Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
Effect of other medicinal products on terbinafine
The plasma clearance of terbinafine may be accelerated by drugs which induce metabolism and may be inhibited by drugs which inhibit cytochrome P450. Where co-administration of such agents is necessary, the dosage of terbinafine may need to be adjusted accordingly.

The following medicinal products may increase the effect or plasma concentration of terbinafine:

Cimetidine decreased the clearance of terbinafine by 30%.

Fluconazole increased the Cmax and AUC of terbinafine by 52% and 69% respectively, due to inhibition of both CYP2C9 and CYP3A4 enzymes. Similar increase in exposure may occur when other drugs which inhibit both CYP2C9 and CYP3A4 such as ketoconazole and amiodarone are concomitantly administered with terbinafine.

The following medicinal products may decrease the effect or plasma concentration of terbinafine:
Rifampicin increased the clearance of terbinafine by 100%.

Effect of terbinafine on other medicinal products
Terbinafine may increase the effect or plasma concentration of the following medicinal products:

Caffeine - Terbinafine decreased the clearance of caffeine administered intravenously by 21%.

Compounds predominantly metabolised by CYP2D6 - In vitro and in vivo studies have shown that terbinafine inhibits the CYP2D6-mediated metabolism. This finding may be of clinical relevance for patients receiving compounds predominantly metabolised by CYP2D6, e.g. certain members of the following drug classes, tricyclic antidepressants (TCA's), p-blockers, selective serotonin reuptake inhibitors (SSRIs), antiarrhythmics (including class 1A, 1B and 1C) and monoamine oxidase inhibitors (MAO-Is) Type B, especially if they also have a narrow therapeutic window (see section 4.4).
Terbinafine decreased the clearance of desipramine by 82%.

In studies in healthy subjects characterized as extensive metabolisers of dextromethorphan (antitussive drug and CYP2D6 probe substrate), terbinafine increased the dextromethorphan/dextrorphan metabolic ratio in urine by 16- to 97- fold on average. Thus, terbinafine may convert extensive CYP2D6 metabolisers (genotype) to poor metaboliser status (phenotype).

Information on other drug concomitantly used with terbinafine resulting in no or negligible interactions
Studies undertaken in vitro and in healthy volunteers suggest that terbinafine shows negligible potential to inhibit or induce the clearance of most drugs that are metabolized via other cytochrome P450 enzymes (e.g. tolbutamine, terfenadine, triazolam, oral contraceptives) with exception of those metabolised through CYP2D6 (see below).
Terbinafine does not interfere with the clearance of antipyrine or digoxin.
There was no effect of terbinafine on the pharmacokinetics of fluconazole. Further there was no clinically relevant interaction between terbinafine and the potential comedications cotrimoxazole (trimethoprim and sulfamethoxazole), zidovudine or theophylline.

Some cases of menstrual disturbance (breakthrough bleeding and irregular cycle) have been reported in patients taking terbinafine concomitantly with oral contraceptives, although the incidence of these disorders remains within the background incidence of patients taking oral contraceptives alone.

Terbinafine may decrease the effect or plasma concentration of the following medicinal products:

Terbinafine increased the clearance of cyclosporine by 15%.

Rare cases of changes in INR and/or prothrombin time have been reported in patients receiving terbinafine concomitantly with warfarin.