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

From the Guidelines

Sinemet can cause several potential side effects, including nausea, vomiting, abdominal pain, dyspepsia, constipation, weight decrease, dry mouth, diarrhea, anorexia, and GI disorders, as well as metabolic effects and hyperhomocysteinemia, particularly with higher doses or long-term use 1.

Common Side Effects

• Nausea and vomiting
• Abdominal pain and dyspepsia
• Constipation and diarrhea
• Weight decrease and anorexia
• Dry mouth and changes in taste

Metabolic Effects

• Levodopa, a component of Sinemet, has been found to induce metabolic changes, including reduction in muscle glucose uptake, which may lead to glucose intolerance 1
• Long-term treatment with levodopa can cause hypersecretion of insulin and growth hormone 1

Hyperhomocysteinemia

• Use of levodopa can cause hyperhomocysteinemia, which may be associated with cardiovascular diseases, dementia, and depression 1
• Patients on levodopa may have higher requirements for vitamins B6, B12, and folate to maintain normal homocysteine levels, and supplementation may be warranted 1

Other Side Effects

• Dyskinesias, particularly after long-term use or at higher doses
• Orthostatic hypotension, causing lightheadedness or fainting
• Psychological effects, such as confusion, hallucinations, or changes in mood, especially in elderly patients
• Sleep disturbances or sudden sleep onset It is essential to monitor patients taking Sinemet for these potential side effects and adjust the treatment plan as needed to minimize their impact on morbidity, mortality, and quality of life.

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 2

The potential side effects of Sinemet (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

From the Research

Sinemet Potential Side Effects

• Abnormal involuntary movements 3
• Hallucinations 3
• Occasional psychosis 3
• Dopa-resistant state 3
• Nausea and vomiting (less frequent with Sinemet compared to levodopa alone) 4
• Dyskinesia (may be worsened by COMT inhibitors) 5, 6
• Protracted dyskinesia with freezing episodes and end-of-dose deterioration (in some cases) 7
• Orthostatic hypotension 5
• Sleep disorders 5
• Diarrhea (more common with tolcapone than entacapone) 5, 6
• Urine discoloration (more common with tolcapone and entacapone) 5
• Elevated liver transaminase levels (more common with tolcapone) 5
• Acute, fatal fulminant hepatitis and potentially fatal neurological reactions (associated with tolcapone) 5