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Over Half of Netherlands Patients Starting DAAs Risk Drug-Drug Interaction
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17th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, June 8-10, 2016, Washington DC
Mark Mascolini
More than half of a nationwide Netherlands cohort starting a direct-acting antiviral (DAA) for HCV infection would have a possible interaction with other drugs they were already taking [1]. One in 10 had a contraindication for a DAA because of a current prescription.
Because of their high efficacy against HCV infection, DAAs already see wide use across the world. Since DAAs rely primarily on the liver for their metabolism, noted Radboud University researchers who conducted this study, the potential for drug-drug interactions with non-DAAs runs high. They conducted a real-life nationwide cohort study to assess potential drug-drug interactions in people starting a DAA in the Netherlands.
The study involved Netherlands residents with HCV genotype 1 infection who started a first-generation DAA from 2011 through 2014. The research team searched medical charts to determine what drugs patients were taking before they started a DAA. Using www.hepdruginteractions.org, the investigators identified potential drug-drug interactions with second-generation regimens approved for genotype 1 infection: sofosbuvir/daclatasvir, sofosbuvir/simeprevir, sofosbuvir/ledipasvir, and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD). They distinguished four drug-drug interaction categories: (1) no interaction, (2) possible interaction, (3) contraindication, and (4) unknown interaction. And they deemed categories 2 and 3 as clinically relevant.
Among 461 people analyzed, age averaged 51 years, and 313 (68%) were men. Among people whose race was determined, 90% were Caucasian. Only 23 people (5%) had decompensated liver disease. Of these 461 people, 356 (77%) used another medication before starting a DAA, taking a median of 2 drugs (range 1 to 17 per patient). These 356 people had 1329 prescriptions for 200 different agents. The most-prescribed classes were antidepressants (7.4%), proton pump inhibitors (7.1%), benzodiazepine derivatives (7.1%), and drugs for opioid dependence (5.6%).
More than half of patients, 59%, ran a risk for a clinically relevant drug interaction with a DAA. While 223 cohort members (48% of 461) had a possible drug interaction, 52 (11%) had a contraindication for one or more DAAs. Sofosbuvir plus an NS5A inhibitor had the lowest number of potential clinically meaningful drug-drug interactions--40 for sofosbuvir/daclatasvir and 38 for sofosbuvir/ledipasvir. The four-drug PrOD regimen had the most potential interactions, 96.
"Concomitant medication use is high and rich in diversity in chronic HCV patients," the researchers concluded. Most people in this cohort risked a clinically relevant interaction that could threaten the success of a DAA or a concomitant drug. The investigators proposed that a multidisciplinary team including a pharmacist should assess and manage potential drug interactions with DAAs.
Reference
1. Smolders EJ, Berden FAC, de Kanter CTMM, et al. High risk of drug-drug interactions with hepatitis C: a nationwide cohort. 17th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, June 8-10, 2016, Washington DC. Abstract P45.
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