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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 20-845/S-002
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`INO Therapeutics, Inc.
`Attention: Ms. Mary Ellen Zamstein
`6 State Route 173
`Clinton, NJ 08809
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`Dear Ms. Zamstein:
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`Please refer to your supplemental new drug application dated January 23, 2004 submitted under section 505(b)
`of the Federal Food, Drug, and Cosmetic Act for INOmax (nitric oxide) for inhalation.
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`We acknowledge receipt of your submission dated April 23, 2004.
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`This “Changes Being Effected in 30 days” supplemental new drug application provides for final printed labeling
`revised as follows:
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`1. The Drug Interactions section has been revised, and now reads as follows:
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`Drug Interactions
`No formal drug-interaction studies have been performed, and a clinically significant interaction with
`other medications used in the treatment of hypoxic respiratory failure cannot be excluded based on the
`available data. INOmax has been administered with tolazoline, dopamine, dobutamine, steroids,
`surfactant, and high-frequency ventilation. Although there are no study data to evaluate the possibility,
`nitric oxide donor compounds, including sodium nitroprusside and nitroglycerin, may have an additive
`effect with INOmax on the risk of developing methemoglobinemia. An association between prilocaine
`and an increased risk of methaemoglobinaemia, particularly in infants, has specifically been described
`in a literature case report. This risk is present whether the drugs are administered as oral, parenteral, or
`topical formulations.
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`2. The word “study” has been added after “NINOS” in the forth paragraph of the ADVERSE
`REACTIONS section.
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`3. A new POST-MARKETING EXPERIENCE section has been added after the OVERDOSAGE
`section that reads as follows:
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`POST-MARKETING EXPERIENCE
`The following adverse events have been reported as part of the post-marketing surveillance. These
`events have not been reported above. Given the nature of spontaneously reported post-marketing
`surveillance data, it is impossible to determine the actual incidence of the events or definitively establish
`their causal relationship to the drug. The listing is alphabetical: dose errors associated with the delivery
`system; headaches associated with environmental exposure of INOmax in hospital staff; hypotension
`associate with acute withdrawal of the drug; hypoxemia associated with acute withdrawal of the drug;
`pulmonary edema in patients with CREST syndrome.
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`NDA 20-845/S-002
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`Page 2
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`4. At the end of the labeling, the corporate name “INO Therapeutics, Inc” has been changed to “INO
`Therapeutics.”
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`MEDWATCH, HFD-410
`FDA
`5600 Fishers Lane
`Rockville, MD 20857
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`We have completed our review of this supplemental new drug application. It is approved, effective on the date
`of this letter, for use as recommended in the final printed labeling (FPL) submitted on April 23, 2004.
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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 the requirements for an approved NDA set forth under 21 CFR
`314.80 and 314.81.
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`If you have any questions, please contact:
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`Mr. Russell Fortney
`Regulatory Health Project Manager
`(301) 594-5311
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`Sincerely,
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`{See appended electronic signature page}
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`Norman Stockbridge, M.D., Ph.D.
`Acting Director
`Division of Cardio-Renal Drug Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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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
`6/15/04 03:53:54 PM
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