Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup
Authors: Berling Ingrid , King Joshua D. , Shepherd Greene , Hoffman Robert S. , Alhatali Badria , Lavergne Valery , Roberts Darren M. , Gosselin Sophie , Wilson Gabrielle , Nolin Thomas D. , Ghannoum Marc ,   for the EXTRIP workgroup
Published: September 2020

Significance Statement
Although poisoning by chloroquine, hydroxychloroquine, or quinine is relatively uncommon, recent use of chloroquine and hydroxychloroquine for COVID-19 has elevated concerns regarding management of such poisonings. To investigate the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs, the Extracorporeal Treatments in Poisoning workgroup conducted systematic reviews of the relevant literature, screened studies, extracted data, and summarized findings. The group concluded that chloroquine, hydroxychloroquine, and quinine are not dialyzable (not amenable to clinically significant removal by extracorporeal treatments) and the current clinical evidence does not support the use of such treatments for chloroquine and quinine poisonings. Considering that data on extracorporeal treatments for hydroxychloroquine toxicity are sparse, the group proposed pharmacokinetic studies to confirm or refute the current impression that the drug is non-dialyzable.

Background
Although chloroquine, hydroxychloroquine, and quinine are used for a range of medical conditions, recent research suggested a potential role in treating COVID-19. The resultant increase in prescribing was accompanied by an increase in adverse events, including severe toxicity and death. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup sought to determine the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs.

Methods
We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods.

Results
A total of 44 studies (three in vitro studies, two animal studies, 28 patient reports or patient series, and 11 pharmacokinetic studies) met inclusion criteria regarding the effect of extracorporeal treatments. Toxicokinetic or pharmacokinetic analysis was available for 61 patients (13 chloroquine, three hydroxychloroquine, and 45 quinine). Clinical data were available for analysis from 38 patients, including 12 with chloroquine toxicity, one with hydroxychloroquine toxicity, and 25 with quinine toxicity. All three drugs were classified as non-dialyzable (not amenable to clinically significant removal by extracorporeal treatments). The available data do not support using extracorporeal treatments in addition to standard care for patients severely poisoned with either chloroquine or quinine (strong recommendation, very low quality of evidence). Although hydroxychloroquine was assessed as being non-dialyzable, the clinical evidence was not sufficient to support a formal recommendation regarding the use of extracorporeal treatments for this drug.

Conclusions
On the basis of our systematic review and analysis, the EXTRIP workgroup recommends against using extracorporeal methods to enhance elimination of these drugs in patients with severe chloroquine or quinine poisoning.