Avoids drug-induced "buzz" or "high"

TRANXENE starts working promptly-yet with no reports
of the initial euphoria that may be seen with the highly
lipid-soluble agent diazepam 2 This "buzz" effect, though
transitory, may reinforce drug-taking behavior, 34

Helps avoid effects that encourage drug-seeking behavior
Tranxene, a long-acting benzodiazepine, has a built-in
tapering action There is no abrupt termination of
pharmacologic effects By contrast, a short-acting agent
(like lorazepam) may cause anxiety-like rebound symptoms.
These can encourage drug-seeking behavior and
unwarranted readministration. 4.

Helps avoid disruptive effects of therapy

Eight years of clinical experience demonstrate that
TRANXENE calms smoothly. It seldom causes problems
due to oversedation and has a low incidence of significant
side effects.

Reference is made to my telephone conversation with Dr. David Scally
on May 15 during which we discussed our proposed revision of the
package insert pertinent to the directions for intravenous use of
VERSED Injection for conscious sedation. A copy of the annotated
changes in the package insert, which are currently being implemented,
is enclosed.

The following changes are being made to help clarify the
VERSED Injection for I.V. conscious sedation:

use of

34

FFL

2)

HOFFMANN-LA ROCHE INC • NUTLEY •

NEW JERSEY

Division of Neuropharmacological Drug Products

June 20, 1986

Page 2

Please note that the dosage per se has not been revised.

The attached revised language of the package insert was discussed with Dr. Scally on May 15 and he concurs with the revision.

These editorial revisions are being made to provide more succinct directions for use and to help prevent the possibility of one starting titration with a dose of 0.1 to 0.15 mg/kg rather than titrating the dosage to this endpoint. Also, the time period over which titration should take place is further clarified.

In accordance with 21 CFR §314.70(c)(2)(iii), these changes are being effected immediately. All stock packaged on or after July 15, 1986 will bear the revised insert (date code 0686). All promotional materials currently being prepared reflect this package insert revision.

Twelve copies of final printed labeling are enclosed herein.