levodopa-carbidopa

Carbidopa-levodopa is used for the management of Parkinson's disease. Carbidopa-levodopa is a combination of two drugs, levodopa and carbidopa. Carbidopa-levodopa is used in the treatment of Parkinson's disease.

Parkinson's disease is believed to be caused by low levels of dopamine in certain parts of the brain. When levodopa is taken orally, it crosses into the brain 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.

Most patients receiving carbidopa-levodopa experience side effects, but these usually are reversible.

Gastrointestinal side effects are common in patients receiving carbidopa-levodopa and these include:

• nausea,
• vomiting,
• loss of appetite, and
• weight loss.

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.

Other important side effects of carbidopa-levodopa therapy include:

• memory loss,
• anxiety,
• nervousness,
• agitation,
• restlessness,
• confusion,
• inability to sleep,
• nightmares,
• daytime tiredness,
• mental depression or
• euphoria.

Occasional involuntary movements are the most common of the serious side effects of carbidopa-levodopa therapy, and these are:

• muscle twitching,
• dizziness,
• muscle jerks during sleep,
• hand tremor,
• chewing,
• gnawing,
• twisting,
• tongue or
• mouth movements,
• head bobbing, or
• movements of the feet, hands, or shoulder which may respond to a reduction in the dose.

Infrequently, patients may develop a drop in white blood cell count during carbidopa-levodopa therapy. This is a significant reason to temporarily, if not permanently, stop treatment.

Carbidopa-levodopa 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. The initial dose using regular tablets is 25/100 mg three times daily. The dose may be increased by one tablet every day or every other day until 8 tablets of 25/100 mg daily is reached. Alternatively 10/100 mg three or four times daily may be used initially and increased by one tablet daily or every other day until a total of eight tablets daily is reached. The dose of controlled release tablets is 50/200 mg twice daily and may increase up to 1.6 grams levodopa daily. Controlled release tablet should be given at least 6 hours apart.

The use of the following drugs with carbidopa-levodopa can enhance the anti-Parkinson's effects of levodopa:

• amantadine (Symmetrel),
• benztropine (Cogentin),
• procyclidine (Kemadrin), or
• trihexyphenidyl (Artane)

The following drugs can inhibit dopamine in the brain and shouldn't be used in combination with levodopa:

• Droperidol,
• haloperidol (Haldol),
• loxapine (Loxitane),
• metoclopramide (Reglan),
• phenothiazines such as prochlorperazine (Thorazine); and
• thioxanthenes as thiothixene (Navane).

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 carbidopa-levodopa and can increase the risk of side effects.

The occurrence of postural hypotension (reduced blood pressure when standing from a sitting or lying down position) may increase when carbidopa-levodopa is combined with drugs that reduce blood pressure. Phenytoin (Dilantin) can increase the break-down of carbidopa-levodopa, reducing its effectiveness. Use of carbidopa-levodopa 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 carbidopa-levodopa therapy.

The side effects associated with levodopa, including dizziness upon rising, confusion, movement disorders, nausea, and hallucinations, all can be increased by selegiline (Eldepryl).

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

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

What preparations of levodopa-carbidopa are available?

Tablets (carbidopa/levodopa): 10/100, 25/100 mg. Tablets (Controlled Release): 25/100 and 50/200 mg.

How should I keep levodopa-carbidopa stored?

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