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Because clinical studies are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment per total number of patients treated) observed in the clinical studies of a drug cannot be directly compared to the incidence of adverse reactions in the clinical studies of another drug and may not reflect the incidence of adverse reactions observed in practice.

A total of 1,450 patients with Parkinson's disease were treated with Comtan in premarketing clinical studies. 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 reactions (incidence at least 3% greater than placebo) in double-blind, placebo-controlled studies (N=1,003) associated with the use of Comtan were: dyskinesia, urine discoloration, diarrhea, nausea, hyperkinesia, abdominal pain, vomiting, and dry mouth. Approximately 14% of the 603 patients given entacapone in the double-blind, placebo-controlled studies discontinued treatment due to adverse reactions, compared to 9% of the 400 patients who received placebo. The most frequent causes of discontinuation in decreasing order were: psychiatric disorders (2% vs. 1%), diarrhea (2% vs. 0%), dyskinesia and hyperkinesia (2% vs. 1%), nausea (2% vs. 1%), and abdominal pain (1% vs. 0%).

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 Comtan group, compared to placebo. In these studies, either Comtan or placebo was added to levodopa and carbidopa (or levodopa and benserazide).

Table 4: Summary of Patients with Adverse Events after Start of Trial Drug Administration At least 1% in Comtan Group and Greater Than Placebo

SYSTEM ORGAN CLASS Preferred term Comtan
(n = 603) % of patients
Placebo
(n = 400)) % of patient
SKIN AND APPENDAGES DISORDERS
Sweating increased 2 1
MUSCULOSKELETAL SYSTEM DISORDERS
Back pain 2 1
CENTRAL AND 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 1 0
RESPIRATORY SYSTEM DISORDERS
Dyspnea 3 1
PLATELET, BLEEDING AND CLOTTING DISORDERS
Purpura URINARY SYSTEM DISORDERS 2 1
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

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.

Postmarketing Reports

The following spontaneous reports of adverse events temporally associated with Comtan have been identified since market introduction and are not listed in Table 4. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish causal relationship to Comtan exposure.

Hepatitis with mainly cholestatic features has been reported.

Drug Abuse And Dependence

Comtan is not a controlled substance. Animal studies to evaluate the drug abuse and potential dependence have not been conducted. Although clinical studies 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.