gms | German Medical Science

17. Jahreskongress für Klinische Pharmakologie

Verbund Klinische Pharmakologie in Deutschland

01. - 02. Oktober 2015, Köln

Drug-Drug-Interactions with new HCV-DAAs

Invited Lecture

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  • corresponding author presenting/speaker Hartwig Klinker - Universitätsklinikum Würzburg, medizinische Klinik II, Schwerpunkt Infektiologie, Würzburg, Germany

17. Jahreskongress für Klinische Pharmakologie. Köln, 01.-02.10.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15vklipha02

doi: 10.3205/15vklipha02, urn:nbn:de:0183-15vklipha029

Published: September 24, 2015

© 2015 Klinker.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at



The introduction of direct antiviral agents (DAA) has revolutionized the treatment of chronic hepatitis C infection. Characteristics for these new treatment options are high cure rates (90-95%), shorter treatment periods (12 weeks in most cases) and favorable side effect profiles. Attention should be paid to pharmacological interactions of various substances.

The HCV NS3 / 4A protease inhibitors simeprevir and paritaprevir, the HCV NS5A inhibitors daclatasvir, ledipasvir and ombitasvir and the HCV RNA polymerase inhibitors sofosbuvir and dasabuvir are - in varying degrees - substrates and inhibitors of cytochrome P450 isoenzymes, UGT and various transport proteins (BCRP, BSEP, MDR1, MRP2, NTCP, OAT1, OAT3, OATP1B1, OATP2B1, OATP1B3, OCT1, OCT2 others).

Therefore, numerous pharmacokinetic interactions are possible. Among HCV DAAs, the interaction profile is most extensive with HCV NS3 / 4A protease inhibitors. Less, it is with HCV NS5A inhibitors, at least with HCV RNA polymerase inhibitors.

Paritaprevir is co-formulated with ritonavir, a pharmacokinetic booster that causes many and clinically relevant interactions by a potent CYP3A4 inhibition.

Pharmacokinetic interactions are related to DDAs itself (e. g. in case of co-medication with inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort, efavirenz, etravirine and nevirapine or inhibitors such as erythromycin, clarithromycin, itraconazole, ketoconazole, posaconazole, voriconazole, ritonavir or cobicistat) or to the concomitant medication such as amlodipine, diltiazem, nifedipine, nisoldipine, atorvastatin, rosuvastatin, simvastatin, digoxin, flecainide, mexiletine, propafenone, amiodarone, sildenafil, tadalafil, vardenafil, dabigatran etexilate, midazolam administered orally, sertraline, Mirtazepin or venlafaxine.

During therapy with sofosbuvir in combination with other DAAs (not in combination with PEG-interferon / ribavirin) and co-medication with the antiarrhythmic amiodarone, symptomatic bradycardia was observed (including one fatal cardiac arrest and cases requiring pacemaker insertion). The cause of this potential interaction remains unclear so far.

The management of Drug-Drug Interactions in HCV therapy requires special attention and cooperation of infectious disease specialists / hepatologists and pharmacists. Valuable for the evaluation of the interaction potential of a particular combination of drugs is the use of databases.