Side Effects of Syndopa (Levodopa/Carbidopa)
Syndopa causes a wide range of side effects, with the most common being dyskinesias (involuntary movements), nausea, and orthostatic hypotension, while long-term use carries significant risk of motor complications including wearing-off phenomena and drug-induced dyskinesias that can develop within 5-6 months of treatment initiation. 1
Most Common Adverse Effects
Motor Complications
- Dyskinesias (choreiform, dystonic, and other involuntary movements) are the most frequently reported adverse reaction with levodopa/carbidopa therapy 1
- Motor fluctuations and dyskinesias occur in the majority of patients after 5 years of levodopa therapy 2
- Dyskinesias can develop as early as 5-6 months with higher doses (600 mg/day showed dyskinesias in clinical trials) 3
- "On-off" phenomenon (bradykinetic episodes) with unpredictable fluctuations in motor response 1
- Younger age at Parkinson's disease onset, disease severity, and high levodopa doses increase dyskinesia risk 4
Gastrointestinal Effects
- Nausea is one of the most common side effects, particularly dose-dependent 1, 3
- Vomiting, anorexia, and weight loss 5, 1
- Abdominal pain, dyspepsia, constipation, diarrhea 1
- Dry mouth and taste alterations 6, 1
- Dark saliva 1
- Gastrointestinal bleeding and development of duodenal ulcer 1
Cardiovascular Effects
- Orthostatic hypotension and other orthostatic effects 1
- Cardiac irregularities, palpitations 1
- Syncope 1
- Hypertension (paradoxically can occur) 1
Neuropsychiatric Side Effects
Psychiatric Manifestations
- Psychotic episodes including delusions, hallucinations, and paranoid ideation 1
- Confusion, agitation, disorientation 1
- Depression with or without suicidal tendencies 1
- Dementia 1
- Impulse control disorders: pathological gambling, increased libido including hypersexuality 1
- Dream abnormalities including nightmares 1
- Anxiety, nervousness, euphoria 1
Neurological Effects
- Dizziness, somnolence, insomnia 1, 3
- Headache, paresthesia 1
- Convulsions (causal relationship not established) 1
- Peripheral neuropathy 1
Metabolic and Nutritional Effects
Weight and Metabolic Changes
- Weight loss is common, especially in women, potentially due to higher levodopa dose per kg body weight 5
- Reduced muscle glucose uptake 5
- Increased plasma free fatty acids, glucose, growth hormone, and cortisol 5
- Hyperhomocysteinemia requiring monitoring of vitamin B status (B6, B12, folate) 5
- Edema and weight gain can also occur paradoxically 1
Hematologic and Laboratory Abnormalities
- Agranulocytosis, hemolytic and nonhemolytic anemia 1
- Thrombocytopenia, leukopenia 1
- Decreased hemoglobin and hematocrit 1
- Abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), LDH, bilirubin, BUN 1
- Positive Coombs test 1
Hypersensitivity Reactions
- Angioedema, urticaria, pruritus 1
- Henoch-Schönlein purpura 1
- Bullous lesions including pemphigus-like reactions 1
Dermatologic Effects
- Rash, increased sweating 1
- Dark sweat 1
- Alopecia 1
- Flushing 1
- Malignant melanoma (association controversial) 1, 7
Urogenital Effects
- Urinary tract infection, urinary frequency 1
- Dark urine 1
- Urinary retention or incontinence 1
- Priapism 1
Critical Clinical Considerations
Dose-Related Effects
- Higher doses increase risk of dyskinesias and nausea in a dose-dependent manner 3
- Increasing levodopa doses are associated with increased risk for malnutrition 5
- Blepharospasm may be an early sign of excess dosage requiring dose reduction 1
Long-Term Complications
- After 5 years, the majority of patients suffer fluctuations, dyskinesias, toxicity, or loss of efficacy 2
- Once dyskinesias are established, they are difficult to treat 4
- Motor complications adversely affect quality of life and increase healthcare costs 4
Important Drug Interactions
- Carbidopa may decrease the effectiveness of droxidopa in Parkinson's patients with neurogenic orthostatic hypotension 8