1) What action is FDA taking regarding unapproved drug products containing sodium nitrite or sodium thiosulfate labeled for the treatment of known or suspected cyanide poisoning?
The FDA is notifying companies to cease manufacture or marketing of unapproved drug products containing sodium nitrite or sodium thiosulfate labeled for the treatment of known or suspected cyanide poisoning. This notification was published in the Federal Register on November 28, 2012 (http://www.gpo.gov/fdsys/pkg/FR-2012-11-28/pdf/2012-28773.pdf).
FDA is taking this action because there are now FDA-approved versions of these drug products on the market (Table 1). This is part of FDA’s on-going effort to ensure that all drugs marketed in the United States have the required FDA approval and are safe, effective, of good quality, and appropriately labeled.
In 2011, FDA approved a New Drug Application (NDA) for Nithiodote, a co-packaged Sodium Nitrite Injection and Sodium Thiosulfate Injection drug product, indicated for the treatment of acute cyanide poisoning that is judged to be life-threatening. Additionally, in 2012, FDA approved NDAs for Sodium Nitrite Injection and Sodium Thiosulfate Injection, which are marketed in separate packaging. Sodium Nitrite Injection and Sodium Thiosulfate Injection are approved to be used sequentially: Sodium Nitrite is injected first, followed immediately by Sodium Thiosulfate, for the treatment of acute cyanide poisoning that is judged to be life-threatening. The unapproved products on the market compete with these approved products, and pose a direct challenge to the drug approval system.
Table 1: Approved Prescription Products
and Product Code
Sodium Nitrite and Sodium Thiosulfate
2) When is the action going to take effect?
Firms subject to this class action will have 90 days to cease manufacturing and 180 days to cease distribution of the unapproved drugs from the date of the Federal Register notice.
3) Are the unapproved products being recalled?
No, this is not a recall. Previously manufactured unapproved products affected by this action may still be available for a short period of time until the inventory has been depleted or the product has expired, whichever occurs first.
4) Is it safe to use the unapproved products?
Since FDA has not evaluated unapproved products for safety, efficacy, and quality, the relative safety and risk of these products is unknown. Sodium nitrite and sodium thiosulfate injection(s) can pose the serious risk of hypotension (low blood pressure). Sodium nitrite may cause methemoglobinemia, a disorder characterized by the presence of a higher than normal level of methemoglobin in the blood. Methemoglobin is a compound in the blood that does not combine with oxygen. Methemoglobinemia can therefore lead to a reduced ability to release oxygen to tissues and oxygen deprivation for affected individuals. The labeling for the approved Sodium Nitrite Injection and Nithiodote products contains a Boxed Warning regarding the serious risk of methemoglobinemia. The unapproved versions of these drugs may lack adequate Boxed Warnings and other important safety information in their labeling.
5) What effect will FDA’s action have on emergency responders and healthcare providers who use unapproved injectable drug products containing sodium nitrite or sodium thiosulfate labeled for the treatment of patients with known or suspected cyanide poisoning? Are there alternatives?
The Agency does not anticipate problems or supply disruptions as healthcare providers switch over to FDA-approved drug products indicated for the treatment of cyanide poisoning.
6) In the case where the unapproved products are packaged as part of a cyanide antidote kit containing other medical items (e.g., tourniquets and syringes), will FDA take action against the entire cyanide antidote kit?
Yes. In the event that unapproved sodium nitrite and sodium thiosulfate are packaged in a kit with other medical items and labeled for treatment of known or suspected cyanide poisoning, FDA will take action against the entire cyanide antidote kit based on the unapproved components.
7) Does this action cover amyl nitrite?
No. Amyl nitrite is not covered by this notice of enforcement. However, if amyl nitrite is a component of an unapproved cyanide antidote kit that also contains sodium nitrite and sodium thiosulfate, FDA may take action against the entire kit.
8) How can consumers know if their products are unapproved?
While the FDA works to ensure that all marketed unapproved drug products obtain approval or are removed from the market, FDA provides various resources that list approved drugs. Health care professionals and consumers can use Drugs@FDA or the National Drug Code (NDC) Directory to determine whether a drug product is FDA-approved. Drugs@FDA contains most FDA-approved drug products. Search results from the NDC directory include a column marked “Application Number.” FDA-approved products will have an associated NDA (new drug application) or ANDA (abbreviated new drug application) number in this column, which is provided by the firm submitting that information.