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` DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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`Food and Drug Administration
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`Rockville, MD 20857
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` NDA 21-272/S-008
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`United Therapeutics Corporation
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`Attention: Kerry McKenzie
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` P.O. Box 14186
`One Park Drive
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`Research Triangle Park, NC 27709
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`SUPPLEMENT APPROVAL
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`Dear Mr. McKenzie:
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`Please refer to your supplemental new drug application (sNDA) dated October 23, 2007, submitted under section 505(b) of
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`the Federal Food, Drug, and Cosmetic Act for Remodulin (treprostinil sodium) Injection 1, 2.5, 5, and 10 mg/mL.
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` We also refer to your submission dated March 28, 2008.
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`This supplemental new drug application provides for the following revisions to the package insert:
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`1. Flolan Sterile Diluent for Injection has been added as an acceptable diluent for intravenous administration to the
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`following sections:
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`• DOSAGE AND ADMINISTRATION/General (section 2.1)
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`• DOSAGE AND ADMINISTRATION/Administration (section 2.6, under the “Intravenous Infusion” and
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`“Step 2” subheadings).
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`• HOW SUPPLIED/STORAGE AND HANDLING (section 16)
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`2. Under INDICATIONS AND USAGE, section 1.2 has been changed from:
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`1.2 Pulmonary Arterial Hypertension In Patients Requiring Transition From Flolan®
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`Remodulin is indicated to diminish the rate of clinical deterioration in patients with pulmonary arterial hypertension
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`requiring transition from Flolan (epoprostenol sodium); the risks and benefits of each drug should be carefully
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`To:
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`1.2 Pulmonary Arterial Hypertension In Patients Requiring Transition From Flolan®
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`In patients with pulmonary arterial hypertension requiring transition from Flolan (epoprostenol sodium), Remodulin is
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`indicated to diminish the rate of clinical deterioration. The risks and benefits of each drug should be carefully
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`considered prior to transition.
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`3. Under CLINICAL PHARMACOLOGY, the first paragraph in the Pharmacokinetics section (12.3) has been changed
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`from:
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`The pharmacokinetics of continuous subcutaneous Remodulin are linear over the dose range of 1.25 to 22.5 ng/kg/min
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`(corresponding to plasma concentrations of about 0.03 to 8 mcg/L) and can be described by a two-compartment model.
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`Dose proportionality at infusion rates greater than 22.5 ng/kg/min has not been studied.
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`To:
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`The pharmacokinetics of continuous subcutaneous Remodulin are linear over the dose range of 1.25 to 125 ng/kg/min
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`(corresponding to plasma concentrations of about 15 pg/mL to 18,250 pg/m) and can be described by a two-
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`compartment model. Dose proportionality at infusion rates greater than 125 ng/kg/min has not been studied.
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`MEDWATCH
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`Food and Drug Administration
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`Suite 12B05
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`5600 Fishers Lane
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`Rockville, MD 20857
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` Page 2
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`NDA 21-272/S-008
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`4. The label has been formatted into the new PLR format.
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`We have completed our review of this application, and it is approved, effective on the date of this letter, for use as
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`recommended in the enclosed labeling text.
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`As soon as possible, but no later than 14 days from the date of this letter, please submit the content of labeling [21 CFR
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`314.50(l)] in structured product labeling (SPL) format as described at http://www.fda.gov/oc/datacouncil/spl.html that is
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`identical to the enclosed labeling. Upon receipt, we will transmit that version to the National Library of Medicine for public
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`dissemination. For administrative purposes, please designate this submission, “SPL for approved NDA 21-272/S-008.”
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`If you issue a letter communicating important information about this drug product (i.e., a “Dear Health Care Professional”
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`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 Dan Brum, Pharm.D., Regulatory Project Manager, at (301) 796-0578.
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`Sincerely,
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`{See appended electronic signature page}
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`Norman Stockbridge, M.D., Ph.D.
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`Director
`Division of Cardiovascular and Renal Products
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`Office of Drug Evaluation I
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`Center for Drug Evaluation and Research
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`Enclosure: Labeling Text
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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/
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`Norman Stockbridge
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`9/12/2008 01:20:23 PM
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