Rotigotine hydrochloride is a transdermal non-ergoline dopamine agonist used for the treatment of Parkinson's disease (PD) and restless leg syndrome (RLS). Effectiveness with and without concomitant levodopa treatment was established in advanced and early stage PD patients, respectively. In one study, median oral doses of levodopa significantly decreased from 1400 mg/day to 400 mg/day during combined therapy with rotigotine. Use of rotigotine can improve motor performance and activities of daily living in patients with PD. This dosage form can also allow the theory to be tested that continuous dopaminergic stimulation from the initiation of PD therapy will help to limit motor complications (i.e., on-off syndrome). Dopamine receptor agonists are widely used as an effective treatment for RLS, presumably because of their longer half-lives and good tolerability compared with levodopa. Rotigotine (Neupro) was approved by the FDA in May 2007 for early stage idiopathic Parkinson's disease, and in April 2012 for advanced stage idiopathic Parkinson's disease and restless legs syndrome.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
Transdermal Patch Formulations
-Apply adhesive side of patch to clean, dry, intact healthy skin on the front of the abdomen, thigh, hip, flank, shoulder, or upper arm. Do not apply to skin that is oily, irritated, damaged, or where it will be rubbed by tight clothing or a waistband. For application to skin which has hair, shave the area at least 3 days prior to placement of the patch.
-Rotate application site daily from between the right and left side as well as the upper and lower body. Do not apply to the same site more than once every 14 days.
-Apply patch at approximately the same time every day. Always remove the old patch before applying a new patch. Apply to skin immediately after opening the pouch and removing the protective liner. Press firmly in place for 20 to 30 seconds, especially around the edges.
-If the next dose is missed at the scheduled time or if it becomes loose, remove the old patch and apply a new patch as soon as possible for the remainder of the 24 hour period.
-Remove patch slowly and carefully to avoid irritation. After removal, fold patch so that it sticks to itself and discard it.
-After removal of patch, wash application site with soap and water to remove any drug or adhesive. Baby oil or mineral oil may be used if needed. Do not use alcohol or other solvents.
-After application, wash hands immediately. After handling the patch, do not touch eyes or objects until hands are washed.
-Avoid direct sunlight exposure to rashes or areas of irritation caused by the patch.
-The effects of applying heat to the patch are unknown. Advise patients to avoid exposing the patch to sources of direct heat such as heating pads, electric blankets, heat lamps, saunas, hot tubs, heated water beds, and prolonged direct sunlight.
Rotigotine is administered transdermally. Application site reactions (ASRs) are among the most common adverse effects reported across all treatment populations in clinical trials. During use of the maximum recommended daily dose for early-stage Parkinson's disease (6 mg/day transdermal), advanced Parkinson's disease (8 mg/day transdermal), and restless legs syndrome (3 mg/day transdermal), ASRs occurred more frequently in the active treatment groups than the placebo groups for all conditions studied including early-stage Parkinson's disease (32% vs. 19%), advanced Parkinson's disease (36% vs. 13%), and restless legs syndrome (43% vs. 4%). ASRs are usually mild to moderate in severity and can manifest as erythema, edema, pruritus, or a maculopapular rash localized to the patch area. These reactions appear to be dose-related. Discontinuation of treatment due to an ASR occurred in 3% of patients treated for early Parkinson's disease, 2% of patients treated for advanced Parkinson's disease, and 12% of patients treated for Restless Legs Syndrome. Rotigotine should be discontinued if a generalized reaction develops. Otherwise, an individual determination should be made for localized effects based upon such factors as increases in severity, size, and duration. Rotation of the application site reduces the incidence of ASRs compared to repeated site administration. Other dermatological reactions include hyperhidrosis, which has been reported in up to 11% of patients.
During clinical trial evaluation of rotigotine, the incidence of somnolence was greater in rotigotine-treated patients than placebo-treated patients with early-stage Parkinson's disease (19% vs. 3%), advanced-stage Parkinson's disease (32% vs. 28%), and restless legs syndrome (10% vs. 4%) during use of maximum doses.The incidence of somnolence was notably greater than placebo during the dose titration phase and persisted into the maintenance phase of treatment. There have been reports of patients who have fallen asleep while performing activities of daily living, including driving. Excessive drowsiness has, in some cases, occurred as late as one year after the initiation of treatment. In some cases, sudden sleep onset due to rotigotine has resulted in auto accidents or other harmful events in the course of daily living. In trials of Restless Legs Syndrome (RLS), 2% of patients treated with the highest recommended rotigotine dose (3 mg/24 hours) reported sleep attacks compared to 0% treated with placebo. Reassessment for oversedation is suggested throughout rotigotine therapy; patients should notify their prescriber if they fall asleep during normal activities. Rotigotine should generally be discontinued in patients who experience episodes of falling asleep while engaged in activities of daily living.
Various cardiovascular effects have been reported during rotigotine administration, such as sinus tachycardia, orthostatic hypotension, hypertension, and syncope. In patients with advanced Parkinson's disease or restless legs syndrome (RLS), risks of sinus tachycardia (more than 100 beats per minute) in those receiving maximum doses of rotigotine were at least 2% and 5%, respectively, compared to no risk in the placebo groups. Electrocardiogram (ECG) T-wave abnormalities were detected in 2% to 3% of patients with early stage Parkinson's disease who received either rotigotine 4 mg/24 hours or 6 mg/24 hours. Dopamine agonists may cause syncope. Although the incidence of syncope with rotigotine was similar to placebo in controlled trials, those with clinically relevant cardiovascular disease were excluded from evaluation; therefore, patients with severe cardiovascular disease should be asked about symptoms of syncope and pre-syncope. Dopamine agonists, including rotigotine, can cause orthostatic hypotension. This dose-related effect may be particularly evident during dosage titration. Orthostatic decreases in systolic blood pressure (20 mmHg or more) were more frequent in patients receiving maximum doses of rotigotine versus placebo for all conditions studied: early-stage Parkinson's disease (16% vs. 14%), advanced Parkinson's disease (32% vs. 27%), and RLS (13% vs. 11%). Severe decreases in systolic blood pressure (40 mmHg or more) and in diastolic blood pressure (20 mmHg or more) also occurred more often in rotigotine-treated early and advanced stage Parkinson's patients (rotigotine 2% or more greater than placebo). Analysis of various terminologies used to describe orthostatic changes (e.g., dizziness, postural dizziness) showed the following incidences of adverse reactions suggestive of orthostatic hypotension for rotigotine compared to placebo during use of maximum doses: early-stage Parkinson's disease (29% vs. 11%), advanced Parkinson's disease (27% vs. 23%), and RLS (8% vs. 7%). Therefore, patients should be monitored closely for symptoms of orthostatic hypotension and informed of this risk. Careful titration may minimize the potential for this adverse effect. Conversely, patients receiving rotigotine may have hypertension, with dose-related elevations in systolic and diastolic blood pressures. In advanced Parkinson's disease, more patients receiving rotigotine than placebo experienced increased systolic blood pressure (more than 180 mmHg, 5% vs. 3%) or increased diastolic blood pressure (more than 105 mmHg, 4% vs. 0%). In patients with RLS, the risk for increased diastolic blood pressure (105 mmHg or more) was 8% for rotigotine and 4% for placebo. Mild to moderate increases (20 mmHg or more systolic and 10 mmHg or more diastolic) occurred more frequently in all patients taking the highest recommend dose of rotigotine. Severe increases in systolic blood pressure (greater than 40 mmHg) and in diastolic blood pressure (20 mmHg or more) occurred more in rotigotine-treated early and advanced stage Parkinson's and RLS patients (rotigotine 2% or more, and greater than placebo). An increased risk for hypertension was observed in patients receiving rotigotine versus placebo in patients with advanced Parkinson's disease (3% vs. 0%) and RLS (4% vs. 0%). Increases and decreases in blood pressure were observed while patients were supine, standing, and changing from supine to standing positions. Some threshold changes in blood pressure appear dose-dependent.Rare cases of pericarditis and cardiac valvulopathy have been reported in patients treated with ergot-derived dopaminergic agents (e.g., bromocriptine, pergolide). Although these adverse events are believed to be related to the ergonine structure, whether non-ergot derived dopamine agonists such as rotigotine can cause them is unknown.
Hallucinations, paranoia, delusions, psychotic-like behavior (psychosis), disorientation, confusion, agitation, aggressive behavior, delirium, and other abnormal thinking and behaviors have been reported during rotigotine administration in patients with Parkinson's disease or restless legs syndrome. Hallucinations are a dose-related effect of rotigotine. During use of the maximum recommended daily dose for early-stage Parkinson's disease (6 mg/day transdermal) or advanced Parkinson's disease (8 mg/day transdermal), hallucinations occurred more frequently in those with advanced Parkinson's disease (7%) or early-stage Parkinson's disease (3%) than with placebo. Hallucination incidences increased further to 14% when the maximum recommended prescription dose was exceeded (e.g., 12 mg/day transdermal). Discontinuation of treatment due to severe hallucinations occurred in 3%. Depression was reported in 2% to 3% of patients with early stage Parkinson's disease. During clinical trials for all indications, changes in sleep patterns occurred in 2% to 14% of patients and included early morning waking (2% to 3%), disturbances in initiating or maintaining sleep (2% to 14%), insomnia (5% to 11%), nightmares (3% to 5%), abnormal dreams (1% to 7%), or other sleep disorders (types unspecified, 0% to 3%).
During clinical trials with rotigotine, weight gain of more than 10% of baseline weight occurred in more frequently in the rotigotine groups than the placebo groups in patients with advanced Parkinson's disease (9% vs. 1%) or early-stage Parkinson's disease (2% vs. 0%). Weight gain was frequently associated with peripheral edema, which occurred in 2 to 14% of patients. The treatment difference incidence for peripheral edema (rotigotine % - placebo %) was 1% for early Parkinson's disease and 8% for advanced Parkinson's disease. Treatment difference continued to increase with treatment above the highest recommended doses. The drug should be used cautiously in patients with any condition pre-disposing to fluid retention such as congestive heart failure.
During rotigotine clinical trials, nausea occurred in 15-48% of rotigotine-treated patients compared to 10%-19% of those treated with placebo. Vomiting was reported in up to 28% of rotigotine treated patients compared to 6% of those using placebo. Nausea and vomiting may be more likely to occur during initiation of therapy. A dosage reduction may be required in some instances. Other GI effects that occurred in at least 2% of patients receiving maximum recommended doses and more frequently than placebo include anorexia or decreased appetite (0 to 8%), xerostomia (3 to 7%), dyspepsia (0 to 3%), diarrhea (5 to 7%), weight loss (0 to 3%), and constipation (2 to 9%).
Centrally-mediated adverse effects associated with rotigotine receipt include fatigue, headache, dizziness, and lethargy. Across clinical trials of rotigotine in patients with early and advanced stage Parkinson's disease or Restless Legs Syndrome, dizziness occurred in 5% to 23% of patients. The incidence of dizziness was notably increased compared to placebo during the titration phases of dose-response trials in patients with Parkinson's disease. Headache has been reported in up to 21% of patients, with fatigue and lethargy occurring in up to 18% and 2%, respectively. Other reported effects with respective incidence rates include balance disorders (2% to 3%), tremor (3% to 4%), vertigo (1% to 4%), and paresthesias/dysesthesia (5% to 6%).
Musculoskeletal pain and arthralgia have been reported in clinical trials of rotigotine, with pain and arthralgias occurring in up to 2% and 11% of treated patients, respectively. Muscle spasms occurred in 1% to 4% of patients, and appear to be dose-dependent. Asthenia or asthenic conditions (i.e., asthenia, malaise, and fatigue) were reported in 3% to 14% of patients. Rhabdomyolysis and dropped head syndrome (antecollis) have been reported during postmarketing use. Dropped head syndrome is characterized by a kyphotic deformity of the cervico-thoracic spine or may be caused by severe muscular weakness, causing a postural deformity where the head droops toward the chest.
Some patients taking rotigotine can experience a lack of impulse control symptoms. They may experience intense urges to gamble or spend money, increased sexual urges, binge eating, and/or other intense urges. In some cases urges stopped with medication dose reduction or discontinuation. Patients may not recognize this behavior as abnormal, so healthcare professionals should inquire about the behaviors with patients and/or caregivers.
Impotence (erectile dysfunction) has been reported in 2-3% of patients with early stage Parkinson's disease using rotigotine compared to 0% of those using placebo.
Respiratory and thoracic disorders associated with rotigotine include sinusitis (0 to 3%), upper respiratory infections, nasal congestion (3%), sinus congestion, cough (3%), hiccups (2 to 3%), and pharnygolaryngeal pain. Naso-pharyngitis was reported in 5 to 10% of patients using rotigotine for Restless Legs Syndrome, compared to 7% in those using placebo. Rare cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and pleural thickening have been reported in patients treated with ergot-derived dopaminergic agents (e.g., bromocriptine, pergolide). Although these adverse events are believed to be related to the ergonine structure, whether non-ergot derived dopamine agonists such as rotigotine can cause them is unknown.
In a fixed dose controlled trial of Parkinson's patients, adverse sensory effects that occurred in at least 2% of patients receiving transdermal rotigotine (2 mg/day up to 8 mg/day) and more frequently than in patients receiving placebo included tinnitus (up to 3% vs. 0%) and unspecified visual impairment (3% to 5% vs. 0%). Similar to other dopamine agonists, rotigotine has been shown to bind to melanin-containing tissues (e.g., the eyes) in animal studies. The clinical relevance of this finding is unknown. Hot flashes have been reported in up to 4% of patients using rotigotine for Restless Legs Syndrome or Parkinson's disease.
Rotigotine may potentiate the dopaminergic effects of levodopa and may cause a dose-related new or worsening dyskinesia. During use of the maximum daily dose, the incidence of dyskinesia was higher in advanced Parkinson's patients treated with rotigotine than placebo (14% vs. 7%). Patients treated with the maximum recommended dose of rotigotine also had an increased risk for early discontinuation from the study compared to placebo because of dyskinesia (3% vs. 0%).
Restless legs syndrome (RLS) augmentation occurs when dopamine agonists, such as rotigotine, cause a worsening of RLS symptom severity above and beyond the level at the time the medication was started or may involve an earlier time of symptom onset each day compared to pre-treatment levels. Augmentation symptoms may include the earlier onset of symptoms in the evening or afternoon, increase in symptoms, or spread of symptoms to involve other extremities. Restless legs syndrome (RLS) rebound is an exacerbation of RLS symptoms and is considered to be an end-of-dose effect related to the half-life of the drug. Rebound has been observed during discontinuation of the dopaminergic agent, and in the early morning hours during ongoing treatment (also known as early-morning rebound). If augmentation or early-morning rebound occurs, the use of rotigotine should be re-assessed, and a dosage adjustment or discontinuation of treatment should be considered. When discontinuing rotigotine, a gradual taper is advisable to minimize rebound effects.
Some laboratory abnormalities occurred during clinical trial evaluations of rotigotine for Parkinson's disease and restless legs syndrome (RLS). In patients with early-stage Parkinson's disease, the following changes in laboratory values to above or below the normal reference range occurred more frequently in patients receiving the maximum recommended rotigotine dose than patients receiving placebo: decreased serum glucose (hypoglycemia) (15% vs. 6%), elevated CPK (40% vs. 17%), increased BUN (11% vs. 2%), decreased hemoglobin (8% vs. 2%), and decreased hematocrit (8% vs. 5%). During a fixed dose study in early Parkinson's patients, white blood cells in the urine occurred more frequently within a range of rotigotine doses than with placebo (1% to 3% vs. 2%). In patients with advanced-stage Parkinson's disease, the following changes in laboratory values to above or below the normal reference range occurred more frequently in patients receiving the maximum recommended rotigotine dose than patients receiving placebo: decreased serum glucose (10% vs. 7%), markedly decreased serum glucose (1% vs. 0%), elevated CPK (39% vs. 20%), increased BUN (3% vs. 2%), decreased hemoglobin (15% vs. 11%), decreased hematocrit (17% vs. 14%), and markedly decreased hemoglobin and hematocrit (2% vs. 0%). In patients with RLS, the following changes in laboratory values to above or below the normal reference range occurred more frequently in rotigotine-treated patients than placebo-treated patients: decreased hemoglobin (15% vs. 12%), markedly decreased hematocrit (1% vs. 0%), and decreased serum ferritin (4% or less vs. 1%).
A withdrawal or discontinuation syndrome has been associated with the abrupt stoppage of dopamine agonist therapy, such as rotigotine, in Parkinson's disease patients. Discontinuation symptoms of apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported in patients with Parkinson's disease during dosage tapering or treatment discontinuation; these symptoms generally do not respond to treatment with levodopa. Closely monitor these patients during and after treatment discontinuation. Re-administration at the lowest effective rotigotine dose may be considered if severe withdrawal symptoms develop. Rarely, neuroleptic malignant syndrome-like symptoms (e.g. hyperpyrexia, muscular rigidity, altered consciousness, autonomic instability) have been reported in association with rapid dose reduction or rapid withdrawal of antiparkinson therapy. It is recommended that the dose be tapered at the end of therapy.
Rotigotine is contraindicated in patients with a rotigotine hypersensitivity or hypersensitivity to any inactive ingredients found in the transdermal patch formulation, including sodium metabisulfite. Anaphylactic reactions and life threatening or less severe asthmatic episodes may develop to sodium metabisulfite in susceptible individuals; sulfite hypersensitivity is seen more frequently in those with asthma than nonasthmatic patients. Localized application site reactions rarely result in drug discontinuation. If a patient reports a persistent application site reaction (of more than a few days), reports an increase in severity, or reports a skin reaction spreading outside the application site, an assessment of the risk and benefits for the individual patient should be conducted. If a generalized skin reaction associated with use, the rotigotine patch should be discontinued.
Rotigotine commonly causes drowsiness or somnolence. There have been reports of patients with Parkinson's disease or restless legs syndrome who have experienced sudden sleep onset while performing activities of daily living, including driving. In some cases, excessive drowsiness has resulted in auto accidents or other harmful events in the course of daily living. Although many of these patients reported somnolence while on rotigotine, some did not perceive warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events have been reported as late as 1 year after initiation of treatment. Patients should be cautioned against driving or operating machinery, or performing other hazardous tasks that require alertness while receiving rotigotine. Those who have experienced somnolence or a sudden episode of sleep while taking the drug should avoid these activities. Concomitant sleep disorders (e.g., narcolepsy, sleep apnea), ethanol ingestion, or coadministration with other CNS depressants may increase the risk of suddenly falling asleep while taking this medication; patients should be assessed for these risk factors prior to initiation of the drug. Assessment for somnolence is suggested throughout rotigotine therapy. If a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), rotigotine should ordinarily be discontinued. It is not known if a reduction in dosage will subsequently reduce or eliminate excessive somnolence or sudden episodes of sleep.
Postmarketing reports indicate that patients may experience new or worsening mental status and behavioral changes which may be severe, including psychotic behavior, during rotigotine initiation, during treatment or after dose increases. Other drugs prescribed to improve the symptoms of Parkinson's disease can have similar effects on thinking and behavior. This abnormal thinking and behavior may consist of one or more of the following: paranoid ideation, delusions, hallucinations, confusion, disorientation, aggressive behavior, agitation, and delirium. These various manifestations of psychotic behavior were also observed during the clinical development of rotigotine for early- and advanced-stage Parkinson's disease and Restless Legs Syndrome (RLS). Patients with a major psychotic disorder, such as schizophrenia, should ordinarily not be treated with rotigotine because of the risk of exacerbating psychosis. Impulse control symptoms have also been reported. Patients may experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge-eating, or other intense urges, and the inability to control these urges while taking 1 or more of the medications, including rotigotine, that increase central dopaminergic tone. Because patients may not recognize these behavioral changes as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending, or other urges while being treated. Further, prescribers should be aware that dopamine dysregulation syndrome, the repeated use of more than the prescribed dose, has been observed in some patients receiving rotigotine. The prescriber should consider dose reduction or stopping the medication if a patient develops such urges while taking rotigotine. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued.
Rotigotine should be used cautiously in those with cardiac disease. An increase in heart rate and/or blood pressure has occurred in advanced stage Parkinson's disease patients as well as those with Restless Legs Syndrome. Additionally, dopamine agonists may cause syncope. Although the incidence of syncope with rotigotine was similar to placebo in controlled trials, those with clinically relevant cardiovascular disease were excluded from evaluation. Dopamine agonists, including rotigotine, can cause orthostatic hypotension. This dose-related effect may be particularly evident during dosage titration. Some Parkinson's disease patients may have an impaired capacity to respond to a postural challenge. Patients should be monitored closely for symptoms of orthostatic hypotension and informed of the risk for syncope. Careful titration and dose escalation may minimize the potential for this adverse effect. Some patients receiving rotigotine may experience increased blood pressure or hypertension, with dose-related elevations in systolic and diastolic blood pressure. Increases and decreases in blood pressure were observed while patients were supine, standing, and changing from supine to standing positions.
Because rotigotine transdermal systems (e.g., Neupro) contain aluminum or other metal components, patients should be instructed to remove the patch before undergoing defibrillation (cardioversion) or magnetic resonance imaging (MRI). Metal components contained in the backing of some transdermal systems can overheat during these procedures and cause skin burns in the area where the patch is adhered.
The effects of applying heat to the rotigotine transdermal system are unknown. However, heat application has been shown to increase drug absorption several fold with other transdermal products. Patients should be advised to avoid exposing the patch to sources of ambient temperature increase or direct heat such as a heating pad, electric blanket, heat lamp, sauna, hot tub, heated water bed, or prolonged direct sunlight (UV) exposure.
Avoid abrupt discontinuation or rapid dose reduction of rotigotine if possible. It is recommended that rotigotine be discontinued by tapering to avoid potential withdrawal reactions. Adverse events resembling neuroleptic malignant syndrome (e.g. hyperpyrexia, muscular rigidity, altered consciousness, rhabdomyolysis, autonomic instability) have been reported in association with rapid dose reductions or abrupt discontinuation of antiparkinson therapy. Further, symptoms of apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported during dosage tapering or after discontinuation of dopamine agonists, such as rotigotine. These symptoms generally do not respond to treatment with levodopa. Inform drug recipients about the potential for withdrawal symptoms prior to stopping rotigotine, and closely monitor these patients during and after treatment discontinuation. Re-administration at the lowest effective dose may be considered if severe withdrawal symptoms develop. Also, reports in the published literature indicate discontinuation or wearing off of dopaminergic medications can result in rebound of restless leg syndrome (RLS) symptoms.
During clinical trials with rotigotine, weight gain of more than 10% of baseline weight occurred in early and advanced stage Parkinson's disease patients. Weight gain was frequently associated with fluid retention and peripheral edema, suggesting that the drug should be used cautiously in patients with any condition pre-disposing to fluid retention such as congestive heart failure or renal impairment.
Rotigotine may potentiate the dopaminergic side effects of levodopa and may cause or exacerbate pre-existing dyskinesia, including tardive dyskinesia. For the maximum recommended rotigotine dose, the incidence of dyskinesia was increased in patients with advanced-stage Parkinson's disease, and this incidence increased with increasing dose. Patients treated with the maximum recommended dose of rotigotine also had an increased risk for early discontinuation because of dyskinesia.
There are limited data regarding the clinical use of rotigotine in human pregnancy. In a prospective case series documenting outcomes of dopamine agonist use for restless legs syndrome during pregnancy, 2 pregnant women were exposed to rotigotine throughout their pregnancies. One patient received rotigotine patch 6 mg/day and delivered via cesarean section because of breech presentation; the baby girl was growth-inhibited but otherwise healthy. The other patient received 3 mg/day until week 6 followed by 1 mg/day from week 7 until her delivery of a healthy boy at week 36. In studies conducted in mice, rats, and rabbits, rotigotine was shown to have adverse effects on embryo-fetal development when administered during pregnancy at doses similar to or lower than those used clinically. Because there are no well-controlled studies documenting safe use of rotigotine during pregnancy, rotigotine should be used in pregnancy only if the potential benefits outweigh the potential risks to the fetus. The effects of rotigotine in labor and delivery are unknown.
The developmental and health benefits of breast-feeding should be considered along with the clinical need of the mother and any potential adverse effects on the breastfed infant from rotigotine or the underlying maternal condition. However, inhibition of lactation may occur because rotigotine decreases secretion of prolactin in humans. Studies in rats have shown that rotigotine and its metabolites are excreted in breast milk. It is not known if rotigotine is excreted in human breast milk and the effects of rotigotine exposure on the nursing infant are unknown.
Safe and effective use of rotigotine has not been established in adolescents, children, or infants.
Clinical trial and other reported practice experience suggests that the geriatric patient responds to rotigotine treatment similarly to the younger adult. No overall differences in plasma levels of rotigotine were observed between patients who were 65 to 80 years old compared with younger patients receiving the same rotigotine doses. However, some elderly patients may be more sensitive to rotigotine. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, antiparkinson medications may cause significant confusion, restlessness, delirium, dyskinesia, nausea, dizziness, hallucinations, and agitation. In addition, there is an increased risk of postural hypotension and falls, particularly during concurrent use of antihypertensive medications.
For the treatment of Parkinson's disease:
-for the treatment of early-stage Parkinson's disease:
Transdermal dosage:
Adults: 2 mg/24 hours transdermally once daily, initially. May increase the dose by 2 mg/24 hours weekly based on clinical response and tolerability. The lowest effective dose is 4 mg/24 hours. Max: 6 mg/24 hours. To discontinue, taper dose by 2 mg/24 hours every other day until completely withdrawn.
-for the treatment of advanced-stage Parkinson's disease:
Transdermal dosage:
Adults: 4 mg/24 hours transdermally once daily, initially. May increase the dose by 2 mg/24 hours weekly based on clinical response and tolerability. Max: 8 mg/24 hours. To discontinue, taper dose by 2 mg/24 hours every other day until completely withdrawn.
For the treatment of Restless Legs Syndrome (RLS):
Transdermal dosage:
Adults: Initially, apply 1 patch (1 mg/24 hours) transdermally once daily. The dosage may be increased by 1 mg/24 hours per week if tolerated and clinically indicated. The lowest effective dose is 1 mg/24 hours. Max: 3 mg/24 hours transdermally once daily. When discontinuing the drug, tapering is recommended. The daily dose should be decreased by 1 mg/24 hours every other day until completely withdrawn.
Maximum Dosage Limits:
-Adults
8 mg/24 hours transdermally for PD; 3 mg/24 hr transdermally for RLS.
-Geriatric
8 mg/24 hours transdermally for PD; 3 mg/24 hr transdermally for RLS.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Moderate hepatic impairment is not expected to have a significant effect on rotigotine clearance. The effects of severe hepatic impairment are unknown.
Patients with Renal Impairment Dosing
Exposure to some rotigotine metabolites is increased in the presence of severe renal impairment (15-29 ml/min); however, no dosage adjustments are recommended.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Major) Concomitant use of rotigotine with other CNS depressants, such as diphenhydramine, can potentiate the sedation effects of rotigotine.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Dextromethorphan; Doxylamine: (Major) Concomitant use of rotigotine with other CNS depressants, such as doxylamine, can potentiate the sedation effects of rotigotine.
Acetaminophen; Diphenhydramine: (Major) Concomitant use of rotigotine with other CNS depressants, such as diphenhydramine, can potentiate the sedation effects of rotigotine.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Alfentanil: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Alprazolam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Amobarbital: (Major) Concomitant use of rotigotine with other CNS depressants, such as amobarbital, can potentiate the sedation effects of rotigotine.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) A reduction in the dose of anxiolytics, sedatives, hypnotics and concomitantly administered dopamine agonists with sedative properties (e.g., ropinirole, pramipexole, rotigotine, apomorphine) should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Aripiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Asenapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of rotigotine with other CNS depressants, such as butalbital, can potentiate the sedation effects of rotigotine.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
atypical antipsychotic: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with rotigotine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking rotigotine, reduce initial dosage and titrate to clinical response. If rotigotine is initiated in a patient taking an opioid agonist, use a lower initial dose of rotigotine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzodiazepines: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Brexpiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Buprenorphine: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as opiate agonists-antagonists, can potentiate the sedation effects of rotigotine.
Buprenorphine; Naloxone: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as opiate agonists-antagonists, can potentiate the sedation effects of rotigotine.
Buspirone: (Major) Concomitant use of rotigotine with other CNS depressants, such as buspirone, can potentiate the sedation effects of rotigotine.
Butalbital; Acetaminophen: (Major) Concomitant use of rotigotine with other CNS depressants, such as butalbital, can potentiate the sedation effects of rotigotine.
Butalbital; Acetaminophen; Caffeine: (Major) Concomitant use of rotigotine with other CNS depressants, such as butalbital, can potentiate the sedation effects of rotigotine.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Major) Concomitant use of rotigotine with other CNS depressants, such as butalbital, can potentiate the sedation effects of rotigotine.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Major) Concomitant use of rotigotine with other CNS depressants, such as butalbital, can potentiate the sedation effects of rotigotine.
Butorphanol: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as opiate agonists-antagonists, can potentiate the sedation effects of rotigotine.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and rotigotine. CNS depressants can potentiate the effects of cannabidiol.
Carbidopa; Levodopa: (Moderate) In clinical studies, concurrent use of L-dopa/carbidopa with rotigotine had no effect on the pharmacokinetics of either agent. However, rotigotine may potentiate the dopaminergic side effects of levodopa via a pharmacodynamic interaction. Subsequent worsening of pre-existing dyskinesias may occur.
Carbidopa; Levodopa; Entacapone: (Moderate) In clinical studies, concurrent use of L-dopa/carbidopa with rotigotine had no effect on the pharmacokinetics of either agent. However, rotigotine may potentiate the dopaminergic side effects of levodopa via a pharmacodynamic interaction. Subsequent worsening of pre-existing dyskinesias may occur.
Cariprazine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Celecoxib; Tramadol: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and rotigotine. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as rotigotine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with rotigotine should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with rotigotine should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Chlordiazepoxide: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Chlordiazepoxide; Amitriptyline: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Chlordiazepoxide; Clidinium: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Chlorpromazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Clonazepam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Clorazepate: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Clozapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Codeine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as rotigotine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Concomitant use of rotigotine with other CNS depressants, such as diphenhydramine, can potentiate the sedation effects of rotigotine.
Diazepam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Diphenhydramine: (Major) Concomitant use of rotigotine with other CNS depressants, such as diphenhydramine, can potentiate the sedation effects of rotigotine.
Diphenhydramine; Ibuprofen: (Major) Concomitant use of rotigotine with other CNS depressants, such as diphenhydramine, can potentiate the sedation effects of rotigotine.
Diphenhydramine; Naproxen: (Major) Concomitant use of rotigotine with other CNS depressants, such as diphenhydramine, can potentiate the sedation effects of rotigotine.
Diphenhydramine; Phenylephrine: (Major) Concomitant use of rotigotine with other CNS depressants, such as diphenhydramine, can potentiate the sedation effects of rotigotine.
Donepezil; Memantine: (Moderate) The pharmacologic effects of dopaminergic agents, including dopamine agonists such as rotigotine, may be enhanced with use of memantine; dosage adjustments of dopaminergic agents may be required when memantine is coadministered.
Doxylamine: (Major) Concomitant use of rotigotine with other CNS depressants, such as doxylamine, can potentiate the sedation effects of rotigotine.
Doxylamine; Pyridoxine: (Major) Concomitant use of rotigotine with other CNS depressants, such as doxylamine, can potentiate the sedation effects of rotigotine.
Dronabinol: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as dronabinol, THC, can potentiate the sedation effects of rotigotine.
Droperidol: (Major) Concomitant use of rotigotine with other CNS depressants, such as droperidol, can potentiate the sedation effects of rotigotine. The concurrent use of rotigotine, a dopamine agonist, and antiemetic agents with dopamine antagonist properties may decrease the effectiveness of either agent. Abrupt and severe worsening of Parkinson's disease symptoms can occur.
Esketamine: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as rotigotine, and CNS depressants, such as esketamine. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep.
Estazolam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Eszopiclone: (Moderate) A reduction in the dose of anxiolytics, sedatives, hypnotics and concomitantly administered dopamine agonists with sedative properties (e.g., ropinirole, pramipexole, rotigotine, apomorphine) should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and rotigotine. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as rotigotine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Fentanyl: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Fluphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Flurazepam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and rotigotine. Concomitant use of gabapentin with rotigotine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as rotigotine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Haloperidol: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. Monitor for changes in movement, moods, or behaviors. In addition, coadministration of haloperidol and rotigotine may result in additive sedation.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydrocodone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking rotigotine. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydromorphone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydroxyzine: (Major) Concomitant use of rotigotine with other CNS depressants, such as hydroxyzine, can potentiate the sedation effects of rotigotine.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Iloperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and rotigotine. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as rotigotine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and rotigotine. Dosage adjustments of lemborexant and rotigotine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with rotigotine should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levodopa: (Moderate) In clinical studies, concurrent use of L-dopa/carbidopa with rotigotine had no effect on the pharmacokinetics of either agent. However, rotigotine may potentiate the dopaminergic side effects of levodopa via a pharmacodynamic interaction. Subsequent worsening of pre-existing dyskinesias may occur.
Levorphanol: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Lofexidine: (Major) Monitor for excessive hypotension and sedation during coadministration of lofexidine and rotigotine. Lofexidine can potentiate the effects of CNS depressants.
Lorazepam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Loxapine: (Major) Due to opposing effects on central dopaminergic activity, loxapine and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to loxapine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Lumateperone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Lurasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Memantine: (Moderate) The pharmacologic effects of dopaminergic agents, including dopamine agonists such as rotigotine, may be enhanced with use of memantine; dosage adjustments of dopaminergic agents may be required when memantine is coadministered.
Meperidine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Meprobamate: (Moderate) A reduction in the dose of anxiolytics, sedatives, hypnotics and concomitantly administered dopamine agonists with sedative properties (e.g., ropinirole, pramipexole, rotigotine, apomorphine) should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Methadone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Metoclopramide: (Major) The concurrent use of rotigotine, a dopamine agonist, and antiemetic agents with dopamine antagonist properties may decrease the effectiveness of either agent. Abrupt and severe worsening of Parkinson's disease symptoms can occur. In addition, sedation caused by the individual agents can be potentiated with combined use. Metoclopramide should be avoided if possible in patients treated with rotigotine.
Midazolam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Molindone: (Major) Due to opposing effects on central dopaminergic activity, molindone and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to molindone. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Morphine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Nabilone: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as nabilone, can potentiate the sedation effects of rotigotine.
Nalbuphine: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as opiate agonists-antagonists, can potentiate the sedation effects of rotigotine.
Olanzapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Olanzapine; Fluoxetine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Olanzapine; Samidorphan: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Oliceridine: (Major) Concomitant use of oliceridine with rotigotine may cause excessive sedation and somnolence. Limit the use of oliceridine with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Opiate Agonists-Antagonists: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as opiate agonists-antagonists, can potentiate the sedation effects of rotigotine.
Oxazepam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Oxycodone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Oxymorphone: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Paliperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Pentazocine; Naloxone: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as opiate agonists-antagonists, can potentiate the sedation effects of rotigotine.
Pentobarbital: (Major) Concomitant use of rotigotine with other CNS depressants, such as pentobarbital, can potentiate the sedation effects of rotigotine.
Perphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Perphenazine; Amitriptyline: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Phenobarbital: (Major) Concomitant use of rotigotine with other CNS depressants, such as phenobarbital, can potentiate the sedation effects of rotigotine.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concomitant use of rotigotine with other CNS depressants, such as phenobarbital, can potentiate the sedation effects of rotigotine.
Phenothiazines: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Pimozide: (Major) Due to opposing effects on central dopaminergic activity, pimozide and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and rotigotine. Concomitant use of pregabalin with rotigotine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as rotigotine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Prochlorperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Promethazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Promethazine; Dextromethorphan: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Promethazine; Phenylephrine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Quazepam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Quetiapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Ramelteon: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as ramelteon, can potentiate the sedation effects of rotigotine.
Remifentanil: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Remimazolam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Risperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Secobarbital: (Major) Concomitant use of rotigotine with other CNS depressants, such as secobarbital, can potentiate the sedation effects of rotigotine.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as rotigotine. Caution is recommended since this combination has not been evaluated.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and rotigotine. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Tapentadol: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Temazepam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Thioridazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Thiothixene: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. In addition, coadministration may result in additive sedation. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Tramadol: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Triazolam: (Major) Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine.
Trifluoperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Zaleplon: (Moderate) A reduction in the dose of anxiolytics, sedatives, hypnotics and concomitantly administered dopamine agonists with sedative properties (e.g., ropinirole, pramipexole, rotigotine, apomorphine) should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ziprasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Zolpidem: (Moderate) A reduction in the dose of anxiolytics, sedatives, hypnotics and concomitantly administered dopamine agonists with sedative properties (e.g., ropinirole, pramipexole, rotigotine, apomorphine) should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Rotigotine is a non-ergoline dopamine agonist that binds to D2 dopamine receptors within the caudate-putamen in the brain. The drug is also an agonist at D3 and D1 dopamine receptors. Although the exact mechanism in the treatment of Parkinson's Disease is unknown, it is thought to be related to the D2 receptor activity of the drug. The mechanism of action in Restless Legs Syndrome (RLS) is unknown. Dopaminergic pathways (e.g., presynaptic dopaminergic dysfunction) are thought to be involved in the pathogenesis of RLS, which presumably explains the benefits of dopamine agonists in the treatment of the syndrome.
Rotigotine is administered as a transdermal patch. Plasma protein binding is about 89.5%. Rotigotine is extensively metabolized by conjugation and N-dealkylation. Cytochrome P450 isoenzymes, sulfotransferases, and glucuronosyltransferases (UGT1A9 and UGT2B15) catalyze the metabolism of the drug. In vitro studies indicate that multiple CYP450 isoenzymes can catalyze the metabolism of rotigotine; however, there is no evidence of significant inhibition of metabolism during co-incubation with CYP450 inhibitors. The drug does not appear to inhibit CYP1A2, CYP2C9,or CYP3A4. There is a low risk of CYP2C19 and CYP2D6 inhibition by the drug, and no indication of enzyme-inducing effects on CYP1A2, CYP2B6, CYP2C9, CYP2C19, or CYP3A4. Following removal of the patch, the terminal half-life is 5-7 hours. The primary elimination route is renal, with 71% of a dose excreted in the urine as inactive conjugates of rotigotine and its N-desalkyl metabolites. Less than 1% of a dose is excreted in the urine as the parent compound. About 11% is excreted in the feces.
-Route-Specific Pharmacokinetics
Other Route(s)
Transdermal Route
After application to the trunk, detectable plasma concentrations of rotigotine are achieved in an average of 3 hours (range: 1-8 hours). An average of 45% of a transdermal dose is released within 24 hours independent of patch size. Absorption is similar between healthy subjects and Parkinson's Disease patients. Relative bioavailability varies between application sites, with differences ranging from less than 1% between abdomen and hip to 64% between shoulder and thigh with shoulder showing higher bioavailability. Steady state plasma concentrations are achieved within 2-3 days.
-Special Populations
Hepatic Impairment
Moderate hepatic impairment does not affect the pharmacokinetics of rotigotine. Data are not available on the effects of severe hepatic impairment.
Renal Impairment
No changes in rotigotine pharmacokinetics were observed in subjects with mild to severe impairment, including those on dialysis. In subjects with severe renal impairment not on dialysis (creatinine clearance 15-29 ml/min), exposure to rotigotine conjugates was doubled; however, no dosage adjustments are recommended.
Pediatrics
Pediatric patients have not been studied.
Geriatric
No differences in plasma concentrations have been identified based upon age. Although there are no differences in plasma concentrations in patients 65-80 years of age compared to younger adults, exposure of rotigotine in geriatric patients older than 80 years may be higher due to age-related skin changes (e.g., atrophy).
Gender Differences
No differences in rotigotine plasma concentrations have been identified based upon gender.
Ethnic Differences
No differences in rotigotine plasma concentrations have been identified based upon race.