Side Effects Of Hydroxychloroquine Research Articles

Hydroxychloroquine in children with proliferative lupus nephritis: a randomized clinical trial

Hydroxychloroquine (HCQ) is an antimalarial agent used to treat mucocutaneous, musculoskeletal, constitutional manifestations of systemic lupus erythematosus (SLE). This study assessed the efficacy and side effects of HCQ in children with proliferative lupus nephritis (LN). This double-blind, randomized, placebo-controlled trial study was conducted on 60 children with proliferative LN classes III and IV treated with steroids and a mycophenolate (MMF) regimen. Patients were categorized into two groups, the HCQ group (n = 30) and the placebo group (n = 30). They were evaluated initially at 6- and a 12-month follow-up by mucocutaneous, ophthalmological examination, and investigations (BUN, creatinine, 24 h proteinuria, triglycerides (TG), cholesterol, Antids-DNA, C3, C4). Disease activity was assessed using the SLE disease activity index (SLEDAI-2 k). After 12 months, TG, cholesterol, 24 h proteinuria, Antids-DNA, and SLEDAI score were significantly decreased in the HCQ group (P: 0.002, 0.012, 0.031, 0.001, respectively). After 12 months, the cumulative probabilities of developing primary end-points (LN partial and complete remission) were 40% and 60% in the HCQ group versus 53.3% and 36.7% in the placebo group (P: 0.002). After 12 months, the HCQ group experienced mucocutaneous alopecia (3.3%), hyperpigmentation (10%), and ophthalmological mild retinal changes (6.7%), but they did not differ significantly from the placebo group. Cunclusion: HCQ improved the disease and LN activity in children with proliferative LN, with documented skin hyperpigmentation and mild retinal changes following HCQ use in a few cases. This study was registered on http://www.clinicaltrials.gov/ with trial registration number (TRN): NCT03687905, September 2018 “retrospectively registered.”What is Known:• Hydroxychloroquine (HCQ) is documented as an adjunctive treatment in children with systemic lupus erythematosus (c-SLE) LN with efficacy in improving lupus musculoskeletal and mucocutaneous manifestations.• Due to the paucity of studies, its effects and side effects in children with LN remain unclear.What is New:• This pilot randomized clinical trial assessed the efficacy and adverse effects of HCQ in children with proliferative LN.• HCQ had numerous advantages for LN, including rapid and sustained remission, antilipidemic effect, and rapid improvement of kidney functions.

The potential and pitfalls of artificial intelligence in clinical pharmacology.

Artificial intelligence (AI) involves using data and algorithms to perform activities normally achieved through human intelligence. AI and its key component machine learning contextualize data and enhance decision making to transform how we operate, discover, and develop drugs. Transforming clinical pharmacology (CP) as AI-augmented CP (AI/CP) requires an ecosystem including digitized data collection, standardized processes, complementary technologies, and an ethical framework. This commentary aims to highlight the future perspectives of AI/CP in drug development.

Use of hydroxychloroquine and azithromycin combination to treat the COVID-19 infection.

Coronavirus disease 2019 (COVID-19) infection is unequivocally the worst crisis in recent decades, which is caused by a severe acute respiratory virus 2. Currently, there is no effective therapy for the COVID-19 infection. Different countries have different guidelines for treating COVID-19 in the absence of an approved therapy for COVID-19. Therefore, there is an imminent need to identify effective treatments, and several clinical trials have been conducted worldwide. Both hydroxychloroquine [HCQS], chloroquine, and azithromycin (AZ) have been widely used for management based on in vitro studies favoring antiviral effects against the COVID-19 virus. However, there is evidence both in favor and against the use of hydroxychloroquine and azithromycin (HCQS+AZ) combination therapy to manage the COVID-19 infection. The combination of hydroxychloroquine and azithromycin was significantly associated with increased adverse events. However, the inference of these findings was from observational studies. Therefore, large randomized trials are imperative to show the future path for the use of HCQS+AZ combination therapy. However, owing to the ban on HCQS use in COVID-19, this may no longer be essential. This review is on the pharmacology, trials, regimens, and side effects of hydroxychloroquine and azithromycin combination therapy.

Psychosocial impact of SARS- CoV-2 outbreak on patients with pediatric-onset systemic lupus erythematosus and their caregivers.

To assess distress, insomnia, and psychosocial impact of SARS-CoV-2 outbreak on children with SLE and their caregivers. Patients with pSLE undergoing treatment in the Department of Pediatrics, PGIMER, Chandigarh, and their caregivers were enrolled. Questionnaires were sent to eligible patients and their parents through email or WhatsApp and telephonic interviews were conducted. Self-designed SLE-COVID-19 stress questionnaire; Peritraumatic Distress Inventory; Insomnia Severity Index, Positive and Negative Affect Schedule were used. Ethical approval was sought from Institutes Ethics Committee (IEC/2020/000583). Telephonic connection was possible with 80 families (160 participants). Telephonic contact was possible with 80 families (160 participants); off these 61 children with pSLE (78.2%) and 55 caregivers (70.5%) responded to the questionnaire. Among participants, 23% patients, and 21.8% caregivers were severely stressed about SARS-CoV-2 infection; 78.7% patients and 80% caregivers had heard about hydroxychloroquine (HCQ) being used for the treatment of COVID-19; 52.7% caregivers exhibited moderate concern about shortage of HCQ; and 52.5% patients, and 43.6% caregivers were worried about side effects of HCQ. We found that 20 (32.8%) patients and 18 (32.7%) caregivers experienced significant distress. Majority of participants reported sleep disturbances. High positive affect scores were seen in 40 (65.5%) patients and 43 (78.2%) caregivers, low positive affect scores were noted in 21 (34.5%) patients and 12 (21.8%) caregivers. Patients with pSLE and their caregivers are at risk of psychosocial problems during the COVID-19 pandemic. Psychological interventions can be very helpful.

Evaluation of optical coherence tomography angiography parameters in patients treated with Hydroxychloroquine

BackgroundOne of the major side effects of Hydroxychloroquine (HCQ) is retinopathy. The aim of this study was to evaluate the Optical coherence tomography angiography (OCTA) parameters in a group of patients who have Hydroxychloroquine-induced retinopathy based on Multifocal electroretinography (mfERG) with a group who do not have retinopathy.MethodThis is a Cross-Sectional Study. In this study, patients with Rheumatoid arthritis (RA) or Systemic lupus erythematosus (SLE) who had been taking Hydroxychloroquine for at least 7 years were included. MfERG and OCTA imaging were performed for all patients. Patients were divided into Normal mfERG and Abnormal mfERG groups based on mfERG results. OCTA parameters were studied in these two groups.ResultSixty-one patients (61 eyes) were included. Forty-one patients had SLE and 20 patients had RA. Forty patients (66.7%) had Abnormal mfERG. The mean vascular density (VD) in Superficial capillary plexus (SCP) layer was not significantly different between Normal mfERG and Abnormal mfERG groups (P-Value> 0.05). Mean VD in SCP layer was not significantly different between Normal mfERG and Abnormal mfERG groups (P-Value> 0.05). In RA subgroup, mean VD in SCP layer in PeriFovea region in Abnormal mfERG group was significantly lower than normal group (P-Value < 0.05). Mean VD in deep capillary plexus (DCP) layer in Whole Image, Superior Hemi, Inferior Hemi, PeriFovea area in Abnormal mfERG group was significantly lower than normal group (P-Value < 0.05). This discrepancy was also observed in the RA subgroup but not in the SLE subgroup. The mean of none of the parameters of foveal avascular zone (FAZ) (mm2), Flow Area of Outer Retina (mm2) and Flow Area of Choriocapillaris (mm2) were not statistically significant between the groups Abnormal mfERG and Normal mfERG. (p-value> 0.05).ConclusionVD in the DCP layer decreased in abnormal mfERG patients compared to patients with normal mfERG. But it seems that VD in SCP layer, FAZ Area and Flow Area are similar in both groups. OCTA may be used as a non-invasive tool in the diagnosis of early stages of HCQ-induced retinopathy, especially in RA patients, but further studies are needed.

Hydroxychloroquine and Chloroquine Induced Cardiomyopathy: A Concise Review

Hydroxychloroquine and Chloroquine are commonly used for the treatment of malaria and autoimmune conditions. Most recently, hydroxychloroquine has been implicated in the treatment armamentarium of Severe acute respiratory syndrome (SARS) caused by SARS-associated coronavirus-2. A rare, underreported side effect of hydroxychloroquine and chloroquine is cardiotoxicity. The cardiomyopathy occurs as a result of inhibition of lysosomal enzymes causing lysosomal dysfunction and intra-cellular accumulation of metabolic byproducts in the myocardium, leading to hypertrophy with or without restrictive physiology and resultant conduction abnormalities. Based on our review of 57 reported cases of hydroxychloroquine or chloroquine induced cardiomyopathy, dyspnea was the most common associated symptom. The most common rhythms seen on EKG were as follows: complete heart block (18.75%), right bundle branch block (RBBB) (18.75%). The most common findings on echocardiography were left ventricular hypertrophy (LVH) (54%), systolic dysfunction (48%) and diastolic dysfunction (32%). A definitive diagnosis is established by endomyocardial biopsy which demonstrates the presence of curvilinear inclusion bodies. The outcome following cessation of the offending agent ranges from complete reversal in 45% of the cases to continued progression with need for cardiac transplantation or even death in 17.5% of the cases.

Hydroxychloroquine and risk of cardiac decompensation

Background Hydroxychloroquine (HCQ) is a 4-aminoquinoline derivative, used in the treatment of malaria and rheumatic diseases. HCQ has also been suggested as a treatment in patients suffering from severe acute respiratory syndrome–coronavirus 2 (SARS–CoV-2). One of the cardiac complications of SARS-CoV-2 is myocarditis and ventricular dysfunction. Case summary We present the case of a 52 year old lady presenting with 2 months history of breathlessness, found to have severely impaired left ventricular function. She had been taking HCQ for 28 months for seronegative inflammatory arthritis. No cause was identified on initial investigation. She was treated with optimal medical therapy, and HCQ was stopped. After 5 months a cardiac MRI scan revealed full remodelling of the ventricle. Discussion This case highlights one of the lesser recognized side effects of HCQ, and the potential for severe cardiac dysfunction. As this drug continues to be investigated and used in the management of SARS-CoV-2 it is important to recognize the potential for cardiac decompensation in patients who are already at increased risk of myocardial dysfunction.

CHLOROQUINE AND HYDROXYCHLOROQUINE: A MAJOR BREAKTHROUGH FOR COVID-19

Coronavirus pandemic or COVID-19 is a global public health emergency at this period. Presently, no pharmacological treatment is known to treat this condition. Hydroxychloroquine (HCQ), a derivative of chloroquine (CQ), was first synthesized in 1946 by adding a hydroxyl group to CQ, which is much less toxic than CQ in animal studies. Other than being an anti-malarial drug, it was revealed to have various pharmacological effects and one of those is its anti-viral property. CQ, as well as HCQ, has been used in SARS (Severe Acute Respiratory Syndrome) coronavirus infection due to its antiviral properties. Even though various scientists have considered HCQ as a better therapeutic approach than CQ for the treatment of coronavirus infection, there are various adverse drug reactions associated with HCQ treatment in COVID-19 patients. In this paper, we review the anti-viral mechanism, various adverse drug reactions, and side effects of HCQ for COVID-19 treatment.

Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: Role of CYP450 isoforms and epigenetic modulations

Antimalaria drugs such as chloroquine (CQ) and hydroxychloroquine (HCQ) have been administered to several inflammatory diseases including rheumatoid arthritis and systemic lupus erythematosus, and infectious diseases such as acquired immune deficiency syndrome and influenza. Recently, several patients infected with novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were given HCQ, and showed a discrepant response. HCQ inhibits SARS-CoV-2 cell entry, and inflammatory cascade by interfering with lysosomal and endosomal activities, and autophagy, impeding virus-membrane fusion, and inhibiting cytokine production resulted from inflammatory pathways activation. Despite ongoing administration of HCQ in a wide spectrum of disorders, there are some reports about several side effects, especially retinopathy in some patients treated with HCQ. Cytochrome P450 (CYP450) and its isoforms are the main metabolizers of HCQ and CQ. Pharmacokinetic properties of CYP enzymes are influenced by CYP polymorphism, non-coding RNAs, and epigenetic mechanisms such as DNA methylation, and histone acetylation. Accumulating evidence about side effects of HCQ in some patients raise the possibility that different response of patients to HCQ might be due to difference in their genome. Therefore, CYP450 genotyping especially for CYP2D6 might be helpful to refine HCQ dosage. Also, regular control of retina should be considered for patients under HCQ treatment. The major focus of the present review is to discuss about the pharmacokinetic and pharmacodynamic properties of CQ and HCQ that may be influenced by epigenetic mechanisms, and consequently cause several side effects especially retinopathy during SARS-CoV-2 therapy.