Oral oncolytic and antiretroviral therapy administration: dose adjustments, drug interactions, and other considerations for clinical use

Drugs in Context

article

Melissa E Badowski¹  Bradley Burton²  Kristy M Shaeer³  John Dicristofano⁴ 

[1]Section of Infectious Diseases Pharmacotherapy, Department of Pharmacy Practice, University of Illinois at Chicago, College of Pharmacy

[2]Johns Hopkins Hospital

[3]Department of Pharmacy Practice, University of South Florida, College of Pharmacy

[4]University of Illinois at Chicago, College of Pharmacy

关键词: adverse events;    antiretroviral therapy;    antiretrovirals;    cancer;    dosage adjustments;    drug–drug interactions;    HIV/AIDS;    oral oncology agents;    oral oncolytics;   

DOI  :  10.7573/dic.212550

学科分类：社会科学、人文和艺术（综合）

来源: C S F Medical Communications Ltd.

【 摘 要 】

The rise in non-AIDS defining cancers (NADCs) is emergingas a leading cause of death for HIV and cancer patients. Toaddress this, current literature and guidelines suggest thecontinuation of antiretroviral therapy (ART) with oral oncolyticagents to prevent adverse complications associated withHIV disease progression. However, such an approach has thepotential for drug–drug interactions and adverse events forpatients on such therapy. Further, recommendations on howto adjust these medications, when used concomitantly, arelimited. As such, our purpose is to evaluate existing literaturethrough such means as drug databases (e.g. Micromedex,Lexi-Comp, etc.) and package inserts along with PubMed/Medline, Embase, and Google Scholar databases to developa reference tool for providers to utilize when there is adecision to treat a patient with ART and oral oncolytic agentsconcurrently. Our findings suggest that there are many druginteractions that should be taken into consideration with dualtherapy. Metabolism is a key determinant of dose adjustment,and many oncolytic agents and ART agents must havetheir dose adjusted as such. Most notably, several tyrosinekinase inhibitors require dose increases when used withnon-nucleoside reverse transcriptase inhibitors (NNRTIs) butmust be decreased when used concomitantly with proteaseinhibitors (PIs) and cobicistat. Further findings suggest thatcertain agents should not be used together, which include, butare not limited to, such combinations as bosutinib with NNRTIs,cobicistat, or PIs; idelalisib with maraviroc or PIs; neratinibwith NNRTIs, cobicistat, or PIs; and venetoclax with NNRTIs.Overall, the most prominent oncolytic drug interactions werediscovered when such agents were used concomitantly withPIs, cobicistat-boosted elvitegravir, or NNRTIs. Future studiesare necessary to further evaluate the use of these agentstogether in disease therapy to generate absolute evidenceof such findings. However, from the studies evaluated, muchevidence exists to suggest that concomitant therapy is notwithout drug interactions. As such, clinical decisions regardingconcomitant therapy should be evaluated in which the riskand benefit of dual therapy are assessed. Dose adjustmentsmust be made accordingly and in consultation with both HIVand oncology clinicians and pharmacists to reduce the riskfor adverse outcomes and disease progression for those withcancer and HIV/AIDS.

【 授权许可】

CC BY-NC-ND