ADVERSE REACTIONS
In controlled clinical trials, patients predominantly with moderate to severe motor fluctuations while on SINEMET (Carbidopa-Levodopa) were randomized to therapy with either SINEMET (Carbidopa-Levodopa) or SINEMET CR. The adverse experience frequency profile of SINEMET CR did not differ substantially from that of SINEMET (Carbidopa-Levodopa), as shown in Table I.
Table I: Clinical Adverse Experiences Occurring in 1% or Greater of Patients | Adverse Experience | SINEMET CR
n = 491
% | SINEMET
(Carbidopa-Levodopa)
n = 524
% |
|---|
| Dyskinesia | 16.5 | 12.2 |
| Nausea | 5.5 | 5.7 |
| Hallucinations | 3.9 | 3.2 |
| Confusion | 3.7 | 2.3 |
| Dizziness | 2.9 | 2.3 |
| Depression | 2.2 | 1.3 |
| Urinary tract infection | 2.2 | 2.3 |
| Headache | 2.0 | 1.9 |
| Dream abnormalities | 1.8 | 0.8 |
| Dystonia | 1.8 | 0.8 |
| Vomiting | 1.8 | 1.9 |
| Upper respiratory infection | 1.8 | 1.0 |
| Dyspnea | 1.6 | 0.4 |
| ‘On-Off’ phenomena | 1.6 | 1.1 |
| Back pain | 1.6 | 0.6 |
| Dry mouth | 1.4 | 1.1 |
| Anorexia | 1.2 | 1.1 |
| Diarrhea | 1.2 | 0.6 |
| Insomnia | 1.2 | 1.0 |
| Orthostatic hypotension | 1.0 | 1.1 |
| Shoulder pain | 1.0 | 0.6 |
| Chest pain | 1.0 | 0.8 |
| Muscle cramps | 0.8 | 1.0 |
| Paresthesia | 0.8 | 1.1 |
| Urinary frequency | 0.8 | 1.1 |
| Dyspepsia | 0.6 | 1.1 |
| Constipation | 0.2 | 1.5 |
Abnormal laboratory findings occurring at a frequency of 1% or greater in approximately 443 patients who received SINEMET CR and 475 who received SINEMET (Carbidopa-Levodopa) during controlled clinical trials included: decreased hemoglobin and hematocrit; elevated serum glucose; white blood cells, bacteria and blood in the urine.
The adverse experiences observed in patients in uncontrolled studies were similar to those seen in controlled clinical studies.
Other adverse experiences reported overall in clinical trials in 748 patients treated with SINEMET CR, listed by body system in order of decreasing frequency, include:
Body as a Whole: Asthenia, fatigue, abdominal pain, orthostatic effects.
Cardiovascular: Palpitation, hypertension, hypotension, myocardial infarction.
Gastrointestinal: Gastrointestinal pain, dysphagia, heartburn.
Metabolic: Weight loss.
Musculoskeletal: Leg pain.
Nervous System/Psychiatric: Chorea, somnolence, falling, anxiety, disorientation, decreased mental acuity, gait abnormalities, extrapyramidal disorder, agitation, nervousness, sleep disorders, memory impairment.
Respiratory: Cough, pharyngeal pain, common cold.
Skin: Rash.
Special Senses: Blurred vision.
Urogenital: Urinary incontinence.
Laboratory Tests: Decreased white blood cell count and serum potassium; increased BUN, serum creatinine and serum LDH; protein and glucose in the urine.
The following adverse experiences have been reported in post-marketing experience with SINEMET CR:
Cardiovascular: Cardiac irregularities, syncope.
Gastrointestinal: Taste alterations, dark saliva.
Hypersensitivity: Angioedema, urticaria, pruritus, bullous lesions (including pemphigus-like reactions).
Nervous System/Psychiatric: Neuroleptic malignant syndrome (see WARNINGS), increased tremor, peripheral neuropathy, psychotic episodes including delusions and paranoid ideation, pathological gambling, increased libido including hypersexuality, impulse control symptoms.
Skin: Alopecia, flushing, dark sweat.
Urogenital: Dark urine.
Other adverse reactions that have been reported with levodopa alone and with various carbidopa-levodopa formulations and may occur with SINEMET CR are:
Cardiovascular: Phlebitis.
Gastrointestinal: Gastrointestinal bleeding, development of duodenal ulcer, sialorrhea, bruxism, hiccups, flatulence, burning sensation of tongue.
Hematologic: Hemolytic and nonhemolytic anemia, thrombocytopenia, leukopenia, agranulocytosis.
Hypersensitivity: Henoch-Schonlein purpura.
Metabolic: Weight gain, edema.
Nervous System/Psychiatric: Ataxia, depression with suicidal tendencies, dementia, euphoria, convulsions (however, a causal relationship has not been established); bradykinetic episodes, numbness, muscle twitching, blepharospasm (which may be taken as an early sign of excess dosage; consideration of dosage reduction may be made at this time), trismus, activation of latent Horner's syndrome, nightmares.
Skin: Malignant melanoma (see also CONTRAINDICATIONS), increased sweating.
Special Senses: Oculogyric crises, mydriasis, diplopia.
Urogenital: Urinary retention, priapism.
Miscellaneous: Faintness, hoarseness, malaise, hot flashes, sense of stimulation, bizarre breathing patterns.
Laboratory Tests: Abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), bilirubin, Coombs test, uric acid.
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