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For your patients with moderate-to-severe primary Restless Legs Syndrome (RLS)‌
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[ Are their legs keeping them up at night? ] CHECK 4 RLS * 1
PATIENT PROFILE—STEPHANIE, 42 YEARS OLD
Reason for visit Annual physical Symptoms Trouble falling asleep Medication Taking sleep aids on and off for a few months
Recognize common descriptors of RLS1,2
Urge to move the legs Temporary relief with movement Onset or worsening of symptoms at rest or inactivity Worsening or onset of symptoms in the evening or at night
Restless Legs Syndrome (RLS)— An Irresistible Urge to Move
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Requip Helps Relieve the Urge to Move After 2 Nights With the Starting Dose
CREEPING CRAWLING TINGLING ACHING BURNING PULLING PAINFUL ITCHING
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RLS affects approximately 10% of the US adult population3,4†‡
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It is important to rule out secondary RLS, which may be related to other underlying conditions (eg, pregnancy, renal failure, iron deficiency)1
CRAMPING
Long-term results maintained at 9 months10
Dopamine agonists Dopamine storage vesicles P resynaptic neuron
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Responders (88/202) from a 24-week, single-blind study were placed into a double-blind phase for an additional 12 weeks (total of 36 weeks)10
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Significantly fewer patients relapsed on ropinirole vs placebo (33% vs 58%; P=0.0156)10
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69% of patients significantly improved with Requip vs 47% with placebo (P=0.0298)10¶
[ S t a rt Appropriate Patients With a 2-Week Sample Kit and 1-mg Pre s c r i p t i on]
Dopamine Postsynaptic neuron
The precise mechanism of action with Requip as t reatment for RLS is unknown; however, it is theorized that dopamine agonists affect RLS.5
Requip is indicated for patients with moderate-to-severe primary RLS.
Dopamine receptors Stimulation of dopamine receptors with a dopamine agonist 6
RLS is classified under DSM-IV 307.47 and ICD-9 333.997,8 diecut Key diagnostic criteria developed by the International Restless Legs Syndrome (IRLS) Study Group in collaboration with the National Institutes of Health. Includes mild, moderate, and severe RLS. A large multinational trial in 23,052 patients to assess frequency, impact, and medical response to RLS in a primary care population. TREAT RLS US=Therapy with Ropinirole, Efficacy and Tolerability in RLS in the United States (n=380): a 12-week, randomized, double-blind, placebo-controlled trial to assess efficacy/safety of Requip vs placebo in the treatment of moderate-to-severe primary RLS. || Overall discontinuation rates due to adverse events (AEs) at 12 weeks in 4 clinical trials for RLS (TREAT RLS 1, TREAT RLS 2, TREAT RLS US, and RESET PLM). ¶ A multicenter, double-blind, randomized, placebo-controlled study to evaluate maintained efficacy and tolerability of Requip at a fixed dose vs placebo in the long-term treatment of moderate-to-severe primary RLS (n=92). Maintenance of response was defined as those who did not relapse, where relapse was defined as a deterioration of at least 6 points on the IRLS Rating Scale to a total score of at least 15 points or withdrawal due to lack of efficacy. Clinicians reported patient improvement on the Clinical Global Impression-Improvement (CGI-I) Scale. *
†
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, particularly during initial treatment or dose titration. Please see Important Safety Information on page 8.
‡ §
2
Please consult the complete Prescribing Information available from your representative. 3
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[ Are their legs keeping them up at night? ] CHECK 4 RLS * 1
PATIENT PROFILE—CHARLES, 58 YEARS OLD
Reason for visit Follow-up appointment Symptoms Anxious and irritable, uncomfortable at rest, leg tingling Medication Taking a benzodiazepine for 3 weeks
Urge to move the legs Temporary relief with movement Onset or worsening of symptoms at rest or inactivity Worsening or onset of symptoms in the evening or at night
Requip Helps Relieve the Urge to Move After 2 Nights
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Requip Helps Relieve the Urge to Move at 9 Months
Dopamine agonists Dopamine storage vesicles P resynaptic neuron Dopamine Postsynaptic neuron
The precise mechanism of action with Requip as t reatment for RLS is unknown; however, it is theorized that dopamine agonists affect RLS.5
RLS symptoms share common ground with depressive symptoms11
Dopamine receptors Stimulation of dopamine receptors with a dopamine agonist 6
RLS is classified under DSM-IV 307.47 and ICD-9 333.997,8 ■
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SLEEP DISTURBANCES
Responders (88/202) from a 24-week, single-blind study were placed into a double-blind phase for an additional 12 weeks (total of 36 weeks)10 Significantly fewer patients relapsed on ropinirole vs placebo (33% vs 58%; P=0.0156)10
Requip is not a controlled substance
LOSS OF ENERGY
[ S t a rt Appropriate Patients With a 2-Week Sample Kit and 1-mg Pre s c r i p t i on]
WORK DIFFICULTIES
Requip is indicated for patients with moderate-to-severe primary RLS.
IRRITABILITY
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, particularly during initial treatment or dose titration.
diecut
Please see Important Safety Information on page 8. *
Key diagnostic criteria developed by the International Restless Legs Syndrome (IRLS) Study Group in collaboration with the National Institutes of Health. TREAT RLS US (n=380): a 12-week, randomized, double-blind, placebo-controlled trial to assess efficacy/safety of Requip vs placebo in the treatment of moderate-to-severe primary RLS. ‡ A multicenter, double-blind, randomized, placebo-controlled study to evaluate maintained efficacy and tolerability of Requip at a fixed dose vs placebo in the long-term treatment of moderate-to-severe primary RLS (n=92). Maintenance of response was defined as those who did not relapse, where relapse was defined as a deterioration of at least 6 points on the IRLS Rating Scale to a total score of at least 15 points or withdrawal due to lack of efficacy. Clinicians reported patient improvement on the Clinical Global Impression-Improvement (CGI-I) Scale. § Overall discontinuation rates due to AEs at 12 weeks in 4 clinical trials for RLS (TREAT RLS 1, TREAT RLS 2, TREAT RLS US, and RESET PLM). †
4
Please consult the complete Prescribing Information available from your representative. 5
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PATIENT PROFILE—PATRICIA, 38 YEARS OLD
Reason for visit Test results Symptoms Creeping leg sensations, kicks legs while sleeping, sleep disturbances Medication Prescribed a dopaminergic agent a month ago
Requip Helps Reduce Periodic Leg Movements With Arousal (PLMA)
[ Are their legs keeping them up at night? ] CHECK 4 RLS * 1
Urge to move the legs Temporary relief with movement Onset or worsening of symptoms at rest or inactivity Worsening or onset of symptoms in the evening or at night
✓ ✓ ✓ ■ ✓ ■ ■ ■
Requip—Improve RLS Symptoms and the Urge to Move
Periodic leg movements often coexist with RLS1,13 SUPPORT AN RLS DIAGNOSIS MAY CAUSE AROUSAL AND FURTHER DISRUPT SLEEP PATIENTS MAY NOT BE AWARE THEY ARE OCCURRING
Requip is metabolized by the liver ■
Hepatically impaired patients may have higher plasma levels and lower clearance of the drug. Therefore, the drug should be titrated with caution in this population
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Dosage adjustment may be required if Requip is used with estrogen or CYP450 1A2 inhibitors, such as ciprofloxacin
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No dosage adjustment is necessary for patients with mild-to-moderate renal impairment (creatinine clearance 30 to 50 mL/min). Requip has not been studied in patients with severe renal impairment
[ S t a rt Appropriate Patients With a 2-Week Sample Kit and 1-mg Pre s c r i p t i on] Requip is indicated for patients with moderate-to-severe primary RLS. 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, particularly during initial treatment or dose titration. Please see Important Safety Information on page 8.
*
Key diagnostic criteria developed by the International Restless Legs Syndrome (IRLS) Study Group in collaboration with the National Institutes of Health. An objective evaluation in a 12-week, randomized, double-blind trial (n=65) of Requip in moderate-to-severe primary RLS patients with periodic leg movements during sleep (PLMS index) and those that cause arousal (PLMA index). Excludes patients who did not have postbaseline polysomnographic (PSG) assessment. ‡ The IRLS Rating Scale contains 10 items designed to assess the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence, impact on activities of daily living, and mood associated with RLS. § A combined post hoc analysis (based on individual analysis of each rating scale item) at week 12 of three 12-week, randomized, double-blind, placebo-controlled trials (TREAT RLS US [n=380], TREAT RLS 1 [n=284], TREAT RLS 2 [n=266]) to assess efficacy/safety of Requip vs placebo in the t reatment of moderate-to-severe primary RLS.
†
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Please consult the complete Prescribing Information available from your representative. 7
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Requip has been extensively studied in 5 core RLS placebo-controlled TREAT RLS 1 TREAT RLS 2 trials with 1197 patients
[ Are their legs keeping them up at night? ] CHECK 4 RLS * 1
Urge to move the legs Temporary relief with movement Onset or worsening of symptoms at rest or inactivity Worsening or onset of symptoms in the evening or at night
✓ ✓ ✓ ■ ✓ ■
9, 10,14-16
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TREAT RLS US RESET PLM Maintenance of Effect
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Important Safety Information 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. P rescribers 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 ro p i n i ro l e plasma levels.
Help Relieve the Urge to Move With Once-a-Day Dosing Helpful information for patients
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Overall low rate of discontinuation due to AEs (5% vs 4% with placebo) with Requip‡
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Instruct patients to take their medication every day, 1 to 3 hours before bedtime, even if symptoms are not present
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Continue dose titration as needed up to 4 mg/day based on adequate clinical response and tolerability
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If a dose is missed, patients should be advised not to double their next dose
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If a significant interruption in therapy with Requip has occurred, retitration of therapy may be warranted
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Occurrence of nausea in clinical trials was generally mild to moderate in intensity. Taking Requip with food may reduce the occurrence of nausea. This has not been established in controlled clinical trials
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When increasing the dosage of Requip, caution patients about the potential for feeling faint, dizzy, or nauseated when standing from a sitting position
+ 1 to 3 hours before bedtime
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The safety and effectiveness of Requip at >4 mg/day in patients with RLS have not been established
[ S t a rt Appropriate Patients With a 2-Week Sample Kit and 1-mg Pre s c r i p t i on] Requip is indicated for patients with moderate-to-severe primary RLS.
diecut
*Key diagnostic criteria developed by the International Restless Legs Syndrome (IRLS) Study Group in collaboration with the National Institutes of Health. † AEs in >5% of patients treated with Requip and twice the rate of patients treated with placebo. ‡ Overall discontinuation rates due to AEs at 12 weeks in 4 clinical trials for RLS (TREAT RLS 1, TREAT RLS 2, TREAT RLS US, and RESET PLM).
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Please consult the complete Prescribing Information available from your representative. 9
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Requip has been extensively studied in 5 core RLS placebo-controlled TREAT RLS 1 TREAT RLS 2 trials with 1197 patients 9, 10, 14-16
TREAT RLS US RESET PLM Maintenance of Effect
Published Clinical Trials for Requip
Treat RLS US Pivotal Trial With Requip
[ S t a rt Appropriate Patients With a 2-Week Sample Kit and 1-mg Pre s c r i p t i on] *Key diagnostic criteria developed by the International Restless Legs Syndrome (IRLS) Study Group in collaboration with the National Institutes of Health. † TREAT= Therapy with Ropinirole, Efficacy and Tolerability. ‡ TREAT RLS US (n=380): a 12-week, randomized, double-blind, placebo-controlled trial to assess efficacy/safety of Requip vs placebo in the treatment of moderate-to-severe primary RLS.
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References: 1. Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology: a report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4:101-119. 2. Ondo W, Jankovic J. Restless legs syndrome: clinicoetiologic correlates. Neurology. 1996;47:1435-1441. 3. Phillips B, Young T, Finn L, Asher K, Hening WA, Purvis C. Epidemiology of restless legs syndrome in adults. Arch Intern Med. 2000;160:2137-2141. 4. Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, Ferini-Strambi L. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med. 2004;5:237-246. 5. Cˇ ervenka S, Pålhagen SE, Comley RA, et al. Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. In press. 6. Webster RA. Diseases of the basal ganglia. In: Webster RA, ed. Neurotransmitters, Drugs and Brain Function. Chichester, England: John Wiley & Sons Ltd; 2001. 7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000. 8. Hart AC, Hopkins CA, eds. ICD-9-CM Professional for Physicians—Volumes 1 & 2: International Classification of Diseases, 9th Revision, Clinical Modification. 6th ed. Salt Lake City, Utah: Ingenix, Inc; 2004. 9. Bogan RK, Fry JM, Schmidt MH, Carson SW, Ritchie SY, for the TREAT RLS US Study Group. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc. 2006;81:17-27. 10. Montplaisir J, Karrasch J, Haan J, Vole D. Ropinirole is effective in the long-term management of restless legs syndrome: a randomized, controlled trial. In press. 11. Hornyak M, Kopasz M, Berger M, Riemann D, Voderholzer U. Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome. J Clin Psychiatry. 2005;66:1139-1145.12. Data on file, GlaxoSmithKline.13. Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lespérance P. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov Disord. 1997;12:61-65. 14. Trenkwalder C, Garcia-Borreguero D, Montagna P, et al, on behalf of the TREAT RLS 1 Study Group. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry. 2004;75:92-97. 15. Walters AS, Ondo WG, Dreykluft T, et al, on behalf of the TREAT RLS 2 Study Group. Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebo-controlled study. Mov Disord. 2004;19:1414-1423. 16. Allen R, Becker PM, Bogan R, et al. Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome. Sleep. 2004;27:907-914.
Requip is indicated for patients with moderate-to-severe primary RLS. 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, particularly during initial treatment or dose titration. Please see Important Safety Information on page 8.
HELP RELIEVE THE URGE TO MOVE After 2 nights Up to 9 months Low rate of AE discontinuation Please consult the complete Prescribing Information available from your representative. 11
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WHEN?
[ Are their legs keeping them up at night? ] CHECK 4 RLS * 1
Urge to move the legs Temporary relief with movement Onset or worsening of symptoms at rest or inactivity Worsening or onset of symptoms in the evening or at night
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In Patients With Moderate-to-Severe Primary RLS… WHY?
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1 to 3 hours before bedtime
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Requip has been extensively studied in 5 core RLS placebo-controlled trials with 1197 patients9,10,14-16 Requip has extensive formulary coverage
For more information about Requip, visit our Web site at WWW.REQUIP.COM HOW?
[ S t a rt Appropriate Patients With a 2-Week Sample Kit and 1-mg Pre s c r i p t i on] Requip is indicated for patients with moderate-to-severe primary RLS. 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, particularly during initial treatment or dose titration. Please see Important Safety Information on page 8. *Key diagnostic criteria developed by the International Restless Legs Syndrome (IRLS) Study Group in collaboration with the National Institutes of Health.
Note to representative: When this information is shown to healthcare p rofessionals, complete Prescribing Information must be left behind.
The Together Rx Access™ Card has eligibility requirements. Retail pharmacy costs may vary.
HELP RELIEVE THE URGE TO MOVE After 2 nights Up to 9 months Low rate of AE discontinuation
©2006 The GlaxoSmithKline Group of Companies
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Printed in USA.
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(Month) 2006