Assessment of potential drug-drug interactions in patients with hereditary angioedema from the ITACA cohort: simulations from a real-life dataset considering danazol versus berotralstat
Year: 2025
Type: article
Abstract: Background: Danazol is regularly used as a prophylactic treatment in patients with Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH). However, this drug is characterized by a risk of drug-drug interactions (DDIs). Berotralstat, the first oral kallikrein inhibitor, has been recently approved for the prevention of HAE attacks. Here, we sought to compare the risk of potential DDIs in real-life HAE patients hypothetically given Danazol or Berotralstat. Methods: Our clinic's database was retrospectively reviewed to identify patients diagnosed with HAE who were treated with at least one concomitant medication. The DDIs were assessed using three freely available drug interaction checkers and scored based on their severity. The agreement between the three drug checkers was evaluated using weighted Cohen's kappa coefficient. Results: 75 HAE patients (64% female, mean age 56 ± 21 years) were considered. They were mainly treated with antihypertensives (37%), hypoglycemic (19%), and hypolipemic agents (17%). Significant discrepancies among the three-drug interaction checkers were found. The first checker identified 18 potential DDIs, all involving Danazol and a statin (simvastatin). The second checker identified, respectively, 66 and 14 DDIs for Danazol (20% severe, regarding Simvastatin and Rivaroxaban) and Berotralstat (0% severe). The third checker identified 49 and 43 DDIs for Danazol (22% severe, regarding Simvastatin) and Berotralstat (0%). Conclusion: Berotralstat was consistently associated with a reduced risk of DDIs compared with Danazol. A rational assessment of DDIs would help select the best prophylactic treatment for HAE.
Source: Frontiers in Pharmacology
Authors: Andrea Zanichelli, Dario Cattaneo, Antonio Gidaro, Riccardo Senter, Francesco Arcoleo, Pietro Accardo, Donatella Bignardi, Paolo Borrelli, Caterina Colangelo, Tiziana De Pasquale, Davide Firinu, Francesca Perego, Massimo Triggiani, Giuseppe Spadaro, Chiara Cogliati, Emanuele Bizzi, Valentina Popescu Janu, Maria Domenica Guarino, Paolina Quattrocchi, Luisa Brussino, Oliviero Rossi, Paola Triggianese, Stefano Agolini, Francesco Giardino, Vincenzo Montinaro, Mauro Cancian
Institutions: University of Milan, IRCCS Policlinico San Donato, Luigi Sacco Hospital, University of Padua, Azienda Ospedale - Università Padova, Ospedale Vincenzo Cervello, Ospedale Policlinico San Martino, Azienda Ospedaliero Universitaria Maggiore della Carita, University of Cagliari, Istituti Clinici Scientifici Maugeri, University of Salerno, University of Naples Federico II, L'organizzazione Ospedale di Civitanova M, University of Messina, University of Turin, Azienda Ospedaliero-Universitaria Careggi, University of Rome Tor Vergata, Azienda Ospedaliero-Universitaria delle Marche, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco", Ospedale Generale Regionale Francesco Miulli
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4409825150