Trovafloxacin

Trovafloxacin (sold as Trovan by Pfizer and Turvel by Laboratorios Almirall) is a broad spectrum antibiotic that inhibits the uncoiling of supercoiled DNA in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV.^[1] It was withdrawn from the market due to the risk of hepatotoxicity. It had better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones.

Adverse reactions

Trovafloxacin is seriously restricted in its use due to its serious potential for inducing serious sometimes fatal liver damage.^[2]

Controversy

In 1996, during a meningitis epidemic in Kano, Nigeria, the then-untested drug was administered to approximately 100 infected children. 11 of the children died and the rest suffered various long term effects. A panel of medical experts later implicated Pfizer in the incident, concluding the drug had been administered as part of an illegal clinical trial without authorization from the Nigerian government or consent from the children's parents.^[3] The case came to light in December 2000 as the result of an investigation by The Washington Post, and sparked significant public outcry. The Nigerian federal government has subsequently sued the drug giant for $8.5bn and Pfizer will face criminal and civil charges brought by the state and federal governments of Nigeria. The most serious error was the falsification and backdating of an ethics approval leader by the lead investigator of the trial, Dr. Abdulhamid Isa Dutse. Dr. Dutse is now the chief medical officer of Aminu Kano Teaching Hospital. The result of the trial was that children treated with oral trovafloxacin had a 5% (5/100) mortality rate compared to a 6% (6/100) mortality rate with intravenous ceftriaxone. This was a non-significant difference.

When it went on the market in 1998 Trovan became one of Pfizer's top-selling drugs. When first-quarter earnings were announced in April of that year, the company's earnings had increased by 15% over the previous year, with analysts attributing much of that increase to the sales of the "new antibiotic" Trovan.^[4] Pfizer had spent hundreds of millions of dollars developing Trovan. In the first year it brought over US$160 million and investors expected it to eventually bring in US$1 billion per year.^[5]

In June 1999 the U.S. Food and Drug Administration advised doctors to limit the prescription of Trovan after it had been found "strongly associated" with 14 cases of acute liver failure and six deaths. The FDA had received over 100 reports of liver problems in people taking Trovan, which was at that time being prescribed at a rate of 300,000 patients per month in the United States. Two days later the Committee for Proprietary Medicinal Products recommended to the European Commission that marketing approval of Trovan be suspended for a year.^[5][6] Between 2002 and 2005 the victims of the Trovan tests in Nigeria filed a series of unsuccessful lawsuits in the United States. However, in January 2009, the United States Court of Appeals for the Second Circuit ruled that the Nigerian victims and their families were entitled to bring suit against Pfizer in the United States under the Alien Tort Statute. A US$75 million settlement with the State of Kano was reached July 30, 2009. ^[7]

The charges filed against Pfizer by Nigeria's federal government, which is still seeking about $6 billion in damages, were not affected by this settlement. Additionally two lawsuits also remain pending in New York, United States.^[7]

See also

• Alatrofloxacin, a prodrug of trovafloxacin for intravenous administration
• Fluoroquinolone toxicity
• Fluoroquinolone

References

External links

• Abdullahi v Pfizer. US Court of Appeals 2d Cir 30 Jan 2009