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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
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`NDA 21-572/S-009
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`Cubist Pharmaceuticals, Inc.
`Attention: David S. Mantus, PhD
`65 Hayden Avenue
`Lexington, MA 02421
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`Dear Dr. Mantus:
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`Please refer to your supplemental new drug application dated April 27, 2006, received April 28, 2006,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for CUBICIN®
`(daptomycin for injection).
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`We also acknowledge receipt of your submissions dated July 17, 2006, and October 16, 2006.
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`These “Changes Being Effected in 30 days” supplemental new drug applications provide for revisions
`to the “PRECAUTONS, Drug Laboratory Test Interactions” section of the labeling text.
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`We completed our review of these applications, as amended, and they are approved, effective on the
`date of this letter, for use as recommended in the agreed-upon labeling text, and with the following
`editorial revisions to the “PRECAUTIONS, Drug-Laboratory Test Interactions” listed below:
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`Drug-Laboratory Test Interactions
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`Clinically relevant plasma levels of daptomycin have been observed to cause a significant
`concentration-dependant false prolongation of prothrombin time (PT) and elevation of
`International Normalized Ratio (INR) when certain recombinant thromboplastin reagents are
`utilized for the assay. The possibility of an erroneously elevated PT/INR result due to
`interaction with a recombinant thromboplastin reagent may be minimized by drawing
`specimens for PT or INR testing near the time of trough plasma concentrations of daptomycin.
`However, sufficient daptomycin levels may be present at trough to cause interaction.
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`If confronted with an abnormally high PT/INR result in a patient being treated with Cubicin, it
`is recommended that clinicians:
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`1. Repeat the assessment of PT/INR, requesting that the specimen be drawn just prior to
`the next Cubicin dose (i.e., at trough concentration). If the PT/INR value drawn at
`trough remains substantially elevated over what would otherwise be expected, consider
`evaluating PT/INR utilizing an alternative method.
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`NDA 21-572/S-009
`Page 2
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`2. Evaluate for other causes of abnormally elevated PT/INR results.
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`The final printed labeling (FPL) must be identical, and include the editorial revisions indicated, to the
`enclosed labeling. These revisions are terms of the approval of these applications.
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`Please submit an electronic version of the FPL according to the guidance for industry titled Providing
`Regulatory Submissions in Electronic Format - NDA. Approval of this submission by FDA is not
`required before the labeling is used.
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`If you issue a letter communicating important information about this drug product (i.e., a “Dear Health
`Care Professional” letter), we request that you submit a copy of the letter to this NDA and a copy to
`the following address:
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`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR
`314.80 and 314.81).
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`If you have any questions, call J. Christopher Davi, Regulatory Project Manager, at (301) 796-0702.
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`MEDWATCH
`Food and Drug Administration
`5515 Security Lane
`HFD-001, Suite 5100
`Rockville, MD 20852
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`Sincerely,
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`{See appended electronic signature page}
`
`Janice M. Soreth, MD, Director
`Division of Anti-Infective and Ophthalmology Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
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`Enclosure: Approved labeling dated May 2006
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`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
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` /s/
`---------------------
`Janice Soreth
`10/24/2006 05:47:25 PM
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