Hi Dick & Margie and All,
This subject was discussed at length about a year and a half ago...

‘Sleep Attacks’ from Drugs?
Parkinson’s Treatment Led to Car Accidents
By Lauran Neergaard - The Associated Press
W A S H I N G T O N,   June 9, 1999 —  Two new drugs for Parkinson’s
disease may suddenly put patients to sleep, a dangerous narcolepsy-like
side effect termed “sleep attack” that has caused at least eight people to
have car wrecks, doctors warned today.
http://www.abcnews.go.com/sections/living/DailyNews/parkinsonsdrug
s990609.html

Detroit News (same story but this link won't *wrap* on you)
http://detnews.com/1999/health/9906/11/06100194.htm

The 2 drugs cited in the news story were mirapex and requip...

This is the study that launched the press releases...
Neurology 1999 Jun 10;52(9):1908-10
Falling asleep at the wheel: motor vehicle mishaps in persons taking
pramipexole and ropinirole.
Frucht S, Rogers JD, Greene PE, Gordon MF, Fahn S
Columbia-Presbyterian Medical Center, New York, NY, USA.
The authors report a new side effect of the dopamine agonists
pramipexole and ropinirole: sudden irresistible attacks of sleep. Eight PD
patients taking pramipexole and one taking ropinirole fell asleep while
driving, causing accidents. Five experienced no warning before falling
asleep. The attacks ceased when the drugs were stopped. Neurologists
who prescribe these drugs and patients who take them should be aware
of this possible side effect.
PMID: 10371546, UI: 99297956
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=Pu
bMed&list_uids=10371546&dopt=Abstract

Narcolepsy-like Side Effect
The FDA is considering requiring the manufacturers of two new drugs
for Parkinson’s disease to add an additional warning to their labeling
after reports of a dangerous side effect called "sleep attack." Sudden
feelings of overwhelming and irresistible sleepiness have occurred in
at least 12 patients receiving Pharmacia & Upjohn’s Mirapex
(pramiprexole) and SmithKline Beecham’s Requip (ropinirole), resulting
in eight car accidents and four  "sleep attacks" during business
meetings and phone calls.  Manufacturers are currently investigating
whether these medications specifically caused the attacks or  whether
patient condition or drug interactions may be at fault. Both medications
were approved in 1997 for the treatment of muscle rigidity, tremors and
difficulty moving  associated with Parkinson’s disease. Caution patients
not to stop taking their medications unless advised to do so by their
physician.
Drug Facts and Comparisons News July  99
http://pswi.org/ltc/summer99/briefs.htm

in Canada... College of Physicians and Surgeons of BC Fall 1999
Warning  
Sudden onset of sleep in patients taking Mirapex (pramipexole) was the
subject of a Dear Health Care Professional letter issued in July. Unlike
typical drug-related sedation, patients taking Mirapex often had no
warning that they were about to fall asleep. Car accidents have been
recorded; tell patients to avoid hazardous activities that require mental
alertness, such as driving a car, while taking Mirapex. The Canadian
ADR Monitoring Program has received a report of a sudden sleep attack
associated with another dopamine agonist, Requip (ropinirole).
http://www.cpsbc.bc.ca/physician/quarterly/26.htm

Who are the ADR?
Adverse Drug Reactions  - New ADR Telephone Number
The telephone number for the BC Regional ADR Centre has just
changed to 806-8625. Both health professionals and patients can call
this line to report a suspected adverse drug reaction and to ask if we
know of previous reports of specific reactions in BC, Canada or reported
to the WHO ADR Monitoring Program. They are also accessible by fax
(604) 806-8262 and e-mail [log in to unmask]

in Germany...
 Nervenarzt 2000 Aug;71(8):670-6
["Sleep attacks" in Parkinson patients. A side effect of nonergoline
dopamine agonists or a class effect of dopamine agonists]?
[Article in German]
Moller JC, Stiasny K, Cassel W, Peter JH, Kruger HP, Oertel WH
Klinik fur Neurologie, Philipps-Universitat Marburg.
Recently, sudden "sleep attacks" have been described in parkinsonian
patients taking the nonergoline dopamine agonists pramipexole and
ropinirole. Due to this possible side effect, patients must be instructed
not to drive vehicles and to refrain from other activities carrying the risk
of self-injury. However, the very existence of sleep attacks remains
controversial in sleep medicine, since a gradual transition from
wakefulness to sleep is normally observed. Accordingly, sudden onset
of sleep, e.g., in narcolepsy or sleep apnea syndrome, is usually
associated with excessive daytime sleepiness. Prevalence of sleep
disorders and daytime sleepiness have been shown to be increased in
Parkinson's disease. Nonergoline dopamine agonists are already known
to induce somnolence. Currently, it is not predictable whether sleep
attacks represent a sudden transition from wakefulness to sleep or result
from an increased propensity to fall asleep, with patients perceiving a
sudden onset. Possible pathophysiological mechanisms and legal
implications of sleep attacks are discussed.
PMID: 10996919, UI: 20451472

in the US....
Mov Disord 2000 Jul;15(4):658-63
Pramipexole-induced somnolence and episodes of daytime sleep.
Hauser RA, Gauger L, Anderson WM, Zesiewicz TA
Department of Neurology, University of South Florida, Tampa General
Hospital, USA.
[Medline record in process]
Pramipexole is a non-ergot dopamine agonist used to treat Parkinson's
disease (PD). Because of concern regarding driving safety, we evaluated
the incidence and nature of somnolence experienced by patients
receiving pramipexole in clinical trials at our center. A retrospective chart
review was performed and structured interviews were conducted with
patients who had reported moderate or severe somnolence. In addition,
two patients underwent polysomnography (PSG) and multiple sleep
latency tests (MSLT) while on and 2 weeks after discontinuation of
pramipexole. Forty patients with PD participating in pramipexole clinical
trials were identified. In the double-blind phases of the studies, 22
patients were randomized to pramipexole and 18 were randomized to
placebo. Six patients assigned to pramipexole reported somnolence as an
adverse event (1 moderate, 5 mild) compared with two patients assigned
to placebo (1 severe, 1 moderate; p = 0.19, one-tailed Fisher's exact test).
Thirty-seven patients participated in open-label extension studies.
Twenty-one (57%) reported somnolence as an adverse event. Eleven
(30%) patients reported moderate somnolence and three (8%) patients
reported severe somnolence. For patients with moderate or severe
somnolence, the onset of worst-reported somnolence occurred at a mean
(+/- standard error) pramipexole dose of 4.0 +/- 0.4 mg (range, 0.75-4.5
mg) per day. Patients had been taking pramipexole for a total of 10.0 +/-
1.5 months (range, .03-22 mos) and at their maximal dose for 6.7 +/- 1.5
months (range, .03-20 mos). During structured interviews with 12 of the
14 patients reporting moderate or severe somnolence, seven reported
falling asleep while driving and two reported minor motor vehicle
accidents caused by falling asleep. Most patients reported relatively
continuous drowsiness that led to falling asleep without acute warning
during periods of inactivity. Three patients reported discreet waves of
irresistible sleepiness heralded by prodromal symptoms occurring
against a background of normal wakefulness. MSLT in two of these
patients revealed decreased latency to sleep without early onset of rapid
eye movements. Sleep latency normalized after withdrawal of
pramipexole. Intensive patient education is necessary to prevent motor
vehicle accidents in patients taking pramipexole. We recommend that
patients who are experiencing generalized drowsiness and falling asleep
during periods of inactivity be instructed not to drive because these
patients do fall asleep without acute warning. Somnolence usually
resolves with pramipexole dose reduction or discontinuation. Patients
should also be alerted to pull over and stop driving immediately if they
feel a wave of sleepiness coming on. Patient education and compliance
are critical to maximize safety.
PMID: 10928575, UI: 20382319

and around the World ... with or without PD...
Accid Anal Prev 1999 Nov;31(6):639-49
Road accidents caused by drivers falling asleep.
Sagberg F
Institute of Transport Economics, Oslo, Norway. [log in to unmask]
About 29600 Norwegian accident-involved drivers received a
questionnaire about the last accident reported to their insurance
company. About 9200 drivers (31%) returned the questionnaire. The
questionnaire contained questions about sleep or fatigue as
contributing factors to the accident. In addition, the drivers reported
whether or not they had fallen asleep some time whilst driving. and what
the consequences had been. Sleep or drowsiness was a contributing
factor in 3.9% of all accidents, as reported by drivers who were at fault
for the accident. This factor was strongly over-represented in night-time
accidents (18.6%), in running-off-the-road accidents (8.3%), accidents
after driving more than 150 km on one trip (8.1%), and personal injury
accidents (7.3%). A logistic regression analysis showed that the
following additional factors made significant and independent
contributions to increasing the odds of sleep involvement in an
accident: dry road, high speed limit, driving one's own car, not driving
the car daily, high education, and few years of driving experience. More
male than female drivers were involved in sleep-related accidents, but
this seems largely to be explained by males driving relatively more than
females on roads with high speed limits. A total of 10% of male drivers
and 4% of females reported to have fallen asleep while driving during
the last 12 months. A total of 4% of these events resulted in an accident.
The most frequent consequence of falling asleep--amounting to more
than 40% of the reported incidents--was crossing of the right edge-line
before awaking, whereas crossing of the centreline was reported by
16%. Drivers' lack of awareness of important precursors of falling asleep-
-like highway hypnosis, driving without awareness, and similar
phenomena--as well as a reluctance to discontinue driving despite
feeling tired are pointed out as likely contributors to sleep-related
accidents. More knowledge about the drivers' experiences immediately
preceding such accidents may give a better background for
implementing effective driver warning systems and other
countermeasures.
PMID: 10487339, UI: 99415261

This from the National Parkinson Foundation & Dr. Lieberman...
"Sleep Attacks: Sudden Episodes of Falling Asleep Without Warning,
Without Being Drowsy, Or Falling Asleep Without Remembering
You Were Drowsy?"  by Abraham Lieberman MD
http://www.parkinson.org/sleepreq.htm

Another opinion - Dr. Stacey...
AH Moderator: My husband is newly diagnosed with PD and is taking
Mirapex, which makes him a little drowsy. We've heard about falling
asleep at the wheel - does he need to stop driving? Should we consider
another dopamine agonist?

Dr. M Stacy: Recently there was a report at a scientific meeting that
found an increased frequency of sleep attacks in several patients on
Mirapex and one patient on ReQuip.  While excessive sleepiness is a
concern with almost all anti-PD medications, the occurrence of a sudden
sleep attack poses a potential personal and public safety risk. In your
case, since your husband reports sleepiness on Mirapex, I believe it is
reasonable to try Permax or ReQuip.  However, in general, I believe that
Mirapex, Permax, and ReQuip are very well tolerated. These do not
usually require any adjustment in patients doing well. I have not advised
my patients to discontinue driving when starting a dopamine agonist
but it is important to know of this potential problem.
http://www.wemove.org/par_pdwc9_30_99.html

and - PDF & Dr. Stanley Fahn...
Risk of "sleep attacks" with some PD medications prompts stern
warning from PDF
http://www.pdf.org/news/index.cfm?fuseaction=details&selectedItem=32

What the Pharmacists say......
Warning on Parkinson`s drugs
An important finding about Mirapex® (pramipexole) and Requip®
(ropinirole) Doctors have noted that a small number of patients who take
these drugs have had "sleep attacks", sudden and overpowering
feelings of intense fatigue. Some of these attacks have led to automobile
accidents. If you take Mirapex or Requip, ask your doctor for more
details about these findings. The risk of sleep attack is very low, but you
should be aware of the possibility.
http://www.rpspharmacy.com/nl/warningOnParkinson.asp

The FDA and Safety Alert...
SafetyAlerts September 22, 1999
FDA Posts Warning of Parkinson's Drug Causing Patients to
Unexpectedly Sleep - Even While Driving
http://www.safetyalerts.com/t/g/mirapex.htm

The bottom line in all of this -
Due to this possible side effect, patients must be instructed not to drive
vehicles and to refrain from other activities carrying the risk of self-
injury.

Thus Dr. Bob Finks caution....

Best regards .......... murray


On 17 Dec 2000, at 18:15, Dick Swindler wrote:

> Bob -
>
> I'm a bit unclear as to how you intend your caution about Mirapex to be
> read.
>  Is it your position that no one should try Mirapex because of possible
>  sleep
> attacks, or are you suggesting that it should be tried with caution?  I
> don't know if there are any studies suggestion that if one hasn't
> experienced a sleep attack after X number of weeks or months on the
> drug, then one isn't likely to experience them at all.  It would be
> interesting to know.
>
> After two-plus years of Dick's taking Mirapex with extremely positive
> results and no problems, ever, with sleepiness or sleep attacks, it
> seems to me that we can feel comfortable that the problem isn't going to
> arise.
>
> Margie

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