DEPARTMENT OF VETERANS AFFAIRS VETERAN HEALTH ADMINISTRATION (VHA)
PHARMACY BENEFITS MANAGEMENT SERVICES (PBM) & MEDICAL ADVISORY PANEL (MAP)
VA CENTER FOR MEDI
CATION SAFETY (VAMedSAFE)
NATIONAL PBM COMMUNICATION
·
January 16
, 2013
Zolpidem and FDA-Proposed Lower Doses Due To Impaired Mental Alertness
FDA mandates making label changes to lower doses of immediate and extended-release zolpidem products (Ambien®, Ambien CR®,
Edluar®, Zolpimist®) at bedtime due to impaired mental alertness the following morning. New dosing recommendations do not apply
to Intermezzo®, a lower dose zolpidem product approved for middle-of–the-night awakenings.
o
Pharmacokinetic a
nd driving simulation studies show that blood levels of zolpidem above 50ng/mL may cause impairment
while operating a vehicle and increase the risk of accidents.
Extended
-
release formulations impart greater next
-
morning impairment than immediate
-
rmulations.
Women are more susceptible to next
-
morning impairment due to a slower rate of elimination for zolpidem than
men.
o
Studies have detected blood levels of zolpidem over 50ng/mL as much as 8 hours post
-
dose.
Trials involving 10 mg Ambien (or bioequi
valent zolpidem products) resulted in 15% of women and 3% of men with
zolpidem concentrations that exceeded 50 ng/mL approximately 8 hours post
-dosing.
Trials of zolpidem extended
-release 12.5 mg resulted in approximately 33% of women and 25% of men with
zolpidem blood concentrations exceeding 50 ng/mL approximately 8 hour
s post
-dosing.
FDA requires that manufacturers of
affected
zolpidem products revise product labeling to reflect lower recommended doses and to
warn that higher than recommended doses may more likely impair activities requiring full alertness the next morn
ing, including
driving.
PRODUCT CURRENT DOSING IN PRODUCT LABEL NEW DOSING RECOMMENDED BY FDA
Ambien, Edluar, Zolpimis
t
(and generic equivalents)
Men and Women:
10 mg once daily, immediately before bedtime
Women:
5 mg once daily, immediately before bedtime
Men:
5 or 10 mg once daily, immediately before bedtime
Ambien CR (and ge
neric
equivanlent)
Men and Women:
12.5 mg once daily, immediately before bedtime
Women:
6.25 mg once daily, immediately before bedtime
Men:
6.25 or 12.5 mg once daily, immediately before bedtime
FDA recommends that healthcare practitioners should:
o
Prescribe the lowest dose capable of treating patients’ insomnia symptoms;
o Caution patients regarding possible impairment in driving and activities that require alertness the next morning, despite
feeling fully awake.
VA MedSAFE recommends that providers should:
o
Consider inquiring about morning driving and other morning activities in patients who take zolpidem or similar medications.
o
Consider discontinuing the medication or l
owering the dose if patients feel drowsy in mornings after using sleeping
medications such as zolpidem
.
o
Notify patients to watch for morning drowsiness and for any signs of impaired driving (or other activities) when taking any
sleeping medication.
o
C
ont
inue to report any adverse reactions with the use of any zolpidem product(s)
or other drugs for the treatment of
insomnia
by entering the in
formation into CPRS’ Allergies/
Adverse Reactions field and/or via local reporting mechanisms.
Adverse events should
also be reported, as appropriate, to the VA ADERS program and FDA MedWatch (1
-
800
-
FDA
-
1088, fax
1
-
800
-
FDA
-
0178, online at
https://www.accessdata.fda.gov/scripts/m
edwatch/medwatch
-
online.htm
, or by mail).
The Zolpi
dem
Immediate Release Recommendation for Use text within the
Primary Care Outpatient Algorithm: Treatment of Acute
and Chronic Insomnia
document is in the process of being updated. Providers/staff are encouraged to become familiar with other
areas within the document that provides additio
nal information/resources regarding the management of insomnia including a basic
sleep history, sleep hygiene ed
u
c
ation, and other modalites such as Cognitive Behavioral Therapy (CBT).
REFERENCES
FDA Drug Safety Communication: Risk of next
-
morning impairm
ent after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem
(Ambien, Ambien CR, Edluar, and
Zolpimist)
.
http://www.fda.gov/Drugs/DrugSafety/uc
m334033.htm
. (Accessed 01/11/13).
ACTIONS:
Facility Director (or physician designee): Forward this document to the Facility Chief of Staff (COS).
Facility COS and Chief Nurse Executives: Forward this document to all appropriate providers who prescribe this agent (e.g.,
primary care providers, including contract providers, etc.). In addition, forward to the Associate Chief of Staff (ACOS) for
Research and Development (R&D). Forward to other VA employees as deemed appropriate.
ACOS for R&D: Forward this document to Principal Investigators (PIs) who have authority to practice at the facility and to your
respective Institutional Review Board (IRB).