August 23, 2003
PRODUCT DISCONTINUATION NOTICE
ORLAAM® (Levomethadyl hydrochloride acetate) Oral Solution, 10
mg/mL, CII
NDC 0054-3649-63
Dear Healthcare Professional:
Roxane Laboratories, Inc. is discontinuing the sale and
distribution of ORLAAM® (Levomethadyl hydrochloride acetate) Oral
Solution, 10 mg/mL after the current inventory is depleted. We
estimate that this will occur early in the first quarter of 2004.
Since the introduction of ORLAAM in 1995, Roxane Laboratories has
received increasing reports of severe cardiac-related adverse
events, including QT interval prolongation (15), Torsades de Pointes
(8) and cardiac arrest (6). Other cardiac-related adverse events
have also been reported, including arrhythmias, syncope, and angina.
These events led to the removal of ORLAAM from the European market
in March 2001, and extensive changes (including additional warnings
& contraindications) were made to the US package insert in April
2001 (Dear Healthcare Professional letter dated April 11, 2001).
Since these changes, the use of ORLAAM has decreased dramatically
over the last two years. While there may be a very small number of
patients who may benefit from ORLAAM, it is our belief that the
risks of continued distribution and use in the face of less toxic
treatment alternatives no longer outweigh the overall benefits.
ORLAAM is a synthetic opioid agonist solution indicated for the
management of opiate dependence, reserved for the treatment of
opiate-addicted patients who fail to show acceptable response to
other adequate treatments for opiate addiction. Other first-line
treatment options are available for the management of opiate
dependence, including methadone and the recently FDA-approved
buprenorphine. Methadone hydrochloride is available as an oral
solution and a dispersible tablet, both which will continue to be
manufactured by Roxane Laboratories and distributed by Cebert
Pharmaceuticals. Buprenorphine hydrochloride is available in two
sublingual formulations: one containing naloxone hydrochloride (Suboxone®,
Reckitt Benckiser Pharmaceuticals) and one without naloxone (Subutex®,
Reckitt Benckiser Pharmaceuticals). With these first-line agents
available for the treatment of opiate addiction, it is our hope that
existing patients can be converted to alternate therapies with
minimal disruption to them and the centers that treat them.
Due to the forecasted unavailability shortly after the beginning
of 2004, no new patients should be initiated on ORLAAM therapy. For
existing ORLAAM patients, it is extremely important for healthcare
providers to transfer patients to alternative treatments as soon as
possible prior to the product’s unavailability. To make sure this
transition occurs with minimal disruption to all patients involved,
we will reserve the right to limit purchase quantities based upon
historical annual volumes. Careful consideration should be given to
the appropriate conversion regimens. The information on the next
page is from the current package insert for ORLAAM:
Transfer from ORLAAM® to Methadone
:
Patients maintained on ORLAAM may be transferred directly to
methadone. Because of the difference between the two compounds’
metabolites and their pharmacological half-lives, it is
recommended that methadone be started on a daily dose at 80% of
the ORLAAM dose being replaced; the initial methadone dose must be
given no sooner than 48 hours after the last ORLAAM dose.
Subsequent increases or decreases of 5 to 10 mg in the daily
methadone dose may be given to control symptoms of withdrawal or,
less likely, symptoms of excessive sedation, in accordance with
clinical observations.
For further information about ORLAAM, please contact our
Technical Information Department at 1-800-962-8364 or our Customer
Service Department at 1-800-520-1631.
Respectfully,
Michael J. Schobelock, PharmD
Associate Director
Medical Affairs Department
Roxane Laboratories, Inc
P.O. Box 16532
Columbus, OH 43216