What are the side effects of Co-Beneldopa (Carbidopa-Levodopa)?

From the Guidelines

Co-beneldopa can cause several side effects, including nausea, vomiting, abdominal pain, dyspepsia, constipation, weight decrease, dry mouth, diarrhea, anorexia, and GI disorders, as reported by patients and attributed to their weight loss, as well as changes in taste and smell of food 1. These side effects are related to the mechanism of action of levodopa, which can influence intake and nutritional status. The use of levodopa may be associated with impaired nutritional status and risk for malnutrition, particularly with increasing doses and levodopa equivalent doses 1. Some of the key side effects to consider include:

• Metabolic effects, such as changes in lipid and carbohydrate metabolism, which can lead to glucose intolerance 1
• Hyperhomocysteinemia, which can be dependent on vitamin B status and may require supplementation 1
• Increased risk for malnutrition, particularly with higher doses of levodopa 1
• Weight loss, which can be due to reduction in body fat mass, and may be more pronounced in women 1 It is essential to monitor patients taking co-beneldopa for these side effects and adjust the dosage or recommend additional medications as needed to manage them.

From the FDA Drug Label

ADVERSE REACTIONS The most common adverse reactions reported with carbidopa and levodopa therapy have included dyskinesias, such as choreiform, dystonic, and other involuntary movements and nausea. The following other adverse reactions have been reported with carbidopa and levodopa: Body as a Whole: chest pain, asthenia Cardiovascular: cardiac irregularities, hypotension, orthostatic effects including orthostatic hypotension, hypertension, syncope, phlebitis, palpitation. Gastrointestinal: dark saliva, gastrointestinal bleeding, development of duodenal ulcer, anorexia, vomiting, diarrhea, constipation, dyspepsia, dry mouth, taste alterations Hematologic: agranulocytosis, hemolytic and nonhemolytic anemia, thrombocytopenia, leukopenia. Hypersensitivity: angioedema, urticaria, pruritus, Henoch-Schönlein purpura, bullous lesions (including pemphigus-like reactions). Musculoskeletal: back pain, shoulder pain, muscle cramps Nervous System/Psychiatric: psychotic episodes including delusions, hallucinations, and paranoid ideation, bradykinetic episodes (“on-off" phenomenon), confusion, agitation, dizziness, somnolence, dream abnormalities including nightmares, insomnia, paresthesia, headache, depression with or without development of suicidal tendencies, dementia, pathological gambling, increased libido including hypersexuality, impulse control symptoms. Convulsions also have occurred; however, a causal relationship with carbidopa and levodopa has not been established. Respiratory: dyspnea, upper respiratory infection. Skin: rash, increased sweating, alopecia, dark sweat. Urogenital: urinary tract infection, urinary frequency, dark urine Laboratory Tests: decreased hemoglobin and hematocrit; abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), LDH, bilirubin, BUN, Coombs test; elevated serum glucose; white blood cells, bacteria, and blood in the urine Other adverse reactions that have been reported with levodopa alone and with various carbidopa and levodopa formulations, and may occur with carbidopa and levodopa orally disintegrating tablets are: Body as a Whole: abdominal pain and distress, fatigue. Cardiovascular: myocardial infarction Gastrointestinal: gastrointestinal pain, dysphagia, sialorrhea, flatulence, bruxism, burning sensation of the tongue, heartburn, hiccups. Metabolic: edema, weight gain, weight loss. Musculoskeletal: leg pain Nervous System/Psychiatric: ataxia, extrapyramidal disorder, falling, anxiety, gait abnormalities, nervousness, decreased mental acuity, memory impairment, disorientation, euphoria, blepharospasm (which may be taken as an early sign of excess dosage; consideration of dosage reduction may be made at this time), trismus, increased tremor, numbness, muscle twitching, activation of latent Horner’s syndrome, peripheral neuropathy. Respiratory: pharyngeal pain, cough. Skin: malignant melanoma, flushing. Special Senses: oculogyric crises, diplopia, blurred vision, dilated pupils. Urogenital: urinary retention, urinary incontinence, priapism. Miscellaneous: bizarre breathing patterns, faintness, hoarseness, malaise, hot flashes, sense of stimulation Laboratory Tests: decreased white blood cell count and serum potassium; increased serum creatinine and uric acid; protein and glucose in urine.

The side effects of co-beneldopa (carbidopa and levodopa) include:

• Dyskinesias: such as choreiform, dystonic, and other involuntary movements
• Nausea
• Cardiovascular effects: cardiac irregularities, hypotension, orthostatic effects, hypertension, syncope, phlebitis, palpitation
• Gastrointestinal effects: dark saliva, gastrointestinal bleeding, development of duodenal ulcer, anorexia, vomiting, diarrhea, constipation, dyspepsia, dry mouth, taste alterations
• Hematologic effects: agranulocytosis, hemolytic and nonhemolytic anemia, thrombocytopenia, leukopenia
• Hypersensitivity reactions: angioedema, urticaria, pruritus, Henoch-Schönlein purpura, bullous lesions
• Musculoskeletal effects: back pain, shoulder pain, muscle cramps
• Nervous System/Psychiatric effects: psychotic episodes, bradykinetic episodes, confusion, agitation, dizziness, somnolence, dream abnormalities, insomnia, paresthesia, headache, depression, dementia, pathological gambling, increased libido, impulse control symptoms
• Respiratory effects: dyspnea, upper respiratory infection
• Skin effects: rash, increased sweating, alopecia, dark sweat
• Urogenital effects: urinary tract infection, urinary frequency, dark urine
• Laboratory test abnormalities: decreased hemoglobin and hematocrit, abnormalities in alkaline phosphatase, SGOT, SGPT, LDH, bilirubin, BUN, Coombs test; elevated serum glucose; white blood cells, bacteria, and blood in the urine 2 3

From the Research

Side Effects of Co-Beneldopa

• Co-beneldopa, a combination of levodopa and carbidopa, is commonly used to treat Parkinson's disease 4, 5, 6.
• The combination of levodopa and carbidopa can cause side effects such as nausea, motor fluctuations, and dyskinesias 4, 5.
• The addition of a COMT inhibitor, such as entacapone, to levodopa and carbidopa can help reduce motor fluctuations and increase "on" time in patients with Parkinson's disease 5.
• However, the use of entacapone with levodopa and carbidopa may not significantly delay the onset of dyskinesias, as shown in the STRIDE-PD study 5.
• Other side effects of co-beneldopa may include infusion-site reactions, as seen with continuous subcutaneous levodopa infusion therapies such as ND0612 and ABBV-951 7.
• Compared to dopamine agonists and monoamine oxidase B inhibitors, levodopa may have a higher risk of side effects, with 28% of patients allocated dopamine agonists and 23% of patients allocated MAOBI discontinuing treatment due to side effects, compared to 2% of patients allocated levodopa 8.

Motor Complications

• Long-term use of co-beneldopa can lead to motor complications, such as wearing off, motor fluctuations, and dyskinesias 4, 5.
• The risk of motor complications can be reduced by using a COMT inhibitor, such as entacapone, in combination with levodopa and carbidopa 5.
• However, the effectiveness of this combination in reducing motor complications may vary, and further research is needed to fully understand its benefits and risks 5, 7.

Quality of Life

• Co-beneldopa can improve quality of life for patients with Parkinson's disease by reducing motor symptoms and increasing "on" time 5, 6.
• The use of a COMT inhibitor, such as entacapone, in combination with levodopa and carbidopa may also improve quality of life by reducing motor fluctuations and increasing central bioavailability of levodopa 5.
• However, the impact of co-beneldopa on quality of life may vary depending on individual patient factors, and further research is needed to fully understand its effects 8.