Agonists are medications which stimulate dopamine sites in the brain which increases the level of dopamine. The increase in dopamine levels relieves the symptoms of Parkinson's disease. They are used often in conjunction with levodopa. These medications may permit a reduction in the levodopa drug levels.
Mirapex (pramipexole), unlike Bromocriptine or Pergolide, is a complete agonist. It can be used alone in early Parkinson's Disease. In late Parkinson's, Mirapex is used along with levodopa/carbidopa. Research has been shown that people who respond to Mirapex have a reduction in the "off" time. In some patients Mirapex has been able to delay the use of levodopa for up to 2 years. Even those people who have had PD for a long time can experience some reduction in their levodopa dose. This is a relatively new drug and further drug studies are currently being done.
Along with the many positive effects of dopamine agonists, you may also experience some side effects. Side effects are unintended or undesirable reactions to medications. Most of the side effects you experience can be lessened with additional medications, dosage changes, or changes in your daily habits. Or, they may simply fade as your body adjusts to the medication. If you experience any side effects, contact your doctor or clinician right away and continue taking your medication.
It is also important to be aware of the risks of dopamine agonists. The risks occur very rarely, but it is important to know what to look for, just in case. If you think you are experiencing one of the risks, contact your doctor or clinician or go to the emergency room right away!
Side effects in early PD - nausea, dizziness, insomnia, hallucinations
Side effects in late PD - hypertension, dyskinesia, insomnia, confusion, constipation, dry mouth
Most people who experience this side effect notice that it disappears in a few weeks. To reduce or eliminate nausea, eat several small meals per day instead of three big ones, or try snacking on dry toast or crackers. Try taking dopamine agonists with food. It may slow the absorption of the drug but it will reduce the nausea.
If you feel dizzy when you sit or stand up quickly, there are some precautions that you can take to avoid injury. Get up very slowly from a laying or sitting position and make sure you have something to hold onto as you get up. Then, wait a moment or two before you start walking.
Confusion occurs more often in older patients. People can seem confused because they can't remember where they are, what they were doing, or how to get back to where they were. They may seem as though they can't figure out a new problem which is presented to them. This side effect may mean that your physician will want to decrease the dose of the dopamine agonist.
Hallucinations occur when a person senses things that aren't really there. The most commonly experienced hallucination for people taking dopamine agonists is seeing people or objects that are not there. People also have hallucinations where they hear, feel, smell or taste something that is not there. If you think that you are having hallucinations as a result of your medication, contact your doctor right away!
These are involuntary movements of the face, neck and extremities. These movements are not tremors but are twitching, nodding and jerking. These types of side effects occur in people who have been taking dopamine agonists for a longer time. To reduce or eliminate this side effect, the doctor may need to reduce the dose. The reduction of agonists may mean that Parkinson symptoms reappear.
Insomnia is difficulty falling asleep. If you experience insomnia as a result of your medication, your doctor may change your dose, prescribe a medicine to help you sleep, or advise you to take the medication in the morning. To combat insomnia, avoid eating heavy meals, exercising, or drinking caffeinated beverages before bed.
Confusion occurs more often in older patients. People can seem confused because they can't remember where they are, what they were doing, or how to get back to where they were. They may seem as though they can't figure out a new problem which is presented to them. This side effect may mean that your physician will want to decrease the dose of the dopamine agonist.
Dopamine agonists can sometimes cause constipation. This side effect usually does not go away, but it can be controlled by increasing the amount of high fiber foods in your diet, such as breads, fruits, vegetables, and bran. It also helps to exercise regularly and drink plenty of fluids. If constipation is still a problem, your doctor may recommend a laxative or fiber product, or may prescribe an additional medication to reduce the side effect.
Some people taking dopamine antagonist medications experience dry mouth. Although dry mouth may not go away completely, it usually gets better with time. Dry mouth can be relieved by sucking on hard candy or crushed ice, drinking plenty of fluids, or eating frozen grapes.
MedWatch is the FDA Medical Products Reporting Program for health-care professionals. It provides a pathway through which medical personnel can report serious adverse events and product problems that occur with the use of all medical products, including drugs, biologics, medical devices, and special nutritional formulations (eg, medical foods, dietary supplements, and infant formulas).
21 September 1999
This is the retyped text of a letter from Pharmacia & Upjohn and Boehringer Ingelheim. Contact the company for a copy of any referenced enclosures.
Dear Health Care Professional:
This letter is to advise you of the possibility of patients falling asleep while performing daily activities, including operation of motor vehicles, while receiving treatment with MIRAPEX (pramipexole dihydrochloride tablets), a dopamine agonist, indicated for the treatment of the signs and symptoms of idiopathic Parkinson's Disease. While somnolence is a common occurrence in patients receiving MIRAPEX and many clinical experts believe that falling asleep while engaged in activities of daily living only occurs in the context of pre-existing somnolence, many patients who have fallen asleep have perceived no warning. Health Care Professionals should be alerted to the potentially serious risks associated with the events and should carefully evaluate their patients for the presence of somnolence, and should have a discussion with them.
To communicate this important safety information, the following has been added to labeling:
Patients treated with MIRAPEX have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles which sometimes resulted in accidents. Although many of these patients reported somnolence while on MIRAPEX, some perceived that they had no 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 one year after the initiation of treatment.
Somnolence is a common occurrence in patients receiving MIRAPEX at doses above 1.5 mg/day. Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing somnolence, although patients may not give such a history. For this reason, prescribers should continually reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.
Before initiating treatment with MIRAPEX, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with MIRAPEX such as concomitant sedating medications, the presence of sleep disorders, and concomitant medications that increase MIRAPEX plasma levels (e.g., cimetidine -- see PRECAUTIONS, Drug Interactions). If a patient develops significant daytime sleepiness or falling asleep during activities that require active participation (e.g., conversations, eating, etc.), MIRAPEX should ordinarily be discontinued. If a decision is made to continue MIRAPEX, patients should be advised to not drive and to avoid other potentially dangerous activities. While dose reduction clearly reduces the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
The PRECAUTIONS-Information for Patients section statement on somnolence has been replaced with the following:
Patients should be alerted to the potential sedating effects associated with MIRAPEX, including somnolence and the possibility of falling asleep while engaged in activities of daily living. Since somnolence is a frequent adverse event with potentially serious consequences, patients should neither drive a car nor engage in other potentially dangerous activities until they have gained sufficient experience with MIRAPEX to gauge whether or not it affects their mental and /or motor performance adversely. Patients should be advised that if increased somnolence or episodes of falling asleep during activities of daily living (e.g., watching television, passenger in a car, etc.) are experienced at any time during treatment, they should not drive or participate in potentially dangerous activities and should contact their physician. Because of possible additive effects caution should be advised when patients are taking other sedating medications or alcohol in combination with MIRAPEX and when taken concomitant medications that increase plasma levels of pramipexole (e.g., cimetidine).
Changes consistent with the added warning have also been made to the ADVERSE EVENTS section and the DOSAGE AND ADMINISTRATION section.
Our primary concern is the safety and well-being of patients who use MIRAPEX. If you become aware of any case(s) of the event described above in patients treated with MIRAPEX or other dopaminergic agents, please report the event promptly. You may contact P&U regarding events associated with MIRAPEX at 1-800-253-8600 or the FDA MedWatch program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857.
Sincerely,
Pharmacia & Upjohn and Boehringer Ingelheim Pharmaceuticals
MIRAPEX is copromoted by Pharmacia & Upjohn and Boehringer Ingelheim Pharmaceutical, Inc.
MILLERSVILLE, Md. Feb. 11, 2005 -- There are claims that a widely prescribed medication for Parkinson's disease drove some patients to compulsive behavior such as sex, gambling, eating and shopping -- behavior that destroyed personal and professional lives.
Joe Neglia, 53, of Millersville, walks with an uneven gait as a result of Parkinson's disease, which was diagnosed in 1994, reported WBAL-TV in Baltimore.
"The stiffness in the left leg and the hand were a dead giveaway," Neglia said.
As his symptoms progressed with no cure in sight, Neglia's doctor suggested a new drug to try.
Mirapex mimics dopamine, a chemical in the brain that allows for smooth, fluid body movements. Like all Parkinson's disease patients, Neglia's body doesn't have enough dopamine, and Mirapex worked.
"It is a helpful drug," Neglia said. "I could move around better, more fluid, not as jerky."
Mirapex, or pramipexole as it is known generically, is manufactured by Boehringer Ingelheim Pharmaceuticals Inc.
Neglia started the drug in late 1998. At the maximum dose of 4.5 milligrams, his brain was racing, and he developed some obsessive-compulsive behavior.
"I could not drive past a McDonald's to save my life," he said. "I would eat voraciously, constantly. I couldn't understand why I'd never been like that before."
Neglia gained 50 pounds, but something even more frightening was happening to him, something no one knew about.
"It turned into the most horrible god-awful obsession -- gambling," he said.
At the time, Neglia lived in California. He discovered he lived within 20 minutes of three casinos. He would go there to gamble three to four times a day -- sitting transfixed in front of a slot machine until the money was gone.
"I couldn't understand what was happening to me," he said. "I totally lost control of myself."
Neglia said he had always been an organized, thoughtful man, but now his life was quickly disintegrating and he had no idea why.
In August 2003, Neglia was online and found a news headline that nearly knocked him out of his chair.
"A news headline jumped out at me," he said. "Parkinson's drug linked to obsessive gambling."
More research led to more stories of people on Mirapex who developed obsessive-compulsive behaviors -- wrecked marriages, attempted suicide, ruined professional lives.
Neglia is now part of a multi-plaintiff lawsuit in California, being handled by attorneys Soheila Azizi and Daniel Kodam. They are seeking reparations and warning labels on Mirapex. They said patients didn't know to ask their doctors about what was happening to them.
Dr. William Weiner is the chairman of neurology at the University of Maryland Medical System. He believes the side effects do exist but are extremely rare and that Mirapex is a valuable drug for hundreds of thousands of people.
Should doctors warn patients?
"To make people worried about every single rare occurrence that happens in a whole population of people taking a drug is just not something that physicians do," Weiner said.
In a written statement, Boehringer Ingelheim Pharmaceuticals claimed "there is no scientific evidence of a causal effect between Pramipexole and compulsive behavior." However, the drug manufacturer also said it recently included compulsive behaviors as a possible adverse reaction in the drug's insert.
Neglia's attorneys said it's a good start, but not enough. Warning people who take Mirapex is exactly what Neglia believes needs to be done.
"If there had been a 2-cent warning label on the bottle, 'Stop in case of compulsive behavior,' it would have saved me a lot of hell," Neglia said.
