Table 2. Cytochrome P450 3A4 (CYP3A4)... | American Society of Hematology

Table 2.

Cytochrome P450 3A4 (CYP3A4) and permeability-glycoprotein (P-gp) metabolism of commonly used drugs in lymphoma treatment

	CYP3A4			P-gp
	Substrate	Inducer	Inhibitor	Substrate	Inducer	Inhibitor
Lymphoma drugs with potential interactions
Acalabrutinib	●	O		O
Belinostat	O			O
Bendamustine				O
Bexarotene	O	◐
Bortezomib	●		O
Brentuximab vedotin	O		O	O
Carfilzomib			O	O		O
Cladribine				O
Cyclophosphamide	O
Dexamethasone	●	O		O
Doxorubicin	●		O	●
Etoposide	●			●
Ibrutinib	●					◐
Idarubicin				O
Idelalisib	●		●	O
Ifosfamide	●		O
Lenalidomide				O
Prednisone	O	O
Romidepsin	●			O
Temsirolimus	●		O	O
Teniposide	●		O	●
Venetoclax	●			O		◐
Vinblastine	●		●	O
Vincristine	●			O
Lymphoma drugs with no known interactions
Bleomycin
Fludarabine
Rituximab
Supportive care drugs
Aprepitant	●		◐
Clonazepam	●
Fosaprepitant	●		O
Fentanyl	●
Methadone	●
Ondansetron	●			O
Strong CYP3A4 and/or P-gp inhibitors (eg, idelalisib, ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, ritonavir, lopinavir/ritonavir, indinavir/ritonavir, cyclosporine, tacrolimus, clarithromycin, conivaptan) or inducers (eg, phenytoin, carbamazepine, rifampin, St. John’s wort) are generally contraindicated with direct oral anticoagulant use (DOAC).^56,57

	CYP3A4			P-gp
	Substrate	Inducer	Inhibitor	Substrate	Inducer	Inhibitor
Lymphoma drugs with potential interactions
Acalabrutinib	●	O		O
Belinostat	O			O
Bendamustine				O
Bexarotene	O	◐
Bortezomib	●		O
Brentuximab vedotin	O		O	O
Carfilzomib			O	O		O
Cladribine				O
Cyclophosphamide	O
Dexamethasone	●	O		O
Doxorubicin	●		O	●
Etoposide	●			●
Ibrutinib	●					◐
Idarubicin				O
Idelalisib	●		●	O
Ifosfamide	●		O
Lenalidomide				O
Prednisone	O	O
Romidepsin	●			O
Temsirolimus	●		O	O
Teniposide	●		O	●
Venetoclax	●			O		◐
Vinblastine	●		●	O
Vincristine	●			O
Lymphoma drugs with no known interactions
Bleomycin
Fludarabine
Rituximab
Supportive care drugs
Aprepitant	●		◐
Clonazepam	●
Fosaprepitant	●		O
Fentanyl	●
Methadone	●
Ondansetron	●			O
Strong CYP3A4 and/or P-gp inhibitors (eg, idelalisib, ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, ritonavir, lopinavir/ritonavir, indinavir/ritonavir, cyclosporine, tacrolimus, clarithromycin, conivaptan) or inducers (eg, phenytoin, carbamazepine, rifampin, St. John’s wort) are generally contraindicated with direct oral anticoagulant use (DOAC).^56,57

Edoxaban and dabigatran are substrates for P-gp. Apixaban and rivaroxaban are substrates of P-gp and CYP3A4. Their levels are influenced by coadministration of inhibitors and inducers of these metabolic pathways. Interactions are identified from the BC Cancer Drug Index, IBM MicroMedex accessed through DynaMed, Lexicomp, and Product Monographs available through the Government of Canada Drug Product Database.^78-81 Clinicians should refer to reference sources for the most updated information and to consult a pharmacist for guidance regarding possible drug–drug interactions whenever new medications are started or stopped. Data are variable between sources and interactions may or may not be clinically relevant. ●, major substrate or strong interaction; ◐, moderate interaction; ○, minor substrate or weak interaction or of uncertain clinical significance.

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