On the Move

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I N T H E T R E AT M E N T O F PA R K I N S O N ’ S D I S E A S E

HELP KEEP YOUR PATIENTS

ON THE MOVE

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Select a Treatment Stategy That Suits Your Patients Patient Profile:

17

Jack

Taking low-dose L-dopa, efficacy “wearing off” • • • •

High Doses of L-dopa Increase the Risk of Dyskinesia %

of early PD patients treated with L-dopa over 40 weeks experienced dyskinesia at 600 mg/day (n=91; P<0.001).2

• Placebo: 3% (n=90) • 150 mg/day: 3% (n=92) • 300 mg/day: 2% (n=88)

58 years of age, works full time Plays golf every weekend Diagnosed 8 months ago, Hoehn and Yahr stage II After 8 months, efficacy of L-dopa (150 mg/day) has diminished (symptoms back to pretreatment intensity)

AAN guidelines recommend DAs to reduce the risk of dyskinesia vs L-dopa3

Treatment Strategy: Instead of increasing L-dopa dose, REQUIP was added to PD treatment regimen

Treatment with REQUIP offers symptom relief, reduced risk of dyskinesia, and less need for L-dopa 4,5 Adjunct Therapy

Monotherapy

✓ Effective control of

For PD patients requiring symptomatic therapy, either L-dopa or a dopamine agonist (DA) can be used.1

✓ Reduced risk of dyskinesia

Changes in total scores from baseline at week 42 on the Unified Parkinson’s Disease Rating Scale (UPDRS)2*

✓ Monotherapy with REQUIP may delay L-dopa use4

Placebo (n=90)

8 150 mg (n=92) 300 mg (n=88) 600 mg (n=91)

4 0 -4 -8 2

6

10

14

18

22

26

30

34

38

42

46

Week Baseline

✓ Decreases awake time spent “off” 5 Offers patients with PD more “on” time each day

Withdrawal of Study Drug

*From the Parkinson’s Disease Study Group. Changes in subjects treated with L-dopa at different doses or with placebo were determined on the basis of total scores on the UPDRS. Scores were obtained by blinded treating investigators who performed the evaluation before the daily morning dose of the study drug. Points on the curves indicate mean changes from baseline in total scores at each visit. Improvement in parkinsonism is represented by lower scores and worsening is depicted by higher scores.

Negative scores on the curves indicate improvement from baseline.The bars indicate standard error.

Lower doses of L-dopa only maintain control for a brief period of time 2 • Many patients who initially achieved symptom relief with L-dopa returned to baseline starting at week 222 • Higher doses of L-dopa (600 mg/day) were necessary for patients to achieve the best results2

✓ Improves PD symptom relief

Supplement with L-dopa when eventually needed PD Study Group, p2502

Change in Total Score (units)

4

Associated with reduced risk of dyskinesia vs L-dopa

12

5

Enables a gradual decrease in L-dopa dose and spares the need for additional L-dopa

PD symptoms Provides benefits comparable to L-dopa

As PD progresses, the efficacy of lower doses of L-dopa wear off 2

2

✓ Reduces L-dopa dose

4

5

Offers patients with motor fluctuations enhanced antiparkinsonian benefits

REQUIP—get your patients started The 8-week Sample Kit of REQUIP allows patients to achieve a daily dose of 9 mg, if needed.

Start patients with It’s Your Move™ to help them stay on therapy.

REQUIP has been associated with sedating effects, including somnolence, and the possibility of falling asleep while engaged in activities of daily living, including operation of a motor vehicle. Syncope or symptomatic hypotension may occur more frequently during initial treatment or with an increase in dose. Hallucinations may occur at any time during treatment.

REQUIP may potentiate the dopaminergic side effects of L-dopa and may cause and/or exacerbate pre-existing dyskinesias.

See Important Safety Information on page 13.

Please consult the complete Prescribing Information available from your representative.

3

REQUIP or L-dopa?

IN THE TREATMENT OF PARKINSON’S DISEASE (PD)

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DYSKINESIA

I N E A R LY P A R K I N S O N ’ S D I S E A S E …

Prescribe REQUIP as Initial Monotherapy to Delay Dyskinesia

Incidence of disabling dyskinesia in a 5-year study4,6‡

Cindy

Newly diagnosed, concerned about dyskinesia

P<0.001

• 62 years of age, works part time • Enjoys arts and crafts • Newly diagnosed (no previous therapy) Hoehn and Yahr stage I • Experiencing rigidity and slowness of movement • Learned about disabling dyskinesia from patient Web site and has concerns about taking a medication

23% Patients (%)

19.1%

Treatment Strategy: Started on monotherapy with REQUIP using the 8-week Sample Kit

8% 1.7% REQUIP (n=179)

L-dopa

(n=89) (prior to L-dopa supplementation)

In the only 5-year study with a DA, monotherapy with REQUIP significantly reduced the risk of dyskinesia vs L-dopa.4

‡

REQUIP +/- L-dopa +/- L-dopa (n=179) (n=89) (regardless of L-dopa supplementation)

Rascol, p1487

Patient Profile:

Decrease Your Patients’ Risk of Disabling Dyskinesia

Disabling dyskinesia was defined as any positive response on items 32 and 33 of the UPDRS.

Percentage of patients who were dyskinesia-free over 5 years4*†

9.5X

P<0.001 REQUIP (n=177) L-dopa (n=88)

80%

§

55%

REQUIP—get your patients started

Prior to L-dopa supplementation

Regardless of L-dopa supplementation

*Excludes 3 patients (1 L-dopa, 2 REQUIP) with baseline dyskinesia. †

Expressed as a hazard ratio of 9.52 (95% Cl [2.77, 32.77]).

64%

A subset analysis of a 5-year, double-blind, multicenter, randomized trial of REQUIP vs L-dopa in patients with early PD (Hoehn & Yahr stage I-III at baseline).

Rascol, p1487

Patients (%)

95%

• Prior to L-dopa supplementation, the risk of disabling dyskinesias with L-dopa was more than 9.5 times greater than with REQUIP (P=0.0004)6§

The 8-week Sample Kit of REQUIP allows patients to achieve a daily dose of 9 mg, if needed.

Start patients with It’s Your Move™ to help them stay on therapy.

REQUIP has been associated with sedating effects, including somnolence, and the possibility of falling asleep while engaged in activities of daily living, including operation of a motor vehicle. Syncope or symptomatic hypotension may occur more frequently during initial treatment or with an increase in dose. Hallucinations may occur at any time during treatment.

REQUIP may potentiate the dopaminergic side effects of L-dopa and may cause and/or exacerbate pre-existing dyskinesias.

See Important Safety Information on page 13.

Please consult the complete Prescribing Information available from your representative.

4

5

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I N E A R LY P A R K I N S O N ’ S D I S E A S E …

It’s Your Move—Prescribe REQUIP From the Start to Reduce PD Symptoms and Maintain ADLs Patient Profile:

Maintains ADLs Comparable With L-dopa Monotherapy with REQUIP maintained activities of daily living (ADLs) for 5 years, comparable with L-dopa: Monotherapy (Part II, UPDRS)4,6‡

Rita

Experiencing tremor P=NS

Mean ADL Score (total range 0-52)

50

Treatment Strategy: Initial monotherapy with REQUIP using 8-week Sample Kit and It’s Your Move™ program

REQUIP L-dopa

20 15 10 5 0

0

1

2

3

4

5

60 51

39 39

29 REQUIP 29 L-dopa

Years 179 89

Improvement in PD-related tremor comparable with L-dopa7

‡

126 72

86 58

Patient numbers

Rascol, p1489

52 years of age Works full time in her home office Cooks every evening for her family Newly diagnosed (no previous therapy) Hoehn and Yahr stage I Experiencing tremor in left arm Family is noticing changes in her ability to move and perform daily activities

TREMOR/ADLs

• • • • • • •

Data from a subset analysis of a 5-year, double-blind, multicenter, randomized trial with REQUIP vs L-dopa in patients with early PD (Hoehn & Yahr stage I-III at baseline). A lower ADL score correlates with an improved ability to perform ADLs.

Improvement in UPDRS motor score item 20: tremor at rest (head, upper, and lower extremities)7*† P=0.47

3 yrs

1.0

0.75

0.8

0.8

REQUIP (n=160)

L-dopa (n=177)

Prescribing initial monotherapy with REQUIP delayed the need for L-dopa a median duration of 3 years.6

0.5

0

*Results from 1 of 3 multicenter, randomized, double-blind trials comparing REQUIP monotherapy with L-dopa, bromocriptine, and †

placebo treatment, respectively, for improvement of resting tremor and postural/action tremor (measured by items 20 and 21 of the motor section of the UPDRS). The study was not powered or designed to demonstrate non-inferiority.

REQUIP group baseline=2.5; L-dopa group baseline=2.3. Improvement represented by a reduction in score between baseline and end point. There was no statistically significant difference between the REQUIP and L-dopa study arms.

Schrag, p255

0.25

REQUIP—get your patients started The 8-week Sample Kit of REQUIP allows patients to achieve a daily dose of 9 mg, if needed.

Start patients with It’s Your Move™ to help them stay on therapy.

REQUIP has been associated with sedating effects, including somnolence, and the possibility of falling asleep while engaged in activities of daily living, including operation of a motor vehicle. Syncope or symptomatic hypotension may occur more frequently during initial treatment or with an increase in dose. Hallucinations may occur at any time during treatment.

REQUIP may potentiate the dopaminergic side effects of L-dopa and may cause and/or exacerbate pre-existing dyskinesias.

See Important Safety Information on page 13.

Please consult the complete Prescribing Information available from your representative.

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IN ADVANCED PARKINSON’S DISEASE…

Patient Profile:

Adjunct Therapy With REQUIP—Reducing the Risk of Motor Complications by Lowering L-dopa Doses Reduction in daily L-dopa dose in patients treated with L-dopa + REQUIP5‡§II

Meredith

Experiencing “off” time • • • • • • •

50

60 years of age Recently retired Enjoys morning hikes with her husband Spends weekends watching her grandchildren Diagnosed 2 years ago Hoehn and Yahr stage II Her “off” time is interfering with daily activities (hiking, playtime with the grandkids)

0 -50 -100

-242 mg/day

-150

31%

Lieberman, p1059

AAN Guidelines Identify REQUIP as an Effective Option for Reducing “Off” Time5,8

-200 -250

Reduction from baseline (n=95)

Treatment Strategy: Prescribe REQUIP in addition to L-dopa

Reduction in dose

L-dopa

Percentage of patients who showed improvement on the Clinical Global Impression-Improvement (CGI-I) Scale5¶

REQUIP enabled close to a 2-hour daily reduction in awake time spent “off” in a 6-month adjunct therapy trial 6*†

P=0.002

1.86 hrs/day reduction

+ placebo (n=54)

0.78 hrs/day reduction

59 % 32 % L-dopa

+ REQUIP

(n=95)

• REQUIP allowed for a reduction in awake time spent “off” by more than 13 hours per week.*†

+ placebo

(n=54)

REQUIP—get your patients started The 8-week Sample Kit of REQUIP allows patients to achieve a daily dose of 9 mg, if needed.

• For the primary end point, 28% of REQUIP patients achieved both a ≥20% reduction in “off” time and L-dopa dose vs 11% for L-dopa + placebo (P=0.003)

REQUIP has been associated with sedating effects, including somnolence, and the possibility of falling asleep while engaged in activities of daily living, including operation of a motor vehicle. Syncope or symptomatic hypotension may occur more frequently during initial treatment or with an increase in dose. Hallucinations may occur at any time during treatment.

REQUIP may potentiate the dopaminergic side effects of L-dopa and may cause and/or exacerbate pre-existing dyskinesias.

L-dopa

Lieberman, p1059, 1060

L-dopa

Patients (%)

REQUIP + L-dopa (n=95)

“ O F F ” T I M E / L - D O PA D O S E

• Adding REQUIP reduced L-dopa dose by 191 mg more than placebo (-242 mg/day [n=95] vs -51 mg/day [n=54], P<0.001)5

Start patients with It’s Your Move™ to help them stay on therapy.

*Data from a 6-month, double-blind, multicenter, randomized, placebo-controlled trial of REQUIP as adjunct therapy with supplemental in patients with PD (Hoehn & Yahr stage II-IV at baseline). The primary end point was a ≥20% reduction in awake time spent “off” and a ≥20% reduction in total daily L-dopa dose between baseline and final visits.

Analysis of the change in total awake hours spent “off” over 2 days. Mean change from baseline for REQUIP (-3.72) vs placebo (-1.86).

An analysis for 1 day was calculated as -3.72/2=1.86 for REQUIP and -1.56/2=0.78 for placebo. ‡ Mean daily dose of L-dopa at baseline: 759 ± 422 mg (REQUIP + L-dopa) and 843 ± 517 mg (placebo + L-dopa). § Includes those patients with reductions due to adverse events.

II Excludes patients with reduction in L-dopa dose due to adverse events and excludes 1 ropinirole patient from the primary efficacy analysis. ¶ Percentage of patients rated as improved (score 1, 2, or 3) on the CGI-I Scale.

L-dopa

†

See Important Safety Information on page 13.

Please consult the complete Prescribing Information available from your representative.

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IN THE TREATMENT OF PARKINSON’S DISEASE…

Manage Your Patients’ Needs With a Long-Term Treatment Strategy Patient Profile:

REQUIP—Your Long-Term Treatment Strategy for Parkinson’s Disease After initial titration, you have the flexibility to increase your patients’ total daily dose of REQUIP, as needed, to a maximum of 24 mg

Richard

Benefits from monotherapy • • • • • •

8-week Sample Kit of REQUIP allows patients to achieve a daily dose of 9 mg

65 years of age Enjoys keeping his garden in bloom Has a passion for travel and sightseeing Diagnosed 5 years ago Hoehn and Yahr stage II Experiencing some slowness of movement that interferes with ADLs

Dose adjustment (up to 24 mg/day) by MD’s prescription as guided by patient symptoms

24.0 mg

22.0 mg 20.0 mg Weeks

1

18.0 mg

8

16.0 mg

9.0 mg

Treatment Strategy: Monotherapy with REQUIP, dose titrated as needed.

Sample Kit allows patients to achieve a daily dose of 9 mg

14.0 mg 12.0 mg

16.5 mg

8.0 mg 6.0 mg 4.0 mg

10.1 mg

2.0 mg

In pooled clinical trials, ≥75% of responders achieved an initial response at doses up to 9 mg/day 9 *†

24 mg/day: maximum daily dose

16.5 mg/day: average dose at 5 years in a 5-year study 4,6‡

10.1 mg/day: average dose at 6 months in a 5-year study 4,6‡

Strategic Management of PD

*Initial response was defined as a 30% reduction in UPDRS motor score from baseline. †

Analysis of pooled data from 3 clinical trials at 6 months in early PD patients (Hoehn & Yahr stage I-III) receiving monotherapy with REQUIP (n=463).

The average daily dose was: at 6 months, 10.1 ± 5.8 mg and at 5 years, 16.5 ± 6.6 mg of ropinirole (plus 427 ± 221 mg of open-label L-dopa in patients requiring supplementation).

‡

Dose

L-dopa

when required

Titrate up to maintain efficacy

Monotherapy with REQUIP Time/Disease Progression

REQUIP—get your patients started Start patients with It’s Your Move™ to help them stay on therapy.

DOSING

The 8-week Sample Kit of REQUIP allows patients to achieve a daily dose of 9 mg, if needed.

REQUIP has been associated with sedating effects, including somnolence, and the possibility of falling asleep while engaged in activities of daily living, including operation of a motor vehicle. Syncope or symptomatic hypotension may occur more frequently during initial treatment or with an increase in dose. Hallucinations may occur at any time during treatment.

REQUIP may potentiate the dopaminergic side effects of L-dopa and may cause and/or exacerbate pre-existing dyskinesias.

See Important Safety Information on page 13.

Please consult the complete Prescribing Information available from your representative.

10

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REQUIP Delivers Progressive Dosing for a Progressive Disease

IN THE TREATMENT OF PARKINSON’S DISEASE…

Important Safety Information

Titrate REQUIP to achieve maximum therapeutic response (up to 24 mg/day)

The 5 most common adverse events occurring with REQUIP in a 5-year comparative clinical trial4,6

Recommended titration schedule based on individual patient response Step

Individual Dose (TID)

Total Daily Dose

Week 1

0.25 mg

0.75 mg/day

Week 2

0.5 mg

1.5 mg/day

Week 3

0.25 mg + 0.5 mg

2.25 mg/day

Week 4

1 mg

3 mg/day

Week 5

1 mg + 0.5 mg

4.5 mg/day

Week 6

2 mg

6 mg/day

Week 7

2 mg + 0.5 mg

7.5 mg/day

Week 8*

3 mg

9 mg/day

Step 9

4 mg

12 mg/day

Step 10

5 mg

15 mg/day

Step 11

6 mg

18 mg/day

Step 12

7 mg

21 mg/day

Step 13

8 mg

24 mg/day

Tablets

• Dosage should be increased to achieve a maximum therapeutic effect, balanced against principal side effects

REQUIP—get your patients started The 8-week Sample Kit of REQUIP allows patients to achieve a daily dose of 9 mg.* • Color-coded Tiltab® Tablets clearly identify different dosage strengths and facilitate easy handling

* The Sample Kit of REQUIP provides dosing up to 9 mg/day. After week 8, if necessary, the total daily dose may be increased to a maximum of 24 mg.

12

REQUIP (± added L-dopa)

L-dopa

(± added L-dopa)

Adverse Event

Withdrawals

Adverse Event

Withdrawals

Nausea

49%

3%

49%

6%

Somnolence

27%

1%

19%

0%

Insomnia

25%

0%

24%

0%

Parkinsonism aggravated

22%

3%

20%

3%

Dyspepsia

21%

0%

17%

1%

• The incidence of hallucinations was greater with REQUIP (17%, n=31/179) than with L-dopa (6%, n=5/89). Other neuropsychiatric adverse events were similar between groups, although the study was not designed or powered to detect differences4 • The percentage of patients remaining in the study was comparable for REQUIP and L-dopa over 5 years4

Requip has been associated with sedating effects, including somnolence, and the possibility of falling asleep while engaged in activities of daily living, including operation of a motor vehicle. Requip should be discontinued if these events occur; it is unknown if dose reduction will eliminate episodes of somnolence. Prescribers should reassess patients for somnolence throughout treatment.

Syncope or symptomatic hypotension may occur, particularly during initial treatment or dose titration. Patients should be cautioned against rising rapidly after sitting or lying down. Because of possible additive effects, caution should be exercised with patients who have sleep disorders or are taking sedating medications, alcohol, CNS depressants, or medications that increase ropinirole plasma levels.

Hallucinations may occur at any time during treatment. REQUIP may potentiate the dopaminergic side effects of L-dopa and may cause and/or exacerbate pre-existing dyskinesias.

Some epidemiologic studies have shown that patients with Parkinson’s disease have a higher risk (perhaps 2- to 4-fold higher) of developing melanoma than the general population. Whether the observed increased risk was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, was unclear.

SAFETY

Please consult the complete Prescribing Information available from your representative.

Adverse Event

Although REQUIP has not been associated with an increased risk of melanoma specifically, its potential role as a risk factor has not been systematically studied. Patients using REQUIP for any indication should be made aware of these results and should undergo periodic dermatologic screening.

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IN THE TREATMENT OF PARKINSON’S DISEASE…

Start Your Patients’ Long-Term Treatment Strategy With REQUIP REQUIP—offering options for a broad range of patients’ needs Early-Onset Patients Initial monotherapy with REQUIP • Significantly reduces the risk of dyskinesia vs L-dopa4 • Maintains patients’ ADLs comparable with L-dopa4

Advanced Parkinson’s Disease Patients Adjunct therapy with REQUIP

• Significantly reduces awake time spent “off”5 • Helps reduce or spare the need for additional L-dopa—which may reduce the risk of developing motor complications, such as dyskinesia5 • Patients experience substantial improvement as measured by the CGI-I Scale5

TRIM FOR POCKET

Early or Advanced Parkinson’s Disease Patients • REQUIP provides progressive dosing to meet individual patient needs • Established safety and tolerability—used in clinical practice in the US since 1997

REQUIP—get your patients started The 8-week Sample Kit of REQUIP allows patients to achieve a daily dose of 9 mg, if needed.

Start patients with It’s Your Move™ to help them stay on therapy.

REQUIP has been associated with sedating effects, including somnolence, and the possibility of falling asleep while engaged in activities of daily living, including operation of a motor vehicle. Syncope or symptomatic hypotension may occur more frequently during initial treatment or with an increase in dose. Hallucinations may occur at any time during treatment.

REQUIP may potentiate the dopaminergic side effects of L-dopa and may cause and/or exacerbate pre-existing dyskinesias.

See Important Safety Information on page 13.

Please consult the complete Prescribing Information available from your representative.

References: 1. Miyasaki JM, et al. Neurology. 2002;58:11-17. 2. The Parkinson Study Group. N Engl J Med. 2004;351:2498-2508.

3. Olanow CW, et al. Neurology. 2001;56(suppl 5):S1-S88. 4. Rascol O, et al. N Engl J Med. 2000;342:1484-1491. 5. Lieberman A, et al. Neurology. 1998;51:1057-1062. 6. Data on file, GlaxoSmithKline. 7. Schrag A, et al. Eur J Neurol. 2002;9:253-257. 8. Pahwa R, et al. Neurology. 2006;66:983-995. 9. Korczyn AD, et al. Acta Neurol Scand. 2002;106:200-204.

Note to representative: When this information is shown to healthcare professionals, complete Prescribing Information must be left behind.

The Together Rx Access™ Card has eligibility requirements. Retail pharmacy costs may vary.

©2006 The GlaxoSmithKline Group of Companies All rights reserved.

Printed in USA. RQP813R0 August 2006

A Progressive Therapy for a Progressive Disease www.requip.com/pd