Note: The following study has been retracted by the journal. Read more here: Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Treatment options for COVID-19: The reality and challenges

Shio-Shin Jean, Ping-Ing Lee, Po-Ren Hsueh, Treatment options for COVID-19: The reality and challenges, Journal of Microbiology, Immunology and Infection, 2020, ISSN 1684-1182, https://doi.org/10.1016/j.jmii.2020.03.034.

Excerpts:

Although the in vitro data of chloroquine is promising (EC90 of 6.90 μM, using Vero E6 cells infected by SARS-CoV-2), an extensive prescription of chloroquine in clinical treatment of SARS-CoV-2 is a completely off-label use. It is not recommended in light of safety concerns (adverse effects on the hematologic, hepatic and renal systems, QTc prolongation with ventricular dysrhythmia) and will likely result in a major shortage of anti-malarial armamentaria.

Hydroxychloroquine is also proposed to control the cytokine storm that occurs in critically ill late phase SARS-CoV-2 infected patients. Hydroxychloroquine is significantly more potent than chloroquine in vitro (EC50 values: 0.72 and 5.47 μM, respectively) and has lower potential for drug–drug interactions than chloroquine. Pharmacokinetic models demonstrate that hydroxychloroquine sulfate is significant superior (5 days in advance) to chloroquine phosphate in inhibiting SARS-CoV-2 in vitro. The Taiwan CDC declared hydroxychloroquine as an important anti-SARS-CoV-2 agent on 26 March, 2020. Of note, patients with retinopathy, deficiency of glucose-6-phosphatase, QTc prolongation in electrocardiograms, history of allergy to hydroxychloroquine or who are pregnant or breastfeeding are contraindicated for receiving hydroxychloroquine therapy.

Consequently, the regimen of hydroxychloroquine in combination with azithromycin might be a promising alternative to remdesivir in the treatment of patients with SARS-CoV-2 infection in the future. Nevertheless, the possibility of complicated QTc prolongation should be concerned.

Chloroquine for SARS-CoV-2: Implications of Its Unique Pharmacokinetic and Safety Properties

Smit, C., Peeters, M.Y.M., van den Anker, J.N. et al. Chloroquine for SARS-CoV-2: Implications of Its Unique Pharmacokinetic and Safety Properties. Clin Pharmacokinet (2020). https://doi.org/10.1007/s40262-020-00891-1

Excerpts:

It is known from reports on chloroquine overdose that it can cause severe life-threatening toxicity, with ingestion of a dose of 5 g in adults being almost universally lethal when untreated. Moreover, among persons ingesting 2.25 g or more, corresponding to only three times a therapeutic dose of 10 mg/kg for a typical adult patient, an overall mortality rate of 19% was reported. Acute toxicity in overdose occurs very rapidly with gastrointestinal and neurological symptoms within the first hour, rapidly followed by impaired ventricular conduction, wide QRS complexes > 100 ms, corrected QT (QTc) prolongation, hypotension, and severe hypokalemia secondary to intracellular potassium shifting, resulting in an increased risk of ventricular dysrhythmias (i.e., torsades de pointes).

Regarding toxicity in children, it is known from many reports that poisoning in children, although infrequent, is extremely dangerous because children are particularly sensitive to chloroquine toxicity. With (accidental) overdose, most children become symptomatic within 30 min after ingestion and may die within the first 3 h even with aggressive treatment. Ingestion of only one tablet of 300 mg was fatal for a 12-month-old infant with a chloroquine serum concentration of 4.4 mg/L (13.6 μmol/L). A 13-year-old boy who took approximately 750 mg of chloroquine developed ventricular fibrillation at a plasma concentration of only 4.2 μmol/L. Another case report presented a 3-year-old child who died after taking two 150-mg base tablets of chloroquine.

With the dosages proposed for malaria or COVID-19, expected toxicity is mainly related to QTc prolongation and widening of the QRS complex. Chloroquine cardiotoxicity seems specifically relevant for COVID-19, since an acute myocarditis was recently reported as a possible

complication of COVID-19. Particularly in the case of co-treatment with other QTc-prolonging agents such as amiodarone, macrolide antibiotics (such as azithromycin), ondansetron, and many others, before the start of chloroquine treatment an electrocardiogram should be performed and QTc time measured and repeated after the start of chloroquine treatment and other potentially QTc-prolonging agents on a daily basis.

Chloroquine and hydroxychloroquine in covid-19

Ferner RE, Aronson JK. BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1432 (Published 08 April 2020)

Excerpt:

Wide use of hydroxychloroquine will expose some patients to rare but potentially fatal harms, including serious cutaneous adverse reactions, fulminant hepatic failure, and ventricular arrhythmias (especially when prescribed with azithromycin); overdose is hazardous and difficult to treat.

Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection

Juurlink DN. CMAJ 2020. doi: 10.1503/cmaj.200528; early-released April 8, 2020

KEY POINTS:

• Chloroquine and hydroxychloroquine are generally well tolerated, but clinicians and patients should be aware of serious adverse events that can occur, even during short courses of treatment.

• Potential risks of treatment include prolongation of the QTc interval (especially in patients with preexisting cardiac disease or if coprescribed with azithromycin), hypoglycemia, neuropsychiatric effects, drug–drug interactions and idiosyncratic hypersensitivity reactions.

• Genetic variability in metabolism of these drugs is considerable and influences their safety and effectiveness.

• Chloroquine and hydroxychloroquine are extremely toxic in overdose.

• As we await stronger evidence on the role, if any, of these drugs in the treatment or prevention of coronavirus disease 2019, uncommon but serious harms of treatment can be mitigated by careful patient selection and monitoring

Preliminary Safety Results of CloroCovid-19 Study

Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study) https://doi.org/10.1101/2020.04.07.20056424

Excerpts:

Findings Out of a pre-defined 440 patients sample size, 81 patients were enrolled. The high dose CQ arm presented more QTc>500ms (25%), and a trend toward higher lethality (17%) than the lower dosage.

Preliminary findings suggest that the higher CQ dosage (10-day regimen) should not be recommended for COVID-19 treatment because of its potential safety hazards. Such results forced us to prematurely halt patient recruitment to this arm.

Commentary:
The high dose arm of this study (600mg CQ twice daily for 10 days or total dose 12g) far exceeds the recommended dose for malaria prophylaxis (500mg weekly). As a result, the conclusions from this study should be interpreted with caution.

Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects

Miller, A. K., Harrell, E., Ye, L., Baptiste-Brown, S., Kleim, J. P., Ohrt, C., Duparc, S., Möhrle, J. J., Webster, A., Stinnett, S., Hughes, A., Griffith, S., & Beelen, A. P. (2013). Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects. British journal of clinical pharmacology, 76(6), 858–867. https://doi.org/10.1111/bcp.12160

Excerpt:

There were no trends for increased Fridericia’s corrected QT intervals when tafenoquine was given alone, nor was there a trend for increased Fridericia’s corrected QT interval when coadministered with chloroquine beyond that seen with chloroquine alone. Safety and tolerability of tafenoquine when coadministered were similar to those when tafenoquine was given alone

Note: The following study has been retracted by the journal. Read more here: Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).

Mercuro NJ, Yen CF, Shim DJ, et al. Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. Published online May 01, 2020. doi:10.1001/jamacardio.2020.1834

Excerpt:

In a cohort study of 90 hospitalized patients with coronavirus disease 2019, use of hydroxychloroquine with or without azithromycin for treatment of COVID-19 was associated with frequent QTc prolongation, and those taking hydroxychloroquine and azithromycin had greater QT prolongation than those taking hydroxychloroquine alone. One patient developed torsades de pointes.

This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020.

Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001).

The QT Interval in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine/Azithromycin

Ehud Chorin, Matthew Dai, Eric Shulman, Lailt Wadhwani, Roi Bar Cohen, Chirag Barbhaiya, Anthony Aizer, Douglas Holmes, Scott Bernstein, Michael Soinelli, David S Park, Larry Chinitz, Lior Jankelosn doi: https://doi.org/10.1101/2020.04.02.20047050

Abstract:

We report the change in the QT interval in 84 adult patients with SARS-CoV-2 infection treated with Hydroxychloroquine/Azithromycin combination. QTc prolonged maximally from baseline between days 3 and 4. In 30% of patients QTc increased by greater than 40ms. In 11% of patients QTc increased to >500 ms, representing high risk group for arrhythmia. The development of acute renal failure but not baseline QTc was a strong predictor of extreme QTc prolongation.

Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19

Joseph Magagnoli, Siddharth Narendran, Felipe Pereira, Tammy Cummings, James W Hardin, S Scott Sutton, Jayakrishna Ambati medRxiv 2020.04.16.20065920; doi: https://doi.org/10.1101/2020.04.16.20065920

Excerpt:

Baseline demographic and comorbidity characteristics were comparable across the three treatment groups. However, hydroxychloroquine, with or without azithromycin, was more likely to be prescribed to patients with more severe disease, as assessed by baseline ventilatory status and metabolic and hematologic parameters. Thus, as expected, increased mortality was observed in patients treated with hydroxychloroquine, both with and without azithromycin. Nevertheless, the increased risk of overall mortality in the hydroxychloroquine-only group persisted after adjusting for the propensity of being treated with the drug. That there was no increased risk of ventilation in the hydroxychloroquine-only group suggests that mortality in this group might be attributable to drug effects on or dysfunction in non-respiratory vital organ systems. Indeed, hydroxychloroquine use in Covid-19 patients has been associated with cardiac toxicity.

Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study

Jennifer C.E Lane, James Weaver, Kristin Kostka, Talita Duarte-Salles, Maria Tereza F. Abrahao, Heba Alghoul, Osaid Alser, Thamir M Alshammari, Patricia Biedermann, Edward Burn, Paula Casajust, Mitch Conover, Aedin C. Culhane, Alexander Davydov, Scott L. DuVall, Dmitry Dymshyts, Sergio Fernández Bertolín, Kristina Fišter, Jill Hardin, Laura Hester, George Hripcsak, Seamus Kent, Sajan Khosla, Spyros Kolovos, Christophe G. Lambert, Johan ver der Lei, Ajit A. Londhe, Kristine E. Lynch, Rupa Makadia, Andrea V. Margulis, Michael E. Matheny, Paras Mehta, Daniel R. Morales, Henry Morgan-Stewart, Mees Mosseveld, Danielle Newby, Fredrik Nyberg, Anna Ostropolets, Rae Woong Park, Albert Prats-Uribe, Gowtham A. Rao, Christian Reich, Jenna Reps, Peter Rijnbeek, Selva Muthu Kumaran Sathappan, Martijn Schuemie, Sarah Seager, Anthony Sena, Azza Shoaibi, Matthew Spotnitz, Marc A. Suchard, Joel Swerdel, Carmen Olga Torre, David Vizcaya, Haini Wen, Marcel de Wilde, Seng Chan You, Lin Zhang, Oleg Zhuk, Patrick Ryan, Daniel Prieto-Alhambra medRxiv 2020.04.08.20054551; doi: https://doi.org/10.1101/2020.04.08.20054551

Associated Website Summary: https://www.ehden.eu/covid19-study-a-thon/

Excerpt:

Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.

Treatment options for COVID-19: The reality and challenges

Shio-Shin Jean, Ping-Ing Lee, Po-Ren Hsueh, Treatment options for COVID-19: The reality and challenges, Journal of Microbiology, Immunology and Infection, 2020, , ISSN 1684-1182, https://doi.org/10.1016/j.jmii.2020.03.034.

Excerpts:

Although the in vitro data of chloroquine is promising (EC90 of 6.90 μM, using Vero E6 cells infected by SARS-CoV-2), an extensive prescription of chloroquine in clinical treatment of SARS-CoV-2 is a completely off-label use. It is not recommended in light of safety concerns (adverse effects on the hematologic, hepatic and renal systems, QTc prolongation with ventricular dysrhythmia) and will likely result in a major shortage of anti-malarial armamentaria.

Hydroxychloroquine is also proposed to control the cytokine storm that occurs in critically ill late phase SARS-CoV-2 infected patients. Hydroxychloroquine is significantly more potent than chloroquine in vitro (EC50 values: 0.72 and 5.47 μM, respectively) and has lower potential for drug–drug interactions than chloroquine. Pharmacokinetic models demonstrate that hydroxychloroquine sulfate is significant superior (5 days in advance) to chloroquine phosphate in inhibiting SARS-CoV-2 in vitro. The Taiwan CDC declared hydroxychloroquine as an important anti-SARS-CoV-2 agent on 26 March, 2020. Of note, patients with retinopathy, deficiency of glucose-6-phosphatase, QTc prolongation in electrocardiograms, history of allergy to hydroxychloroquine or who are pregnant or breastfeeding are contraindicated for receiving hydroxychloroquine therapy.

Consequently, the regimen of hydroxychloroquine in combination with azithromycin might be a promising alternative to remdesivir in the treatment of patients with SARS-CoV-2 infection in the future. Nevertheless, the possibility of complicated QTc prolongation should be concerned.

Hydroxychloroquine prophylaxis for COVID-19 contacts in India

Rathi S, Ish P, Kalantri A, Kalantri S. Lancet Infect Dis. 2020 Apr 17. pii: S1473-3099(20)30313-3. doi: 10.1016/S1473-3099(20)30313-3.

Excerpts:

The Indian Council of Medical Research, under the Ministry of Health and Family Welfare, has recommended chemoprophylaxis with hydroxychloroquine (400 mg twice on day 1, then 400 mg once a week thereafter) for asymptomatic healthcare workers treating patients with suspected or confirmed COVID-19, and for asymptomatic household contacts of confirmed cases.

In these chaotic times, no healthcare system can screen such a large number of healthy contacts for concomitant QTc prolonging medicines, long QT syndromes, or glucose-6-phosphate dehydrogenase deficiency. Even a 0·1% proportion of serious complications would amount to more than 10 000 severe adverse events in New Delhi alone, a number an already overwhelmed health-care system would not be able to cope with.

Cardiovascular risks of hydroxychloroquine in treatment and prophylaxis of COVID-19 patients: A scientific statement from the Indian Heart Rhythm Society

Kapoor, A., Pandurangi, U., Arora, V., Gupta, A., Jaswal, A., Nabar, A., Naik, A., Naik, N., Namboodiri, N., Vora, A., Yadav, R., & Saxena, A. (2020). Cardiovascular risks of hydroxychloroquine in treatment and prophylaxis of COVID-19 patients: A scientific statement from the Indian Heart Rhythm Society. Indian pacing and electrophysiology journal, S0972-6292(20)30038-3. Advance online publication. https://doi.org/10.1016/j.ipej.2020.04.003

Excerpts:

Government authorities have issued guidelines to health care workers and to the public at large, uniformly advising strict adherence to above measures and acknowledge the limited role of drugs in the treatment and prophylaxis of COVID-19 infection.
This statement from Indian Heart Rhythm Society (IHRS) addresses specifically the drug hydroxychloroquine (HCQ) mentioned in these guidelines. This includes a brief review of its cardiovascular effects, with respect to its propensity to cause QT interval prolongation and potentially lethal cardiac arrhythmia in certain patients. Identification of high-risk population and monitoring for prevention of such adverse events of sudden cardiac death are also discussed.

HCQ can lead to QT interval prolongation and torsades de pointes (TdP) in susceptible individuals. The risk of TdP is not a linear function of basal QTc or drug-induced prolongation in QTc interval. Moreover, not all patients with drug-induced QTc prolongation will develop TdP. This side effect is rare, but co-prescription of other drugs such as azithromycin (which is also being recommended for the treatment of COVID-19) could amplify this risk. Many other drugs such as quinolones, antihistamines etc. which are often used may also add to the risk of TdP (refer to https://www.crediblemeds.org/drugsearch for list of drugs associated with QT prolongation). HCQ also interacts with other cardiac drugs such as beta blockers and digoxin and increases the blood levels of these drugs.

Patients can be categorized into a low-risk group with a normal QTc interval (group A), a moderate-risk group with slightly prolonged (up to 500 ms; group B) and a high-risk group with a prolonged QTc interval ≥500 ms (group C)

Chloroquine and hydroxychloroquine in covid-19

Ferner RE, Aronson JK. BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1432 (Published 08 April 2020)

Excerpt:

Wide use of hydroxychloroquine will expose some patients to rare but potentially fatal harms, including serious cutaneous adverse reactions, fulminant hepatic failure, and ventricular arrhythmias (especially when prescribed with azithromycin); overdose is hazardous and difficult to treat.

Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection

Juurlink DN. CMAJ 2020. doi: 10.1503/cmaj.200528; early-released April 8, 2020

KEY POINTS:

• Chloroquine and hydroxychloroquine are generally well tolerated, but clinicians and patients should be aware of serious adverse events that can occur, even during short courses of treatment.

• Potential risks of treatment include prolongation of the QTc interval (especially in patients with preexisting cardiac disease or if coprescribed with azithromycin), hypoglycemia, neuropsychiatric effects, drug–drug interactions and idiosyncratic hypersensitivity reactions.

• Genetic variability in metabolism of these drugs is considerable and influences their safety and effectiveness.

• Chloroquine and hydroxychloroquine are extremely toxic in overdose.

• As we await stronger evidence on the role, if any, of these drugs in the treatment or prevention of coronavirus disease 2019, uncommon but serious harms of treatment can be mitigated by careful patient selection and monitoring

Towards Optimization of Hydroxychloroquine Dosing in Intensive Care Unit COVID-19 Patients

Sophie Perinel, Manon Launay, Élisabeth Botelho-Nevers, Éric Diconne, Aurore Louf-Durier, Raphaël Lachand, Martin Murgier, Dominique Page, Régine Vermesch, Guillaume Thierry, Xavier Delavenne, Towards Optimization of Hydroxychloroquine Dosing in Intensive Care Unit COVID-19 Patients, Clinical Infectious Diseases, , ciaa394, https://doi.org/10.1093/cid/ciaa394

Excerpts:

As of March 30, 2020, no treatment has demonstrated clinical efficacy against COVID-19. However, several treatment strategies are being considered and evaluated in numerous clinical trials. Among these strategies, the use of hydroxychloroquine (HCQ) appears to be a promising option, although only limited evidence is available at the present time.

HCQ can be responsible for adverse events and probably an increased incidence of adverse events in the case of inappropriate dosing regimens. One of the most serious adverse events in this population is cardiac toxicity, characterized by prolongation of the QT interval, which can lead to arrhythmia in patients at risk.

HCQ was withdrawn in two patients: due to QT interval prolongation (381 to 510 ms and 432 to 550 ms) on day 2 and 3 with HCQ blood levels of 0.03 mg/L and 1.74 mg/L, respectively.

Severe QT Prolongation in SLE patient (Case study)

O'Laughlin, J. P., Mehta, P. H., & Wong, B. C. (2016). Life Threatening Severe QTc Prolongation in Patient with Systemic Lupus Erythematosus due to Hydroxychloroquine. Case reports in cardiology, 2016, 4626279. https://doi.org/10.1155/2016/4626279

Excerpt:

QT interval prolongation is the result of abnormal repolarization of the ventricular myocardium resulting in lengthening of the QT interval on electrocardiogram [1–3]. In females the normal corrected QT interval is 470 ms, with males slightly lower at 450 ms [4]. It can be the result of congenital genetic mutations in cardiac myocyte ion channels [5], acquired from electrolyte derangements (hypocalcemia, hypokalemia, and hypomagnesemia), or from use of numerous medications. Common classes of medications include antibiotics, antiarrhythmics, antidepressants, and antipsychotics (Table 1) [6]. Clinical manifestations of prolonged QT interval include syncope and sudden cardiac death from a fatal cardiac arrhythmia known as Torsades de Pointes (TdP). TdP is a form of polymorphic ventricular tachycardia with a heart rate greater than 100 beats per minute with characteristic twisting around the isoelectric baseline every 5–20 beats [7, 8].

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

Capel, R. A., Herring, N., Kalla, M., Yavari, A., Mirams, G. R., Douglas, G., Bub, G., Channon, K., Paterson, D. J., Terrar, D. A., & Burton, R. A. (2015). Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential. Heart rhythm, 12(10), 2186–2194. https://doi.org/10.1016/j.hrthm.2015.05.027

Excerpt:

We describe novel mechanistic insights relating to the action of HCQ in cardiac preparations. We observe interesting inhibitory effects on If, IKr, and ICaL. Cardiac arrhythmia is not a reported side effect of HCQ, despite its widespread use in healthy (antimalarial) and diseased (rheumatological) populations. It is possible that blockade of ICaL could be countering some of the effect of the hERG channel block. The experiments described herein studying the funny current closely mirror those first performed to investigate the effects of known If blockers (eg, ZD7288, ivabradine), and suggest that further studies regarding cardiac modulation by HCQ is warranted.

Commentary:
This study highlights the difficulty in predicting TdP in humans, especially with those agents that modulate several ion currents. In addition to QT prolongation, there are several other risk factor which contribute to TdP such as gender, bradycardia (demonstrated here), hypokalemia and hypomagnesemia.

suspected hydroxychloroquine-associated qt prolongation in SLE patient (case study)

Morgan N, Patel S, Dvorkina O (2013) Suspected Hydroxychloroquine-Associated QT-Interval Prolongation in a Patient With Systemic Lupus Erythematosus, Journal of Clinical Rheumatology. 19(5):286–288, AUGUST 2013 DOI: 10.1097/RHU.0b013e31829d5e50, PMID: 23872551

Excerpt:

The observed QTc prolongation in our patient may have been multifactorial. Serological testing disclosed positivity to anti-Ro/SSA antibodies, which have been associated with increased risk of QTc prolongation. Her QTc interval did not approach normal values until 1 year after complete discontinuation of hydroxychloroquine therapy. This may be attributed to the long half-life of hydroxychloroquine potentiated by the patient’s renal impairment, permitting potential toxic effects even after discontinuation of therapy.

Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases

N. Costedoat-Chalumeau, J.-S. Hulot, Z. Amoura, G. Leroux, P. Lechat, C. Funck-Brentano, J.-C. Piette, Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases, Rheumatology, Volume 46, Issue 5, May 2007, Pages 808–810, https://doi.org/10.1093/rheumatology/kel402

Excerpts:

Antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ), are used in long-term treatment of connective tissue diseases (CTDs) and dermatological disorders, and are generally regarded as safe. However, rare but severe toxic effects may develop following prolonged use of these treatments. These side effects include retinopathy, neuropathy, vacuolar myopathy and/or cardiotoxicity, with both heart conduction disturbances and congestive heart failure.

To our knowledge, this is the first study that assessed electrocardiographic abnormalities in unselected patients with CTD treated with HCQ as the sole antimalarial. Only one case of QT interval prolongation has been reported after chronic exposition to HCQ. In our study, PR interval, QTc interval and heart rate were not different from those in a population of healthy young adults with a high proportion of women.

Chronic Hydroxychloroquine Use Associated with QT Prolongation and Refractory Ventricular Arrhythmia

Chun-Yu Chen, Feng-Lin Wang & Chih-Chuan Lin (2006) Chronic Hydroxychloroquine Use Associated with QT Prolongation and Refractory Ventricular Arrhythmia, Clinical Toxicology, 44:2, 173-175, DOI: 10.1080/15563650500514558

Excerpt:

The chronic use of HCQ for rheumatic diseases, or as an anti-malarial drug, should be balanced against the risk of developing potentially lethal cardiac arrhythmias.