Rotigotine (Transdermal)

Rotigotine is a non-ergoline dopamine agonist that has proven effective in the treatment of Parkinson's disease and restless leg syndrome and which is marketed in the United States as a transdermal patch under the brand name Neupro.

Overview

Developed in 1985, Rotigotine is a member of the family of medicines known as dopamine agonists. It is a non-selective dopamine agonist that is non-ergoline in nature. Dopamine is an important chemical in the brain that controls emotions, mood, movement, muscle control, behavior, recognition of pain and pleasure, and cognition. Dopamine is produced in a part of the brain called the substantia nigra and naturally decreases as human beings age. However, in diseases like Parkinson's disease, the brain produces substantially less dopamine, which is what leads to the loss of motor control experienced by patients suffering from the condition.

There are five classes of dopamine receptors in the brain. Rotigotine is one of the few known medications that impact all five dopamine receptors, making it particularly effective in the treatment of Parkinson's disease and more recently in the treatment of restless leg syndrome. The medication functions by activating those dopamine receptors in the brain to stimulate the production of more dopamine. The stimulation provided by drugs like Rotigotine help patients control more of their muscle movements. It can also help stabilize the mood of the patient as dopamine elevates emotional and mental states. Given the impact of Rotigotine on levels of depression and anxiety in patients with Parkinson's, there has been a body of research conducted over the last several decades into the efficacy of Rotigotine in the treatment of generalized depression with a focus on dopamine production through the neurotransmitters in the brain rather than serotonin reuptake inhibitors, which is the mechanism in most antidepressants such as sertraline or fluoxetine.

Rotigotine interacts with over 550 medications but has significant negative interactions with only four. Alcohol use by the patient may also interact negatively with Rotigotine, exacerbating some of the side effects linked to balance, orientation and mood. It also may be contraindicated for patients suffering from some other medical conditions such as cardiovascular disease or low blood pressure because of how it interacts with the medications necessary for treatment of those diseases.

Rotigotine is generally well tolerated, but it is linked to several clusters of side effects, some of them very dangerous. Side effects range from physical effects like joint pain, weakness or upset stomach to mental side effects such as hallucinations or increased risk of depression. It is marketed in the United States as Neupro and is prescribed as a transdermal patch. There have been some issues with the patch and its delivery of the medication. It was recalled in 2008. The pharmaceutical company Schwarz Pharma recalled the medication and adjusted the patch to release the medication more effectively and safely. It was reintroduced in the United States and Europe in 2012, again under the brand name Neupro.

Conditions Treated

  • Parkinson's disease
  • Restless leg syndrome
  • May be used to treat depression

Type of Medicine

  • Non-ergoline class of dopamine agonist

Side Effects

Like most medications, Rotigotine carries the risk of side effects. Some side effects will fade over time as the patient's body becomes more accustomed to the medication. These side effects do not usually require medical attention and the patient should be able to continue using Rotigotine. These include:

  • Weight loss
  • Drowsiness
  • Constipation
  • Loss of appetite
  • Indigestion
  • Painful joints
  • Painful muscles
  • Dry mouth
  • Unusual dreams
  • Unusual stiffness
  • Insomnia
  • Sense of vertigo, lack of orientation
  • Upset stomach
  • Heartburn
  • Unusual belching

Some reactions or side effects do require medical attention, and may indicate discontinuation of Rotigotine:

  • Swelling in the extremities (edema)
  • Skin rash, itching or burning where patch is applied
  • Blood in the urine
  • Dizziness or disorientation
  • Vision changes
  • Pain in the bladder
  • Difficulty urinating
  • Headache
  • Pain in the lower back
  • Frequent need to urinate
  • Anxiety
  • Pain in the side
  • Ringing in the ears
  • Irregular heartbeat
  • Hallucinations

It is possible for a patient to have a very dangerous reaction to Rotigotine, either in terms of an allergic reaction from the patient or an overdose. In either situation, immediate medical treatment is required. Those symptoms include:

  • Seizures and convulsions
  • Excessive sweating
  • Extreme weakness
  • Chronic and excessive fatigue
  • Nausea and vomiting
  • Dizziness, disorientation or vertigo-like sensation

Dosage

Rotigotine is sold under the brand name Neupro and is delivered through a transdermal patch. It comes in six different strengths:

  • 1mg/24hr
  • 2mg/24hr
  • 3mg/24hr
  • 4mg/24hr
  • 6mg/24hr
  • 8mg/24hr

Different dosages are indicated both for the condition being treated and the level of severity of the condition.

In the initial treatment of Parkinson's disease, the patient should begin the prescription by applying one 2mg/24hr patch and adjusting upward until the most effective level of dosage is reached.

If the patient is in late-stage Parkinson's, the initial dose should start at 4mg/24hr and adjust from there. Dosage should not exceed 8mg/24hr, even for patients in the most advanced stages of the disease.

Patients should not discontinue use of Neupro abruptly. To stop taking the medication, dosage should be gradually reduced at a rate of 2mg/24hr every two days until the patient is completely off Neupro.

In the treatment of restless leg syndrome, the standard initial dosage is 1mg/24hr. Dosage levels can be adjusted upward by moving up to 2mg/24hr after one week of treatment. If a stronger dosage is indicated, the dosage level may move to 3mg/24hr after another week. 3mg/24hr is the maximum dosage levels for patients with restless leg syndrome. These patients should not discontinue use of Neupro abruptly either. Dosage levels should be reduced by 1mg/24hr every two days until the patient is completely off the medication.

The Neupro patch should be applied at the same time every day. The patient should rotate the site of application to reduce the risk of rash or other skin issues. Patients should avoid using the same spot on the body for at least 14 days. It should be placed on clean, dry skin that is free of any sort of cut or wound. If hair is present in the application site, it should be shaved clear three days prior to application to that site. It can be placed on the upper arm, the abdomen, the thigh or the shoulder. The patch should be pressed firmly on the application site and held there for 30 seconds to one minute to ensure that it will not come loose.

The Neupro patch is designed to maintain adherence to the skin through normal movements, bathing and modest exercise. Should it come off during the 24-hour period, the patient should replace it with a new one immediately to maintain dopamine levels.

There is no current recommended dosage level of rotigotine for the treatment of depression. However, there have been several clinical trials conducted over the past twenty years that indicate that a dosage level of 1mg/24hr has a positive effect on dopamine levels in patients with depression. The efficacy of rotigotine in positively affecting depression levels in patients with Parkinson's Disease has been well documented and so Neupro represents a promising possible treatment for other patients who suffer only from depression.

Interactions

Rotigotine interacts with many medications but is not absolutely contraindicated with any known medication. There are several that require close supervision if prescribed concomitantly with rotigotine. These include:

  • Acetaminophen
  • Aspirin
  • Propoxyphene
  • Sodium oxybate
  • Loxapine

It is not recommended that rotigotine be prescribed in conjunction with medication that is designed to reduce dopamine levels in the brain as the two medications will decrease the effectiveness of each other. These medications would include:

  • Prochlorperazine
  • Metoclopramide
  • Chlorpromazine
  • Flupentixol

These medications are usually prescribed for patients with serious psychoses conditions and help reduce psychotic episodes by decreasing dopamine production.

The following medications require monitoring and supervision of the patient if they are prescribed concomitantly with rotigotine:

  • Phenylephrine
  • Buprenorphine buccal
  • Ephedrine for pulmonary disease
  • Clobazam
  • Ketotifen for ophthalmic conditions
  • Enflurane

Rotigotine interacts moderately with the following medications:

  • Aluminum hydroxide
  • Amoxapine
  • Asenapine
  • Apomorphine
  • Cellulase
  • Apraclonidine
  • Anhydrous calcium iodide
  • Aripiprazole
  • Codeine
  • Chlordiazepoxide
  • Phenobarbital
  • Amitriptyline
  • Aminophylline
  • Atropine
  • Azelastine
  • Azatadine
  • Fluticasone
  • Baclofen
  • Belladonna
  • Lidocaine
  • Dextromethorphan
  • Brexpiprazole
  • Brimonidine for ophthalmic conditions
  • Brivaracetam
  • Biperiden
  • Brompheniramine
  • Bromocriptine
  • Fentanyl
  • Cariprazine
  • Guaifenesin
  • Clophedianol
  • Clonidine
  • Chlorpromazine
  • Clorazepate
  • Cyclazine
  • Cyproheptadine
  • Conjugated estrogens
  • Coxepin
  • Droperidol
  • Dezocine
  • Desvenlafaxine
  • Diazepam
  • Dantrolene
  • Ezogabine
  • Entacapone
  • Ethanol
  • Ethosuximide
  • Eszopiclone
  • Ethotoin
  • Ethchlorvynol
  • Fosphenytoin
  • Felbamate
  • Flibanserin
  • Fluvoxamine
  • Flavoxate
  • Hydrocodone
  • Heroin
  • Halazepam
  • Hydromorphone
  • Haloperidol
  • Ibuprofen
  • Isocarboxazid
  • Imipramine
  • Ioflupane
  • Ketamine
  • Kava
  • Lithium
  • Lurasidone
  • Levomethadyl acetate
  • Magnesium salicylate
  • Morphine
  • Methadone
  • Meprobamate
  • Molindone
  • Naloxone
  • Nortriptyline
  • Naltrexone
  • Nefazodone
  • Olanzapine
  • Opium and opiate derivatives
  • Oxycodone
  • Pregabalin
  • Pentobarbital
  • Paraldehyde
  • Pergolide
  • Procyclidine
  • Pyrilamine
  • Quetiapine
  • Quazepam
  • Rasagiline
  • Rufinamide
  • Ramelteon
  • Ropinirole
  • Risperidone
  • St. John's Wort
  • Sertraline
  • Suvorexant
  • Secobarbital
  • Tramadol
  • Thalidomide
  • Thioridazine
  • Valerian
  • Vigabatrin
  • Valproic acid
  • Ziconotide
  • Zonisamide

Rotigotine also interacts negatively with alcohol. Patients prescribed the Neupro patch (rotigotine) should avoid consumption of alcohol as the combination can lead to increased dizziness, loss of balance, disorientation and excessive drowsiness.

For patients suffering from hypotension, careful monitoring of the use of rotigotine is indicated as the dopamine produced by the medication can cause difficulty in regulating blood pressure. The same is true for patients with high blood pressure who are also taking anti-hypertensive medications. Blood pressure of these patients should be taken regularly and under medical supervision.

For patients with psychosis conditions, rotigotine can present a real risk of exacerbating symptoms and manifestations of the illness in the form of hallucinations, psychotic episodes and dramatic changes in mood.

Patients with cardiovascular disease or limited renal function should know that rotigotine has been linked to an increase in fluid retention, which can cause complications in either or both of these conditions. Use of rotigotine could possibly cause the development of congestive heart failure in patients with known cardiovascular disease. For these patients, the Neupro patch has also been linked to unregulated blood pressure problems, particularly when changing position from seated to standing or lying down to standing. It can also cause changes to heart rate, increasing the number of beats per minute.

There is a moderate risk of anaphylactic response from patients prescribed rotigotine if they also are asthmatic. Patients with asthma tend to more allergic to or sensitive to sulfites, which are one of the chemical agents in rotigotine. The presence of sulfites can cause an asthma attack, and so these patients should be monitored when beginning their initial course of treatment in case of allergic reaction.

Warnings

Rotigotine may cause an allergic reaction in patients with sulfite sensitivity, and that reaction may be as severe as anaphylaxis.

Rotigotine has been linked rarely to the development of basal cell carcinoma, so monitoring for melanoma over a long dosage period is recommended.

Patients may experience almost narcoleptic symptoms when taking rotigotine, with sudden bouts of sleepiness that interfere with the normal course of daily life. Rotigotine can also cause low blood pressure (hypotension) and fainting, which can be dangerous and lead to injury.

In some patients, it can have the opposite effect, escalating blood pressure which can lead to a host of other medical issues that would need to be controlled and treated.

Patients who are using the Neupro patch to treat restless leg syndrome may find their symptoms worsen as the medication wears off.

Patients that are particularly sensitive to dopamine may experience dyskinesia from mild to moderate that actually mirrors the Parkinson's symptoms that are being treated.

It is not unusual for patients to experience irritation and rash at the application site of the patch, often related to the level of dosage.

Some patients experience some weight gain, especially with regard to fluid retention and edema, which can also be linked to the dosage level.

Patients should avoid too much heat (e.g. too many blankets or a heating pad) as this increases levels of absorption and changes the rate of delivery of the medication. The patch should also be removed before the patient has an MRI.

Some patients have reported changes to skin color linked to their use of rotigotine.

It is very important for patients to avoid completely withdrawing from rotigotine too abruptly. An accelerated discontinuation of the medication can cause fever, stiffness, mild psychosis, muscle failure, and potential renal failure. Withdrawal must be supervised medically and over time.

It is not known whether or not rotigotine affects a human fetus. Trial studies have been inconclusive. It is generally considered safe if the benefits of its use outweigh the risks to the baby. It is not recommended that mothers continue to nurse their infant since it is not known whether rotigotine is passed through breast milk.

Patients should be sure to wash their hands after applying the Neupro patch before touching their face, eyes or mouth.

Rotigotine has not been clinically tested in children and is not recommended for pediatric use.

Storage

Rotigotine patches should be kept at room temperature in the original pouch/container. Patches should be kept in the pouch until used. They should not be stored in the bathroom to avoid exposure to moisture. Rotigotine patches should be kept dry until used. Once the patient has finished with the skin patch, it should be disposed of properly, which includes folding the patch in on itself using the sticky side.

Summary

For patients struggling with diseases like Parkinson's, rotigotine represents a safe and effective treatment for their muscular and motor control symptoms. While not a cure, the dopamine production stimulated through the use of this medication can significantly improve the quality of life for patients, especially in the early stages of the disease. However, rotigotine is a strong medication that finds it efficacy by changing the chemical balance of the brain. Because of this, it carries with it the risk of many side effects and other health risks that weaker medications do not. It can cause significant changes to blood pressure, both by rapidly lowering it or elevating it. The Neupro patch it comes in can cause irritation at the application site. It can cause changes in sleep patterns and behavior, often very seriously. Rotigotine interacts with a range of medications, although in most cases, only mildly to moderately. The most danger in interactions exists in patients who have a combination of conditions that includes Parkinson's and some other serious illness such as cardiovascular disease.

Because rotigotine has been available since the mid-1980s, it has been studied thoroughly. It is through these clinical trials that rotigotine's effectiveness in the treatment of restless leg syndrome was found. There is current research into its efficacy in the treatment of generalized depression that is not linked to Parkinson's.

Dosage levels vary depending on the severity of the patient's condition and the weight of the patient. Dosing should begin at 1mg/24hr to 2mg/24hr and ramp up from that point over a period of several weeks. Likewise, if a patient is planning to discontinue use of rotigotine, that should be handled gradually over a period of a few weeks. Rapid withdrawal may have dangerous side effects and is not safe. Rotigotine has not been tested in children and is not recommended for young patients. It has not been found to be unsafe for pregnant women, but falls in category C for pregnancy, meaning it may be prescribed if the physician feels its use outweighs any known risks to the mother or the child. It is not recommended for nursing mothers. If a new mother needs the Neupro patch, she should discontinue nursing.

 

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Last Reviewed:
January 31, 2018
Last Updated:
January 27, 2018
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