Drug Interaction Report

GENERALLY AVOID: Coadministration with isotretinoin may decrease the therapeutic efficacy of valoctocogene roxaparvovec, an adeno-associated virus (AAV) vector designed to help replace missing coagulation factor VIII. Decreased factor VIII activity (75 international units/dL at week 60 to less than 3 international units/dL at week 64) occurred in one patient starting treatment with systemic isotretinoin following valoctocogene roxaparvovec infusion. Factor VIII activity increased to 46 international units/dL at week 122 after discontinuing isotretinoin at week 72.

MANAGEMENT: In patients who are benefiting from valoctocogene roxaparvovec, isotretinoin is not recommended.

GENERALLY AVOID: Coadministration with other hepatotoxic agents such as alcohol may increase the risk of liver injury and decrease the therapeutic efficacy of valoctocogene roxaparvovec, a liver-directed adeno-associated virus (AAV) vector designed to help replace missing coagulation factor VIII. Most of the patients treated with valoctocogene roxaparvovec in clinical studies experienced ALT elevations, presumably due to immune-mediated injury of transduced hepatocytes, which may decrease the therapeutic efficacy of valoctocogene roxaparvovec. In a clinical trial of adults with severe hemophilia (n=134) receiving a single dose of valoctocogene roxaparvovec (6 x 10[13] vector genomes [vg]/kg), 107 patients (96%) experienced increased ALT levels greater than or equal to 1.5 times baseline or greater than the upper limit of normal (ULN), while 12 patients (9%) experienced increased ALT levels greater than 5 to 20 times ULN. Some of the ALT elevations were associated with decreased factor VIII activity, and some were attributed to alcohol consumption. Most patients treated with valoctocogene roxaparvovec required immunosuppressive medications, including corticosteroids, to control elevations in transaminases and prevent loss of transgene expression.

MANAGEMENT: After administration of valoctocogene roxaparvovec, alcohol consumption should be avoided for at least 1 year and limited thereafter.

GENERALLY AVOID: The combined use of ethanol and isotretinoin may result in a disulfiram-like reaction. The mechanism has not been established.

MANAGEMENT: Alcohol consumption should be avoided during isotretinoin therapy.