Parcopa (Carbidopa / Levodopa) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Caution should be exercised when the following drugs are administered concomitantly with PARCOPA™ (carbidopa-levodopa orally disintegrating tablets).

Symptomatic postural hypotension has occurred when carbidopa-levodopa was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with PARCOPA™ 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-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 PARCOPA™ 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 PARCOPA™ is the same as management of acute overdosage with levodopa. Pyridoxine is not effective in reversing the actions of PARCOPA™.

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 anti-arrhythmic therapy should be given. The possibility that the patient may have taken other drugs as well as PARCOPA™ 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 1500-2000 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 PARCOPA™. These inhibitors must be discontinued at least two weeks prior to initiating therapy with PARCOPA™. PARCOPA™ may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl) (See PRECAUTIONS, Drug Interactions).

PARCOPA™ 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, PARCOPA™ should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.