Trovafloxacin

Overview

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. It was withdrawn from the market due to the risk of hepatotoxicity. It had better Gram-positive bacterial coverage but less Gram-negative coverage than the previous fluoroquinolones.[1] WP

Risks and side effects

Adverse reactions

Trovafloxacin use is significantly restricted due to its high potential for inducing serious and sometimes fatal liver damage. Currently, the drug is not approved for use in the U.S. or the European Union due to association with cases of acute liver failure and death.[2] WP

Legal status

Legal status

The U.S. Food and Drug Administration approved trovafloxacin for therapeutic use in December 1997 for use in patients aged 18 years and older. In June 1999, the agency advised doctors to limit the prescription of trovafloxacin due to adverse events associated with the drug (over 100 cases of acute liver injury reported to FDA). In May 2000, the FDA withdrew marketing authorisation for trovafloxacin.[3] WP

Trovafloxacin received marketing authorisation in the European Union in October 1998. In June 1999, in view of reported adverse events, the Committee for Proprietary Medicinal Products recommended suspension of the marketing authorisation for a year. The suspension took effect in August 1999 and was renewed in September 2000. In October 2000, Pfizer notified the European Commission of its decision to voluntarily withdraw the marketing authorisation which was approved by EMA in March 2001.[4][5][6] WP

Economics

Trovan sales during its first full year on the market contributed US$160 million of Pfizer's total revenue of US$12.6 billion. Investors expected it to eventually bring in US$1 billion per year.[5] WP

Nigerian clinical trial controversy

In 1996, during a meningitis epidemic in Kano, Nigeria, the drug was administered to approximately 200 infected children. Eleven children died in the trial: five after taking Trovan and six after taking an older antibiotic used for comparison in the clinical trial. Others suffered blindness, deafness and brain damage, common consequences of meningitis that have not been seen in patients treated with trovafloxacin for other infection types. An investigation by the Washington Post concluded that Pfizer had administered the drug as part of an illegal clinical trial without authorization from the Nigerian government or consent from the children's parents. The case came to light in December 2000 as the result of an investigation by The Washington Post, and sparked significant public outcry. The most serious error was the falsification and backdating of an ethics approval letter 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 intramuscular ceftriaxone.[7–12] WP

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 on July 30, 2009. Two remaining federal lawsuits were settled in 2011. According to Wikileaked US embassy cables, Pfizer's country manager admitted that "Pfizer had hired investigators to uncover corruption links to federal attorney general Michael Aondoakaa to expose him and put pressure on him to drop the federal cases."[13–16] WP

Chemistry

Formula

C20H15F3N4O3 PC

CAS number

147059-72-1 PC

Molar mass (g/mol)

416.4 PC

IUPAC name (computed by PubChem)

7-[(1R,5S)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl]-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid PC

SMILES

C1[C@@H]2[C@@H](C2N)CN1C3=C(C=C4C(=O)C(=CN(C4=N3)C5=C(C=C(C=C5)F)F)C(=O)O)F PC

InChIKey

WVPSKSLAZQPAKQ-SOSAQKQKSA-N PC

PubChem CID

62959

IUPAC name

7-(6-Amino-3-azabicyclo WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Gootz TD, Zaniewski R, Haskell S, Schmieder B, Tankovic J, Girard D, Courvalin P, Polzer RJ. Activity of the new fluoroquinolone trovafloxacin (CP-99,219) against DNA gyrase and topoisomerase IV mutants of Streptococcus pneumoniae selected in vitro. Antimicrobial Agents and Chemotherapy. December 1996. doi:10.1128/AAC.40.12.2691 · PMID 9124824 · PMC163605
2. Journal / agency Pannu HK, Gottlieb L, Fishman EK. Acute liver failure due to trovafloxacin: CT findings. Emergency Radiology. 2001. doi:10.1007/PL00011876
3. Journal / agency Trovafloxacin – Approval Letter & Printed Labelling
4. Journal / agency Public statement on Trovan / Trovan IV / Turvel / Turvel IV: Withdrawal of the marketing authorisations
5. Other Petersen M. Unforeseen Side Effects Ruined One Blockbuster. August 27, 2000
6. Other Suspension of Trovan Drug in Europe Is Urged. June 12, 1999
7. Journal / agency Oldani M. The SAGE Encyclopedia of Pharmacology and Society. 2016. doi:10.4135/9781483349985.n409
8. Other Report of the Investigation Committee on the Clinical Trial of Trovafloxacin (Trovan) by Pfizer, Kano, 1996
9. Journal / agency Williams D, Hopkins S. Safety of trovafloxacin in treatment of lower respiratory tract infections. European Journal of Clinical Microbiology & Infectious Diseases. June 1998. doi:10.1007/bf01691582 · PMID 9758292
10. Journal / agency Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clinical Infectious Diseases. February 1999. doi:10.1086/515104 · PMID 10064255
11. Journal / agency Sabatini C, Bosis S, Semino M, Senatore L, Principi N, Esposito S. Clinical presentation of meningococcal disease in childhood. Journal of Preventive Medicine and Hygiene. June 2012. PMID 23240173
12. Other Stephens J. Panel Faults Pfizer in '96 Clinical Trial In Nigeria. May 7, 2006
13. Other Stephens J. Pfizer to Pay $75 Million to Settle Nigerian Trovan Drug-Testing Suit. July 31, 2009
14. Other Pfizer settles remaining Nigeria, US Trovan suits. 22 February 2011
15. Other Pfizer Settles Remaining District Court Litigation on Trovan Nigerian Clinical Trial. 25 February 2025
16. Other Boseley S. WikiLeaks cables: Pfizer 'used dirty tricks to avoid clinical trial payout'. 9 December 2010

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.