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GENERIC NAME: levodopa-carbidopa

BRAND NAME: Sinemet

DRUG CLASS AND MECHANISM: Levodopa-carbidopa is a combination of two drugs, levodopa and carbidopa. Levodopa-carbidopa is used in the treatment of Parkinson's disease. Parkinson's disease is believed to be related to low levels of dopamine in certain parts of the brain. When levodopa is taken orally, it crosses through the "blood- brain barrier." Once it crosses, it is converted to dopamine. The resulting increase in brain dopamine concentrations is believed to improve nerve conduction and assist the movement disorders in Parkinson disease. Carbidopa does not cross the blood-brain barrier. Carbidopa is added to the levodopa to prevent the breakdown of levodopa before it crosses into the brain. The addition of carbidopa allows lower doses of levodopa to be used. This reduces the risk of side effects from levodopa such as nausea and vomiting. This combination medicine was approved by the FDA in 1988.

PREPARATIONS: Oval tablets (doses stated are for levodopa/carbidopa): 100mg/10mg, 200mg/20mg, 200mg/25mg, 250mg/ 25mg, and a sustained-release preparation (Sinemet CR) containing 200mg/50mg.

STORAGE: Tablets should be kept at room temperature, 15- 30°C (59-86°F).

PRESCRIBED FOR: Levodopa-carbidopa is indicated for the management of Parkinson's disease.

DOSING: Levodopa-carbidopa is taken several times per day. It may be administered with food to reduce the likelihood of nausea. However, a high-protein diet may reduce its absorption.

DRUG INTERACTIONS: The use of amantadine (Symmetrel), benztropine (Cogentin), procyclidine (Kemadrin), or trihexyphenidyl (Artane) with levodopa-carbidopa can enhance the anti- Parkinson's effects of levodopa. Droperidol, haloperidol (Haldol), loxapine (Loxitane), metoclopramide (Reglan), phenothiazines such as prochlorperazine (Thorazine); thioxanthenes as thiothixene (Navane) inhibit dopamine in the brain. These drugs, therefore, can worsen Parkinson's disease and reverse the beneficial effects of levodopa. Methyldopa (Aldomet) and reserpine also can interfere with the beneficial actions of levodopa- carbidopa and can increase the risk of side effects.
Phenytoin (Dilantin) can increases the break-down of levodopa- carbidopa, reducing its effectiveness.
Use of levodopa-carbidopa with monoamine oxidase inhibitors (MAOI's) antidepressants, for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and procarbazine (Matulane), can result in severe and dangerous elevations in blood pressure. MAOI's should be stopped 2-4 weeks before starting levodopa-carbidopa therapy.
The side effects associated with levodopa, including dizziness upon rising, confusion, movement disorders, nausea, and hallucinations, all can be increased by selegiline (Eldepryl).

PREGNANCY: Although there are no human studies that have examined the effects of levodopa-carbidopa on the fetus, animal studies have shown adverse effects. Therefore, in prescribing levodopa- carbidopa for a pregnant woman, the physician must weigh the potential risks to the fetus against the potential benefits to the mother.

NURSING MOTHERS: Levodopa is distributed into breast milk. It also may inhibit production of milk. It is generally recommended that levodopa-carbidopa should not be given to women who are breast- feeding.

SIDE EFFECTS: Most patients receiving levodopa-carbidopa experience side effects, but these are usually reversible. Occasional involuntary movements are the most common of the serious side effects of levodopa-carbidopa therapy. These may include chewing, gnawing, twisting, tongue or mouth movements, head bobbing, or movements of the feet, hands, or shoulder. These may respond to a reduction in the dose. Muscle twitching, dizziness, muscle jerks during sleep, and hand tremor also may occur. Various psychiatric disturbances may occur during levodopa-carbidopa therapy. Such disturbances include memory loss, anxiety, nervousness, agitation, restlessness, confusion, inability to sleep, nightmares, daytime tiredness, mental depression or euphoria.
Gastrointestinal side effects are common in patients receiving levodopa-carbidopa. Nausea, vomiting, loss of appetite, and weight loss may occur. Patients may experience dizziness upon standing up, associated with a drop in blood pressure. Fortunately, the body develops tolerance to this side effect within a few months.
Infrequently, patients may develop a drop in white blood cell count during levodopa-carbidopa therapy. This is a cause to temporarily, if not permanently, stop treatment.