Anyone heard of Mirapex?

July 3, 2004

Hi there: just had a visit with the rheumy and he is trying me on a

new drug " Mirapex " he said it is experimental using for RA and is

used for Parkinsons.........It is supposed to help with the

fatigue. I just started it and go back to rheumy in 10 days.......

I also take Plaquenil, Prednisone....Darvocet and some anti-

inflammatories............

Would like to know if anyone knows anything about this drug.

Thanks and hopefully you will all enjoy your 4th of July holiday

painfree.

Hugs

Pat in So. Oregon

July 5, 2004

In a message dated 03/07/2004 12:43:55 Central Standard Time,

bureau97504@... writes:

> Would like to know if anyone knows anything about this drug.

>

Mirapex is often used for restless leg syndrome as well, but initially was a

Parkinson's drug. Cary

July 5, 2004

Pat,

Here is the prescribing info from their website.

http://www.mirapex.com/C/about.asp

I can¹t find anything on the web that Mirapex is being used experimentally

for RA. It is used for Parkinson's and restless leg syndrome. I found

where it is being used off label for depression, but this site says it makes

you more tired, so I can¹t see where it will help with fatigue.

http://www.crazymeds.org/mirapex.html

All the sites listed fatigue as a side effect, so I¹m really curious why it

was prescribed for you.

When you go back to your doctor, maybe you want to ask more questions.

a

> Hi there: just had a visit with the rheumy and he is trying me on a

> new drug " Mirapex " he said it is experimental using for RA and is

> used for Parkinsons.........It is supposed to help with the

> fatigue. I just started it and go back to rheumy in 10 days.......

> I also take Plaquenil, Prednisone....Darvocet and some anti-

> inflammatories............

>

> Would like to know if anyone knows anything about this drug.

>

> Thanks and hopefully you will all enjoy your 4th of July holiday

> painfree.

>

> Hugs

> Pat in So. Oregon

>

July 6, 2004

Maybe I am mixed up about what my rhemy told

me.......I have fibro too so maybe it was for

that.......guess I had better listen more closely,

huh? I go back soon so I will clarify exactly what he

said..........

Thanks again!

Pat in So Ore.

-- a <paula54@...> wrote:

> Pat,

> Here is the prescribing info from their website.

>

> http://www.mirapex.com/C/about.asp

>

> I can¹t find anything on the web that Mirapex is

> being used experimentally

> for RA. It is used for Parkinson's and restless leg

> syndrome. I found

> where it is being used off label for depression, but

> this site says it makes

> you more tired, so I can¹t see where it will help

> with fatigue.

>

> http://www.crazymeds.org/mirapex.html

>

> All the sites listed fatigue as a side effect, so

> I¹m really curious why it

> was prescribed for you.

> When you go back to your doctor, maybe you want to

> ask more questions.

> a

>

> > Hi there: just had a visit with the rheumy and he

> is trying me on a

> > new drug " Mirapex " he said it is experimental

> using for RA and is

> > used for Parkinsons.........It is supposed to help

> with the

> > fatigue. I just started it and go back to rheumy

> in 10 days.......

> > I also take Plaquenil, Prednisone....Darvocet and

> some anti-

> > inflammatories............

> >

> > Would like to know if anyone knows anything about

> this drug.

> >

> > Thanks and hopefully you will all enjoy your 4th

> of July holiday

> > painfree.

> >

> > Hugs

> > Pat in So. Oregon

> >

July 6, 2004

Pat, since RLS is so common in fibromyalgia, some physicians have been

treating their FMS patients with Mirapex (pramipexole dihydrochloride)

in the hopes that their sleep quality improves and, thus, lessens

daytime fatigue.

Below is a recent letter to the Journal of Rheumatology that should

explain what you need to know.

*************************

Journal of Rheumatology

December 2003

Letter to the Editor

Fibromyalgia and Pramipexole: Promise and Precaution

To the Editor:

Despite 13 years of research after the establishment of criteria1,

fibromyalgia syndrome (FM) remains difficult to understand and even more

difficult to treat effectively. However, 2 articles provide important

insight into pathogenesis and lead to a new treatment paradigm involving

pramipexole.

First, Moldofsky and colleagues describe FM symptoms in healthy controls

after an auditory arousal from stage IV sleep over 4 nights2. Second,

Yunus and Aldag identified restless legs syndrome (RLS)

disproportionately in subjects with FM versus healthy controls (31 % vs

2%, respectively)3. Therefore, FM could be the predictable consequence

of prolonged and intense stage IV sleep deprivation, but reduction of

the arousal (perhaps RLS as one example) was more important than

induction of stage IV sleep with antidepressants.

Lorazepam and clonazepam (2 mg qhs) reduce RLS4. In a retrospective

chart review, they also reduced FM tenderness scores for 82% of 202

patients at 2 weeks5 and for 62% of 174 patients at one year6 when added

to nighttime antidepressants. By intention-to-treat (ITT) analysis at

one year, 54% had = 50% decrease in tenderness score using either

clonazepam or lorazepam 2 mg qhs.

Pramipexole is a second-generation dopamine 2 (D2) receptor agonist,

approved by the US Food and Drug Administration in 1997 for Parkinson's

disease, that is remarkably effective treatment for RLS7. It has strong

affinity for the dopamine 3 receptor subtype in the D2 family, mild

affinity for the central alpha-2 adrenoreceptor (target of clonidine),

and no affinity for other dopamine, benzodiazepine, norepinepherine, or

serotonin receptors.

A retrospective chart review of pramipexole for 166 patients with FM

revealed encouraging results8. Patients added pramipexole to their best

regimen to date and increased by 0.125-0.25 mg weekly, similar to its

use for RLS. For those who continued pramipexole for more than 7 days (n

= 127), the tenderness score decreased 54% at a mean dose of 1.55 mg qhs

for 2-12 months (mean 4 mo). Inefficacy correlated with seeing a

psychiatrist (p < 0.05, chi-square test), but not with age, pretreatment

tenderness score, or disability. Twenty-three percent quickly

discontinued for non-serious intolerances, usually nausea or anxiety.

There were no serious adverse events even with doses up to 6.0 mg qhs.

By ITT analysis (n = 166), 58% achieved = 50% decrease in tenderness

score, even though 22 (13%) discontinued pramipexole before they could

be evaluated. Other measures of FM activity were not collected. Further,

for 19 patients unresponsive or intolerant to pramipexole, ITT analysis

showed that 74% achieved = 50% decreased tenderness score after adding

the other known dopamine 3-specific agonist, ropinirole, for a mean of 4

months9. Unfortunately, 13 of 19 also eventually discontinued for

non-serious intolerances, especially nausea.

Since then, a strategy to decrease gastrointestinal intolerance has been

very helpful. Of 89 consecutive patients given pramipexole scheduled to

increase by 0.25 mg weekly to 2.0 mg qhs, 57 (75%) noted some nausea

when interviewed at 3 weeks (0.75 mg dose). However, 39 of 57 continued

treatment and controlled nausea by using one of 4 branded proton pump

inhibitors (PPI) qhs at supratherapeutic doses (3 tablets). Of 16 who

discontinued pramipexole, 8 refused the PPI and 6 took < 3 tablets qhs.

Diarrhea and other PPI intolerances were infrequent. At 8 weeks

(pramipexole 2.0 mg qhs), PPI use was not different from pretreatment

use (16% vs 15%, respectively). Individual PPI success was

unpredictable, ranging from 33% to 54%.

Finally, much higher pramipexole doses have been prescribed, as the most

therapeutic dosage for FM appears to be 4.5 mg qhs achieved over 12

weeks. With careful monitoring, doses have been increased up to 10.5 mg

qhs in select, previously injured, narcotic-dependent patients. A

retrospective chart review of usual clinical practice for consecutive

patients taking = 2.25 mg qhs (2.25-10.5 mg qhs) revealed 195 patients

taking a mean dose of 4.2 mg for 7.6 months (range 2-25 mo). Patients

discontinued because of cost (0.5%), inefficacy (5%), and intolerance

(4%), including nausea (1.6%), daytime somnolence (1.1%), anxiety

(0.8%), headache (0.2%), and dizziness (0.2%). Certainly, more patients

had intolerances, but discontinuation rates were unexpectedly low,

possibly because the patients were a select group (already tolerating =

2.25 mg qhs) or because the efficacy of pramipexole outweighed the

degree of intolerance.

In summary, pramipexole may become an important option for patients with

FM, but further studies are required to confirm these results and

improve its application. Nevertheless, manipulating dopamine-related

central nervous system regulatory mechanisms must be gradual, and

initial nausea prevented whenever possible. These preliminary safety

data are incomplete, but to date, there are no published data at single

pramipexole doses > 2.25 mg for any condition. Until more sophisticated,

randomized, blinded, placebo-controlled studies are completed, these

data may illustrate potential benefits and important precautions when

considering pramipexole for FM.

ANDREW J. HOLMAN, MD, Pacific Rheumatology Associates, 4300 Talbot Road

South, Suite 101, Seattle, Washington 98055, USA.

REFERENCES

1. Wolfe F, Smythe HA, Yunus MB, et al. The American College of

Rheumatology 1990 criteria for the classification of fibromyalgia.

Report of the Multicenter Criteria Committee. Arthritis Rheum

1990;33:160-72.

2. Moldofsky H, Scarisbrick P, England R, Smythe H. Musculoskeletal

symptoms and non-REM sleep disturbance in patients with " fibrositis

syndrome " and healthy subjects. Psychosom Med 1975;37:341-51.

3. Yunus M, Aldag J. Restless legs syndrome and leg cramps in

fibromyalgia syndrome: a controlled study. BMJ 1996;312:1339.

4. Saletu M, Anderer P, Saletu-Zyhlarz G, et al. Restless legs

syndrome and periodic limb movement: acute placebo-controlled sleep

laboratory studies with clonazepam. Eur Neuropsychopharmacol

2001;11:153-61.

5. Holman AJ. Effect of lorazepam on pain score for refractory

fibromyalgia [abstract]. Arthritis Rheum 1998;41 Suppl:A1359.

6. Holman AJ. Safety and efficacy of lorazepam for fibromyalgia after

one year [abstract]. Arthritis Rheum 1999;42 Suppl:A487.

7. Lin SC, Kaplan J, Burger CD, Fredrickson PA. Effect of

pramipexole in treatment of resistant restless legs syndrome. Mayo Clin

Proc 1998;73:497-500.

8. Holman AJ. Safety and efficacy of the dopamine agonist,

pramipexole, on pain score for refractory fibromyalgia [abstract].

Arthritis Rheum 2000;43 Suppl:A1599.

9. Holman AJ. Ropinirole, a dopamine agonist, for refractory

fibromyalgia: preliminary observations [letter]. J Clin Rheumatol

2003;9:277-9.

http://www.jrheum.com/subscribers/03/12/letters.html

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I'll tell you where to go!