Drug Class Description
Dopamine agonists
Generic Name
Rotigotine
Drug Description
Each patch releases 2 mg of rotigotine per 24 hours. Each patch of 10 cm2 contains 4.5 mg of rotigotine.
Presentation
Transdermal patch.Thin, matrix-type, square-shaped with rounded edges, consisting of three layers. The outside of the backing layer is tan-coloured and imprinted with Neupro 2 mg/24 h.
Indications
Restless Legs SyndromeNeupro is indicated for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in adults.Parkinson's diseaseNeupro is indicated for the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease as monotherapy (i.e. without levodopa) or in combination with levodopa, i.e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or 'on-off' fluctuations).
Adult Dosage
Neupro is applied once a day. The patch should be applied at approximately the same time every day. The patch remains on the skin for 24 hours and will then be replaced by a new one at a different site of application.If the patient forgets to apply the patch at the usual time of the day or if the patch becomes detached, another patch should be applied for the remainder of the day.DosageThe dose recommendations made are in nominal dose.Restless Legs SyndromeA single daily dose should be initiated at 1 mg/24 h. Depending on the individual patient response, the dose may be increased in weekly increments of 1 mg/24 h to a maximal dose of 3 mg/24 h. The need for treatment continuation should be reconsidered every 6 months.Parkinson's diseaseDosing in patients with early-stage Parkinson's disease:A single daily dose should be initiated at 2 mg/24 h and then increased in weekly increments of 2 mg/24 h to an effective dose up to a maximal dose of 8 mg/24 h.4 mg/24 h may be an effective dose in some patients. For most patients an effective dose is reached within 3 or 4 weeks at doses of 6 mg/24 h or 8 mg/24 h, respectively.The maximal dose is 8 mg/24 h.Dosing in patients with advanced stage Parkinson's disease with fluctuations:A single daily dose should be initiated at 4 mg/24 h and then increased in weekly increments of 2 mg/24 h to an effective dose up to a maximal dose of 16 mg/24 h.4 mg/24 h or 6 mg/24 h may be effective doses in some patients. For most patients an effective dose is reached within 3 to 7 weeks at doses of 8 mg/24 h up to a maximum dose of 16 mg/24 h.For doses higher than 8 mg/24 h multiple patches may be used to achieve the final dose e.g. 10 mg/24 h may be reached by combination of a 6 mg/24 h and a 4 mg/24 h patch.Treatment discontinuationRestless Legs SyndromeNeupro should be discontinued gradually. The daily dose should be reduced in steps of 1 mg/24 h with a dose reduction preferably every other day, until complete withdrawal of Neupro. Following this procedure, rebound (worsening of symptoms beyond initial intensity after discontinuation of treatment) was not observed.Parkinson's diseaseNeupro should be discontinued gradually. The daily dose should be reduced in steps of 2 mg/24 h with a dose reduction preferably every other day, until complete withdrawal of Neupro.Hepatic and renal impairment: Adjustment of the dose is not necessary in patients with mild to moderate hepatic impairment or in patients with mild to severe renal impairment including those requiring dialysis. Caution is advised when treating patients with severe hepatic impairment, which may result in lower rotigotine clearance. Neupro has not been investigated in this patient group. A dose reduction might be needed in case of worsening of the hepatic impairment. Unexpected accumulation of rotigotine levels may also occur at acute worsening of renal function.Children and adolescents: Neupro is not recommended for use in children and adolescents due to a lack of data on safety and efficacy.Method of administrationThe patch should be applied to clean, dry, intact healthy skin on the abdomen, thigh, hip, flank, shoulder, or upper arm. Reapplication to the same site within 14 days should be avoided. Neupro should not be placed on skin that is red, irritated or damaged.Use and handling:Each patch is packed in a sachet and should be applied directly after the sachet has been opened. One half of the protective liner should be removed and the sticky side should be applied and pressed firmly to the skin. Then, the patch is fold back and the second part of the release liner is removed. The sticky side of the patch should not be touched. The patch should be pressed down firmly with the palm of the hand for about 20 to 30 seconds, so that it sticks well.In the event that a patch should fall off, a new patch should be applied for the remainder of the 24 hour dosing interval.The patch should not be cut into pieces.
Child Dosage
Neupro is not recommended for use in children and adolescents due to a lack of data on safety and efficacy.
Elderly Dosage
See Adult Dosage
Contra Indications
Hypersensitivity to the active substance or to any of the excipients.Magnetic resonance imaging or cardioversion
Special Precautions
If a Parkinson's disease patient is insufficiently controlled while on treatment with rotigotine switching to another dopamine agonist might provide additional benefit.The backing layer of Neupro contains aluminium. To avoid skin burns, Neupro should be removed if the patient has to undergo magnetic resonance imaging (MRI) or cardioversion.Dopamine agonists are known to impair the systemic regulation of the blood pressure resulting in postural/orthostatic hypotension. These events were also observed during treatment with Neupro, however the incidence was similar to that in placebo-treated patients.Syncope was observed in association with Neupro, but also at a similar rate in patients treated with placebo.It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of orthostatic hypotension associated with dopaminergic therapy.Neupro has been associated with somnolence and episodes of sudden sleep onset. Sudden onset of sleep during daily activities, in some cases without awareness of any warning signs, has been reported. Prescribers should continually reassess patients for drowsiness or sleepiness, as patients may not acknowledge drowsiness or sleepiness until directly questioned. A reduction of dosage or termination of therapy should be carefully considered.Pathologic gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists, including rotigotine.Although not reported with Neupro, symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy. Therefore it is recommended to taper treatment.Hallucinations have been reported and patients should be informed that hallucinations can occur.Fibrotic complications: Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis and cardiac valvulopathy have been reported in some patients treated with ergot-derived dopaminergic agents. While these complications may resolve when treatment is discontinued, complete resolution does not always occur.Although these adverse reactions are believed to be related to the ergoline structure of these compounds, whether other, nonergot derived dopamine agonists can cause them is unknown.Neuroleptics given as antiemetic should not be given to patients taking dopamine agonists.Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.Reports in the literature indicate that treatment of Restless Legs Syndrome with dopaminergic medicinal products can result in augmentation. Augmentation refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in severity of symptoms, and spread of symptoms to involve other body parts.External heat (excessive sunlight, heating pads and other sources of heat such as sauna, hot bath) should not be applied to the area of the patch.Application site skin reactions may occur and are usually mild or moderate in intensity. It is recommended that the application site should be rotated on a daily basis (e.g. from the right side to the left side and from the upper body to the lower body). The same site should not be used within 14 days. If application site reactions occur which last for more than a few days or are persistent, if there is an increase in severity, or if the skin reaction spreads outside the application site, an assessment of the risk/benefit balance for the individual patient should be conducted.If there is a skin rash or irritation from the transdermal system, direct sunlight on the area should be avoided until the skin heals. Exposure could lead to changes in the skin color.If a generalised skin reaction (e.g. allergic rash, including erythematous, macular, papular rash or pruritus) associated with the use of Neupro is observed, Neupro should be discontinued.The incidence of some dopaminergic adverse events, such as hallucinations, dyskinesia, and peripheral oedema generally is higher when given in combination with L-dopa in Parkinson's patients. This should be considered when prescribing rotigotine.In clinical studies in Parkinson's patients, the 6 month-specific rates of peripheral edema remained at about 4% through the entire observation period up to 36 months.
Interactions
Because rotigotine is a dopamine agonist, it is assumed that dopamine antagonists, such as neuroleptics (e.g. phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of Neupro, and co-administration should be avoided. Because of possible additive effects, caution should be advised when patients are taking sedating medicinal products or other CNS (central nervous system) depressants (e.g. benzodiazepines, antipsychotics, antidepressants) or alcohol in combination with rotigotine.Co-administration of Ldopa and carbidopa with rotigotine had no effect on the pharmacokinetics of rotigotine, and rotigotine had no effect on the pharmacokinetics of Ldopa and carbidopa.Co-administration of domperidone with rotigotine had no effect on the pharmacokinetics of rotigotine.Co-administration of omeprazole (inhibitor of CYP2C19), in doses of 40 mg/day, had no effect on the pharmacokinetics and metabolism of rotigotine in healthy volunteers.Neupro may potentiate the dopaminergic adverse reaction of L-dopa and may cause and/or exacerbate pre-existing dyskinesia, as described with other dopamine agonists.Co-administration of rotigotine (3 mg/24 h) did not affect the pharmacodynamics and pharmacokinetics of oral contraceptives (0.03 mg ethinylestradiol, 0.15 mg levonorgestrel).Interactions with other forms of hormonal contraception have not been investigated.
Adverse Reactions
Restless Legs SyndromeBased on the analysis of pooled placebo-controlled clinical trials comprising a total of 748 Neupro- and 214 placebo-treated patients, 65.0% of the patients on Neupro and 32.7% of patients on placebo reported at least one adverse reaction.At the beginning of therapy dopaminergic adverse reactions such as nausea and vomiting may occur. These are usually mild or moderate in intensity and transient even if treatment is continued.Adverse drug reactions (ADRs) reported in more than 10% of patients treated with Neupro are nausea, application site reactions, fatigue and headache.In trials where the application sites were rotated as reflected in the instructions provided in the SPC and package leaflet, 34.2% of 748 patients using Neupro, experienced application site reactions. The majority of these reactions were mild or moderate in intensity, limited to the application areas and resulted in discontinuation of Neupro in 7.2% of subjects.The following table covers adverse drug reactions from all studies in patients with Restless Legs Syndrome. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.System/organ classes acc. to MedDRAVery common 1/10Common 1/100, <1/10Uncommon 1/1,000, <1/100Rare1/10,000, 1/1,000 Gastrointestinal disordersNauseaVomiting, DyspepsiaGeneral disorders and administration site conditionsApplication and instillation site reactionsa (incl. erythema, pruritus, irritation, rash, dermatitis, vesicles, pain, eczema, inflammation, swelling, discolouration, papules, excoriation, urticaria, hypersensitivity) FatigueIrritabilityImmune system disordersHypersensitivityNervous system disordersHeadacheSomnolencePsychiatric disordersSleep attacks, Sexual desire disordera (incl. hypersexuality, libido increased), Insomnia, Sleep disorder, Abnormal dreamsImpulse control disordera (incl. pathological gambling, punding)Obsessive compulsive disorderSkin and subcutaneous tissue disordersPruritusVascular disordersHypertensionOrthostatic hypotensiona) High Level TermParkinson's diseaseBased on the analysis of pooled placebo-controlled clinical trials comprising a total of 1,083 Neupro- and 508 placebo-treated patients, 73.0% of the patients on Neupro and 56.3% of patients on placebo reported at least one adverse reaction.At the beginning of therapy dopaminergic adverse reactions such as nausea and vomiting may occur. These are usually mild or moderate in intensity and transient even if treatment is continued.Adverse drug reactions (ADRs) reported in more than 10% of patients treated with Neupro transdermal patch are nausea, dizziness, somnolence and application site reactions.In trials where the application sites were rotated as reflected in the instructions provided in SPC and package leaflet, 35.7% of 830 patients using the Neupro transdermal patch, experienced application site reactions. The majority of these reactions were mild or moderate in intensity, limited to the application areas and resulted in discontinuation of treatment with Neupro in only 4.3% of all subjects receiving Neupro.Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.The following table covers adverse drug reactions from all studies in patients with Parkinson's disease.System/organ classes acc. to MedDRAVery common> 1/10Common>1/100, 1/10Uncommon>1/1,000, 1/100Rare1/1,000 Immune system disorderhypersensitivityMetabolism and nutrition disordersanorexia, decreased appetitePsychiatric disordersperception disturbancesb (hallucinationa , visual hallucinationa , auditory hallucination, illusion), confusion state, abnormal dreamsa , insomniaasleep attacksa , psychotic disorder (including paranoid psychosis), compulsive disorders (including pathologic gambling, punding), increased libido (including hypersexuality), anxiety, sleep disordera , nightmares, disorientationNervous system disorderssomnolencea , dizzinessadyskinesiaa , dizziness postural, headacheasyncope, vasovagal syncope, dystonia, hypersomnia, lethargia, disturbance in attention, memory impaired, paraesthesia, dysgeusia, balance disorder, tremorconvulsion, loss of consciousnessEye disordersvisual disturbance, photopsia, blurred visionEar and labyrinth disordersvertigo (incl. positional)Cardiac disordersatrial fibrillation, heart rate increased, palpitationssupraventricular tachycardiaVascular disordersorthostatic hypotensionhypertensiona , hypotensionRespiratory, thoracic and mediastinal disorderscough, hiccupa , dyspnoeaGastrointestinal disordersnauseaavomitinga , diarrhoeaa , constipationa , dyspepsiaa , dry mouthaabdominal pain (incl. upper abdominal pain), stomach discomfortHepato-biliary disorderhepatic enzyme increased (including GGT, ALAT, ASAT)Skin and subcutaneous tissue disordersrash (incl. rash, allergic; macular, exanthema)erythemaa ; pruritus, hyperhydrosisa ,generalized pruritus, dermatitis contact, skin irritationMusculoskeletal and connective tissue disorderjoint swellingReproductive system and breast disordererectile dysfunctionGeneral disorders and administration site conditionsapplication site reactionsb (including erythemaa , pruritusa , irritationa , burninga , dermatitisa , inflammation, papulae,vesicle, blister, pain, hypersensitivity)oedema peripherala , asthenic conditionsb (incl. fatiguea , asthenia, malaise), weight decreasedgait disturbancea , feeling abnormal, weight increaseda ,Injury, poisoning and procedural complicationsfalla These adverse drug reactions have been reported in the pooled placebo-controlled trials 1% more frequent than in the placebo-treated patientsb High Level TermBoth indicationsNeupro has been associated with somnolence including excessive daytime somnolence and sudden sleep onset episodes. In isolated cases “sudden onset of sleep” occurred while driving and resulted in motor vehicle accidents.Patients treated with dopamine agonists including Neupro, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, generally reversible upon reduction of the dose or treatment discontinuation.
Manufacturer
UCB Pharma Limited
Drug Availability
(POM)
Updated
12 August 2009
