Are there any interactions between terbinafine and ropinirole or carbidopa/levodopa?/nBackground: A

Fråga: Are there any interactions between terbinafine and ropinirole or carbidopa/levodopa?

Background: A female patient is on treatment with Requip (ropinirole) and Sinemet (carbidopa/levodopa). Because of a fungal nail infection oral treatment with Lamisil (terbinafine) is considered.

Sammanfattning: Clinical data on the combination of terbinafine with ropinirole/levodopa/carbidopa are lacking. Importantly, there is no support in the literature for an interaction between the drugs, why co-administration should be possible. However, increased attention for adverse drug reactions seems motivated, since there is no documentation about this combination of drugs.

Svar: Many antifungal drugs are known to interact with hepatic drug metabolism by inhibition of one or several cytochrome P450 (CYP) enzymes (1). Terbinafine has been found to be a highly potent inhibitor of CYP2D6 but not other P450-enzymes (3). Therefore, it is reasonable to assume that clearance of drugs metabolised by other P450s are unaffected. This is supported by both in vitro studies (4) and clinical observations reviewed in (1, 2).

Importantly, terbinafine did not affect the CYP1A2-dependent metabolism of caffeine in vivo (5). Ropinirole is metabolised almost exclusively by CYP1A2 in vitro at concentrations which are relevant to the situation in vivo (6). Levodopa is mainly metabolised by catechol-O-methyl transferase and not cytochrome P450 (7). There is no apparent pharmacokinetic interaction between ropinirol and levodopa (8).

No interaction is evident at the pharmacodynamic level between the antifungal drug terbinafine and the antiparkinsonian drugs levodopa/carbidopa. 1 Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Effects of the antifungal agents on oxidative drug metabolism. Clin Pharmakokinet 2000; 38: 111-8 2 Albengres E, Le Louet H, Tillement J-P: Systemic antifungal agents. Drug interactions and clinical significance. Drug Safety 1998; 18: 83-97 3 Abdel-Rahman SM, Marcucci K, Boge T, Gotschall RR, Kearns GL, Leeder JS: Potent inhibition of cytochrome P-450 2D6-ediated dextromethorphan O-demethylation by terbinafine. Drug Metab Dispos 1999; 27: 770-5 4 Vickers AEM, Sinclair JR, Zollinger M, Heitz F, Glänzel U, Johanson L, Fischer V: Multiple cytochrome P-450s involved in the metabolism of terbinafine suggest a limited potential for drug-drug interactions. Drug Metab Dispos 1999; 27: 1029-1038 5 Trepanier EF, Nafziger AN, Kearns GL, Kashuba ADM, Amsden GW: Absence of effect of terbinafine on the activity of CYP1A2, NAT-2, and xanthine oxidase. J Clin Pharmacol 1998; 38: 424-428 6 Bloomer JC, Clarke SE, Chenery RJ: In vitro identification of the P450 enzymes responsible for the metabolism of ropinirole. Drug Metab Dispos 1997; 25: 840-4 7 Cedarbaum JM: Clinical pharmacokinetics of anti-parkinsonian drugs. Clin Pharmakokinet 1987; 13: 141-178 8 Taylor AC, Beerahee A, Citerone DR, Cyronak MJ, Leigh TJ, Fitzpatrick KL, Lopez-Gil A, Vakil SD, Burns E, Lennox G: Lack of a pharmacokinetic interaction at steady state between ropinirole and L-dopa in patients with parkinson´s disease. Pharmacotherapy 1999; 19: 150-156