Sept. 6, 2005

FDA NOTICE

Determination That Penthrane (Methoxyflurane) Inhalation Liquid, 99.9 Percent, Was Withdrawn From Sale for Reasons of Safety or Effectiveness

SUMMARY: September 6, 2005 -- The Food and Drug Administration (FDA) has determined that Penthrane (methoxyflurane) Inhalation Liquid, 99.9 percent, was withdrawn from sale for reasons of safety or effectiveness. The agency will not accept or approve abbreviated new drug applications (ANDAs) for methoxyflurane inhalation liquid, 99.9 percent.

Penthrane (methoxyflurane) Inhalation Liquid, 99.9 percent, was the subject of NDA 13-056, held by Abbott Laboratories (Abbott). Penthrane is a potent inhalation anesthetic indicated to provide anesthesia for surgical procedures in which total duration of administration is anticipated to be 4 hours or less (not to be used at concentrations that provide skeletal muscle relaxation). Penthrane was also indicated to provide analgesia in obstetrics and in minor surgical procedures and for use by self-administration using hand held inhalers. In the Federal Register of August 16, 2001 (66 FR 43017), FDA withdrew approval of NDA 13-056 for Penthrane after Abbott notified the agency that Penthrane was no longer being marketed under NDA 13-056 and requested withdrawal of that application. Penthrane was then moved to the "Discontinued Drug Product List" section of the Orange Book.

In a citizen petition dated August 25, 2004 (Docket No. 2004P-0379/CP1), submitted under § 10.30 (21 CFR 10.30), and in accordance with § 314.161, AAC Consulting Group requested that the agency determine whether Penthrane (methoxyflurane) Inhalation Liquid, 99.9 percent, was withdrawn from sale for reasons of safety or effectiveness.

We have carefully reviewed our files for records concerning the withdrawal of Penthrane (methoxyflurane) Inhalation Liquid, 99.9 percent, including the NDA file for this drug product. We have also independently evaluated relevant literature and data for possible postmarketing adverse event reports. FDA has determined under §§ 314.161 and 314.162(a)(2) that Penthrane (methoxyflurane) Inhalation Liquid, 99.9 percent, was withdrawn from sale for reasons of safety. FDA's review shows that methoxyflurane, a volatile anesthetic agent, is associated with serious, irreversible, and even fatal nephrotoxicity and hepatotoxicity in humans. FDA has also reviewed the latest approved labeling for Penthrane and has determined that this labeling is inadequate. FDA believes that the risks of toxicity outweigh any potential benefits if methoxyflurane is used according to the latest approved labeling. Since the initial approval of Penthrane in 1962, with a subsequent finding of efficacy in the Federal Register of December 11, 1981 (46 FR 60652), alternative safe and effective anesthetics have been approved by FDA and entered the market. FDA has determined that new clinical studies are necessary before methoxyflurane could be considered for reintroduction to the market. The agency has determined, under § 314.161, that Penthrane (methoxyflurane) Inhalation Liquid, 99.9 percent was withdrawn from sale for reasons of safety. Therefore, Penthrane (methoxyflurane) Inhalation Liquid, 99.9 percent, will be removed from the list of drug products published in the Orange Book. FDA will not accept or approve ANDAs that refer to this drug product.

FOR FURTHER INFORMATION CONTACT:  Mary Catchings, Center for Drug Evaluation and Research (HFD-7), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-594-2041.