Buy Stalevo (Levodopa with Carbidopa and Entacapone) online

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STALEVO (LEVODOPA WITH CARBIDOPA AND ENTACAPONE) TABLETS: DRUG INTERACTIONS

Caution should be exercised when the following drugs are administered concomitantly with Stalevo (Levodopa, Carbidopa and Entacapone).

Anti-hypertensive agents

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

MAO inhibitors

Concomitant therapy with selegiline and carbidopa-levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa-levodopa alone.

Tricyclic antidepressants

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., butyrophenones, phenothiazines, risperidone) and isoniazid: Dopamine D2 receptor antagonists (e.g., risperidone, phenothiazines, butyrophenones) and isoniazid may reduce the therapeutic effects of levodopa.

Phenytoin and papaverine

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-levodopa should be carefully observed for loss of therapeutic response.

Iron salts

Iron salts may reduce the bioavailability of Stalevo (Levodopa, Carbidopa and Entacapone) tablets. The clinical relevance is unclear.

Metoclopramide

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.

Drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidase (probenecid, cholestyramine, erythromycin, rifampicin, ampicillin and chloramphenicol)

As most entacapone excretion is via the bile, caution should be exercised when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidase are given concurrently with entacapone. These include probenecid, cholestyramine, and some antibiotics (e.g., rifampicin, erythromycin, ampicillin and chloramphenicol).

Pyridoxine

Stalevo (Levodopa plus Carbidopa and Entacapone) can be given to patients receiving supplemental pyridoxine. Oral coadministration of 10-25 mg of pyridoxine hydrochloride (vitamin B6) with levodopa may reverse the effects of levodopa by increasing the rate of aromatic amino acid decarboxylation. Carbidopa inhibits this action of pyridoxine; therefore, Stalevo can be given to patients receiving supplemental pyridoxine.

Effect of levodopa and carbidopa in Stalevo on the metabolism of other drugs

Inhibition or induction effect of levodopa and carbidopa has not been investigated.

Effect of entacapone in Stalevo on the metabolism of other drugs

Entacapone is unlikely to inhibit the metabolism of other drugs that are metabolized by major P450s including CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A. In vitro studies of human CYP enzymes showed that entacapone inhibited the CYP enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A only at very high concentrations (IC50 from 200 to over 1000 mM; an oral 200 mg dose achieves a highest level of approximately 5 mM in people); these enzymes would therefore not be expected to be inhibited in clinical use. However, no information is available regarding the induction effect from entacapone.

Drugs that are highly protein bound (such as salicylic acid, warfarin, phenylbutazone, and diazepam)

Levodopa

Levodopa is bound to plasma protein only to a minor extent (about 10%-30%).

Carbidopa

Carbidopa is approximately 36% bound to plasma protein.

Entacapone

Entacapone is highly protein bound (98%). In vitro studies have shown no binding displacement between entacapone and other highly bound drugs, such as warfarin, phenylbutazone, salicylic acid, and diazepam.

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