Food and Drug Administration
U.S. Department of Health and Human Services
Public Health Service 5600 Fishers Lane Rockville, MD 20857
FDA Talk Papers are prepared by the Press Office to guide FDA personnel in responding with consistency and accuracy to questions from the public on subjects of current interest. Talk Papers are subject to change as more information becomes available.
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August 31, 2000
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Inhalational anthrax is an extremely rare disease, resulting from exposure to contaminated animal hides and hairs, usually in an industrial setting. The causative organism, B. anthracis, is a spore-forming gram positive rod that can be used as a biological weapon. Inhalational anthrax is thought to be the most likely form of this infection to result from the intentional use of an aerosolized preparation of spores of B. anthracis.
FDA approved this new use, for inhalational anthrax (post-exposure), under its accelerated approval regulations. Approval was based on the use of a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, together with the available information about the concentration needed to inhibit or kill B. anthracis.
The use of the surrogate endpoint was further supported by ciprofloxacin serum concentrations in the Rhesus monkey model of post-exposure inhalational anthrax that demonstrated a significantly improved survival rate for animals that received ciprofloxacin compared to animals that did not receive an antimicrobial following exposure to aerosolized B. anthracis. The serum levels measured in monkeys that survived exposure to anthrax bacteria can be achieved or exceeded in humans who receive the recommended doses.
The applicability of this model is based upon data attesting to the similarities between experimental animals and humans regarding the pathogenesis, clinical course, and tissue pathology of inhalational anthrax. Because of the high mortality rate, this disease cannot ethically be studied in humans under circumstances of intentional exposure. Therefore, human ciprofloxacin serum concentrations served as the surrogate endpoint considered reasonably likely to predict clinical benefit and provide the basis for this approval.
The approval of Cipro® for this indication represents both the manufacturer's and FDA's response to a public health need. This is the first antimicrobial drug application submitted to the FDA for an indication which would result from the intentional use of a biological agent.
Cipro® was first approved in the US in l987. It has been used in more than 100 million patients in the US, and approximately 250 million patients worldwide. It is now approved for a total of 14 indications. These include a number of serious infections such as lower respiratory tract, intra-abdominal, typhoid fever, bone, and joint infections, in addition to the newly-approved indication, inhalational anthrax (post-exposure).
Because of concerns about long-term safety, including effects on cartilage, until now, Cipro was not approved for any indication in the pediatric population. However, because inhalational anthrax is lethal, the risk-benefit assessment indicates that use of Cipro for this indication in pediatric patients is appropriate. Studies are currently under way to evaluate long-term safety, including effects on cartilage, in pediatric patients.
On July 28, 2000, the FDA's Anti-Infective Drug Products Advisory Committee unanimously recommended the approval of Cipro® for inhalational anthrax (post-exposure) based on the available scientific data and consideration of the special circumstances surrounding the potential use of the drug.
The recommended adult dose of Cipro® for post-exposure inhalational anthrax is 500 milligrams given orally twice a day. The recommended pediatric dose of Cipro® for post-exposure inhalational anthrax is 15 mg/kg given orally twice a day. The adult intravenous dose is 400 mg twice a day; the pediatric intravenous dose is 10 mg/kg twice a day. Treatment with ciprofloxacin should begin as soon as possible after exposure. The Drug should be administered for a total of 60 days.
The most common adverse drug reactions observed with the use of ciprofloxacin include nausea, vomiting, diarrhea, abdominal pain, rash, headache, restlessness. In patients who have received ciprofloxacin for 60 days or longer, no new or unexpected adverse reactions were identified compared to patients receiving shorter approved regimens.
Bayer Corp of West Haven, Conn. manufactures Cipro® (ciprofloxacin).
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Hypertext uploaded by clb 2000-AUG-31.