TEVA-ENTACAPONE

A total of 1450 patients with Parkinson’s Disease received entacapone during the pre-marketing clinical trials. 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 for entacapone vs. placebo 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%). Incidence of Adverse Events in Placebo Controlled Trials The most frequently observed adverse events reported with entacapone were dyskinesias/ hyperkinesia (25%/10%), nausea (14%), abnormal urine (intensification of the color of urine, 10%), diarrhea (10%), dizziness (8%) and abdominal pain (8%).

Dyskinesia, nausea and abdominal pain, may be more common with higher doses (> 1,400 mg/day) than with lower doses of entacapone. Adverse events related to the treatment with entacapone are usually mild to moderate in severity, leading only rarely to discontinuation of the treatment.

Table 3:

Adverse events, irrespective of causal relationship to study drug, occurring in > 1% of Entacapone patients and > placebo during controlled Phase 3 studies. 5 Additional adverse events that are not included in the above table but that have been identified as common adverse events associated with the use of entacapone in clinical trials and post-market spontaneous reports include insomnia, parkinsonism aggravated and dystonia.

Adverse Events reported in <1% of patients treated with entacapone in Phase 3 trials Body As A Whole - General Disorders: malaise, hot flushes, temperature changed sensation, aspiration, oedema generalised, carpal tunnel syndrome, leg pain; Cardiovascular Disorders, General: hypertension, heart valve disorders; Central & Peripheral Nervous System Disorders: hypoaesthesia, muscle contractions involuntary, eye abnormality, hypotonia; impulse control disorders (obsessive-compulsive disorder, hypersexuality, akathisia, compulsive lip biting, gambling, libido increased, obsessive thoughts, pathological gambling, sexual activity increased); 22 Endocrine Disorders: hyperthyroidism; Gastrointestinal System Disorders: gastroenteritis, oesophagitis, tooth disorder, saliva increased, dysphagia, faeces discoloured, diverticulitis, change in bowel habits, faecal abnormality; Heart Rate And Rhythm Disorders: extrasystoles, bradycardia, bundle branch block, fibrillation atrial; Liver & Biliary System Disorders: gamma-gt increased, cholelithiasis, bilirubinaemia, cholangitis; Metabolic & Nutritional Disorders: hyperglycaemia, hypoglycaemia, phosphatase alkaline increased, hypercholesterolaemia; Musculoskeletal System Disorders: bursitis, arthritis, tendinitis; Myo-, Endo-, Pericardial & Valve Disorders: angina pectoris; Platelet, Bleeding & Clotting Disorders: epistaxis, thrombocytopenia; Psychiatric Disorders: nervousness, thinking abnormal, concentration impaired, dreaming abnormal, delusion, paranoid reaction; Reproductive Disorders, Female: breast fibroadenosis; Reproductive Disorders, Male: impotence, sexual function abnormal; Resistance Mechanism Disorders: herpes simplex; Respiratory System Disorders: pneumonia, pharyngitis, sinusitis; Secondary Terms - Events: inflicted injury; Skin And Appendages Disorders: pruritus, skin disorder, dermatitis, eczema, dermatitis fungal; Special Senses Other, Disorders: taste loss; Urinary System Disorders: urinary incontinence, haematuria, albuminuria, dysuria, nocturia, renal pain; Vascular (Extracardiac) Disorders: skin cold clammy, claudication intermittent; Vision Disorders: diplopia, conjunctivitis, cataract, photopsia; White Cell & Res Disorders: leucopenia.