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Carbidopa and Levodopa (Carbidopa / Levodopa) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

Caution should be exercised when the following drugs are administered concomitantly with carbidopa and levodopa.

Symptomatic postural hypotension has occurred when carbidopa and levodopa was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with carbidopa and levodopa is started, dosage adjustment of the antihypertensive drug may be required.

For patients receiving MAO inhibitors (Type A or B), see CONTRAINDICATIONS. Concomitant therapy with selegiline and carbidopa-levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa-levodopa alone (see CONTRAINDICATIONS).

There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and carbidopa and levodopa.

Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the therapeutic effects of levodopa. In addition, the beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with carbidopa and levodopa should be carefully observed for loss of therapeutic response.

Iron salts may reduce the bioavailability of levodopa and carbidopa. The clinical relevance is unclear.

Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also adversely affect disease control by its dopamine receptor antagonistic properties.

OVERDOSAGE

Management of acute overdosage with carbidopa and levodopa is the same as management of acute overdosage with levodopa. Pyridoxine is not effective in reversing the actions of this product.

General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered judiciously and an adequate airway maintained. Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs as well as carbidopa and levodopa tablets should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdosage is not known.

Based on studies in which high doses of levodopa and/or carbidopa were administered, a significant proportion of rats and mice given single oral doses of levodopa of approximately 1500 to 2000 mg/kg are expected to die. A significant proportion of infant rats of both sexes are expected to die at a dose of 800 mg/kg. A significant proportion of rats are expected to die after treatment with similar doses of carbidopa. The addition of carbidopa in a 1:10 ratio with levodopa increases the dose at which a significant proportion of mice are expected to die to 3360 mg/kg.

CONTRAINDICATIONS

Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with carbidopa and levodopa. These inhibitors must be discontinued at least two weeks prior to initiating therapy with carbidopa and levodopa. Carbidopa and levodopa may be administered concomitantly with the manufacturer’s recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline hydrochloride) (see PRECAUTIONS, Drug Interactions).

Carbidopa and levodopa 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, carbidopa and levodopa should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.

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