ADVERSE REACTIONS
During the pre-marketing development of entacapone, 1450 patients with Parkinson's Disease were treated with entacapone. Included were patients with fluctuating symptoms, as well as those with stable responses to levodopa therapy. All patients received concomitant treatment with levodopa preparations, however, and were similar in other clinical aspects.
The most commonly observed adverse events (>5%) in the double-blind, placebo-controlled trials (N=1003) associated with the use of Comtan (entacapone) and not seen at an equivalent frequency among the placebo-treated patients were: dyskinesia/hyperkinesia, nausea, urine discoloration, diarrhea, and abdominal pain.
Approximately 14% of the 603 patients given entacapone in the double-blind, placebo-controlled trials discontinued treatment due to adverse events compared to 9% of the 400 patients who received placebo. The most frequent causes of discontinuation in decreasing order are: psychiatric reasons (2% vs. 1%), diarrhea (2% vs. 0%), dyskinesia/hyperkinesia (2% vs. 1%), nausea (2% vs. 1%), abdominal pain (1% vs. 0%), and aggravation of Parkinson's Disease symptoms (1% vs. 1%).
ADVERSE EVENT INCIDENCE IN CONTROLLED CLINICAL STUDIES
Table 4 lists treatment emergent adverse events that occurred in at least 1% of patients treated with entacapone participating in the double-blind, placebo-controlled studies and that were numerically more common in the entacapone group, compared to placebo. In these studies, either entacapone or placebo was added to levodopa/carbidopa (or levodopa/benserazide).
Table 4
Summary of Patients with Adverse Events after Start of Trial Drug Administration At least 1% in Comtan® (entacapone) group and > Placebo
SYSTEM ORGAN CLASS
Preferred term
|
Comtan
(n = 603)
% of patients
|
Placebo
(n = 400)
% of patients
|
|
| SKIN AND APPENDAGES DISORDERS |
|
Sweating increased
|
2
|
1
|
| MUSCULOSKELETAL SYSTEM DISORDERS |
|
Back pain
|
2
|
1
|
| CENTRAL & PERIPHERAL NERVOUS SYSTEM DISORDERS |
|
Dyskinesia
|
25
|
15
|
|
Hyperkinesia
|
10
|
5
|
|
Hypokinesia
|
9
|
8
|
|
Dizziness
|
8
|
6
|
| SPECIAL SENSES, OTHER DISORDERS |
|
Taste perversion
|
1
|
0
|
| PSYCHIATRIC DISORDERS |
|
Anxiety
|
2
|
1
|
|
Somnolence
|
2
|
0
|
|
Agitation
|
1
|
0
|
| GASTROINTESTINAL SYSTEM DISORDERS |
|
Nausea
|
14
|
8
|
|
Diarrhea
|
10
|
4
|
|
Abdominal pain
|
8
|
4
|
|
Constipation
|
6
|
4
|
|
Vomiting
|
4
|
1
|
|
Mouth dry
|
3
|
0
|
|
Dyspepsia
|
2
|
1
|
|
Flatulence
|
2
|
0
|
|
Gastritis
|
1
|
0
|
|
Gastrointestinal disorders nos
|
1
|
0
|
| RESPIRATORY SYSTEM DISORDERS |
|
Dyspnea
|
3
|
1
|
| PLATELET, BLEEDING & CLOTTING DISORDERS |
|
Purpura
|
2
|
1
|
| URINARY SYSTEM DISORDERS |
|
Urine discoloration
|
10
|
0
|
| BODY AS A WHOLE - GENERAL DISORDERS |
|
Back pain
|
4
|
2
|
|
Fatigue
|
6
|
4
|
|
Asthenia
|
2
|
1
|
| RESISTANCE MECHANISM DISORDERS |
|
Infection bacterial
|
1
|
0
|
|
The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical studies. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures do, however, provide the prescriber with some basis for estimating the relative contribution of drug and nondrug factors to the adverse events observed in the population studied.
EFFECTS OF GENDER AND AGE ON ADVERSE REACTIONS
No differences were noted in the rate of adverse events attributable to entacapone by age or gender.
DRUG ABUSE AND DEPENDENCE
Comtan (entacapone) is not a controlled substance. Animal studies to evaluate the drug abuse and potential dependence have not been conducted. Although clinical trials have not revealed any evidence of the potential for abuse, tolerance or physical dependence, systematic studies in humans designed to evaluate these effects have not been performed.
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