Comtan Drug Interactions

No interaction of entacapone with carbidopa has been observed with the recommended treatment schedule. Pharmacokinetic interaction with benserazide has not been studied.
In single-dose studies in healthy volunteers, no interactions were observed between entacapone and imipramine or between entacapone and moclobemide. Similarly, no interactions between entacapone and selegiline were observed in repeated-dose studies in parkinsonian patients. However, the experience of the clinical use of entacapone with several drugs, including MAO-A inhibitors, tricyclic antidepressants, noradrenaline reuptake inhibitors such as desipramine, maprotiline and venlafaxine and medicinal products that are metabolized by COMT (e.g. catechol-structured compounds: rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, dobutamine, alpha-methyldopa, apomorphine and paroxetine) is still limited. Caution should be exercised when these medicinal products are used concomitantly with entacapone (see Contraindications and Precautions).
Entacapone may be used with selegiline (a selective MAO-B inhibitor), but the daily dose of selegeline should not exceed 10 mg.
Entacapone may form chelates with iron in the gastrointestinal tract. Entacapone and iron preparations should be taken at least 2 to 3 hours apart (see Adverse Reactions).
Entacapone binds to human albumin binding site II which also binds several other medicinal products, including diazepam and ibuprofen. Clinical interaction studies with diazepam and non-steroidal anti-inflammatory drugs have not been carried out. According to in vitro studies, significant displacement is not anticipated at therapeutic concentrations of the medicinal products.
Due to its affinity to CYP450 2C9 in vitro (see Pharmacology: Pharmacokinetics under Actions), entacapone may potentially interfere with drugs whose metabolism is dependent on this isoenzyme such as S-warfarin. However, in an interaction study in 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 to 26%]. The INR values increased on average by 13% [CI₉₀ 6 to 19%]. Thus, control of INR is recommended when entacapone treatment is initiated for patients receiving warfarin.