Experience of a nirmatrelvir/ritonavir drug–drug interaction expert advice service

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Experience of a nirmatrelvir/ritonavir drug–drug interaction expert advice service

Florian Lemaitre, Camille Tron, Sébastien Lalanne, Bénédicte Franck, Christelle Boglione-Kerrien, Fabrice Taïeb and Marie-Clémence Verdier

Biological Pharmacologie Department, Rennes University Hospital

Background: Nirmatrelvir/ritonavir is a protease inhibitor antiviral drug indicated in the treatment of severe acute respiratory syndrome coronavirus-2 infections in high-risk patients for a severe disease. Unfortunately, ritonavir, used to boost nirmatrelvir pharmacokinetics, can also inhibit or induce the metabolism of other co-administered drugs substrates. This may lead to a subsequent drug–drug interaction (DDI) risk and thus to adverse drug reaction. To secure the drug's prescription and help clinicians with drug indication, we developed a DDI expert advice service dedicated to nirmatrelvir/ritonavir. The aim of this study was to describe this service provided by the clinical pharmacology department of the Rennes University Hospital, Rennes, France.

Material and methods: We collected all DDI advices provided by the five senior clinical pharmacologists of the department regarding nirmatrelvir/ritonavir in 2022 and 2023. These advices were given by phone, email or through a tele-expertise system. The following data were gathered: patient's age and sex, renal function, date of nirmatrelvir/ritonavir initiation, clinical department requiring the expert advice, patient's treatments and advice provided. Data were presented as medians and interquartile and percentages.

Results: In 2022 and 2023, the expert advice services provided advices for 123 and 224 patients, respectively. These 347 advices relate on 2858 prescription lines. In 2022, advices were provided for 881 prescription lines for patients of median age of 69 years [57–76] and estimated glomerular filtration rate (eGFR) of 77 mL/min [59–91]. The main pharmacological classes were: cardiology drugs (26.8%), endocrinology drugs (16.9%) and immunosuppressive agents (13.6%). The advice was distributed as follows: treatment continuation, treatment discontinuation during the antiviral course, dosage adjustment and treatment switch in 71%, 19%, 7%, 3% of the cases, respectively. Only three patients (2.4%) were denied the drug due to contraindications. Drug monitoring was proposed in 5% of prescription lines. The top drug request was tacrolimus in 2022.

In 2023, advices were provided for 1977 prescription lines for patients of median age of 77 years [67–85] and estimated glomerular filtration rate (eGFR) of 77 mL/min [55–90]. The most common requests were for endocrinology drugs (22%), cardiac drugs (21%) and neurology drugs (18%). The advice was distributed as follows: treatment continuation, treatment discontinuation during the antiviral course, dosage adjustment and treatment switch in 77%, 14%, 6% and 3% of the cases, respectively. Treatment was denied for 18 patients (8%). Drug monitoring was proposed in only 0.6% of prescription lines. The top drug request was acetaminophen in 2023.

Some serious risks were prevented by the services notably DDI with calcineurin inhibitors (n = 44), statins (122), lercanidipine (n = 14) or colchicin (n = 7).

Conclusions: This DDI expert service advice provided by clinical pharmacologists allows securing the combination of nirmatrelvir/ritonavir with other concomitant drugs. Most of eligible patients to the antiviral drug can benefit from it despite the risk of drug–drug interaction. The typology of advices shifted with time with initially more specialized advices, notably for transplant recipients, to more general practitioner requests probably due to the dissemination of the information beyond the tertiary centre and the increase experience gained by hospital practitioners in our centre.