71006 Federal Register / Vol. 77, No. 229 / Wednesday, November 28, 2012 / Notices FOR FURTHER INFORMATION CONTACT: drug products compete with approved to be life-threatening, and NDA 203923 Daniel Gittleson, Office of Information products, and thus pose a direct for Sodium Thiosulfate Injection for Management, Food and Drug challenge to the drug approval system. sequential use with sodium nitrite for Administration, 1350 Piccard Dr., PI50– Injectable drug products containing treatment of acute cyanide poisoning 400B, Rockville, MD 20850, 301–796– sodium nitrite or sodium thiosulfate that is judged to be life-threatening. 5156, [email protected]. that are labeled for the treatment of Sodium thiosulfate and sodium nitrite SUPPLEMENTARY INFORMATION: On August cyanide poisoning are new drugs that pose the risk of hypotension (low blood 9, 2012, the Agency submitted a require approved new drug applications pressure), and sodium nitrite also poses proposed collection of information (NDAs) or abbreviated new drug the risk of methemoglobinemia, a entitled ‘‘Registration and Product applications (ANDAs) in order to be disorder characterized by the presence Listing for Owners and Operators of legally marketed. of a higher than normal level of Domestic Tobacco Product DATES: This notice is effective methemoglobin in the blood. Establishments and Listing of November 28, 2012. For information Methemoglobin is an oxidized form of Ingredients in Tobacco Products’’ to about enforcement dates, see hemoglobin that has a decreased affinity OMB for review and clearance under 44 SUPPLEMENTARY INFORMATION, section IV. for oxygen, resulting in a reduced ability U.S.C. 3507. An Agency may not ADDRESSES: All communications in to release oxygen to body tissue. conduct or sponsor, and a person is not response to this notice should be Methemoglobinemia can lead to required to respond to, a collection of identified with Docket No. FDA–2012– neurological and cardiac symptoms due information unless it displays a N–1134 and directed to the appropriate to lack of adequate oxygen in body currently valid OMB control number. office listed in this document. tissues. The approved Sodium Nitrite OMB has now approved the information Applications under section 505(b) of Injection and Nithiodote carry Boxed collection and has assigned OMB the Federal Food, Drug, and Cosmetic Warnings for these serious adverse control number 0910–0650. The Act (the FD&C Act) (21 U.S.C. 355(b)): reactions. approval expires on October 31, 2015. A Division of Anesthesia, Analgesia, and FDA is aware of several unapproved copy of the supporting statement for this Addiction Products, Office of New drug products containing sodium nitrite information collection is available on Drugs, Center for Drug Evaluation and or sodium thiosulfate labeled to treat the Internet at http://www.reginfo.gov/ Research, Food and Drug cyanide poisoning. These unapproved public/do/PRAMain. Administration, 10903 New Hampshire drug products containing sodium nitrite Dated: November 21, 2012. Ave., Bldg. 22, Silver Spring, MD or sodium thiosulfate are sold Leslie Kux, 20993–0002. individually, as well as in cyanide Applications under section 505(j) of antidote kits. Unapproved cyanide Assistant Commissioner for Policy. the FD&C Act (21 U.S.C. 355(j)): Office antidote kits may also contain other [FR Doc. 2012–28774 Filed 11–27–12; 8:45 am] of Generic Drugs, Center for Drug unapproved drugs (e.g., amyl nitrite) or BILLING CODE 4160–01–P Evaluation and Research, Food and medical products (e.g., syringes) that are Drug Administration, 7519 Standish Pl., intended for potential use with sodium Rockville, MD 20855. nitrite and sodium thiosulfate. This DEPARTMENT OF HEALTH AND All other communications: Lori notice is issued under sections 502 (21 HUMAN SERVICES Cantin, Office of Unapproved Drugs and U.S.C. 352) and 505 of the FD&C Act Food and Drug Administration Labeling Compliance, Division of and applies to unapproved injectable Prescription Drugs, Center for Drug drug products containing sodium nitrite [Docket No. FDA–2012–N–1134 Evaluation and Research, Food and or sodium thiosulfate labeled to treat Drug Administration, 10903 New cyanide poisoning that are currently Sodium Nitrite Injection and Sodium Hampshire Ave., Bldg. 51, Rm. 5239, being manufactured or distributed. Thiosulfate Injection Drug Products Silver Spring, MD 20993–0002. Labeled for the Treatment of Cyanide II. Safety Concerns With Unapproved FOR FURTHER INFORMATION CONTACT: Lori Poisoning; Enforcement Action Dates New Drugs Cantin, Center for Drug Evaluation and AGENCY: Food and Drug Administration, Research, Food and Drug Because marketed unapproved new HHS. Administration, 10903 New Hampshire drug products have not been through ACTION: Notice. Ave., Bldg. 51, Rm. 5239, Silver Spring, FDA’s approval process, there are safety MD 20993–0002, 301–796–1212, email: risks associated with them. Some SUMMARY: The Food and Drug [email protected]. unapproved drug product labeling omits Administration (FDA) is announcing its SUPPLEMENTARY INFORMATION: safety warnings, such as the Boxed intention to take enforcement action Warnings required on Sodium Nitrite against unapproved injectable drug I. Background Injection and Nithiodote, which are products containing sodium nitrite Cyanide is highly toxic in humans important for safe use of the drug labeled for the treatment of cyanide and can be fatal if not immediately products. Without these warnings, the poisoning and unapproved injectable treated with an effective antidote. On unapproved drug products may be used drug products containing sodium January 14, 2011, FDA approved NDA in inappropriate circumstances or thiosulfate labeled for the treatment of 201444 for Nithiodote, a co-packaged without appropriate monitoring, posing cyanide poisoning, and persons who Sodium Nitrite Injection and Sodium an increased risk to public health. manufacture or cause the manufacture Thiosulfate Injection drug product, Patients being treated for cyanide or distribution of such products in labeled for treatment of acute cyanide poisoning require close monitoring and interstate commerce. Cyanide antidotes poisoning that is judged to be life- may require repeat doses of antidote, carry serious risks and some threatening. On February 14, 2012, FDA supplemental oxygen, and ventilatory unapproved drug products may lack approved NDA 203922 for Sodium support. Cyanide antidotes containing Boxed Warnings and other warnings Nitrite Injection for sequential use with sodium nitrite or amyl nitrite may required in the labeling of approved sodium thiosulfate for treatment of induce methemoglobinemia, which may cyanide antidotes. These unapproved acute cyanide poisoning that is judged require additional treatment. VerDate Mar<15>2010 13:52 Nov 27, 2012 Jkt 229001 PO 00000 Frm 00016 Fmt 4703 Sfmt 4703 E:\FR\FM\28NON1.SGM 28NON1 erowe on DSK2VPTVN1PROD with Federal Register / Vol. 77, No. 229 / Wednesday, November 28, 2012 / Notices 71007 The expected risks associated with 201.100(c)(2) and 21 CFR 201.115). Unapproved Drugs CPG, the Agency use of sodium nitrite or sodium Because the unapproved prescription may, at its discretion, identify a period thiosulfate drug products are also drug products subject to this notice do of time during which the Agency does potentially greater for unapproved drug not have approved applications with not intend to initiate an enforcement products because the quality, safety, and approved labeling, they fail to qualify action against a currently marketed efficacy of unapproved formulations for the exemptions to the requirement unapproved drug solely on the grounds have not been demonstrated to FDA. For that they bear ‘‘adequate directions for that it lacks an approved application example, information on the ingredients use,’’ and they are misbranded under under section 505 of the FD&C Act. and data on the bioavailability of section 502(f)(1). With respect to drug products covered unapproved drug products have not IV. Notice of Intent To Take by this notice, the Agency intends to been submitted for FDA review, nor has Enforcement Action exercise its enforcement discretion for FDA had the opportunity to assess the only a limited period of time because adequacy of their chemistry, Although not required to do so by the there are safety risks with respect to the manufacturing, and control Administrative Procedure Act, the products covered by this notice, and specifications. Also, unapproved drug FD&C Act (or any rules issued under its there are FDA-approved drug products products have unapproved labeling that authority), or for any other legal reason, to meet patient needs. Therefore, the may not contain appropriate dosing FDA is providing this notice to persons 1 Agency intends to implement this information. For example, the sodium who are marketing unapproved and notice as follows. thiosulfate component of Nithiodote is misbranded drug products containing For the effective date of this notice, dosed for children based on body sodium nitrite and sodium thiosulfate see the DATES section of this document. weight or body surface area, whereas labeled to treat cyanide poisoning, Any drug product covered by this notice FDA is aware of unapproved sodium either sold individually or as part of a that a company (including a thiosulfate products labeled for use in kit. The Agency intends to take manufacturer or distributor) began children at a lower dose based only on enforcement action against such marketing