MIRACLE DRUG UNDER FIRE: HYDROXYCHLOROQUINE OVERDOSE TOXICOKINETICS EXPLORED

Abstract

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hydroxychloroquine (HCQ) is a medication used in the treatment of malaria, lupus and rheumatoid arthritis. The drug gained popularity during the early stage of the Coronavirus Disease 2019 (COVID-19) pandemic as an emergency use therapy. It has since been shown in numerous studies that HCQ can actually cause more harm than good. However, its media attention has led to an increase in overdose cases, which can be fatal due to cardiac complications. We present a case of a patient with access to HCQ for COVID-19 prophylaxis who overdosed in a suicide attempt with a favorable outcome. CASE PRESENTATION: A 38-year old Asian American female with no significant history was found 4-6 hours after ingesting approximately 27 grams of oral HCQ. She was admitted to the intensive care for shock and severe hypokalemia (1.7 mmol/L). The pills were obtained from an overseas third party vendor for COVID-19 prophylaxis. Vitals on arrival were BP 60/30 mmHg, HR 66 bpm, temperature 94.9 fahrenheit. Based on previous case reports and studies on chloroquine, the patient was started on an epinephrine and versed drip, including 2 doses of 60mg diazepam. A single dose of activated charcoal was administered. Initial electrocardiogram revealed conduction abnormalities with QT interval of 549ms (629ms with Bazett's correction). The patient received 240 meq of potassium in a span of 25 hour and began to develop hyperkalemia of up to 6.4 mmol/L. After 48 hours, the patient's blood pressure and potassium levels normalized. On hospital day 4, she was successfully extubated with a favorable remaining hospital course. DISCUSSION: The most life threatening sequelae seen in HCQ overdoses are cardiac arrhythmias due to electrolyte imbalances, mainly potassium. Hyperkalemia after initial severe hypokalemia has been observed in numerous case reports of HCQ overdose and thought to be intracellular shifts rather than relative depletion. Thus, caution should be taken in the correction of initial hypokalemia. A review of previous cases shows an inverse relationship between potassium and HCQ levels, as with our case. Reported toxicity half-life ranges between 11.6 and 31 hours. Our case had an approximate peak concentration of 27 µg/ml after 4-6 hours after ingestion with an estimated observed half-life of 27 hours based on recorded concentrations over 45 hours, assuming 1st order elimination. Our patient's hypokalemia began to reverse during the 2nd half-life period which is also consistent with other reported cases. CONCLUSIONS: We believe that during the 2nd half-life, when more than 50% of the drug is eliminated, is the period when correction of hypokalemia should be taken with more caution. While these are only observations based on a few case reports, they can provide more insight on how to better manage electrolyte imbalances which can avoid fatal arrhythmias and circulatory arrest. REFERENCE #1: de Olano, J., Howland, M. A., Su, M. K., Hoffman, R. S., & Biary, R. (2019). Toxicokinetics of hydroxychloroquine following a massive overdose. The American journal of emergency medicine, 37(12), 2264-e5. REFERENCE #2: Jordan, P., Brookes, J. G., Nikolic, G., Le Couteur, D. G., & Le Couteur, D. (1999). Hydroxychloroquine overdose: toxicokinetics and management. Journal of Toxicology: Clinical Toxicology, 37(7), 861-864. REFERENCE #3: Palatnick, W., Meatherall, R., Sitar, D., & Tenenbein, M. (1997). Hydroxychloroquine kinetics after overdose. J Toxicol Clin Toxicol, 35, 496.Miller, D., & Fiechtner, J. (1989). Hydroxychloroquine overdosage. The Journal of rheumatology, 16(1), 142-143. DISCLOSURES: No relevant relationships by Fatima Anjum, source=Web Response No relevant relationships by James Kang, source=Web Response No relevant relationships by Hyfaa Mashaal, source=Web Response No relevant relationships by James Pellegrini, source=Web Response