Parkinson's Disease -Side Effects of Drugs

Parkinson's is progressive, patients need to take drugs to manage some symptoms, but the disease wasn't
about to go away. Recently, Permax (pergolide) and its generic versions used by several thousand patients with
Parkinson's disease are being pulled from the market because of reports of heart valve damage. [1]

At least 14 patients have needed to replace their heart valves. Indeed, after some reports of heart valve
problems in 2002, its label warnings have been revised. Two recent studies suggested that up to 20% of the
pergolide users developed valve leakage. Moreover, other dopamine agonists used for Parkinson's disease are
not associated with such high rate of heart valve problems. [1] This article reviews the side effects of a few
popular medicines for Parkinson's disease.


It has been known that low dopamine levels are associated with Parkinson's disease. Logically, dopamine
supplementation should be the first line treatment for Parkinson's disease. Unfortunately, dopamine cannot get
through the body's blood-brain barrier. Because levodopa can pass through the barrier, levodopa becomes the
gold standard of Parkinson's therapy. Approved in 1970, levodopa helps restore muscle control when it is
converted to dopamine in the brain.

However, only a small amount of levodopa actually makes it into the brain. Most change to dopamine before
reaching the brain. So to relieve symptoms, many patients need to take fairly large doses, which can cause side
effects such as nausea and dyskinesias (involuntary movements).


To reduce these drawbacks, doctors often prescribe levodopa mixed with carbidopa, a drug that is marketed as
Sinemet or in generic versions. About 80 percent of Parkinson's patients take this drug in 1998. Carbidopa
delays the conversion of levodopa to dopamine until it reaches the brain, often lessening or even preventing
levodopa side effects. Carbidopa also decreases the amount of levodopa needed. Because each Parkinson's
patient reacts differently to treatment, doctors and patients must work closely to find a tolerable balance
between the drug's benefits and side effects.

Though the levodopa-carbidopa combination can be so effective that some patients forget for a while that they
have Parkinson's, the drug is far from perfect. Side effects aside, doses typically must be increased over time,
and the disease often manifests an "on-off" syndrome in advanced patients.

In 1996, FDA approved Exelon (rivastigmine tartrate) for the treatment of mild to moderate dementia (chronic
loss or impairment of intellectual capacity) associated with Parkinson's disease. The use of Exelon has been
associated with significant gastrointestinal adverse side effects. In clinical trials, 47 percent of the patients
treated with the drug developed nausea, and 26 percent of women and 18 percent of men on high doses of
Exelon experienced significant weight loss. Other common adverse side effects reported by patients on Exelon
include vomiting,
anorexia, dyspepsia and asthenia (loss of strength). In some patients with Parkinson's
disease, treatment with Exelon was associated with a worsening of tremor. [3]

Mirapex and Requip

In 1997, FDA approved three drugs to treat Parkinson's disease and they are Mirapex (pramipexole
dihydrochloride), Requip (ropinirole hydrochloride), and Tasmar (tolcapone). Mirapex and Requip, which mimic
dopamine's role in the brain, allow patients to regain some of their lost muscle control. Both are approved for
use alone or with levodopa drugs. In clinical trials, patients taking Mirapex alone saw as much as a 30 percent
improvement in symptoms. Combining Mirapex with levodopa drugs allowed advanced patients to reduce those
doses by up to 25 percent. Requip trials showed similar benefits, allowing patients to reduce levodopa doses by
an average of 31 percent.

In the three double-blind, placebo-controlled trials of patients with early Parkinson's disease, the most
commonly observed adverse events (>5%) that were numerically more frequent in the group treated
with MIRAPEX (pramipexole dihydrochloride) tablets were nausea, dizziness, somnolence, insomnia,
constipation, asthenia, and hallucinations. [6]


Tasmar is a kind of drug called a COMT inhibitor. It also is indicated for use with levodopa drugs. It seems that
Tasmar blocks a key enzyme responsible for breaking down levodopa before it reaches the brain. In trials,
patients with a stable response to levodopa drugs who took Tasmar experienced significant improvements in
daily activities such as talking, writing, walking, and dressing. However, on November 16, 1998, FDA and the
manufacturer of the drug Tasmar for patients with Parkinson's Disease, are advising doctors about reports of a
new finding of fatal liver injury associated with use of the drug. The warning calls for increased liver monitoring
(every two weeks) if a prescriber elects to treat patients with Tasmar. Doctors should also advise their patients
to self-monitor for classical signs of liver disease such as jaundice and nonspecific ones such as fatigue and
loss of appetite and other signs of side effects. [4]

Some doctors also described levodopa together with Parlodel (bromocriptine) or Permax (pergolide, withdrawn
from market) to improve response. Parlodel (bromocriptine) and Permax (pergolide) can mimic dopamine's role
in the brain.


Doctors may also use Eldepryl (selegiline hydrochloride) or deprenyl to delay the breakdown of naturally
occurring and levodopa-formed dopamine and allow the chemicals to accumulate in surviving nerve cells. Thus,
the levodopa response is prolonged.


1999, FDA approved Comtan together with carbidopa/ levodopa to treat people with Parkinson’s disease that
experience the signs and symptoms of end-of-dose "wearing-off". The side effects of the treatment include
Abnormal jerky movements, nausea, discolored (brownish orange) urine, diarrhea, abdominal pain, dizziness or
fainting especially upon quickly standing or going from a laying down to an upright position, confusion and
sweating. You should inform your healthcare if you have the following symptoms: severe diarrhea,
hallucinations, muscle pain or prolonged rigidity and high fever. [5]

FDA approved Azilect (rasagiline) for the treatment of Parkinson's disease. The drug is a monoamine oxidase
type--B (MAO-B) inhibitor that blocks the breakdown of dopamine.


Azilect was approved for use as an initial single drug therapy in early Parkinson's disease, and as an addition to
levodopa in more advanced patients.  Levodopa is a standard treatment for Parkinson's disease. The safety
and effectiveness of Azilect was demonstrated in three 18- to 26-week controlled clinical trials.

In one study, the condition of patients with early Parkinson's on Azilect showed significantly less worsening on a
rating scale that measures the ability to perform mental and motor tasks as well as daily living activities.
compared with patients on placebo. In the other two studies, patients at advanced stage using Azilect together
with levodopa had significantly less time per day with relatively poor function and mobility as compared with
patients on levodopa and placebo.

However, Azilect may be associated with hypertensive crisis if patients also consume tyramine-rich foods,
beverages (such as cheese and red wine) or dietary supplements or amines contained in many cough/cold
medications. As with most other medications for Parkinson's, Azilect has the potential to cause involuntary
movements (dyskinesias), hallucinations and lowered blood pressure.  Check the product label for details of
side effects. In addition, intake of Azilect may also be associated with an increased risk for melanoma.  [2]

GDNF,  glial cell-derived neurotrophic factor has been shown to enhance dopaminergic cell survival and fiber
outgrowth of the graft site as well as promote behavioral recovery in rodent models of Parkinson's disease. But,
its safety is a concern. It may cause cerebellar lesions.

Other Articles Related to Parkinson's Disease
Parkinson's Disease - Supplements
Parkinson's Disease - Herbs
Parkinson's Disease - Side Effects of Drugs
Parkinson's Disease - Symptoms

Though the article has been updated on July 21, 2013, most of the information is collected in 2007. It is unlikely
the side effects of medications become less over the time, but, researchers may find more side effects over the
time. The users must consult with their medical doctors or at least pharmacists on the side effects of the
medications, before taking the medications. Thanks.
Reference Parkinson's Disease: New Treatments Slow Onslaught of Symptoms FDA Consumer magazine (July-
August 1998) [1] Parkinson's drug pulled from market, AP, March 29, 2007. FDA Drug Safety Podcasts
Pergolide (marketed as Permax)  Transcript March 29, 2007  [2] FDA Approves New Treatment for Parkinson's
Disease FDA News May 17, 2006. [3] FDA Approves the First Treatment for Dementia of Parkinson's Disease
November 16, 1998. [5] Comtan, Consumer Drug Information Sheet December 29, 2004 [6] Mirapex, Product
Insert, NDA 20-667/S-011/S-013