Fear of terrorists leads to new indication for Cipro
Rare disease and a rare type of approval
In the first antimicrobial drug application submitted to the Food and Drug Administration to fight the intentional use of a biological agent, the federal government recently approved Bayer’s antimicrobial ciprofloxacin (Cipro) to use on people exposed to inhaled anthrax.
Ciprofloxacin is designed to reduce the incidence or progression of inhalational anthrax following exposure to aerosolized bacillus anthracis, the bacterium that causes anthrax. Inhalational anthrax is an extremely rare disease resulting from exposure to contaminated animal hides and hairs, usually in an industrial setting.
The causative organism, bacillus anthracis, is a spore-forming, gram-positive rod that can be used as a biological weapon. Inhalational anthrax is considered the most likely form of infection from intentional use of an aerosolized preparation of spores of bacillus anthracis.
Anthrax and animal testing
On July 28, the FDA approved ciprofloxacin under accelerated approval regulations, based on the use of a surrogate endpoint and ciprofloxacin serum concentrations in humans. The use of a surrogate endpoint was supported by ciprofloxacin serum concentrations in the rhesus monkey model of post-exposure inhalational anthrax, showing a significantly improved survival rate for animals receiving ciprofloxacin vs. animals that did not receive an antimicrobial after exposure to aerosolized bacillus anthracis. The serum levels measured in monkeys that survived exposure to anthrax bacteria can be achieved or exceeded in humans receiving the recommended doses.
This model is based on the similarities between experimental animals and humans regarding the pathogenesis, clinical course, and tissue pathology of inhalational anthrax. Because of its high mortality rate, anthrax is not studied in intentionally exposed humans.
Because of concerns about its long-term safety, including effects on cartilage, ciprofloxacin was not approved for the elderly. But because the risk-benefit assessment says using ciprofloxacin for pediatric patients is appropriate, studies are under way to evaluate potential long-term safety effects on the elderly.
The recommended adult dose of ciprofloxacin for post-exposure inhalational anthrax is 500 mg given orally twice a day. The recommended pediatric dose of ciprofloxacin 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 60 days.
The most common adverse drug reactions from ciprofloxacin include nausea, vomiting, diarrhea, abdominal pain, rash, headache, and restlessness. In patients who have received ciprofloxacin for 60 days or longer, no new or unexpected adverse reactions were identified, compared with patients receiving shorter approved regimens.