Daclavir Drug Interactions

Contraindications of concomitant use (see Contraindications): Daclavir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, e.g. phenytoin, carbamazepine, oxcarbazepine, phenobarbital, rifampicin, rifabutin, rifapentine, systemic dexamethasone, and the herbal product St. John's wort (Hypericum perforatum), and thus may lead to lower exposure and loss of efficacy of Daclavir.
Potential for interaction with other medicinal products: Daclatasvir is a substrate of CYP3A4, P-gp and organic cation transporter (OCT) 1. Strong or moderate inducers of CYP3A4 and P-gp may decrease the plasma levels and therapeutic effect of daclatasvir. Coadministration with strong inducers of CYP3A4 and P-gp is contraindicated while dose adjustment of Daclavir is recommended when coadministered with moderate inducers of CYP3A4 and P-gp (see Table 14). Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of Daclavir is recommended when coadministered with strong inhibitors of CYP3A4 (see Table 14). Coadministration of medicines that inhibit P-gp or OCT1 activity is likely to have a limited effect on daclatasvir exposure.
Daclatasvir is an inhibitor of P-gp, organic anion transporting polypeptide (OATP) 1B1, OCT1 and breast cancer resistance protein (BCRP). Administration of Daclavir may increase systemic exposure to medicinal products that are substrates of P-gp, OATP 1B1, OCT1 or BCRP, which could increase or prolong their therapeutic effect and adverse reactions. Caution should be used if the medicinal product has a narrow therapeutic range (see Tables 14a, 14b and 14c).
Daclatasvir is a very weak inducer of CYP3A4 and caused a 13% decrease in midazolam exposure. However, as this is a limited effect, dose adjustment of concomitantly administered CYP3A4 substrates is not necessary.
Refer to the respective Summary of Product Characteristics for drug interaction information for other medicinal products in the regimen.
Patients treated with vitamin K antagonists: As liver function may change during treatment with Daclavir, a close monitoring of International Normalized Ratio (INR) values is recommended.
Tabulated summary of interactions: Table 14 provides information drug interactions studies with daclatasvir including clinical recommendations for established or potentially significant drug interactions. Clinically relevant increase in concentration is indicated as "↑", clinically relevant decrease as "↓", no clinically relevant change as "↔". If available, ratios of geometric means are shown, with 90% confidence intervals (CI) in parentheses. The studies presented in Table 14 were conducted in healthy adult subjects unless otherwise noted. The table is not all-inclusive. (See Tables 14a, 14b and 14c.)

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No clinically relevant effects on the pharmacokinetics of either medicinal product are expected when daclatasvir is coadministered with any of the following: PDE-5 inhibitors, medicinal products in the ACE inhibitor class (e.g. enalapril), medicinal products in the angiotensin II receptor antagonist class (e.g. losartan, irbesartan, olmesartan, candesartan, valsartan), disopyramide, propafenone, flecainide, mexilitine, quinidine or antacids.
Paediatric population: Interaction studies have only been performed in adults.