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Two thirds of Montreal in-hospital
HCV group have interactions with DAAs
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20th International Workshop on Clinical Pharmacology of HIV, Hepatitis & Other Antiviral Drugs. May 14-16, 2019. Noordwijk, the Netherlands
Mark Mascolini
Two thirds of Montreal hospital patients taking direct-acting antivirals (DAAs) for HCV had potential interactions with non-HCV drugs [1]. Researchers classified 4% of the interactions as contraindications.
Prior work established a high potential for drug-drug interactions involving DAAs in ambulatory patients, with interaction prevalence ranging from 10% to 80% [2-4]. Proton pump inhibitors and H2 antagonists emerged as the most frequent interaction perpetrators. Because similar data do not exist for inpatients with HCV, a team from the Centre Hospitalier de l'Universite de Montreal (CHUM) conducted this retrospective single-center analysis.
The study included HCV-infected adults treated with an interferon-free DAA regimen during admission to the CHUM from December 2013 through December 2017. The CHUM investigators identified drug-drug interactions with the University of Liverpool online interaction tool [5], with the HIV/HCV Drug Therapy Guide [6], or by a committee of three pharmacists with DAA expertise. The primary goal of the study was to determine cumulative incidence of interactions between DAAs and comedications during the hospital stay. The researchers used univariate and multivariate logistic regression to identify predictors of DAA interactions.
The 116 patients went to the hospital 168 times. Eighty-five people (73%) were men, 10 (9%) had HIV infection, and age averaged 57 years. More than 90% of participants took a sofosbuvir regimen, often with ribavirin. Median hospital stay reached 5 days (interquartile range [IQR] 2 to 10), and people took a median of 15 comedications (IQR 10 to 20).
The CHUM team recorded at least one DAA interaction during almost two thirds of hospital stays (64.6%) and in more than two thirds of patients (68.1%). Among all drug-drug interactions detected, 3.8% were contraindications. The most frequent interactions per hospital stay involved paritaprevir/ritonavir + ombitasvir + daclatasvir +/- ribavirin (5.5 interactions), sofosbuvir/ledipasvir +/- ribavirin (2.1), and sofosbuvir/simeprevir (2.1). The highest proportion of interactions, 39%, involved gastric acid drugs (proton pump inhibitors, H2 antagonists, and cation antacids).
Among people taking 10 or more comedications, about three quarters of hospital stays involved at least one drug-drug interaction. Multivariate analysis confirmed two independent predictors of a DAA interaction: People taking 10 or more comedications had more than 5-fold higher odds of an interaction (adjusted odds ratio [aOR] 5.64, 95% confidence interval [CI] 2.48 to 12.85, P < 0.001). Compared with men, women had almost 3-fold higher odds of an interaction (aOR 2.91, 95% CI 1.21 to 7.00, P = 0.017). There were trends toward higher odds of an interaction with older age (aOR 1.05, 95% CI 1.00, 95% CI 1.00 to 1.09, P = 0.061) and lower estimated glomerular filtration rate (aOR 2.83, 95% CI 0.94 to 8.53, P = 0.064). Cirrhosis, liver transplant, or HIV coinfection did not affect odds of interactions in this analysis.
The researchers concluded that these in-hospital HCV patients have higher rates of DAA interactions than reported for outpatients [2-4]. They urged colleagues to assess patients for potential interactions with DAAs before DAA therapy begins and whenever a new medication gets added to a person's regimen. The CHUM investigators called for more real-life data "to evaluate the clinical significance and management of these interactions."
References
1. Messier L, Verreault V, Arbour P, et al. High incidence of drug-drug interactions with hepatitis C direct-acting antivirals in patients hospitalized during their treatment. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis & Other Antiviral Drugs. May 14-16, 2019. Noordwijk, the Netherlands. Abstract 41.
2. Honer Zu Siederdissen C, Maasoumy B, Marra F, et al. Drug-drug interactions with novel all oral interferon-free antiviral agents in a large real-world cohort. Clin Infect Dis. 2016;62:561-567.
3. Langness JA, Nguyen M, Wieland A, Everson GT, Kiser JJ. Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions. World J Gastroenterol. 2017;23:1618-1626.
4. Ottman AA, Townsend ML, Hashem MG, DiMondi VP, Britt RB. Incidence of drug interactions identified by clinical pharmacists in veterans initiating treatment for chronic hepatitis C infection. Ann Pharmacother. 2018;52:763-768.
5. University of Liverpool. HEP Drug Interactions. https://www.hep-druginteractions.org
6. HIV/HCV Drug Therapy Guide. http://app.hivclinic.ca
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