Levodopa + Carbidopa

Indications
Levodopa and carbidopa is indicated in the treatment of Parkinson's disease, post-encephalitic Parkinsonism, and symptomatic Parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

Therapeutic Class
Antiparkinson drugs

Pharmacology
Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Levodopa, the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain. Carbidopa inhibits decarboxylation of peripheral levodopa. Since its decarboxylase inhibiting activity is limited to extracerebral tissues, administration of carbidopa with levodopa makes more levodopa available for transport to the brain.

Dosage & Administration
Usual Initial Dosage: The optimum daily dosage must be determined by careful titration in each patient. If Levodopa 100 mg and Carbidopa 10 mg is used, dosage may be initiated with one tablet three or four times a day. Dosage may be increased by one tablet every day or every other day until a total of eight tablets (2 tablets q.i.d.) is reached.
Maintenance dose: Therapy should be individualized & adjusted according to the desired therapeutic response. When more levodopa is required, Levodopa 250 mg and Carbidopa 25 mg should be substituted for Levodopa 100 mg and Carbidopa 10 mg. If necessary, the dosage of Levodopa 250 mg and Carbidopa 25 mg may be increased by one-half or one tablet every day or every other day to a maximum of eight tablets a day. Experience with total daily dosages of carbidopa greater than 200 mg is limited.

Interaction
Pyridoxine reverses effects of levodopa. Type B MAOIs have synergistic effect. Effect reduced by phenothiazines, haloperidol, reserpine, pyridoxine, diazepam, oxazepam, chlordiazepoxide, phenobarbitone. Effects of levodopa enhanced by carbidopa, amantadine, anticholinergics, amphetamine. Effects of sympathomimetic agents enhanced.

Contraindications
Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with Levodopa and carbidopa. These inhibitors must be discontinued at least two weeks prior to initiating therapy with Levodopa and carbidopa. Levodopa and carbidopa is contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma.

Side Effects
The most common adverse reactions reported with Levodopa and Carbidopa have included dyskinesias, such as choreiform, dystonic, and other involuntary movements, and nausea.

Pregnancy & Lactation
Pregnancy Category C. Levodopa has been detected in human milk. Caution should be exercised when administered to a nursing woman.

Precautions & Warnings
Levodopa alone, as well as combination, is associated with dyskinesias. The occurrence of dyskinesias may require dosage reduction. It should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.

Use in Special Populations
Use in children: Safety and effectiveness of Carbidopa-Levodopa in infants and children have not been established, and its use in patients below the age of 18 years is not recommended.

Storage Conditions
Protect from light and moisture, store below 30°C. Keep the medicine out of the reach of children.