Stalevo Drug Interactions

Other Antiparkinsonian Medicinal Products: To date there has been no indication of interactions that would preclude concurrent use of standard antiparkinsonian medicinal products with Stalevo therapy. Entacapone in high doses may affect the absorption of carbidopa. However, no interaction with carbidopa has been observed with the recommended treatment schedule (200 mg of entacapone up to 10 times daily). Interactions between entacapone and selegiline have been investigated in repeated dose studies in Parkinson's disease patients treated with levodopa/DDC inhibitor and no interaction was observed. When used with Stalevo, the daily dose of selegiline should not exceed 10 mg.
Because Stalevo contains entacapone, it should not be used concurrently with Comtan (entacapone).
Caution should be exercised when the following active substances are administered concomitantly with levodopa therapy.
Antihypertensives: Symptomatic postural hypotension may occur when levodopa is initiated in patients already receiving antihypertensives. Dosage adjustment of the antihypertensive agent may be required.
Antidepressants: Rarely, reactions including hypertension and dyskinesia have been reported with the concomitant use of tricyclic antidepressants and levodopa/carbidopa. Interactions between entacapone and imipramine and between entacapone and moclobemide have been investigated in single-dose studies in healthy volunteers. No pharmacodynamic interactions were observed. A significant number of Parkinson's disease patients have been treated with the combination of levodopa, carbidopa and entacapone with several active substances including MAO-A inhibitors, tricyclic antidepressants, noradrenaline reuptake inhibitors eg, desipramine, maprotiline and venlafaxine and medicinal products that are metabolised by COMT (eg, catechol-structured compounds: Rimiterol, isoprenaline, adrenaline, noradrenaline, dopamine, dobutamine, α-methyldopa, apomorphine and paroxetine). No pharmacodynamic interactions have been observed. However, caution should be exercised when these medicinal products are used concomitantly with Stalevo (see also Contraindications and Precautions).
Other Active Substances: Dopamine receptor antagonists (eg, some antipsychotics and antiemetics), phenytoin and papaverine may reduce the therapeutic effect of levodopa. Patients taking these medicinal products with Stalevo should be carefully observed for loss of therapeutic response.
Due to entacapone's affinity to cytochrome P-450 2C9 in vitro (see Pharmacokinetics), Stalevo may potentially interfere with active substances whose metabolism is dependent on this isoenzyme eg, S-warfarin. However, in an interaction study with healthy volunteers, entacapone did not change the plasma levels of S-warfarin, while the AUC for R-warfarin increased on average by 18% (CI₉₀ 11-26%). The INR values increased on average by 13% (CI₉₀ 6-19%). Thus, a control of INR is recommended when Stalevo is initiated in patients receiving warfarin.
Other Forms of Interactions: Since levodopa competes with certain amino acids, the absorption of Stalevo may be impaired in some patients on a high-protein diet.
Levodopa and entacapone may form chelates with iron in the gastrointestinal tract. Therefore, Stalevo and iron preparations should be taken at least 2-3 hrs apart (see Adverse Reactions).
Stalevo may be given to patients with Parkinson's disease who are taking vitamin preparations that contain pyridoxine HCl (vitamin B6).
Incompatibilities: Not applicable.