Carbidopa/Levodopa - Dosage, Side Effects and Withdrawal Effects
SINEMETÂ (Carbidopa-Levodopa) is a sustained-release combination of carbidopa and levodopa for the treatment of Parkinson's disease and syndrome, as well as parkinsonism-like symptoms and Dopa-Responsive Dystonia (DRD). It is sold under several brand names, including Sinemet, Parcopa, and Atamet.
Carbidopa/Levodopa - Mechanism Of Action
When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues - only a small portion is transmitted unchanged to the central nervous system. Levodopa is converted to dopamine via the action of a naturally occurring enzyme called DOPA decarboxylase. Hence, large doses of levodopa are necesary for adequate therapeutic effectwhich often can cause nausea and other adverse reactions.
For this reason levodopa is usually administered in combination with a DOPA decarboxylase inhibitor (DDCI), in this case carbidopa, which does not cross the blood brain barrier but prevents peripheral conversion of levodopa to dopamine and thereby reduces the unwanted peripheral side-effects of levodopa. Use of carbidopa also increases the quantity of levodopa in the bloodstream that is available to enter the brain.
Carbidopa/Levodopa - Contraindications
Carbidopa/Levodopa (Sinemet) is contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma.
Because levodopa may activate a malignant melanoma, SINEMET should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.
Symptomatic postural hypotension occurred when SINEMET was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with SINEMET is started, dosage adjustment of the antihypertensive drug may be required.
Side effects of Carbidopa/Levodopa (Sinemet)
Various side effects have been noted in patients during the clinical trials . The most common side effects reported with SINEMET have included dyskinesias, such as choreiform, dystonic, and other involuntary movements and nausea.The following other adverse reactions have been reported with SINEMET
- 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 non-hemolytic anemia, thrombocytopenia, leukopenia.
- Hypersensitivity: angioedema, urticaria, pruritus, Henoch-Schonlein 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, neuroleptic malignant syndrome , 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 SINEMET has not been established.
- Respiratory: dyspnea, upper respiratory infection.
- Skin: rash, increased sweating, alopecia, dark sweat.
- Urogenital: urinary tract infection, urinary frequency, dark urine.
Carbidopa/Levodopa (Sinemet) Dosage
The Sinemet dosage varies as per the individual. Your doctor is the best judge.The Typical initial Dosage is one tablet of SINEMET 25-100 (25 mg of carbidopa and 100 mg of levodopa) three times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage of eight tablets of SINEMET 25-100 a day is reached.
Carbidopa/Levodopa Withdrawal Effects
Sporadic cases of a symptom complex resembling Neuroleptic Malignant Syndrome (NMS) have been associated with dose reductions and withdrawal of SINEMET. Patients should be observed carefully if abrupt reduction or discontinuation of SINEMET is required, especially if the patient is receiving neuroleptics.
Carbidopa-Levodopa - Availability And Packaging
Carbidopa/Levodopa is available as Sinemet Tablets in Sinemet 25-100 (Carbidopa 25 mg & Levodopa 100 mg) , Sinemet 50-200 (Carbidopa 50 mg & Levodopa 200 mg), and Sinemet 50-250 (Carbidopa 50 mg & Levodopa 250 mg).