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Rotigotine (Monograph)

Brand name: Neupro
Drug class: Nonergot-derivative Dopamine Receptor Agonists
- Antiparkinsonian Agents
VA class: CN500
Chemical name: 5,6,7,8-Tetrahydro-6-[propyl [2-(2-thienyl)ethyl]amino-(6S)-1-naphthalenol
Molecular formula: C19H25NOS
CAS number: 99755-59-6

Medically reviewed by on Apr 25, 2024. Written by ASHP.


Nonergot-derivative dopamine receptor agonist.

Uses for Rotigotine

Parkinsonian Syndrome

Symptomatic management of parkinson disease.

May be used as monotherapy in patients with early disease or as an adjunct to levodopa in patients with advanced disease.

Levodopa is currently the most effective drug for relieving motor symptoms of parkinson disease. However, the effectiveness of levodopa decreases over time, and most patients develop motor complications (e.g., wearing-off symptoms, dyskinesias) with long-term use. Strategies to reduce these complications include adjusting dosage of levodopa, adding other antiparkinsonian agents (i.e., dopamine receptor agonists), or initiating other agents first to delay use of levodopa.

Restless Legs Syndrome

Symptomatic management of moderate-to-severe primary restless legs syndrome (RLS; Willis-Ekbom disease).

Nonergot-derivative dopamine receptor agonists (e.g., pramipexole, ropinirole, rotigotine) are considered one of several drugs of choice for reducing symptoms of RLS.

Rotigotine Dosage and Administration


Transdermal Administration

Administer percutaneously by topical application of a transdermal system (patch). Apply transdermal system once daily at a convenient time (day or night) and at approximately the same time each day. May apply without regard to meals.

Instruct patients in the proper use and disposal of the transdermal system.

Apply transdermal system immediately after removal from its pouch and removal of the protective liner.

Apply to clean, dry, intact healthy skin on the front of the abdomen, thigh, hip, flank, shoulder, or upper arm by firmly pressing the system with the palm of the hand for 30 seconds with the adhesive side touching the skin to ensure good contact, particularly around the edges.

Avoid application sites that are oily, irritated, or damaged; also avoid sites where the patch may be rubbed by tight clothing, under a waistband, and skin folds.

If application to a hairy area is necessary, shave hair at the application site at least 3 days prior to application; do not use creams, lotions, oils, ointments, or powders on skin where patch will be placed.

Move application site on a daily basis (i.e., from the right side to the left side, from the upper body to the lower body). Do not apply transdermal system to the same application site more than once every 14 days. (See Application Site Reactions under Cautions.)

Wear each transdermal system continuously for 24 hours. If a system becomes dislodged during period of use or if a patient forgets to change the system, apply a new system for the remainder of the day; on the following day, change the patch according to regular time schedule. May tape edges of the transdermal system in place with bandage tape if patient experiences difficulty with patch adhesion.

After handling a transdermal system, wash hands to remove any drug; avoid touching eyes or other objects prior to handwashing.

Because the backing layer of the rotigotine transdermal system contains aluminum, remove patch prior to magnetic resonance imaging (MRI) or cardioversion to avoid skin burns.


Rotigotine transdermal system (Neupro) is labeled in terms of the approximate rate of drug delivery per 24 hours.

May use either single or multiple patches to achieve prescribed dosage.


Parkinsonian Syndrome

Early parkinson disease: Initially, 2 mg/24 hours; may increase dosage weekly by 2 mg/24 hours if tolerated and additional therapeutic effect is needed up to a maximum dosage of 6 mg/24 hours. Lowest effective dosage in clinical studies was 4 mg/24 hours.

Advanced parkinson disease: Initially 4 mg/24 hours; may increase dosage weekly by 2 mg/24 hours if tolerated and additional therapeutic effect is needed up to a maximum dosage of 8 mg/24 hours.

When discontinuing treatment, reduce daily dosage by a maximum of 2 mg/24 hours with a dosage reduction preferably every other day, until complete withdrawal is achieved.

Restless Legs Syndrome

Initially, 1 mg/24 hours; may increase dosage weekly by 1 mg/24 hours if tolerated and if additional therapeutic effect is needed up to a maximum dosage of 3 mg/24 hours.

When discontinuing treatment, reduce daily dosage by 1 mg/24 hours preferably every other day, until complete withdrawal is achieved.

Prescribing Limits


Parkinsonian Syndrome

Early parkinson disease: Maximum recommended dosage is 6 mg/24 hours.

Advanced parkinson disease: Maximum recommended dosage is 8 mg/24 hours.

Restless Legs Syndrome

3 mg/24 hours.

Special Populations

Hepatic Impairment

Manufacturer makes no specific recommendations for dosage adjustment.

Renal Impairment

Manufacturer makes no specific recommendations for dosage adjustment.

Geriatric Patients

Manufacturer makes no specific recommendations for dosage adjustment.

Cautions for Rotigotine



Sulfite Sensitivity

Rotigotine transdermal system (Neupro) contains sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

Falling Asleep During Activities of Daily Living and Somnolence

Episodes of falling asleep while engaged in activities of daily living (e.g., driving) reported; sometimes resulted in accidents. Reported as late as 1 year after initiation of transdermal rotigotine therapy. Some patients perceived no warning signs (e.g., excessive drowsiness) and believed that they were alert immediately prior to the event. Falling asleep while engaged in such activities usually occurs in a setting of preexisting somnolence, although patients may not give such a history.

Somnolence commonly occurs in patients receiving transdermal rotigotine and appears to be more frequent in patients with parkinson disease than in patients with RLS.

Continually reassess patients for drowsiness or sleepiness. Patients may not acknowledge drowsiness or sleepiness until directly questioned about such adverse effects during specific activities. Ask patients about any factors that may increase the risk of somnolence (e.g., concomitant sedating drugs, presence of sleep disorders).

In general, discontinue therapy if a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating). If the drug is continued, advise patient not to drive and to avoid other potentially dangerous activities. Insufficient information to establish whether dosage reduction will eliminate this adverse effect.

Hallucinations/Psychotic-like Behavior

Increased risk of hallucinations reported in patients with advanced parkinson disease treated with transdermal rotigotine.

During postmarketing experience, other new or worsening mental status and behavioral changes (e.g., paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, delirium) reported during therapy or after initiating or increasing dosage. Other antiparkinsonian agents can produce similar effects.

Use generally not advised in patients with a major psychotic disorder. Concomitant use with antipsychotic agents may exacerbate parkinsonian symptoms and decrease effectiveness of rotigotine.

Symptomatic Hypotension and Syncope

Dopamine agonists appear to impair systemic regulation of BP, resulting in postural/orthostatic hypotension, especially during dosage escalation. Orthostatic hypotension can also be a manifestation of parkinson disease. Monitor patients for signs and symptoms of orthostatic hypotension, particularly during dosage escalation.

Syncope also reported in patients receiving dopamine agonists. Monitor patients, especially those with severe cardiovascular disease, for symptoms of syncope or presyncope.

Impulse Control/Compulsive Behaviors

Intense urges and compulsive behaviors (e.g., urge to gamble, increased sexual urges, uncontrolled spending, binge eating, other intense urges) and inability to control these urges reported in some patients receiving dopaminergic agents. In some cases, urges stopped when dosage was reduced or drug was discontinued.

Consider reducing dosage or discontinuing therapy if a patient develops such urges. (See Advice to Patients.)

Elevation of BP and Heart Rate

Increases in BP and heart rate reported.

Consider possibility of BP and heart rate elevations when treating patients with cardiovascular disease.

Weight Gain and Fluid Retention

Weight gain and fluid retention reported; weight gain frequently associated with the development of peripheral edema in patients with parkinson disease.

Monitor for weight gain and fluid retention in patients with risk factors (e.g., CHF, renal insufficiency).


May potentiate adverse dopaminergic effects of levodopa and cause and/or exacerbate preexisting dyskinesia.

Application Site Reactions

Dose-dependent application site reactions (e.g., localized erythema, edema, pruritus) reported.

Generalized (nonapplication) skin reactions (e.g., allergic rash [including erythematous, maculopapular rash or pruritus]) also reported, but less frequently.

Daily rotation of application sites may reduce incidence of application site reactions. If a persistent application site reaction (i.e., more than a few days), an increase in severity of a reaction, or a skin reaction spreading outside the application site occurs, assess risks versus benefits of continuing therapy. If a generalized skin reaction occurs, discontinue transdermal rotigotine.

Augmentation and Rebound in RLS

Augmentation (worsening of RLS symptoms during treatment) is a major adverse effect of long-term RLS treatment with dopaminergic agents; can manifest as an increase in overall symptom severity or earlier time of symptom onset each day. Risk of clinically relevant augmentation with transdermal rotigotine appears to be low.

Rebound (exacerbation of RLS symptoms) also reported and is considered an end-of-dose effect related to the half-life of the drug. Discontinuance or wearing off of dopaminergic medications can result in rebound.

Magnetic Resonance Imaging (MRI) and Cardioversion

Because the backing layer of rotigotine transdermal system contains aluminum, remove the patch prior to MRI or cardioversion to avoid skin burns.

Heat Application

Effect of heat application to the rotigotine transdermal system not specifically studied, but has been shown to increase drug absorption several fold with other transdermal formulations. Avoid exposure of the application site to external sources of direct heat (e.g., heating pads, electric blankets, heat lamps, saunas, hot baths, hot tubs, heated water beds, hair dryers, prolonged direct sunlight).

Hyperpyrexia and Confusion

A symptom complex resembling neuroleptic malignant syndrome (NMS; e.g., elevated temperature, muscular rigidity, altered consciousness, rhabdomyolysis, autonomic instability) reported following rapid dosage reduction, withdrawal of, or changes in antiparkinsonian therapy. Taper transdermal rotigotine dosage when discontinuing therapy.

Fibrotic Complications

Fibrotic complications, including retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and/or cardiac valvulopathy, reported with ergot-derivative dopamine receptor agonists; presumably related to the ergoline structure of these compounds. Not known whether nonergot-derivative dopamine agonists can also cause such fibrotic reactions.

Binding to Melanin

Binding to melanin-containing tissues (e.g., eyes) evident in the pigmented rat and monkey after a single dose of rotigotine; the binding cleared slowly over a 14-day observation period. Similar binding to melanin reported with other dopamine agonists.

Specific Populations


No adequate data in pregnant women. In animal studies, adverse developmental effects (e.g., delayed skeletal ossification, decreased fetal body weight, embryofetal death) observed with sub-Q administration of rotigotine.


Rotigotine and/or its metabolites distribute into milk in rats; not known whether distributed into human milk, affects milk production, or affects the breast-fed infant. Consider known benefits of breast-feeding along with mother's clinical need for rotigotine and any potential adverse effects on the infant from drug or underlying maternal condition.

Decreases prolactin secretion; may inhibit lactation.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

No substantial differences in efficacy, safety, or pharmacokinetics relative to younger adults; however, possibility of greater sensitivity in some geriatric patients cannot be ruled out.

Geriatric patients with parkinson disease are at increased risk for hallucinations.

Hepatic Impairment

No relevant changes in plasma concentrations in patients with moderate hepatic impairment (Child-Pugh class B).

Effects of severe hepatic impairment on pharmacokinetics not studied.

Renal Impairment

No relevant changes in plasma concentrations of rotigotine in individuals with mild to severe renal impairment (including those with end-stage renal impairment undergoing dialysis). Exposure to conjugated rotigotine metabolites doubled in individuals with severe renal impairment not receiving dialysis.

Common Adverse Effects

Patients with early parkinson disease (not receiving concomitant levodopa): Nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, hyperhidrosis, insomnia, headache, fatigue, anxiety, peripheral edema, dyspepsia.

Patients with advanced parkinson disease (receiving concomitant levodopa): Application site reactions, nausea, dyskinesia, dizziness, peripheral edema, insomnia, hallucinations.

Patients with RLS: Application site reactions, nausea, somnolence, headache, insomnia.

Drug Interactions

In vitro studies indicate that rotigotine is metabolized by multiple CYP isoenzymes.

Metabolized by multiple sulfotransferases and uridine diphosphate-glucuronosyltransferases (UGT1A9 and UGT2B15).

In vitro data indicate little to no potential for inhibition of CYP1A2, 2C9, 3A4, 2C19, and 2D6. In vitro data indicate no potential for induction of CYP isoenzymes 1A2, 2B6, 2C9, 2C19, and 3A4.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP inhibitors: Clinically important pharmacokinetic interactions unlikely; if an individual CYP isoenzyme is inhibited, other isoenzymes can metabolize rotigotine.

CYP substrates: Pharmacokinetic interactions unlikely.

Drugs Affecting Uridine Diphosphate-glucuronosyltransferase (UGT)

Because rotigotine is metabolized by multiple pathways, clinically important pharmacokinetic interactions unlikely.

Specific Drugs





Additive CNS depression may occur, including somnolence and falling asleep during activities of daily living

Use concomitantly with caution


No effect on steady-state pharmacokinetics of rotigotine

CNS depressants (e.g., sedatives, anxiolytics, antidepressants, antipsychotics, opiate analgesics)

Additive CNS depression may occur, including somnolence and falling asleep during activities of daily living

Use concomitantly with caution


Pharmacokinetics of digoxin not expected to be altered

Dopamine agonists

Additive therapeutic and/or adverse dopaminergic effects (e.g., dyskinesia)

Dopamine antagonists (e.g., antipsychotics, metoclopramide)

May diminish effectiveness of rotigotine

Hormonal contraceptives

Ethinyl estradiol/levonorgestrel: Pharmacodynamics and pharmacokinetics not substantially affected

Possible interactions with other forms of hormonal contraceptives not evaluated to date


Additive therapeutic and/or adverse dopaminergic effects (e.g., dyskinesia); no effect on steady-state pharmacokinetics of any of the drugs


No effect on steady-state pharmacokinetics of rotigotine


No potential for displacement of warfarin by rotigotine (and vice versa) from albumin binding sites

Rotigotine Pharmacokinetics



Following topical application, approximately 45% of rotigotine is released from the transdermal system within 24 hours.

Following topical application of single 8 mg/24 hours doses to the trunk, average lag time of approximately 3 hours (range: 1–8 hours) before detected in plasma. Peak concentrations typically occur 15–18 hours post-dose, but can occur from 4–27 hours post-dose. No characteristic peak concentration observed.

Steady-state plasma concentrations achieved within 2 to 3 days of once-daily dosing in healthy individuals.

Differences in relative bioavailability at steady state by application site ranged from less than 1% (abdomen versus hip) to 46% (shoulder versus thigh).


Because administered transdermally, food should not affect absorption.

Special Populations

Mild to severe renal impairment (up to end-stage renal disease requiring hemodialysis): No relevant changes in plasma concentrations. Exposure to conjugated metabolites was doubled in individuals with severe renal impairment (Clcr 15 to <30 mL/min) not receiving dialysis.

Moderate hepatic impairment: No relevant changes in plasma concentrations.

Severe hepatic impairment: Not studied.

Geriatric patients: Plasma concentrations in healthy individuals and patients 65–80 years of age similar to those in younger adults. Exposure in geriatric patients >80 years of age not studied, but may be higher due to skin changes with aging.



Distributes into milk in rats; not known whether the drug and/or its metabolites distribute into human milk.

Plasma Protein Binding

Approximately 92% to human plasma proteins in vitro; 89.5% in vivo.



Extensively metabolized by conjugation and N-dealkylation.

Major metabolites in urine include rotigotine sulfate, rotigotine glucuronide, N-despropyl-rotigotine sulfate, and N-desthienylethyl-rotigotine sulfate.

Elimination Route

Approximately 71 and 23% of a single IV dose excreted in urine and feces, respectively, as metabolites; less than 1% excreted as unchanged drug in urine.


Biphasic (after removal of patch); initial half-life of 3 hours and terminal half-life of 5–7 hours.




Transdermal System

20–25°C (may be exposed to 15–30°C). Store in original pouch.


Advice to Patients


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.



Dosage Forms


Brand Names



Transdermal System

1 mg/24 hours (2.25 mg/5 cm2)



2 mg/24 hours (4.5 mg/10 cm2)



3 mg/24 hours (6.75 mg/15 cm2)



4 mg/24 hours (9 mg/20 cm2)



6 mg/24 hours (13.5 mg/30 cm2)



8 mg/24 hours (18 mg/40 cm2)



AHFS DI Essentials™. © Copyright 2024, Selected Revisions May 5, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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