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

From the Guidelines

Sinemet (Carbidopa-Levodopa) can cause a range of side effects, including nausea, vomiting, abdominal pain, dyspepsia, constipation, weight decrease, dry mouth, diarrhea, anorexia, and GI disorders, as well as metabolic effects such as impaired nutritional status, weight loss, and hyperhomocysteinemia 1.

Common Side Effects

• Nausea and vomiting
• Abdominal pain and dyspepsia
• Constipation and diarrhea
• Weight decrease and loss of appetite
• Dry mouth and GI disorders

Metabolic Effects

• Impaired nutritional status and risk for malnutrition, particularly with increasing doses of levodopa 1
• Weight loss, especially in women, and after starting levodopa treatment 1
• Hyperhomocysteinemia, which may be dependent on vitamin B status and require supplementation 1

Other Potential Side Effects

• Involuntary movements (dyskinesia)
• "On-off" phenomena where the medication's effectiveness fluctuates throughout the day
• Confusion, hallucinations, and sleep disturbances
• Orthostatic hypotension (drop in blood pressure when standing)
• Darkened urine or sweat
• Rarely, impulse control disorders like gambling or hypersexuality It is essential to monitor patients taking Sinemet for these side effects and adjust the dose or consider alternative medications if necessary, as the relationship between levodopa use and weight loss, as well as other metabolic effects, is still not well understood and requires further investigation 1.

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 Sinemet (Carbidopa-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

From the Research

Side Effects of Sinemet (Carbidopa-Levodopa)

The side effects of Sinemet (Carbidopa-Levodopa) include:

• Nausea and vomiting, which were previously associated with levodopa treatment but have been reduced with the use of carbidopa 3
• Abnormal involuntary movements, such as dyskinesias 3, 4, 5
• Hallucinations and occasional psychosis 3
• Dizziness, insomnia, abdominal pain, headache, and depression 4
• Dyskinesia, which can be peak-dose, diphasic, or off-period dyskinesia 5
• Motor fluctuations, which can be reduced with the use of controlled-release Sinemet CR 4, 6

Common Adverse Reactions

The most common drug-related effects of Sinemet (Carbidopa-Levodopa) are:

• Nausea, seen in 20% of patients 4
• Dizziness, insomnia, abdominal pain, dyskinesia, headache, and depression 4
• Drug-related withdrawals, which were less than 10% of all patients, primarily due to nervous/psychiatric complaints 4

Treatment-Related Complications

The treatment of Parkinson's disease with Sinemet (Carbidopa-Levodopa) can also lead to complications such as:

• Abnormal involuntary movements, which can be a limiting factor in treatment efficacy 3
• Motor fluctuations, which can be reduced with the use of controlled-release Sinemet CR 4, 6
• Dyskinesias, which can be treated with various strategies, including reducing individual doses of levodopa and adding amantadine and dopamine agonists 5