Rotigotine
FDA Drug Information • Also known as: Neupro
- Brand Names
- Neupro
- Drug Class
- Nonergot Dopamine Agonist [EPC]
- Route
- TRANSDERMAL
- Dosage Form
- PATCH, EXTENDED RELEASE
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION NEUPRO is a transdermal system that provides continuous delivery of rotigotine, a non-ergoline dopamine agonist, for 24 hours following application to intact skin. NEUPRO is available in six strengths as shown in Table 4. Table 4 Nominal Dose, Drug Content, and Transdermal System Size NEUPRO Nominal Dose Rotigotine Content per System NEUPRO System Size 1 mg/24 hours 2.25 mg 5 cm 2 2 mg/24 hours 4.5 mg 10 cm 2 3 mg/24 hours 6.75 mg 15 cm 2 4 mg/24 hours 9 mg 20 cm 2 6 mg/24 hours 13.5 mg 30 cm 2 8 mg/24 hours 18 mg 40 cm 2 The chemical name of rotigotine is (6S)-6-{propyl[2-(2-thienyl)ethyl]amino}-5,6,7,8-tetrahydro-1-naphthalenol. The empirical formula is C 19 H 25 NOS. The molecular weight is 315.48. The structural formula for rotigotine is: The asterisk designates the chiral center. Chemical Structure System Components and Structure NEUPRO is a thin, matrix-type transdermal system composed of three layers as shown in Figure 1: Backing film Drug matrix Protective liner Figure 1: System Schematic A flexible, tan-colored backing film, consisting of an aluminized polyester film coated with a pigment-layer on the outer side. The backing provides structural support and protection of the drug-loaded adhesive layer from the environment. A self-adhesive drug matrix layer, consisting of the active component rotigotine and the following inactive components: ascorbyl palmitate, povidone, silicone adhesive, sodium metabisulfite, and dl-alpha-tocopherol. A protective liner, consisting of a transparent fluoropolymer-coated polyester film. This liner protects the adhesive layer during storage and is removed just prior to application. Figure 1
What Is Rotigotine Used For?
1 INDICATIONS AND USAGE NEUPRO is a dopamine agonist indicated for the treatment of: Parkinson's disease ( 1.1 ) Moderate-to-severe primary Restless Legs Syndrome ( 1.2 ) 1.1 Parkinson's Disease (PD) NEUPRO is indicated for the treatment of Parkinson's disease. 1.2 Restless Legs Syndrome (RLS) NEUPRO is indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Parkinson's disease: Initially, 2 mg/24 hours for early-stage disease or 4 mg/24 hours for advanced-stage disease. The dose may be increased as needed by 2 mg/24 hours at weekly intervals, up to 6 mg/24 hours for early-stage disease and up to 8 mg/24 hours for advanced-stage disease. ( 2.1 ) Restless Legs Syndrome: Initially, 1 mg/24 hours, increased as needed by 1 mg/24 hours at weekly intervals, up to 3 mg/24 hours. ( 2.2 ) Apply once a day to the skin; press firmly in place for 30 seconds. Do not place NEUPRO on oily, irritated, or damaged skin, or where it will be rubbed by tight clothing. Do not use the same site more than once every 14 days. The prescribed dose may be achieved using single or multiple patches. ( 2.3 ) To discontinue treatment, reduce the dose gradually until complete withdrawal of NEUPRO. ( 2.4 ) 2.1 Dosage in Parkinson's Disease Early-Stage Parkinson's Disease In patients with early-stage Parkinson's disease, the recommended starting dose for NEUPRO is 2 mg/24 hours. Based upon individual patient clinical response and tolerability, NEUPRO dosage may be increased weekly by 2 mg/24 hours if additional therapeutic effect is needed. The lowest effective dose is 4 mg/24 hours. The maximum recommended dose for early-stage Parkinson's disease is 6 mg/24 hours. Advanced-Stage Parkinson's Disease In patients with advanced-stage Parkinson's disease, the recommended starting dose for NEUPRO is 4 mg/24 hours. Based upon individual patient clinical response and tolerability, NEUPRO dosage may be increased weekly by 2 mg/24 hours if additional therapeutic effect is needed. The maximum recommended dose for advanced-stage Parkinson's disease is 8 mg/24 hours. 2.2 Dosage in Restless Legs Syndrome In patients with Restless Legs Syndrome, the recommended starting dose for NEUPRO is 1 mg/24 hours. Based upon individual patient clinical response and tolerability, NEUPRO dosage may be increased weekly by 1 mg/24 hours if additional therapeutic effect is needed. The lowest effective dose is 1 mg/24 hours. The maximum recommended dose is 3 mg/24 hours. 2.3 Administration Information NEUPRO is applied once a day. The adhesive side of the transdermal system should be applied to clean, dry, intact healthy skin on the front of the abdomen, thigh, hip, flank, shoulder, or upper arm. The transdermal system should be applied at approximately the same time every day, at a convenient time for the patient. Because NEUPRO is administered transdermally, food is not expected to affect absorption and it can be applied irrespective of the timing of meals. The application site for NEUPRO should be moved on a daily basis (for example, from the right side to the left side and from the upper body to the lower body). NEUPRO should not be applied to the same application site more than once every 14 days and should not be placed on skin that is oily, irritated, or damaged, or where it will be rubbed by tight clothing. If it is necessary to...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and elsewhere in the labeling: Sulfite Sensitivity [see Warnings and Precautions (5.1) ] Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions (5.2) ] Hallucinations/Psychosis [see Warnings and Precautions (5.3) ] Symptomatic Hypotension [see Warnings and Precautions (5.4) ] Syncope [see Warnings and Precautions (5.5) ] Impulse Control/Compulsive Behaviors [see Warnings and Precautions (5.6) ] Elevation of Blood Pressure and Heart Rate [see Warnings and Precautions (5.7) ] Weight Gain and Fluid Retention [see Warnings and Precautions (5.8) ] Dyskinesia [see Warnings and Precautions (5.9) ] Application Site Reactions [see Warnings and Precautions (5.10) ] Augmentation and Rebound in RLS [see Warnings and Precautions (5.11) ] Hyperpyrexia and Confusion [see Warnings and Precautions (5.14) ] Withdrawal Symptoms [see Warnings and Precautions (5.15) ] Fibrotic Complications [see Warnings and Precautions (5.16) ] Parkinson's disease: Most common adverse reactions (at least 5% greater than placebo) were nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, disturbances in initiating and maintaining sleep, hyperhidrosis, visual disturbance, peripheral edema, and dyskinesia. ( 6.1 ) Restless Legs Syndrome: Most common adverse reactions (at least 5% greater than placebo) were application site reactions, nausea, disturbances in initiating and maintaining sleep, somnolence, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 1-844-599-2273 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment/total number of patients treated) observed in the clinical trials of a drug cannot be directly compared to incidence of adverse reactions in the clinical trials of another drug and may not reflect the incidence of adverse reactions observed in practice. Adverse Reactions in Early-Stage Parkinson's Disease The safety of NEUPRO was evaluated in a total of 649 early-stage Parkinson's disease patients who participated in three double-blind, placebo-controlled studies with durations of 3 to 9 months. Additional safety information was collected in short-term studies and two open-label extension studies in patients with early-stage Parkinson's disease. In the double-blind, placebo-controlled, dose-response study in patients with early-stage Parkinson's disease, the most common adverse reactions (at least 5% greater than placebo) for the maximum recommended dose of NEUPRO (6 mg/24 hours) were nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, disturbances in initiating and maintaining sleep, hyperhidrosis, and visual disturbance. In this trial, 12% of patients treated with the maximum recommended NEUPRO dose (6 mg/24 hours) discontinued treatment because of adverse reactions, compared with 6% of patients who received placebo. Table 1 summarizes the adverse reactions that occurred in greater than 2% of NEUPRO-treated patients and more frequent than in placebo-treated patients in a double-blind, placebo-controlled, fixed-dose trial in patients with early-stage Parkinson's disease. Incidences for the non-recommended 8 mg/24 hours dose are also shown. Table 1 Adverse Reactions in a Placebo-Controlled, Fixed-Dose Trial in Patients with Early-Stage Parkinson's Disease Adverse Reaction Placebo N=64 % NEUPRO Dose 2 mg/24h N=67 % 4 mg/24h N=63 % 6 mg/24h N=65 % 8 mg/24h N=70 % Nausea 13 34 38 48 41 Vomiting 3 10 16 20 11 Somnolence 3 12 14 19 20 Application and instillation site reactions 19 21 19 32 43 Dizziness 11 21 14 22 20 Anorexia 0 2 2 9 4 Disturbances in initiating and maintaining sleep 6 6 11 14 11 Hyperhidrosis 3 3 3 11 3 Visual disturbance 0...
Drug Interactions
7 DRUG INTERACTIONS 7.1 Dopamine Antagonists Dopamine antagonists, such as antipsychotics or metoclopramide, may diminish the effectiveness of NEUPRO [see Clinical Pharmacology (12.3) ] .
Contraindications
4 CONTRAINDICATIONS NEUPRO is contraindicated in patients who have demonstrated hypersensitivity to rotigotine or the components of the transdermal system. History of hypersensitivity to rotigotine or components of the transdermal patch. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of NEUPRO in pregnant women. In animal studies, rotigotine was shown to have adverse effects on embryofetal development when administered during pregnancy at doses similar to or lower than those used clinically [ see Data ]. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage in the indicated population is unknown. Data Animal Data Rotigotine administered subcutaneously (0, 10, 30, or 90 mg/kg/day) to pregnant mice during organogenesis (gestation days 6 through 15) resulted in increased incidences of delayed skeletal ossification and decreased fetal body weights at the two highest doses and an increase in embryofetal death at the high dose. The no-effect dose for embryofetal developmental toxicity in mice is approximately 6 times the maximum recommended human dose (MRHD) for Parkinson's disease (8 mg/24 hours) on a body surface area (mg/m 2 ) basis. Rotigotine administered subcutaneously (0, 0.5, 1.5, or 5 mg/kg/day) to pregnant rats during organogenesis (gestation days 6 through 17) resulted in increased embryofetal death at all doses. The lowest effect dose is less than the MRHD on a mg/m 2 basis. This effect in rats is thought to be due to the prolactin-lowering effect of rotigotine. When rotigotine was administered subcutaneously (0, 5, 10, or 30 mg/kg/day) to pregnant rabbits during organogenesis (gestation days 7 through 19), an increase in embryofetal death occurred at the two highest doses tested. The no-effect dose is 12 times the MRHD on a mg/m 2 basis. In a study in which rotigotine was administered subcutaneously (0, 0.1, 0.3, or 1 mg/kg/day) to rats throughout pregnancy and lactation (gestation day 6 through postnatal day 21), impaired growth and development...
Overdosage
10 OVERDOSAGE 10.1 Overdose Symptoms The most likely symptoms of overdose would be those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hypotension, involuntary movements, hallucinations, confusion, convulsions, and other signs of excessive dopaminergic stimulation. 10.2 Overdose Management There is no known antidote for overdosage of dopamine agonists. In case of suspected overdose, the excess transdermal system(s) should immediately be removed from the patient. Concentrations of rotigotine decrease after patch removal. The terminal half-life of rotigotine is 5 to 7 hours. The pharmacokinetic profile showed a biphasic elimination with an initial half-life of 3 hours. The patient's heart rate, heart rhythm, and blood pressure should be monitored. As shown in a study of renally impaired patients, dialysis is not expected to be beneficial. Treatment of overdose may require general supportive measures to maintain vital signs. If it is necessary to discontinue use of rotigotine after overdose, it should be discontinued gradually to prevent hyperpyrexia and confusion [see Dosage and Administration (2.4) and Warnings and Precautions (5.14) ].
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Each transdermal system is packaged in a separate pouch. Each strength is available in cartons of 30 transdermal systems. 1 mg/24 hours 30 transdermal systems NDC #50474-801-03 2 mg/24 hours 30 transdermal systems NDC #50474-802-03 3 mg/24 hours 30 transdermal systems NDC #50474-803-03 4 mg/24 hours 30 transdermal systems NDC #50474-804-03 6 mg/24 hours 30 transdermal systems NDC #50474-805-03 8 mg/24 hours 30 transdermal systems NDC #50474-806-03 Store at 20º - 25ºC (68º - 77ºF); excursions permitted between 15º - 30ºC (59º - 86ºF). [See USP Controlled Room Temperature] NEUPRO should be stored in the original pouch. Do not store outside of pouch. Apply the transdermal system immediately upon removal from the pouch. Discard used systems in household trash in a manner that prevents accidental application or ingestion by children, pets, or others.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.