CHEMOTHERAPY
CHEMOTHERAPY REGIMENS: FOR NON-HODGKIN’S LYMPHOMA, HODGKIN’S LYMPHOMA, ANAL CARCINOMA, & PROSTATE CANCER
INSTIs NNRTIs PIs RTI
xBICTEGRAVIR xELVITEGRAVIR/ x DORAVIRINE x EFAVIRENZ xATAZANAVIR • TENOFOVIR • TENOFOVIR (Biktarvy) COBICISTAT (Pifeltro, (Sustiva, Atripla) (Reyataz/Norvir, ALAFENAMIDE, DISOPROXIL, TDF (Stribild, Genvoya) Delstrigo) Evotaz) TAF (Descovy, (Viread,Truvada, DOLUTEGRAVIR ETRAVIRINE x x Biktarvy, Genvoya, Atripla, Complera, (Tivicay, Triumeq, RILPIVIRINE (Intelence) DARUNAVIR x x Odefsey, Symtuza) Delstrigo, Stribild) Juluca) (Edurant, (Prezista/Norvir, x NEVIRAPINE Complera, Prezcobix, x RALTEGRAVIR (Viramune) •ABACAVIR (Kivexa, Odefsey, Juluca) Symtuza) (Isentress) Ziagen, Triumeq) xLOPINAVIR (Kaletra)
FOR NON -HODGKIN’S LYMPHOMA
xCHOP, CHOP-R n ƉŽƚĞŶƚŝĂůљ n (doxorubicin, cyclophosphamide, doxorubicin, cyclophosphamide, vincristine, doxorubicin, vincristine, doxorubicin, cyclophosphamide, vincristine, prednisone ; vincristine, prednisone ± prednisone and risk potential n toxicity prednisone and risk rituximab) of toxicity of of toxicity cyclophosphamide
HODGKIN’S LYMPHOMA
xABVD (doxorubicin, n doxorubicin & ƉŽƚĞŶƚŝĂůљ n doxorubicin & vinblastine, vinblastine and risk doxorubicin & vinblastine and risk bleomycin, of toxicity vinblastine of toxicity dacarbazine)
CHEMOTHERAPY
INSTIs NNRTIs PIs RTI
xBICTEGRAVIR xELVITEGRAVIR/ x DORAVIRINE x EFAVIRENZ xATAZANAVIR • TENOFOVIR • TENOFOVIR (Biktarvy) COBICISTAT (Pifeltro, (Sustiva, Atripla) (Reyataz/Norvir, ALAFENAMIDE, DISOPROXIL, TDF (Stribild, Genvoya) Delstrigo) Evotaz) TAF (Descovy, (Viread,Truvada, DOLUTEGRAVIR ETRAVIRINE x x Biktarvy, Genvoya, Atripla, Complera, (Tivicay, Triumeq, RILPIVIRINE (Intelence) DARUNAVIR x x Odefsey, Symtuza) Delstrigo, Stribild) Juluca) (Edurant, (Prezista/Norvir, x NEVIRAPINE Complera, Prezcobix, x RALTEGRAVIR (Viramune) •ABACAVIR (Kivexa, Odefsey, Juluca) Symtuza) (Isentress) Ziagen, Triumeq) xLOPINAVIR (Kaletra)
ANAL CARCINOMA x5-FU, mitomycin Potential additive nephrotoxicity with TDF & mitomycin xFOLFOX (oxaliplatin, leucovorin, 5-FU)
PROSTATE CANCER xAbiraterone (Zytiga) WŽƚĞŶƚŝĂůĨŽƌј WŽƚĞŶƚŝĂůĨŽƌј xDenosumab (Prolia) abiraterone but abiraterone but xLenalidomide likely not clinically likely not clinically (Revlimid) significant significant xAplutamide p INSTI p INSTI p NNRTI p NNRTI p PI p TAF (Erleada) xEnzalutamide (Xtandi)
CHEMOTHERAPY
Mechanism of Drug Interactions, Management and Monitoring
Class Mechanism of Interaction Main Interacting ARVs Management Monitoring Cyclophosphamide Transformation to inactive Ritonavir and cobicistat- Adjust dose or consider Close monitoring of side and possibly toxic boosted protease inhibitors replacing antiretrovirals with effects metabolites CYP 3A4 and cobicistat-boosted alternate agents elvitegravir Inhibition of CYP3A4 may increase drug availability for hydroxylation route thereby leading to increased efficacy and toxicity of cyclophosphamide.
Cyp2B6 and CYP2C19 induction by ritonavir may possibly increased the active metabolite. Induction of CYP 3A4 may Efavirenz, etravirine, Adjust dose or consider Close monitoring of side increase toxic metabolite nevirapine replacing antiretrovirals with effects (neurotoxicity) alternate agents Doxorubicin Enzyme inhibitors may Ritonavir and cobicistat- Adjust dose or consider Close monitoring efficacy decrease reduction to free boosted protease inhibitors replacing antiretrovirals with and side effects radicals and cobicistat-boosted alternate agents via inhibition of cytochrome elvitegravir P450 which may decrease both antineoplastic and cytotoxic properties; however, they may also increase intracellular accumulation of doxorubicin via inhibition of PgP, which may enhance cytotoxic effects and/or systemic toxicity. CHEMOTHERAPY
Class Mechanism of Interaction Main Interacting ARVs Management Monitoring Doxorubicin Enzyme inductors may Efavirenz, etravirine, Adjust dose or consider Close monitoring efficacy increased reduction to free nevirapine replacing antiretrovirals with and side effects radicals alternate agents via induction of cytochrome P450 which may increased both antineoplastic and cytotoxic properties Enzalutamide, apalutamide Strong inducers of CYP3A4, May decrease If possible, consider non- Antiretroviral efficacy 2C19, UGT, Pgp, BCRP, concentrations of INSTIs, inducing antiandrogen agent. (viral load, CD4, OATP1B1. PIs, NNRTI, and TAF. May consider using increased antiretroviral antiretroviral doses with concentrations if therapeutic drug monitoring available) Prednisone Possible increased level with Ritonavir and cobicistat- Not well studied. Dose Close monitoring of CYP3A4 inhibitors boosted protease inhibitors modification could be corticosteroids side and cobicistat-boosted suggested effects elvitegravir Prednisone Possible decreased level with Efavirenz, etravirine, Not well studied. Dose None. Steroid efficacy? CYP3A4 inducers nevirapine modification could be suggested Vinblastine, vincristine Possible increased level with Ritonavir and cobicistat- Adjust dose or consider Close monitoring of side CYP3A4 inhibitors boosted protease inhibitors replacing antiretrovirals with effects (peripheral and and cobicistat-boosted alternate agents autonomic neuropathy, elvitegravir myelosuppression) Vinblastine, vincristine Possible decreased level with Efavirenz, etravirine, Adjust dose or consider Close monitoring of CYP3A4 inducers nevirapine replacing antiretrovirals with efficacy alternate agents
Legend: No dose adjustment required.
Use combination with caution. Adjustment in drug dose or frequency or additional/more frequent monitoring may be required. May wish to
consult with a pharmacist knowledgeable in HIV drug interactions. Contraindicated/avoid combination.
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