ed by CYP3A4
Refer to the ombitasvir/paritaprevir/ritonavir Summary of Product Characteristics for details. (see also Table 2).
Medicinal products transported by the OATP family
Refer to the ombitasvir/paritaprevir/ritonavir Summary of Product Characteristics for details on OATP1B1, OATP1B3 and OATP2B1 substrates (see also Table 2).
Medicinal products transported by BCRP
Dasabuvir is an inhibitor of BCRP in vivo. Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir together with medicinal products that are substrates of BCRP may increase plasma concentrations of these transporter substrates, potentially requiring dose adjustment/clinical monitoring. Such medicinal products include sulfasalazine, imatinib and some of the statins (see Table 2). See also Table 2 for specific advice on rosuvastatin which has been eva luated in a drug interaction study.
Medicinal products transported by Pgp in the intestine
While dasabuvir is an in vitro inhibitor of P-gp, no significant change was observed in the exposure of the P-gp substrate, digoxin, when administered with Exviera with ombitasvir/paritaprevir/ritonavir. It may not be excluded that the systemic exposure of dabigatran etexilate is increased by dasabuvir due to inhibition of P-gp in the intestine.
Medicinal products metabolised by glucuronidation
Dasabuvir is an inhibitor of UGT1A1 in vivo. Co-administration of dasabuvir with medicinal products that are primarily metabolized by UGT1A1 result in increased plasma concentrations of such medicinal products; routine clinical monitoring is recommended for narrow therapeutic index medicinal products (i.e. levothyroxine). See also Table 2 for specific advice on raltegravir and buprenorphine which have been eva luated in drug interaction studies. Dasabuvir has also been found to inhibit UGT1A4, 1A6 and intestinal UGT2B7 in vitro at in vivo relevant concentrations.
Medicinal products metabolised by CYP2C19
Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir can decrease exposures of medicinal products that are metabolized by CYP2C19 (e.g. lansoprazole, esomeprazole, s- mephenytoin), which may require dose adjustment/clinical monitoring. CYP2C19 substrates eva luated in drug interaction studies include omeprazole and escitalopram (Table 2).
Medicinal products metabolised by CYP2C9
Dasabuvir administered with ombitasvir/paritaprevir/ritonavir did not affect the exposures of the CYP2C9 substrate warfarin. Other CYP2C9 substrates (NSAIDs (e.g. ibuprofen), antidiabetics (e.g. glimepiride, glipizide) are not expected to require dose adjustments.
Medicinal products metabolised by CYP2D6 or CYP1A2
Dasabuvir administered with ombitasvir/paritaprevir/ritonavir did not affect the exposures of the CYP2D6 /CYP1A2 substrate duloxetine. Other CYP1A2 substrates (e.g. ciprofloxacin, theophylline and caffeine) and CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.
Medicinal products renally excreted via transport proteins
Dasabuvir does not inhibit organic anion transporter (OAT1) in vivo as shown by the lack of interaction with tenofovir (OAT1 substrate). In vitro studies show that dasabuvir is not an inhibitor of organic cation transporters (OCT2), organic anion transporters (OAT3), or multidrug and toxin extrusion proteins (MATE1 and MATE2K) at clinically relevant concentrations.
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