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In controlled clinical trials, patients predominantly with moderate to severe motor fluctuations while on SINEMET were randomized to therapy with either SINEMET or SINEMET CR. The adverse experience frequency profile of SINEMET CR did not differ substantially from that of SINEMET, as shown in Table 1.

Table 1: Clinical Adverse Experiences Occurring in 1% or Greater of Patients

Adverse Experience SINEMET CR
n=491 %
SINEMET
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 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 postmarketing 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

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 non-hemolytic anemia, thrombocytopenia, leukopenia, agranulocytosis.

Hypersensitivity

Henoch-Schönlein 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.