Clinically Significant Drug Interaction Profiles of Chloroquine Analogues with Adverse Consequences and Risk Management

Abstract

The popularity of chloroquine (CQ) analogues, for malaria treatment in many countries emanates from it being cheap, widely available, relatively well tolerated, and having a rapid onset of action. Thus, CQ analogues are commonly sold as over-the-counter (OTC) medications. CQ analogues like hydroxychloroquine (HCQ) alone and/or other drugs in combination have been used as anti-inflammatory and immunomodulatory drugs in the treatment of various rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, dermatomyositis, Sjögrens syndrome, chronic juvenile arthritis, psoriatic arthritis, and have shown clinical benefits with an acceptable safety profile. As anti-inflammatory mechanism, CQ inhibits pro-inflammatory cytokine release, antigen processing and blocking the actions of histamine and phospholipase A₂. CQ analogue has also been studied for its potential as an enhancing agent in cancer therapies in various clinical trials. In many cases, the lysosomotrophic property of CQ appears to be important for the increase in ef?cacy and speci?city to inhibit inflammatory disorders. Moreover, it is indicated that the ef?cacy of conventional therapies can be dramatically enhanced if CQ analogues are given in combination. Although majority of CQ analogue in combination therapies improves overall the outcome, such treatments are often associated with serious toxicities leading to fatal.