Overview of Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Targeted Therapy and Supportive Care for Lung Cancer

A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19

“…The study reported that within 30 days, nirmatrelvir/ritonavir can significantly decrease the risk of hospital admission or death of a positive outpatient SARS-CoV-2 test [ 22 , 23 ]. Except for ISDs, many other drugs may have drug-drug interactions with nirmatrelvir/ritonavir, for example, the antiepileptic drugs [ 24 ], conazole drugs [ 25 ], and so on [ 26 ], so the coprescription of nirmatrelvir/ritonavir with other drugs necessitates the close monitoring of their exposure. In renal impairment patients, the exposure of nirmatrelvir increased along with the increasing renal impairment [ 27 ], and renal impairment patient may require a dose reduction.…”

Oral antivirals for COVID-19 among patients with cancer

“…It should be noted that DDIs between medications that oncologic patients often take and Paxlovid® may signi cantly affect the risk-bene t ratio or even be prohibitive of its administration [12][13][14]. Nirmatrelvir, an antiviral protease inhibitor against SARS-CoV-2, is pharmacokinetically enhanced by ritonavir, a potent CYP3A4 inhibitor, to achieve therapeutic plasma concentrations [25].…”

“…A post hoc analysis from the aforementioned RCT [5] showed that molnupiravir treatment of mild-to-moderate COVID-19 in non-hospitalized, unvaccinated, immunocompromised adults was safe, but the clinical bene t from its administration, although numerically substantial, did not reach statistical signi cance [8,11]. Importantly, adverse effects due to drug-drug interactions (DDI) between medications that immunocompromised patients may already be taking, and nirmatrelvir/ritonavir may impact its tolerability among patients with cancer [12][13][14]. Moreover, recently completed RCTs of both drugs showed a lack of clinical bene t from their use among low-risk patients or even vaccinated high-risk patients in the current era of Omicron variants and widespread immunity to SARS-CoV-2 [15][16][17][18] To our knowledge, no studies to date have speci cally appraised the effectiveness of molnupiravir and nirmatrelvir/ritonavir in preventing hospitalization and mortality, exclusively among patients with solid or hematologic malignancies, using appropriate, concurrent controls.…”

Strategies for mitigating adverse events related to selective RET inhibitors in patients with RET-altered cancers

“…For example, ritonavir, used in ritonavir-boosted nirmatrelvir antiviral therapy, is a strong inhibitor of CYP3A4, which is involved in metabolism of both selpercatinib and pralsetinib. 66 , 67 Concomitant use can increase the risk for TRAEs, so selpercatinib and pralsetinib should be temporarily discontinued during antiviral treatment. Another FDA-approved drug to treat COVID-19 is molnupiravir, for which preliminary data on pharmacokinetics (PK) and metabolism suggest that the risk for drug interaction with other drugs is low.…”