CENTER FOR DRUG EVALUATION AND
`
`_ RESEARCH
`
`APPLICA TION NUMBER:
`
`‘NDA 22-253 & 22-254
`
`RISK ASSESSMENT and RISK MITIGATION -
`
`REVIEW(S)
`
`

`

`
`
`Department of Health and Human Services
`Public Health Service
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`October 17, 2008
`
`Russell Katz, M.D., Director
`Division of Neurology Products
`
`Jodi Duckhorn, M.A., Team Leader
`Patient Labeling and Education Team
`Division of Risk Management (DRISK)
`
`Sharon R. Mills, BSN, RN, CCRP
`Patient Product Information Specialist
`Patient Labeling and Education Team
`Division of Risk Management (DRISK)
`
`Subject:
`
`Memo to file Re: Review of Patient Labeling (Medication Guide)
`
`Drug Name'(s) and
`Application
`Type/Number(s):
`
`0 VIMPAT (lacosamide) Tablet, Film Coated for Oral use,
`NDA- 22-253
`0 VIMPAT (lacosamide) Injection for Intravenous Use, NDA
`22-254
`,
`.m .
`
`“Al
`
`Applicant/sponsor:
`
`Schwartz Biosciences
`
`OSE RCM #:
`
`2008-847
`
`

`

`Schwartz Biosciences submitted parallel original New Drug Applications for:
`
`O NDA 22-253 for Iacosamide tablets,
`
`“For the treatment of Epilepsy as adjunctive therapy in patients with partial onset seizures
`aged 16 years and older”
`
`“For the management of neuropathic pain associated with diabetic peripheral
`neuropathy.”
`
`0 NDA 22-254 Iacosamide Injection,
`
`“For the treatment of Epilepsy as adjunctive therapy in patients with partial onset seizures
`aged 16 years and older when oral administration is temporarily not feasible.”
`
`0
`
`>
`
`w ‘
`
`'
`
`H
`
`mm
`
`M4)
`
`OSE reviewed a Class Medication Guide (MG) for Antiepileptic Drugs, drafted by the Division
`of Neurology Products (DNP) in March 2008, which was modeled after the Class Antidepressant
`MG. Following a joint meeting of the Peripheral and Central Nervous System Drugs Advisory
`Committee (PCNS) and Psychopharmacologic Drugs Advisory Committee on July 10, 2008 to
`discuss the results of FDA’s meta-analysis and issues related to antiepileptic drugs and
`suicidality, the review division decided to develop Class labeling for the Professional Information
`and MGs for these products. The review division worked in collaboration with the Patient
`Labeling and Education Team in DRISK in developing the MG template for the Antiepileptic
`Drugs.
`
`This memo serves to document our findings and close out our consult request.
`
`The Tradename VIMPAT has been accepted by FDA for Iacosamide. VIMPAT (Iacosamide)
`requires a MG because it is part of the Antiepileptic Class of drugs. The Patient Labeling and
`Education Team was requested to review the proposed MG for VIMPAT; however, the review
`division has decided that the MG for VIMPAT will only contain the class-specific language
`regarding suicidality that has been agreed upon by DNP and DRISK, and will not contain product
`specific language. See attached. Therefore, no further review is necessary at this time.
`
`We have made two minor changes at the end of the VIMPAT MG as follows:
`
`/
`
`/
`
`/
`
`hm
`
`Please let us know if you have any questions.
`
`

`

`a Page(s) Withheld
`
`___Trade Secret / Confidential (b4)
`i 4 Draft Labeling (b4)
`
`,
`
`Draft Labeling (b5)
`
`—— Deliberative Process (b5)
`
`

`

`u-g--__.'.—u-—-—m
`
`
`
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`/S/
`
`Sharon Mills
`
`10/17/2008 09:33:41 AM
`DRUG SAFETY OFFICE REVIEWER
`
`Jodi Duckhorn
`10/17/2008 09:44:40 AM
`DRUG SAFETY OFFICE REVIEWER
`
`

`

`Department of Health and Human Services
`
`Public Health Service
`
` Office of Surveillance and Epidemiology
`
`Food and Drug Administration
`
`Center for Drug Evaluation and Research
`
`Date:
`
`To:
`
`Thru:
`
`From:
`
`'May 15, 2008
`
`»
`
`Russell Katz, MD, Director
`Division of Neurology Products
`
`Bob Rappaport, MD, Director
`Division of Anesthesia, Analgesia and Rheumatology Products
`
`Kellie Taylor, PharmD, MPH, Team Leader
`Denise Toyer, PhannD, Deputy Director
`Division of Medication Error Prevention
`
`Judy Park, PharmD, Safety Evaluator
`Division of MedicatiOn Error Prevention
`
`Subject:
`
`.
`
`‘
`
`Labeling Review
`
`Drug Name(s):
`
`Vimpat (Lacosamide) Tablets, f” and Injection
`
`_
`
`Application Type/Number: NDA 22-253, NDA 22—254. / b(4§
`
`Applicant:
`
`Schwarz Biosciences, Inc.
`
`OSE RCM #:
`
`2008-633
`
`

`

`CONTENTS
`
`EXECUTIVE SUMMARY ............................................................................................................. 3
`1
`BACKGROUND ............L ........................................................................................................ 3
`1.1
`Introduction .................................................................................................................... 3
`
`Product Information ....................................................................................................... 3
`1.2
`2 METHODS AND MATERIALS ............................................................................................ 3
`
`RESULTS ................................................................................................................................ 4
`‘3
`4 DISCUSSION ................................... 5
`5
`CONCLUSIONS and recommendations ................................................................................. 5
`5.1
`Cements To The Division ........................................................................................... 6
`
`Comments To TheApphcant............... 6
`5.2
`APPENDICES ................................................................................................................................. 8
`
`

`

`EXECUTIVE SUMMARY
`
`The results of the Label and Labeling Risk Assessment found that the presentation of information
`and design of the proposed carton and container labels appears to be vulnerable to confusion that
`could lead to medication errors. The Division of Medication Error Prevention believes the risks
`we have identified can be addressed and-mitigated prior to drug approval, and provides
`recommendations in Section 5.2 that aim at reducing the risk of medication errors.
`
`1
`
`BACKGROUND
`
`1.1
`
`INTRODUCTION
`
`This consult was written in response to a request from the Division ofNeurology to evaluate the
`container labels and carton labeling of Vimpat for its potential to contribute to medication errors.
`The proprietary name, Vimpat, and the insert labeling were evaluated under a separate review
`(OSE Review #2007-161 1).
`
`1.2
`
`PRODUCT INFORMATION
`
`Vimpat (Lacosamide)1s a new molecular entity indicated for partial-onset seizures as adjunctive
`therapyin patients aged 16 years and older, as well as for management ofneuropatlnc pain
`associated with diabetic peripheral neuropathy. The recommended dose for partial onset seizures
`is 100 mg per day twice daily initially, then increased to 200 mg per day to 400 mg per day. The
`
`recommended initial dose for diabetic peripheral neuropathic pain i!
`
`M
`
`/ the max1mum daily dosage of Vimpat is ~— mg per day. When switching from oral
`to intravenous dose, the initial total daily intravenous dosage should equal the oral total daily
`dosage and frequency. The parenteral formulation of Vimpat can be administered without further
`
`dilution or may be mixed1n a compatible diluent and should be administered intravenously over
`at least
`Vimpat will be available1n 50 mg, 100 mg, 150 mg, 200 m2. 250 mg, and
`' 300 mg tablets, N— and 10 mg/mL solution for injection ~_.__.___§
`___=;——1 is indicated for neuropathic pain. For partial seizure indication, tablets,—-»-’——-
`and injectables are indicated.
`
`2 METHODS AND MATERIALS
`
`This section consists of two sections which describe the methods and materials used by the
`Division of Medication Error Prevention staff conducting a label, labeling, and/or packaging risk
`assessment. The primary focus of the assessments is to identify and remedy potential sources of
`medication error prior to drug approval. The Division of Medication Error Prevention defines a
`medication error as any preventable event that may cause or lead to inappropriate medication use
`or patient harm while the medication13 in the control of the health care professional, patient, or
`consumer.I
`
`The label and labeling of a drug product are the primary means by which practitioners and
`patients (depending on configuration) interact with the pharmaceutical product. The container
`labels and carton labeling communicate critical information including proprietary and established
`
`‘ National Coordinating Council for Medication Error Reporting and Prevention.
`http://www.nccmerp.orglaboutMedErrorshtml. Last accessed 10/11/2007.
`
`W)"
`
`

`

`name, strength, form, container quantity, expiration, and so on. The insert labeling is intended to
`communicate to practitioners all information relevant to the approved uses of the drug, including
`the correct dosing and administration.
`
`Given the critical role that the label and labeling has in the safe use of drug products, it is not
`surprising that 33 percent of mediCation errors reported to the USP—ISM? Medication Error ‘
`Reporting Program may be attributed to the packaging and labeling of drug products, including
`30 percent of fatal errors.2
`
`Because our staff analyze reported misuse of drugs, our staff are able to use this experience to
`identify potential errors with all medication similarly packaged, labeled or prescribed. We use
`FMEA and the principles of human factors to identify potential sources of error with the proposed
`product labels and insert labeling, and provided recommendations that aim at reducing the risk of
`medication errors.
`
`For this product the Applicant submitted on April 9, 2008 following labels and labeling for our
`review (see Appendices A, B, C, D, E, F, and G for images):
`
`0 Retail Container for Injection: 10 mg/mL (20 mL vial)
`
`0 Retail Carton for Injection: 10 mg/mL (20 mL vial)
`
`0 Retail Container for Tablets : 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, and 300 mg (60,
`180, f counts)
`
`3 RESULTS
`
`N43.-
`
`/ / /
`
`2 Institute of Medicine. Preventing Medication Errors. The National Academies Press: Washington DC.
`2006. p275,
`
`

`

`M4)
`
`5
`
`CONCLUSIONS AND RECOMMENDATIONS
`
`The Label and Labeling Risk Assessment findings indicate that the presentation of information
`and design of the proposed container labels and carton labeling introduces vulnerability to
`confusion that Could lead to medication errors. We believe the n'sks we have identified can be
`
`

`

`addressed and mitigated prior to drug approval, and provides recommendations in Section 5.2 that
`aim at reducing the risk of medication errors.
`
`5.1
`
`COMMENTS TO THE DIVISION
`
`Based upon our assessment of the labels and labeling, we have identified areas needed of
`improvement. We have provided recommendations in Section 5.2 and request this information be
`forwarded to the Applicant.
`
`We would appreciate feedback on the final outcome of this review. Please copy us on any
`communication to the Applicant with regard to this review. We would be Willing to meet with
`the Division for further discussion, if needed. If you have We: questions or need clarifications,
`please contact Daniel Brounstein, Project Manager, at 301-796-0674.
`
`5.2
`
`COMMENTS TO THE APPLICANT
`
`

`

`/, / /
`
`APPEARS FHHS WAY
`ON OfilGlNAL
`
`

`

`'
`
`‘ 3
`
`> Page(s) Withheld
`
`’
`
`/TradeSecret/Confiderltial (b4)
`
`I
`
`Draft Labelirlg (b4) .
`
`- Draft Labeling (b5)
`
` Deliberative Process :(bS)
`
`

`

`This is a representation of an electronic record that was signed electronically and
`
`Judy Park
`5/15/2008 10:11:10 AM
`DRUG SAFETY OFFICE‘REVIEWER
`
`Kellie Taylor
`5/15/2008 10:45:46 AM
`DRUG SAFETY OFFICE REVIEWER
`
`Denise Toyer
`5/15/2008 12:35:59 PM
`DRUG SAFETY OFFICE REVIEWER
`
`