What are the side effects of Carbidopa, Amantadine, and Ropinirole?

Side Effects of Carbidopa, Amantadine, and Ropinirole

Amantadine Side Effects

Amantadine causes CNS side effects in approximately 13% of patients at standard dosing (200 mg/day), significantly higher than placebo (4%), and requires mandatory dose reduction to ≤100 mg/day in elderly patients due to dose-dependent toxicity. 1, 2

Common CNS and Gastrointestinal Effects

• Nervousness, anxiety, insomnia, difficulty concentrating, and lightheadedness occur in 13% of patients at 200 mg/day versus 4% with placebo 1, 2
• Nausea is the most frequently reported adverse reaction at recommended doses 2
• Dizziness (lightheadedness) is common 2
• Gastrointestinal side effects (nausea and anorexia) occur in approximately 1-3% of patients, comparable to placebo rates of 1% 1, 2
• Constipation is a less common side effect 2

Serious CNS Toxicity

• Marked behavioral changes, delirium, hallucinations, agitation, and seizures can occur, particularly in high-risk patients 1, 2
• These severe effects are associated with high plasma drug concentrations and occur most often in patients with renal insufficiency, seizure disorders, psychiatric disorders, and elderly persons taking 200 mg/day 1, 2
• Dosage reduction significantly reduces the incidence and severity of these side effects 1, 2

Cardiovascular and Other Effects

• Constipation, cardiovascular dysfunction including QT prolongation, orthostatic hypotension, and edema are common adverse reactions 3
• Acute respiratory failure, pulmonary edema, and adult respiratory distress syndrome (ARDS) are potential complications in acute overdosage 2
• CNS, renal, respiratory, and cardiac toxicity, including arrhythmias, have been reported in acute overdosage 1

Anticholinergic Effects

• Amantadine has anticholinergic effects and can cause mydriasis; it should not be used in patients with untreated angle-closure glaucoma 2
• Urinary retention is an anticholinergic manifestation 2
• Livedo reticularis can occur 3
• Corneal degeneration is rare but critical 3

Time Course

• Most side effects are mild and cease soon after discontinuing the drug 1, 2
• Side effects can diminish or disappear after the first week despite continued use 1, 2

Critical Dosing Considerations for Elderly

• The daily dose for persons aged ≥65 years must not exceed 100 mg for either prophylaxis or treatment due to dose-dependent toxicity 2
• Elderly women are at higher risk than elderly men for side effects at 100 mg/day due to smaller average body size 2
• Some elderly persons require further dose reduction below 100 mg/day to minimize serious CNS toxicity 2
• Renal function declines with increasing age, necessitating dose reduction in all elderly patients 2
• Dosage reduction is required for creatinine clearance ≤50 mL/min/1.73m² to prevent drug accumulation 2

Ropinirole Side Effects

Ropinirole most commonly causes nausea and sleepiness, with a significantly higher risk of hypotension and somnolence compared to pramipexole when compared to placebo. 4, 5

Common Side Effects

• Nausea is the most common side effect 5, 6
• Extreme sleepiness and/or sudden sleep attacks are common 5
• Dizziness occurs frequently 5, 6
• Dyskinesia is a common side effect, particularly when used as adjunct to levodopa 6
• Vertigo occurs in some patients 5

Cardiovascular Effects

• Orthostatic hypotension can occur 5
• The risk of hypotension is approximately four times higher with ropinirole than pramipexole when compared with placebo (RR 6.46 [95% CI 1.47-28.28] for ropinirole versus 1.65 [0.88-3.08] for pramipexole) 4
• Leg edema occurs in some patients 5

Neuropsychiatric Effects

• Hallucinations can occur, though the risk is lower than with pramipexole when compared to placebo (RR 2.75 [95% CI 0.55-13.73] for ropinirole versus 5.2 [95% CI 1.97-13.72] for pramipexole) 4
• Somnolence risk is significantly higher with ropinirole compared to pramipexole when compared to placebo (RR 5.73 [95% CI 2.34-14.01] for ropinirole versus 2.01 [95% CI 2.17-3.16] for pramipexole) 4

Less Common Effects

• Dyspepsia occurs less commonly 5
• Dry cough and hypersalivation are recorded sporadically 5
• Depression occurs in particular cases 5

Tolerability

• There was no significant difference in overall incidence of adverse effects between ropinirole (59.5%) and bromocriptine (59%) in comparative studies 6
• Ropinirole is generally safe and well-tolerated, with no patients withdrawn from studies due to side effects in some trials 6

Carbidopa Side Effects

Note: The provided evidence does not contain specific information about carbidopa side effects as a standalone medication. Carbidopa is typically combined with levodopa (as carbidopa/levodopa) and functions as a decarboxylase inhibitor to prevent peripheral conversion of levodopa, thereby reducing peripheral side effects of levodopa such as nausea. The evidence focuses on amantadine and ropinirole specifically.

Combined Therapy Considerations

Infection and Inflammation Risk

• During combined application of antiparkinsonics and antipsychotics, risks of infection and inflammation should be given key attention 7
• The median time to onset for infection and inflammation is 716.00 days, and for psychiatric symptoms is 823.00 days 7
• Female patients are more inclined to have adverse events related to infection and inflammation 7

High-Risk Populations Requiring Monitoring

• Patients with renal insufficiency require dose reduction for amantadine 1, 2
• Patients with seizure disorders require close observation for increased seizure activity with amantadine 2
• Patients with psychiatric disorders are at higher risk for serious CNS toxicity with amantadine 1, 2
• Elderly patients require mandatory dose reduction of amantadine to ≤100 mg/day 2