key: cord-0745829-temt8b6f authors: Brown, Ronald title: Hydroxychloroquine and “off-label” utilization in the treatment of oral conditions date: 2020-04-11 journal: Oral Surg Oral Med Oral Pathol Oral Radiol DOI: 10.1016/j.oooo.2020.03.047 sha: 775a42a05c5e3ce09d907bf7c22bb59d13b756cc doc_id: 745829 cord_uid: temt8b6f nan Hydroxychloroquine and "off-label" utilization in the treatment of oral conditions To the Editor: In response to President Trump's remarks made on March 19, 2020, concerning the potential of chloroquine and hydroxychloroquine (HCQ) as treatment for the novel coronavirus-19 infections: "The U.S. Food and Drug Administration (FDA) swiftly issued a statement to clarify that, no, these drugs are not approved as treatments for COVID-19, the disease caused by the coronavirus SARS-CoV-2. Both drugs are approved to treat malaria, lupus, and rheumatoid arthritis but must still be assessed in clinical trials before being declared a safe and effective COVID-19 treatment. Doctors in the United States have wide latitude to prescribe drugs "off-label," meaning for conditions beyond their initial FDA approval." 1 HCQ may or may not pan out to be a successful therapeutic agent in the treatment for COVID-19 infections. However, it appears likely that many health care providers may begin using this drug without knowledge of accepted dosage regimens and toxicity. HCQ is a drug specifically approved for the prevention and treatment of malaria. However, it is utilized extensively by both physicians and dentists (oral medicine clinicians) in the treatment of rheumatologic conditions, such as systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, chronic ulcerative stomatitis, immune thrombocytopenia purpura, lichen planopilaris, and oral lichen planus. In the realm of treatment of autoimmune secretory and oral mucosal conditions, HCQ has been deemed safe and effective for such oral conditions as Sjogren syndrome, chronic ulcerative stomatitis, and oral lichen planus. [2] [3] [4] [5] [6] [7] [8] [9] A noted possible negative effect of HCQ is druginduced conjunctivitis. This toxicity is typically addressed by advising the patient to see his or her ophthalmologist at least once yearly. 10 Recently, it has been noted that there is a rare complication related to HCQ use, that is, sudden death resulting from a particular cardiac arrhythmia. Torsade de pointes arrhythmia is associated with prolonged QT duration secondary to high-dose HCQ administration. 11, 12 However, as reported by O'Laughlin et al., 13 HCQ-related QT interval prolongation and secondary arrhythmia are extremely rare and may be related to higher dosage regimens. Danielsson et al. 14 reported that the results of their recent study on sudden death in older patients indicated an increased risk of torsade de pointes arrhythmia with the use of the selective serotonin reuptake inhibitor citalopram. Therefore, there appears to be the possibility of additive drug interactions when prescribing HCQ to patients already taking citalopram and other drugs that significantly prolong the QT duration and increase the risk of a torsade de pointes arrhythmia. 15 Over 20 years ago, it was noted that the antihistamine H1 blocker terfenadine was cardiotoxic in higher doses and that particular drugs used in dentistry, such as ketoconazole and erythromycin, and even grapefruit juice could result in a drugÀdrug interaction and potentially lethal serum values, with the possible result of cardiotoxicity (specifically the torsade de pointes arrhythmia) and death. The danger of this sudden death condition resulted in the eventual removal of terfenadine as a clinical therapeutic agent worldwide. [16] [17] [18] [19] At rheumatologic therapeutic dosage levels, HCQ has been regarded as a reasonably safe therapeutic agent. However, oral medicine clinicians and other health care providers should be advised of the potential issues with the use of HCQ, such as drugÀdrug interactions, the additive toxicity of QT duration prolongation, and the association with sudden death, in the treatment of older patients. Could the anti-malarial drug chloroquine treat COVID-19? Available at Bhattacharyya I. Chronic ulcerative stomatitis: diagnostic and management challenges-four new cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis Chronic ulcerative stomatitis: a distinct clinical entity Effects of hydroxychlorquine on salivary flow rates and oral complaints of Sjogren patients: a prospective Ó Hydroxychloroquine: a multifaceted treatment in lupus The role of hydroxychloroquine as a steroid-sparing agent in the treatment of immune thrombocytopenia: a review of the literature Hydroxychloroquine and lichen planopilaris: efficacy and introduction of Lichen Planopilaris Activity Index scoring system Hydroxychloroquine sulphate therapy of erosive oral lichen planus. Australas Ocular adverse effects associated with systemic medications: recognition and management Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature Life threatening severe QTc prolongation in patient with systemic lupus erythematosus due to hydroxychloroquine Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide registerbased cohort study The role of adenosine receptors and endogenous adenosine in citalopram-induced cardiovascular toxicity Grapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram Cardiotoxicity of histamine and the possible role of histamine in the arrhythmogenesis produced by certain antihistamines Cardiac K+ channels and drug-acquired long QT syndrome Next generation antihistamines: therapeutic rationale, accomplishments and advances