Side Effects of Syndopa (Levodopa and Carbidopa) in Parkinson's Disease
The most common side effects of Syndopa (levodopa and carbidopa) include dyskinesias (involuntary movements), nausea, orthostatic hypotension, and various neuropsychiatric symptoms including hallucinations and confusion. 1, 2
Common Side Effects
Motor Complications
- Dyskinesias: Choreiform, dystonic, and other involuntary movements
- "On-off" phenomenon: Bradykinetic episodes with unpredictable fluctuations in motor response
- Increased tremor
- Extrapyramidal disorders
- Ataxia and gait abnormalities
Cardiovascular Effects
- Orthostatic hypotension: Drop in blood pressure upon standing
- Cardiac irregularities
- Hypertension
- Syncope
- Palpitations
- Phlebitis
Gastrointestinal Effects
- Nausea
- Vomiting
- Dark saliva
- Gastrointestinal bleeding
- Development of duodenal ulcer
- Anorexia
- Constipation
- Dyspepsia
- Dry mouth
- Taste alterations
Neuropsychiatric Effects
- Psychotic episodes: Including delusions and hallucinations
- Paranoid ideation
- Confusion
- Agitation
- Dizziness
- Somnolence
- Dream abnormalities and nightmares
- Insomnia
- Depression (potentially with suicidal tendencies)
- Dementia
- Impulse control disorders: Including pathological gambling and hypersexuality
Less Common Side Effects
Hematologic
- Agranulocytosis
- Hemolytic and non-hemolytic anemia
- Thrombocytopenia
- Leukopenia
Hypersensitivity Reactions
- Angioedema
- Urticaria
- Pruritus
- Henoch-Schönlein purpura
- Bullous lesions
Other Side Effects
- Skin: Rash, increased sweating, alopecia, dark sweat
- Respiratory: Dyspnea, upper respiratory infection
- Urogenital: Urinary tract infection, urinary frequency, dark urine, urinary retention, incontinence
- Laboratory abnormalities: Decreased hemoglobin and hematocrit, abnormal liver enzymes, elevated serum glucose
Management of Side Effects
For Orthostatic Hypotension
Non-pharmacological approaches:
Pharmacological interventions:
For Motor Fluctuations
- Adjust levodopa dosing regimen (timing around meals, smaller more frequent doses) 3
- Consider using the lowest effective dose to minimize side effects 3
- Implement protein redistribution diet (low-protein breakfast/lunch, normal protein dinner) 3
For Dyskinesias
- Approximately 80% of patients develop levodopa-induced dyskinesia in advanced stages 4
- Consider amantadine as an adjunctive treatment 4
For Neuropsychiatric Symptoms
- Monitor for worsening confusion or hallucinations 3
- Consider acetylcholinesterase inhibitors for cognitive symptoms 3
- SSRIs may be used for depression and anxiety (with caution) 3
- Clozapine can be effective for hallucinations in patients with psychosis 3
Important Considerations
- Side effects tend to increase with disease progression and longer duration of therapy
- Levodopa remains the most potent dopaminergic therapy for PD despite side effects 5
- Taking levodopa 30 minutes before meals maximizes absorption 3
- For patients receiving low doses of levodopa (<750 mg daily), increasing the carbidopa component may decrease peripheral adverse reactions 6
Pitfalls and Caveats
Don't ignore early signs of dyskinesia: Blepharospasm may be an early sign of excess dosage; consider dose reduction 2
Monitor for impulse control disorders: These can develop insidiously and cause significant social problems
Be vigilant about orthostatic hypotension: This can lead to falls and injury, especially in elderly patients
Watch for signs of psychosis: Early intervention is important to prevent worsening symptoms
Avoid abrupt discontinuation: This can precipitate a neuroleptic malignant-like syndrome
Consider drug interactions: Many medications can interact with levodopa/carbidopa and either reduce efficacy or increase side effects
By understanding and anticipating these side effects, clinicians can optimize Syndopa therapy to improve quality of life and reduce morbidity in patients with Parkinson's disease.