Table 7.

Regimens/Agents Used in the Management of COVID-19 That Interact With Therapies for CLL

COVID-19 Treatment	Metabolism/Elimination	CLL Treatment With Potential Drug Interaction	CLL Treatment Considerations
Tocilizumab66	Inhibition of IL-6 may lead to increased metabolism of drugs that are CYP450 substrates	Acalabrutinib, duvelisib, ibrutinib, idelalisib, venetoclax, zanubrutinib	Caution should be exercised when coadministering tocilizumab with CYP3A4 substrate drugs where decrease in effectiveness is undesirable. The effect of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy
Remdesivir67	In vitro, remdesivir is a substrate for drug metabolizing enzyme CYP3A4 and P-gp transporters	Acalabrutinib, duvelisib, ibrutinib, idelalisib, venetoclax, zanubrutinib	Because remdesivir is an inhibitor of CYP3A4, coadministration of remdesivir and CLL drugs may increase levels and toxicities of CLL drugs. It is not clear if remdesivir is a strong or moderate CYP3A4 inhibitor. Either interrupt dosing or reduce dose of CLL drug while remdesivir is being used; refer to USPIs of CLL drugs for dose modification recommendations
Nirmatrelvir plus ritonavir68	A strong inhibitor of CYP3A; components are CYP3A substrates	Ibrutinib, venetoclax, acalabrutinib, idelalisib, zanubrutinib	Because nirmatrelvir plus ritonavir is a strong inhibitor of CYP3A, coadministration of nirmatrelvir plus ritonavir and CLL drugs (ibrutinib, venetoclax, acabrutinib, duvelisib, idelalisib, zanubrutinib) may increase levels and toxicities of CLL drugs. Avoid coadministration or interrupt dosing of CLL drug while nirmatrelvir plus ritonavir is being used

CLL = chronic lymphocytic leukemia; COVID-19 = coronavirus disease 2019; IL = interleukin; IV = intravenous; mAb = monoclonal antibody; MoA = mechanism of action; OATP1B1 = organic anion transporting polypeptides 1B1; P-gp = P-glycoprotein; USPI = United States Prescribing Information.