The following adverse reactions are discussed in more detail in the WARNINGS AND PRECAUTIONS section of labeling.
- Risk for Hypertension [see WARNINGS AND PRECAUTIONS]
- Risk of Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
- Falling Asleep During Activities of Daily Living and Somnolence [see WARNINGS AND PRECAUTIONS]
- Hypotension/Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
- Dyskinesia [see WARNINGS AND PRECAUTIONS]
- Hallucinations/Psychotic-Like Behavior [see WARNINGS AND PRECAUTIONS]
- Impulse Control / Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
- Withdrawal Emergent Hyperpyrexia and Confusion [see WARNINGS AND PRECAUTIONS]
- Melanoma [see WARNINGS AND PRECAUTIONS]
- Irritation of the Buccal Mucosa [see WARNINGS AND PRECAUTIONS]
- Risk for Phenylketonuric Patients [see WARNINGS AND PRECAUTIONS]
- Effect on Renal Function [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction per total number of patients treated) observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the incidence of adverse reactions observed in clinical practice.
Because the controlled trials performed during premarketing development both used a titration design (1.25 mg per day for 6 weeks, followed by 2.5 mg per day for 6 weeks), with a resultant confounding of time and dose, it was impossible to adequately evaluate the effects of dose on the incidence of adverse events.
The most common adverse reactions (treatment difference incidence at least 3% greater than placebo incidence) reported in the double-blind, placebo-controlled trials during ZELAPAR treatment were constipation, skin disorders, vomiting, dizziness, dyskinesia, insomnia, dyspnea, myalgia, and rash (See Table 1).
Of the 194 patients treated with ZELAPAR in the double-blind, placebo-controlled trials, 5% discontinued due to adverse reactions compared to 1% of the 98 patients who received placebo. Most common adverse reactions causing discontinuation of treatment included dizziness, chest pain, accidental injury, and myasthenia.
Incidence In Controlled Clinical Trials
Table 1 lists the adverse events reported in the placebo-controlled trials after at least one dose of ZELAPAR (incidence 2% or greater).
Table 1: Treatment-Emergent Adverse Events* Incidence in Double-Blind, Placebo-Controlled Trials (Events ≥ 2% of Patients Treated with ZELAPAR and Numerically More Frequent than the Placebo Group)
|Body System/ Adverse Event||ZELAPAR† 1.25/2.5 mg
|Body as a Whole|
|Hemic and Lymphatic System|
|Metabolic and Nutritional Disorders|
|Skin and Appendages|
|* Patients may have reported multiple adverse experiences during the study or at discontinuation; thus patients may be included in more than one category.
** Skin disorders represent any new skin abnormality that would not be characterized as rash or neoplastic lesion. These include events such as skin ulcer, fungal dermatitis, skin hypertrophy, contact dermatitis, herpes simplex, dry skin, sweating, urticaria, and pruritus.
† Patients received concomitant levodopa.
Treatment-emergent adverse reactions for certain events were reported at a higher frequency by patients ≥ 65 years of age compared to patients < 65 years [see Use in Specific Populations].
No consistent differences in the incidences of adverse reactions were observed between male and female patients.
There were insufficient data to assess the impact of race on the incidence of adverse reactions.