Pink Sheet is part of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC’s registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 8860726.

This copy is for your personal, non-commercial use. For high-quality copies or electronic reprints for distribution to colleagues or customers, please call +44 (0) 20 3377 3183

Printed By



Executive Summary

TEMAZEPAM DOSAGE STRENGTH CHANGES MAY ALTER RATE OF ABSORPTION and thus alter effectiveness over time, FDA told Wyeth in a Sept. 29 letter denying the firm's ANDA suitability petition for 10 mg and 20 mg temazepam soft gelatin capsules. The reference drug cited by Wyeth is Sandoz' Restoril capsules, 15 mg and 30 mg. "The information you have provided regarding your proposed 10 mg and 20 mg products indicates that they are more rapidly absorbed than the reference listed drug products but that total absorption is proportional to the total amount of the drug present," FDA Office of Drug Standards Director Peter Rheinstein stated. "Although the proposed products might, because of the initial rapid absorption, be expected to be equally effective with respect to sleep latency as the reference products, the smaller total dose and lower blood levels later at night might diminish the effectiveness of your drug products with respect to the duration of sleep or number of wakenings." FDA has approved a number of ANDA suitability petitions for changes in dosage strength from a listed product. Wyeth's temazepam petition is the first ANDA suitability request to be denied when both a higher strength and lower strength (for the proposed 20 mg product) are currently marketed. FDA said it has particular concerns regarding changes in dosage strength for two drug classes, narcotics and hypnotics. Rheinstein explained that the proposed 10 mg product "constitutes a strength that is one-third lower than the lowest approved strength of the listed reference drug product. Therefore, investigations are necessary to establish the effectiveness of the proposed product, including a demonstration of effectiveness with respect to sleep duration and number of wakenings." The 20 mg product "raises questions of both safety and effectiveness," Rheinstein stated. He noted that "based on its Cmax, the 20 mg capsule would be expected to substitute for, and be used in patients for whom the 30 mg dose of the reference product is labeled" even though the total absorption "would raise a question as to the proposed product's effectiveness for duration of sleep." Moreover, Rheinstein said, "if the proposed 20 mg product was used by people who would ordinarily use the referenced 15 mg product, the elderly or debilitated, the 20 mg product would provide a Cmax about twice as high as the 15 mg product." He stated that "this increase in Cmax raises concern regarding safety in people who need only the lower dose."

You may also be interested in...

Part D Discount Liability Coming Into Focus: CMS Releases Drug Cost Data

Newly released Medicare Part D data sheds light on the sales hit that branded pharmaceutical manufacturers will face when the coverage gap discount program gets under way in 2011

FDA Skin Infections Guidance Spurs Debate On Endpoint Relevance

FDA appears headed for a showdown with clinicians and the pharmaceutical industry over the proposed new clinical trial endpoints for acute bacterial skin and skin structure infections, the guidance's approach for justifying a non-inferiority margin and proposed changes in the types of patients that should be enrolled in trials

Shire Hopes To Sow Future Deals With $50M Venture Fund

Specialty drug maker Shire has quietly begun scouting deals with a brand-new $50 million venture fund, the latest of several in-house investment arms to launch with their parent company's pipelines, not profits, as the measure of their worth




Ask The Analyst

Please Note: You can also Click below Link for Ask the Analyst
Ask The Analyst

Your question has been successfully sent to the email address below and we will get back as soon as possible. my@email.address.

All fields are required.

Please make sure all fields are completed.

Please make sure you have filled out all fields

Please make sure you have filled out all fields

Please enter a valid e-mail address

Please enter a valid Phone Number

Ask your question to our analysts