug Administration.
they were originally distributed as the parent safinamide
compound.18
Taking safinamide with food slows absorption (Tmax 3.254.83 hours). However, food did not affect area under the
curve (AUC) or maximum plasma concentration.2,13,17 The
absolute bioavailability of safinamide is 95%, and first-pass
metabolism is negligible.17
Safinamide is distributed well into tissues. The volume
of distribution is 165 L.2,15,18 Plasma protein binding is 88%
to 89%.2
Safinamide does not inhibit cytochrome P450 (CYP-450)
2C9, 2C19, 2D6, 2E1, and 3A4 isoforms. It does inhibit
CYP1A1/2 to a negligible extent.13
Safinamide undergoes extensive hepatic metabolism,
with only approximately 5% of the drug eliminated
unchanged, mainly in the urine.2,15 Major enzymes involved
in the metabolism of safinamide are MAO-B, amidase, aldehyde dehydrogenase, and uridine diphosphate-glucuronosyltransferase, with minor contributions from CYP3A4 and
2C19.2,15
Metabolism of safinamide results in the major forms
N-dealkylated acid and deaminated acid, and in the
minor forms N-dealkylated glycine conjugate and
2-[4-hydroxylbenzylamino]-propanamide. None of these
metabolites have been shown to be therapeutically active
compounds.2,17,18 While the half-life of safinamide is 20 to
26 hours, the half-life of circulating safinamide metabolites
is longer (about 80 hours).2,18
Clearance is 4.6 to 5.8 L/h after oral exposure and 4.8
L/h after IV exposure.2,15,17,18 Clearance of safinamide
and its metabolites occurs mainly via the kidneys (76%
to 84%).2,15,18
Steady-state levels for safinamide are reached in 5 to 6
days, with a corresponding half-life of 20 to 26 hours.2,13,15,18
The half-life of safinamide is not affected by the route of
administration; exposure to oral safinamide (taken with or
without food) and IV safinamide both resulted in a half-life
of 26 hours.17
Comparative Efficacy
Indication: Add-On Therapy for Management of
Parkinson Disease
Guidelines
Guideline: The scientific and clinical basis for the treatment of Parkinson disease
Reference: Olanow CW, et al, 200919
Comments: The guideline recommends starting a neuroprotective agent at the time of diagnosis. Drugs that have
demonstrated neuroprotective effects include selegiline,
rasagiline, coenzyme Q10, pramipexole, and ropinirole;
however, no agents have conclusively demonstrated neuroprotective or disease-modifying effects in Parkinson
disease to date. The guideline also recommends starting
an agent for symptomatic therapy at the time of diagnosis
or soon thereafter. Levodopa is the agent most commonly
used for symptom management of Parkinson disease and
others include dopamine agonists (eg, pramipexole, ropinirole), catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone), MAO-B inhibitors (eg, selegiline,
rasagiline), amantadine, and anticholinergics. Safinamide
is mentioned in the guidelines as a promising agent for
symptomatic therapy because it is the only MAO-B inhibitor studied as an add-on to levodopa and/or dopamine
agonists.
Studies
Drug: Safinamide vs Placebo
Reference: Stocchi F, et al, 200420
Study Design: Randomized, double-blind, placebo-controlled, multicenter, dose-ranging study
Study Funding: Newron Pharmaceuticals
Patients: 167 patients 30 to 72 years of age with idiopathic Parkinson disease (Hoehn and Yahr stage I or II)
for a maximum of 5 years. Patients who were treatment
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