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Rotigotine: Drug information

Rotigotine: Drug information
(For additional information see "Rotigotine: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
Health Canada Dopamine Agonists Safety Alert June 2021

Health Canada's review of the available information has established a link between use of the dopamine agonists pramipexole, quinagolide, or ropinirole and the risk of dopamine agonist withdrawal syndrome (DAWS). DAWS may occur after reducing the dose of or discontinuing dopamine agonists, and includes symptoms such as apathy, anxiety, depression, fatigue, sweating, panic attacks, insomnia, irritability, and pain. The Canadian product information for pramipexole has been updated to include a warning on the risk of DAWS. Health Canada will work with the manufacturers of quinagolide and ropinirole to update the product information to include a warning on the risk of DAWS. At this time, there is not enough information to establish a link between other dopamine agonists that were assessed as part of this safety review (ie, apomorphine, bromocriptine, cabergoline, pergolide [no longer marketed], and rotigotine) and DAWS. As a precaution, Health Canada will work with the manufacturers of these dopamine agonists to include the potential risk of DAWS in the product information.

Further information is available at https://hpr-rps.hres.ca/reg-content/summary-safety-review-detail.php?lang=en&linkID=SSR00269.

Brand Names: US
  • Neupro
Brand Names: Canada
  • Neupro
Pharmacologic Category
  • Anti-Parkinson Agent, Dopamine Agonist
Dosing: Adult

Parkinson disease:

Early-stage: Transdermal: Initial: Apply 2 mg/24 hours patch once daily; may increase daily dose by 2 mg/24 hours weekly based on clinical response and tolerability. Maximum: 6 mg/24 hours according to the prescribing information; higher doses (eg, 8 mg/24 hours) have been studied in clinical trials (Giladi 2007).

Advanced-stage: Transdermal: Initial: Apply 4 mg/24 hours patch once daily; may increase daily dose by 2 mg/24 hours weekly based on clinical response and tolerability. Maximum: 8 mg/24 hours; higher doses (eg, 12 to 16 mg/24 hours) have been studied in clinical trials (LeWitt 2007; Poewe 2007).

Discontinuation of treatment in Parkinson disease: Do not discontinue abruptly; decrease daily dose by ≤2 mg/24 hours preferably every other day until withdrawal complete.

Restless legs syndrome (alternative agent):

Initial: Transdermal: Apply 1 mg/24 hours patch once daily; may increase daily dose by 1 mg/24 hours weekly, based on clinical response and tolerability to a maximum of 3 mg/24 hours (AAN [Winkelman 2016]; manufacturer's labeling).

Note: If augmentation occurs (worsening symptoms during dopaminergic therapy), consider increasing dose (keeping at or below 3 mg/24 hours) or switching to alternative therapy (IRLSSG/EURLSSG/RLS-F [Garcia-Borreguero 2016]).

Discontinuation of therapy for restless legs syndrome: Do not discontinue abruptly; the manufacturer recommends decreasing daily dose by 1 mg/24 hours every other day.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Mild-to-moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe hepatic impairment: There are no dosage adjustments provided in manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Patch 24 Hour, Transdermal:

Neupro: 1 mg/24 hr (30 ea); 2 mg/24 hr (30 ea); 3 mg/24 hr (30 ea); 4 mg/24 hr (30 ea); 6 mg/24 hr (30 ea); 8 mg/24 hr (30 ea) [contains sodium metabisulfite]

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Patch 24 Hour, Transdermal:

Neupro: 1 mg/24 hr (7 ea, 20 ea, 28 ea, 30 ea, 42 ea, 50 ea, 56 ea, 60 ea, 84 ea, 90 ea, 100 ea); 2 mg/24 hr (7 ea, 20 ea, 28 ea, 30 ea, 50 ea, 56 ea, 60 ea, 84 ea, 90 ea, 100 ea); 3 mg/24 hr (7 ea, 20 ea, 28 ea, 30 ea, 42 ea, 50 ea, 56 ea, 60 ea, 84 ea, 90 ea, 100 ea); 4 mg/24 hr (7 ea, 20 ea, 28 ea, 30 ea, 50 ea, 56 ea, 60 ea, 84 ea, 90 ea, 100 ea); 6 mg/24 hr (7 ea, 20 ea, 28 ea, 30 ea, 42 ea, 56 ea, 60 ea, 84 ea, 90 ea, 100 ea); 8 mg/24 hr (7 ea, 20 ea, 28 ea, 30 ea, 50 ea, 56 ea, 60 ea, 84 ea, 90 ea, 100 ea) [contains sodium metabisulfite]

Administration: Adult

Transdermal patch: Apply patch to clean, dry, hairless area of intact healthy skin on the front of the abdomen, thigh, hip, flank, shoulder, or upper arm at approximately the same time daily. Remove from pouch immediately before use and press patch firmly in place on skin for 30 seconds. Application sites should be rotated on a daily basis. Do not apply to same application site more than once every 14 days or apply patch to skin that is oily, irritated, or damaged, or where it will be rubbed by tight clothing. Avoid exposing patch to external heat sources (eg, heating pad, electric blanket, heat lamp, hot tub, direct sunlight). If applied to hairy area, shave ≥3 days prior to applying patch. If patch falls off, immediately apply a new one to a new site.

Use: Labeled Indications

Parkinson disease: For the treatment of Parkinson disease.

Restless legs syndrome: For the treatment of moderate to severe primary restless legs syndrome.

Medication Safety Issues

Sound-alike/look-alike issues:

Neupro may be confused with Neupogen

Transdermal patch contains metal (eg, aluminum); remove patch prior to MRI or cardioversion

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Orthostatic hypotension (8% to 29%), peripheral edema (3% to 14%), systolic hypotension (13% to 32%)

Dermatologic: Hyperhidrosis (1% to 11%)

Endocrine & metabolic: Decreased serum glucose (1% to 15%)

Gastrointestinal: Nausea (15% to 48%), vomiting (2% to 20%)

Hematologic & oncologic: Decreased hematocrit (8% to 17%; severely decreased hematocrit: ≤2%), decreased hemoglobin (8% to 15%; severely decreased hemoglobin: ≤2%)

Local: Application site reaction (21% to 46%)

Nervous system: Dizziness (7% to 23%), drowsiness (5% to 32%), fatigue (≤18%), hallucination (3% to 13%), headache (10% to 21%), malaise (≤14%), sleep disorder (including disturbance in initiating/maintaining sleep: 2% to 14%)

Neuromuscular & skeletal: Arthralgia (8% to 11%), asthenia (≤14%), dyskinesia (14% to 17%)

Renal: Increased blood urea nitrogen (3% to 11%)

1% to 10%:

Cardiovascular: Abnormal T waves on ECG (2% to 3%), first degree atrioventricular block (3%), hypertension (1% to 5%), increased diastolic blood pressure (4% to 8%), increased systolic blood pressure (5%)

Dermatologic: Erythema of skin (2% to 6%), pruritus (4% to 9%)

Endocrine & metabolic: Change in libido (4% to 6%), hot flash (3% to 4%), low serum ferritin (2%), menstrual disease (1% to 2%), weight gain (2% to 9%)

Gastrointestinal: Anorexia (2% to 9%), constipation (5% to 9%), diarrhea (5% to 7%), dyspepsia (2% to 3%), viral gastroenteritis (1% to 2%), xerostomia (7%)

Hematologic & oncologic: Basal cell carcinoma of skin (3%), leukocyturia (3%)

Infection: Herpes simplex infection (3%), influenza (1% to 3%)

Nervous system: Abnormal dreams (1% to 7%), balance impairment (2% to 3%), depression (2% to 3%), hypoesthesia (3%), irritability (1% to 3%), nightmares (3% to 5%), paresthesia (3% to 4%), sudden onset of sleep (1% to 2%), vertigo (3% to 4%)

Neuromuscular & skeletal: Muscle spasm (3% to 4%), tremor (4%)

Ophthalmic: Visual disturbance (3% to 5%)

Otic: Tinnitus (2% to 3%)

Respiratory: Cough (3%), nasal congestion (3%), nasopharyngitis (8% to 10%), paranasal sinus congestion (2% to 3%), sinusitis (2% to 3%)

Frequency not defined: Cardiovascular: Increased pulse

Postmarketing:

Cardiovascular: Syncope

Dermatological: Allergic skin rash (including erythematous maculopapular rash), dermatological reaction

Nervous system: Aggressive behavior, agitation, confusion, delirium, delusion, disorientation, heavy headedness (dropped head syndrome), impulse control disorder (including Dopamine dysregulation syndrome), manic behavior, neuroleptic malignant syndrome (resembling), paranoid ideation, psychomotor agitation, psychotic symptoms, withdrawal syndrome

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen, rhabdomyolysis

Contraindications

Hypersensitivity to rotigotine or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Application site reactions: Dose-dependent application site reactions, potentially severe, have been observed; daily rotation of application sites has been shown to decrease incidence of reactions. If a generalized (nonapplication site) skin reaction occurs; discontinue therapy.

• Fibrosis: Rare cases of pleural effusion, pleural thickening, pulmonary infiltrates, retroperitoneal fibrosis, pericarditis and/or cardiac valvulopathy have been reported in patients treated with ergot-derived dopamine agonists. The potential of rotigotine, a non–ergot-derived dopamine agonist, to cause similar fibrotic complications is unknown. Discontinuation of therapy may resolve complications, but not in all cases.

• Fluid retention: Weight gain and fluid retention have been reported, primarily associated with development of peripheral edema in Parkinson disease patients; use caution and monitor in patients with concomitant illnesses (eg, heart failure or renal insufficiency).

• Hallucinations/psychotic-like behavior: May cause hallucinations (dose-related) and other psychotic-like behaviors (eg, agitation, delirium, delusions, aggression). In general, avoid use in patients with preexisting major psychotic disorders.

• Impulse control disorders: Dopamine agonists used for Parkinson disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.

• Orthostatic hypotension: Dopamine agonists may cause orthostatic hypotension and syncope; Parkinson disease patients appear to have an impaired capacity to respond to a postural challenge. Use with caution in patients at risk of hypotension (such as those receiving antihypertensive drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Monitor for postural hypotension, especially during dose escalation.

• Somnolence: Use is commonly associated with somnolence. In addition, falling asleep during activities of daily living, including while driving, has also been reported and may occur without significant warning signs. Monitor for daytime somnolence or pre-existing sleep disorder. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive agents; discontinue if significant daytime sleepiness or episodes of falling asleep occur. Effects with other sedative drugs or ethanol may be potentiated.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with pre-existing cardiovascular disease; therapy has been associated with increases in blood pressure (as well as orthostatic hypotension), which may be significant (>40 mm Hg or ≥20 mm Hg increase in systolic or diastolic measurements, respectively), increased heart rate, syncope, and weight gain/fluid retention.

• Dyskinesia: Use with caution in patients with preexisting dyskinesia; therapy may cause or exacerbate dyskinesia.

Special populations:

• Restless legs syndrome: Augmentation (earlier onset of symptoms each day and/or worsening symptoms during dopaminergic therapy) may occur in some restless leg syndrome (RLS) patients. Risk factors for dopaminergic-induced augmentation include higher doses of dopaminergic agents, use of shorter-acting dopamine agonists (ie, pramipexole, ropinirole) or levodopa, low iron stores, and increased severity of symptoms prior to treatment initiation. To minimize risk of augmentation, use the lowest effective dose and avoid exceeding recommended doses. Patients may also be switched to alternative therapy if augmentation occurs (Garcia-Borreguero 2016). End-of-dose rebound (reappearance of symptoms in the early morning hours) may also occur. Consider dosage adjustment or discontinuation of treatment if rebound symptoms occur.

Dosage form specific issues:

• Aluminum: Patch contains aluminum; remove patch prior to magnetic resonance imaging or cardioversion to avoid skin burns.

• Heat application: Avoid exposure of application site to any direct external heat sources (eg, hair dryers, heating pads, electric blankets, saunas, hot tubs, direct sunlight); heat exposure has not been studied with the rotigotine patch, but an increase in the rate and extent of absorption has been observed with other transdermal products.

• Sulfites: Patch contains sodium metabisulfite which may cause allergic reaction in susceptible individuals.

Other warnings/precautions:

• Discontinuation of therapy: Taper treatment when discontinuing therapy; do not stop abruptly. Other dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on withdrawal and/or significant dosage reduction. Apathy, anxiety, depression, fatigue, insomnia, pain, and sweating have occurred during taper or after discontinuation of therapy, which may not respond well to levodopa. Educate patient on potential of withdrawal symptoms; consider readministration of a dopamine agonist at the lowest effective dose in patients experiencing symptoms.

Metabolism/Transport Effects

None known.

Drug Interactions

Alcohol (Ethyl): May enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alizapride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amisulpride (Injection): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Amisulpride (Oral): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride (Oral). Amisulpride (Oral) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Antipsychotic Agents (First Generation [Typical]): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Brivudine [INT]: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Specifically, the risk of chorea may be increased. Risk C: Monitor therapy

Bromopride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. Risk C: Monitor therapy

CNS Depressants: May enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Kava Kava may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Methotrimeprazine: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Methotrimeprazine. Risk X: Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Solriamfetol: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy

Sulpiride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination

Pregnancy Considerations

Information related to the use of rotigotine in pregnancy is limited (Dostal 2013).

Available guidelines note there is insufficient evidence to recommend rotigotine for use in pregnant females with restless leg syndrome (Picchietti 2015) or Parkinson disease (Seier 2017)

Breastfeeding Considerations

It is not known if rotigotine is present in breast milk.

Rotigotine decreases prolactin secretion and lactation may be inhibited.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Blood pressure (including orthostatic); daytime alertness; weight gain in patients at risk for fluid retention (eg, heart failure, renal insufficiency).

Mechanism of Action

Rotigotine is a nonergot dopamine agonist with specificity for D3-, D2-, and D1-dopamine receptors. Although the precise mechanism of action of rotigotine is unknown, it is believed to be due to stimulation of postsynaptic dopamine D2-type auto receptors within the substantia nigra in the brain, leading to improved dopaminergic transmission in the motor areas of the basal ganglia, notably the caudate nucleus/putamen regions.

Pharmacokinetics

Distribution: Vd: ~84 L/kg.

Protein binding: ~90%.

Metabolism: Extensive via conjugation and N-dealkylation; multiple CYP isoenzymes, sulfotransferases, and two UDP-glucuronosyltransferases involved in catalyzing the metabolism.

Half-life elimination: After removal of patch: 5 to 7 hours.

Time to peak, plasma: 15 to 18 hours; can occur 4 to 27 hours post application.

Excretion: Urine (~71% as inactive conjugates and metabolites, <1% as unchanged drug); feces (~23%).

Pharmacokinetics: Additional Considerations

Renal function impairment: In subjects with severe renal impairment not on dialysis (eg, CrCl 15 to <30 mL/minute), exposure to conjugated rotigotine metabolites was doubled.

Geriatric: Although not studied, exposures in older subjects (older than 80 years of age) may be higher because of skin changes with aging.

Pricing: US

Patch, 24-hour (Neupro Transdermal)

1 mg/24 hrs (per each): $30.47

2 mg/24 hrs (per each): $30.47

3 mg/24 hrs (per each): $30.47

4 mg/24 hrs (per each): $30.47

6 mg/24 hrs (per each): $30.47

8 mg/24 hrs (per each): $30.47

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Leganto (BE, CZ, DE, IE, MT, NL, PL, PT);
  • Neupro (AE, AR, AT, AU, BB, BE, BH, BM, BR, CH, CL, CY, CZ, DE, DK, EE, ES, FR, GB, GR, HK, HR, HU, IE, IL, IT, JP, KR, KW, LB, LT, LU, MT, MY, NL, NO, PH, PL, PT, RO, SE, SG, SI, SK, TH, TR, TW, UA, VN);
  • Nubrenza (CR, DO, GT, HN, NI, PA, SV)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. Dostal M, Weber-Schoendorfer C, Sobesky J, Schaefer C. Pregnancy outcome following use of levodopa, pramipexole, ropinirole, and rotigotine for restless legs syndrome during pregnancy: a case series. Eur J Neurol. 2013;20(9):1241-1246. doi: 10.1111/ene.12001. [PubMed 23083216]
  2. Garcia-Borreguero D, Silber MH, Winkelman JW, et al. Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation. Sleep Med. 2016;21:1-11. doi: 10.1016/j.sleep.2016.01.017. [PubMed 27448465]
  3. Giladi N, Boroojerdi B, Korczyn AD, et al. Rotigotine transdermal patch in early Parkinson's Disease: a randomized, double-blind, controlled study versus placebo and ropinirole. Mov Disord. 2007;22(16):2398-2404. [PubMed 17935234]
  4. LeWitt PA, Lyons KE, Pahwa R; SP 650 Study Group. Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology. 2007;68(16):1262-1267. doi:10.1212/01.wnl.0000259516.61938.bb [PubMed 17438216]
  5. Neupro (rotigotine) [prescribing information]. Smyrna, GA: UCB Inc; July 2021.
  6. Picchietti DL, Hensley JG, Bainbridge JLet al; International Restless Legs Syndrome Study Group (IRLSSG). Consensus clinical practice guidelines for the diagnosis and treatment of restless legs syndrome/Willis-Ekbom disease during pregnancy and lactation. Sleep Med Rev. 2015;22:64-77. doi: 10.1016/j.smrv.2014.10.009. [PubMed 25553600]
  7. Poewe WH, Rascol O, Quinn N, et al; SP 515 Investigators. Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson's disease: a double-blind, double-dummy, randomised controlled trial. Lancet Neurol. 2007;6(6):513-520. doi:10.1016/S1474-4422(07)70108-4 [PubMed 17509486]
  8. Seier M, Hiller A. Parkinson's disease and pregnancy: An updated review. Parkinsonism Relat Disord. 2017;40:11-17. doi: 10.1016/j.parkreldis.2017.05.007. [PubMed 28506531]
  9. Winkelman JW, Armstrong MJ, Allen RP, et al. Practice guideline summary: treatment of restless legs syndrome in adults: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2016;87(24):2585-2593. doi:10.1212/WNL.0000000000003388 [PubMed 27856776]
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