`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`NDA 21083/S056
`NDA 21110/S074
`
`
`
`
`
`
`
`
`
`
`Food and Drug Administration
`
`
` Silver Spring MD 20993
`
`
`SUPPLEMENT APPROVAL
`
`
`
`
` PF PRISM, C.V.
`
` c/o Pfizer, Inc
`
`
` Attention: Deneen Stewart, PhD
`
` Director, Worldwide Safety and Regulatory
`
` 500 Arcola Road
` Collegeville, PA 19426
`
`
`
`Dear Dr. Stewart:
`
`
`
`
`Please refer to your Supplemental New Drug Applications (sNDAs), submitted under section
`
`
`
`
`
`
`505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) as follows:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Dated and Received on
`
`
`
` Supplement # Drug Name
`
`
`
`
`
`NDA
`
` Number
`
` 21083
`
` 21110
`
`
`
`
`
`
` 056
`
` 074
`
`
`
`
` Rapamune (sirolimus) Oral Solution December 24, 2014
`
` December 24, 2014
`
`
` Rapamune (sirolimus) Tablets
`
`
`
`
`
`
` We acknowledge receipt of your amendments dated February 12, 2015.
`
`
`
`
`
`
`
` These “Changes Being Effected” supplemental new drug applications provide for the following
`
` changes to the Package Insert and Medication Guide (additions are noted by underlined text).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`1.
`
`
`
`In the 6.1 Clinical Studies Experience in Prophylaxis of Organ Rejection Following
`
`
`Renal Transplantation section, under the header “The following adverse reactions were
`
`
`reported less frequently (≥ 3%, but < 20%), Metabolic/Nutritional bullet, the words
`
`
`
`
`
`“diabetes mellitus” are added to read:
`
`• Metabolic/Nutritional – Abnormal healing, increased lactic dehydrogenase
`
`
`
`
`
`
`
`(LDH), hypokalemia, diabetes mellitus
`
`
`
`
`
`
`
`Reference ID: 3711999
`
`

`

`
`
` NDA 21083/S056
`
`
` NDA 21110/S074
` Page 2
`
`
`
`
`
`
`
`
` 2. In the 6.6 Postmarketing Experience section, under Metabolic/Nutritional, the words
`
`
`
`
`
` “diabetes mellitus” are added to read:
`
`
`
`
`
`
`
`
`
`• Metabolic/Nutritional-Liver function test abnormal, AST/SGOT increased,
`
`
`
`
` ALT/SGPT increased, hypophosphatemia, hyperglycemia, diabetes mellitus
`
`3. In the 6.6 Postmarketing Experience section, a new bullet is added as follows:
`
`
`
`
`• Nervous system - Posterior reversible encephalopathy syndrome.
`
`
`
`
`4. In the MEDICATION GUIDE, the Common side effects with RAPAMUNE
`
`
`
`
`subsection, a new bullet is added as follows:
`
`
`• high blood sugar (diabetes)
`
`
`
`
`
`We also note numerous editorial changes, including the sequential numbering of the tables all
`
`throughout the labeling.
`
`
`
`APPROVAL & LABELING
`
`
`We have completed our review of these supplemental applications, as amended. They are
`
`
`
`
`
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling text, which is identical to the labeling text submitted on February 12, 2015.
`
`
`
`CONTENT OF LABELING
`
`
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`
`
`
`automated drug registration and listing system (eLIST), as described at
`
`
`
`
`
`
`
`
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`
`of labeling must be identical to the enclosed labeling (text for the package insert and Medication
`
`
`
`
`
`
`
`
`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
`
`
`
`
`
`
`
`
`
`
`
`supplements, as well as annual reportable changes not included in the enclosed labeling.
`
`
`Information on submitting SPL files using eList may be found in the guidance for industry titled
`
`
`
`
`
`
`
`“SPL Standard for Content of Labeling Technical Qs and As at
`
`
`
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf
`
`
`The SPL will be accessible from publicly available labeling repositories.
`
`
`
`
`
`
`
`
`Reference ID: 3711999
`
`

`

`
`
` NDA 21083/S056
`
`
` NDA 21110/S074
` Page 3
`
`
`
`
`
`
`
`
` Also within 14 days, amend all pending supplemental applications that includes labeling changes
`
` for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`
` with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`
`
`
`
`
`
` changes approved in this supplemental application, as well as annual reportable changes and
`
`
`
`
`
`
` annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`
`
`
` up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
`
`
`
`
`
`
`
`
`
` should provide appropriate annotations, including supplement number(s) and annual report
`
`
`
`date(s).
`
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`
`
`
`(21 CFR 314.80 and 314.81).
`
`
`If you have any questions, call Judit Milstein, Chief, Project Management Staff at 301-796-0763.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Sincerely,
`
`
`{See appended electronic signature page}
`
`
`Ozlem Belen, MD, MPH
`
`
`
`
`Deputy Director for Safety
`
`
`Division of Transplant and Ophthalmology Products
`
`Office of Antimicrobial Products
`
`
`Center for Drug Evaluation and Research
`
`
`
`
`
`
`
`
`ENCLOSURE: Content of Labeling
`
`
`
`Reference ID: 3711999
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`OZLEM A BELEN
`03/06/2015
`
`Reference ID: 3711999
`
`