Trovafloxacin mesylate - Generic Drug Details

What are the generic sources for trovafloxacin mesylate and what is the scope of patent protection?

Trovafloxacin mesylate is the generic ingredient in one branded drug marketed by Pfizer and is included in one NDA. Additional information is available in the individual branded drug profile pages.

Summary for trovafloxacin mesylate

US Patents:	0
Tradenames:	1
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	44
Patent Applications:	1,392
DailyMed Link:	trovafloxacin mesylate at DailyMed

Anatomical Therapeutic Chemical (ATC) Classes for trovafloxacin mesylate

J01MA	Fluoroquinolones
J01M	QUINOLONE ANTIBACTERIALS
J01	ANTIBACTERIALS FOR SYSTEMIC USE
J	Antiinfectives for systemic use

US Patents and Regulatory Information for trovafloxacin mesylate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Pfizer	TROVAN	trovafloxacin mesylate	TABLET;ORAL	020759-001	Dec 18, 1997		DISCN	No	No
Pfizer	TROVAN	trovafloxacin mesylate	TABLET;ORAL	020759-002	Dec 18, 1997		DISCN	No	No

Expired US Patents for trovafloxacin mesylate

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Pfizer	TROVAN	trovafloxacin mesylate	TABLET;ORAL	020759-001	Dec 18, 1997
Pfizer	TROVAN	trovafloxacin mesylate	TABLET;ORAL	020759-001	Dec 18, 1997
Pfizer	TROVAN	trovafloxacin mesylate	TABLET;ORAL	020759-002	Dec 18, 1997
Pfizer	TROVAN	trovafloxacin mesylate	TABLET;ORAL	020759-002	Dec 18, 1997

Market Dynamics and Financial Trajectory of Trovafloxacin Mesylate

Introduction

Trovafloxacin mesylate, marketed under the brand name Trovan by Pfizer, is a broad-spectrum antibiotic that was introduced to the market with high expectations but ultimately faced significant challenges.

Approval and Initial Market Performance

FDA Approval

Trovafloxacin mesylate was approved by the U.S. Food and Drug Administration (FDA) in December 1997 for use in patients aged 18 years and older[2].

Initial Sales

During its first full year on the market, Trovan contributed $160 million to Pfizer's total revenue of $12.6 billion. This was a promising start, with investors anticipating that the drug could eventually generate $1 billion in annual sales[2].

Market Reception and Usage

Clinical Applications

Trovafloxacin mesylate was designed to inhibit the uncoiling of supercoiled DNA in bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It showed broad-spectrum activity against both Gram-positive and Gram-negative bacteria, as well as anaerobic organisms. This made it a potential candidate for treating a wide range of bacterial infections[1][3].

Pharmacokinetics and Metabolism

The drug had a favorable pharmacokinetic profile, with an approximately 11-hour elimination half-life, allowing for once-daily administration. It also demonstrated good tissue penetration and was metabolized primarily by the liver through phase II metabolism[4].

Challenges and Adverse Events

Hepatotoxicity

One of the most significant challenges faced by trovafloxacin mesylate was its association with hepatotoxicity. Over 100 cases of acute liver injury were reported to the FDA, leading to a significant reevaluation of its safety profile[2].

Regulatory Actions

In June 1999, the FDA advised doctors to limit the prescription of trovafloxacin due to these adverse events. By May 2000, the FDA withdrew the marketing authorization for the drug. Similar actions were taken in the European Union, where the marketing authorization was suspended and eventually withdrawn in 2001[2].

Controversies and Litigation

Kano Trovafloxacin Trial

A major controversy surrounding trovafloxacin mesylate was the clinical trial conducted by Pfizer in Kano, Nigeria, in 1996. The trial was criticized for ethical violations, including the use of a reduced dose of the comparator drug, ceftriaxone, which could have skewed the results in favor of trovafloxacin. This led to significant public outcry and legal action against Pfizer[5].

Financial Impact

Revenue and Projections

Despite the initial revenue of $160 million in its first full year, the drug's financial trajectory was severely impacted by the withdrawal from the market. The anticipated annual sales of $1 billion never materialized, and the drug became a financial liability for Pfizer due to the costs associated with litigation and regulatory actions[2].

Economic Consequences

The withdrawal of trovafloxacin mesylate not only affected Pfizer's revenue but also led to a loss of investor confidence. The drug's failure highlighted the risks associated with pharmaceutical development and the importance of rigorous safety testing and ethical clinical practices.

Key Takeaways

• Approval and Initial Success: Trovafloxacin mesylate was approved by the FDA in 1997 and showed promising initial sales.
• Hepatotoxicity Concerns: The drug was associated with significant liver injury, leading to regulatory actions and its eventual withdrawal from the market.
• Controversies and Litigation: The Kano clinical trial controversy further damaged the drug's reputation and led to legal consequences.
• Financial Impact: The drug's financial trajectory was severely impacted, failing to meet projected sales and becoming a financial liability.

FAQs

What was the primary mechanism of action of trovafloxacin mesylate?

Trovafloxacin mesylate exerted its antibiotic activity by inhibiting the uncoiling of supercoiled DNA in bacteria by blocking the activity of DNA gyrase and topoisomerase IV[1][3].

Why was trovafloxacin mesylate withdrawn from the market?

Trovafloxacin mesylate was withdrawn due to the risk of hepatotoxicity, with over 100 cases of acute liver injury reported to the FDA[2].

What was the Kano trovafloxacin trial controversy about?

The controversy involved ethical violations in a clinical trial conducted by Pfizer in Kano, Nigeria, including the use of a reduced dose of the comparator drug, ceftriaxone, and falsification of ethics approval documents[5].

How did the withdrawal of trovafloxacin mesylate affect Pfizer financially?

The withdrawal led to a significant loss in projected revenue, with the drug failing to achieve its anticipated annual sales of $1 billion. It also resulted in costs associated with litigation and regulatory actions[2].

What were the pharmacokinetic advantages of trovafloxacin mesylate?

Trovafloxacin mesylate had an approximately 11-hour elimination half-life, allowing for once-daily administration, and demonstrated good tissue penetration. It was primarily metabolized by the liver through phase II metabolism[4].

Sources

1. Drugs.com - Trovan: Package Insert / Prescribing Information
2. Wikipedia - Trovafloxacin
3. TOKU-E - Trovafloxacin Mesylate
4. PubMed - Pharmacokinetics and metabolism of single oral doses of trovafloxacin
5. Wikipedia - Abdullahi v. Pfizer, Inc.