Drug Interactions between chlorpromazine and Roctavian

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: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.