Neupro is a transdermal delivery system that provides rotigotine, a non-ergolinic dopamine agonist, continuously over a 24-hour period. The exact mechanism of action of rotigotine in the treatment of Parkinson’s disease is unknown. However, it is thought to be related to its ability to stimulate dopamine D2 receptors within the caudate-putamen in the brain.
Currently, FDA has approved Neupro for the once-daily treatment of early-stage Parkinson's disease only. It has, however, been studied to be used with levodopa at all stages of the disease, including the later stages when levodopa becomes less effective. These later-stage studies are promising demonstrating a decrease in patients’. "off" time of 2.1.-2.7 hours/day compared to only 0.9 hours decrease of “ off" time for the placebo.
Neupro may also sometimes be chosen by your doctor to treat other conditions. Such use should be considered off-label and experimental. The possible adverse side-effects when used this way are largely unknown and ongoing close medical supervision is required.
The principal advantage of the Neupro delivery system over other previously available medication delivery systems to deliver dopamine or dopamine agonists is that it is easier to use and controls the dosage of a dopamine agonist better.
In randomized, controlled studies, the Neupro patch showed superior relief of symptoms of early stage PD over placebo. Clinical benefit was defined as a 20% improvement in the UPDRS score. In one study 48% of the Neupro patients showed a 20% improvement while upon only 19% showed this improvement while taken placebo. However, one study that compared Neupro, Requip and placebo found that while Neupro was significantly better than placebo treatment, Requip was significantly better than Neupro.
Dopamine agonist are drugs that mimic the action of dopamine but are not dopamine. Dopamine is a neurotransmitter (chemical messenger) that helps in the transmission of messages between nerve cells in the brain to produce smooth, coordinated movement. A shortage of dopamine allows creates a neurotransmitter unbalance that causes the chemical that activates muscles etc; to cause the tremors of Parkinson's disease.
Dopamine agonists may also be used to treat other neurological conditions such as Progressive Supranuclear Palsy but such usage is not approved by the FDA and must be considered experimental. Any treatment should be done only under close ongoing medical supervision.
Neupro is mainly an improved way to administer a dopamine agonist. If a specific medical condition is not normally helped by other dopamine agonists, they will probably also not be helped by the use of the Neupro delivery system.
Neupro is available as 2mg, 4mg, and 6mg strength patches designed for transdermal application. The medication, rotigotine, is released and absorbed through the skin continuously over a 24 hour period.
The patient is started on the 2mg patch which is increased by 2mg/week until the desired effect is reached. The lowest effective dose was found to be 4 mg/24 hours. The highest recommended doses is 6 mg/24 hours.
The discontinuance of Neupro should be done gradually. The daily dose should be reduced by 2 mg/24 hours, with a dose reduction preferably every other day, until complete withdrawal. FDA approval of Neupro was based on the results of three clinical studies.>/P>
It is recommended that the patient select 14 places on the abdomen, thigh, hip, side, shoulder or upper arm to rotate the patch (visualize the Macarena dance!) The patch is changed daily rotating through the 14 spots so that each spot is used every 2 weeks. The patch does contain aluminum so should be removed prior to have an MRI or cardioversion to prevent skin burns. In addition, direct heat may cause too much of the rotigotine to pass through the skin so use of heating pads electric blankets and hot tubs are discouraged.
Data from three clinical trials show that Neupro is effective and generally well-tolerated in patients with early-stage PD.
These trials also showed that Neupro improved the ability to perform activities of daily living, such as handwriting, walking and balance, and motor skills, including facial expression, leg movement, and hand control.
Benefits have been seen as early as the second week of treatment in some patients.
Neupro does not claim (and has not been shown) to cure or slow the progression of any disease. It does block the tremor which is one of the most troublesome symptoms of Parkinson's disease and so enables the patient to experience a better overall quality of life.
In two of the trials participants with early-stage Parkinson's disease had the opportunity to continue taking Neupro beyond the initial trial. Over 90% chose this option.
Neupro is in the same class, dopamine agonists, as Mirapex and Requip and thus has similar side effects (SEs). Most common are dizziness, nausea, vomiting, drowsiness and it and insomnia. In addition, many patients experienced skin irritation at the application site. With some the skin irritation is reduced after a few days of use.
Similarly, the manufacturer’s data shows that many of the SEs are evident during the titration period but subside once the final dose is reached and maintenance occurs. For example, 35% of the patients reported nausea during the titration phase but only 8% reported nausea once the final dose was reached and maintained. The titration phase lasts approximately 2-3 weeks.Dr. Burton Scott, Movement Disorder Specialist at Duke, states his patients have experienced less nausea with Neupro than with the oral agents Mirapex and Requip. In addition, none of his patients thus far have experienced the fluid retention or swelling of the ankles that is seen with other agonists. He has patients that have experienced the hallucinations and compulsive behaviors that are reported with the other agonists. In general, Neupro has the same SE profile as the other dopamine agonists but a patient may experience different SEs with the individual medications.
Some patients on other dopamine agonists such as Mirapex or Requip find it difficult to take their medications two and three times a day. Some may be experiencing extreme SEs such as swelling or sleepiness and want to try another dopamine agonist.
some patients previously taking Mirapex and/or Requip have changed to Neupro - some switched successfully - some not. One patient was having a lot of swelling in her ankles and feet. Her neurologist told her to stop the Mirapex, wait for the swelling to decrease and begin the Neupro. Immediately, upon stopping the Mirapex she was "stiff all over and could barely move." Five days after stopping the Mirapex, she was in the ER where she received a muscle relaxant. Clearly, not a successful switch method!
Another patient was slowly weaned off the Mirapex and then started the Neupro tapering up 2mg/week up to the 6mg patch. She is doing well.
One doctor, familiar with the problem, has suggested starting with the 2mg Neupro patch while, at the same time, reducing the Mirapex/Requip dose so that at any one time - using two agonists - the patient has a similar level of dopamine agonist medication to what they have been use to. The doctor states that 1 1/2 mg of Mirapex is approximately equivalent 8mg of Requip which is approximately equivalent to 6mg Neupro.
The Neupro manufacturer, Schwarz Pharma has conducted “switch" trials. Dr. James Patton, a neurologist in Asheville NC, was involved in these trials. In summary, patients were switched overnight from their Pramipexole salt (such as Mirapex) or Ropinirole (such as Requip) to an equivalent dose of Neupro the next morning. Patients receiving a total daily dose of 2mg of ropinirole or 0.5 daily dose of pramipexole received the 2mg Neuoro patch; 4mg daily of ropinirole or 1 mg daily of pramipexole, the 4mg patch; or 6mg daily of ropinirole or 1,5 mg daily of pramipexole received the 6mg Neupro patch. The conclusions of the study were:
Neupro is indicated for the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease. Some patients treated with Neupro reported falling asleep while engaged in activities of daily living, including operation of motor vehicles, which sometimes resulted in accidents. Some patients perceived no warning signs, such as excessive drowsiness. Hallucinations were reported in 2.0% of patients treated with Neupro compared to 0.7% of patients on placebo.
Neupro should be used with caution in patients, especially those at risk for cardiovascular disease, because of the potential for symptomatic hypotension, syncope, elevated heart rate, elevated blood pressure, fluid retention, and/or weight gain.
Neupro should be used with caution in patients, especially those at risk for cardiovascular disease, because of the potential for symptomatic hypotension, syncope, elevated heart rate, elevated blood pressure, fluid retention, and/or weight gain. All Parkinson's disease patients are at a higher risk for melanoma and should be monitored regularly. The most commonly reported side effects in clinical trials were nausea, application site reactions, somnolence, dizziness, headache, vomiting, and insomnia. Some subjects who received Neupro experienced a decline in blood hemoglobin levels (about 2% relative to subjects who received placebo). It is not known whether this change is readily reversible with discontinuation of Neupro.
The Neupro patch is another alternative for the treatment of early-stage Parkinson's disease. It is a dopamine agonist so exhibits many of the same side effects of other agonists, such as Mirapex and Requip. It has the advantage of being a once a day treatment and is released continuously over a 24 hour period offering a constant level of medication. It is about 25% more expensive than the other agonists. A call to a Wal-Mart pharmacy in North Carolina (2007) revealed that 84 tablets (28 day supply) of 0.5mg Mirapex were $218.46. Eighty four tablets of the 2mg Requip were $212.64. and 28 of the 6mg Neupro patches was $267.84.
Neupro® is a registered trademark of UCB, Inc.
