Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 93
Filter
1.
Am J Emerg Med ; 61: 235.e5-235.e6, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2075854

ABSTRACT

The return of COVID-19 symptoms after Nirmatrelvir/Ritonavir (Nm/R) treatment is being increasingly reported. Limited evidence suggests most cases of rebound symptoms are mild and do not require further intervention. Here we present a male veteran reporting rebound symptoms who was found to be hypoxic with pulmonary emboli. Our case highlights the need to evaluate known complications of SARS-CoV-2 including venous thromboembolism in patients reporting recurring symptoms. Further, cases of severe rebound phenomenon should continue to be reported by clinicians to better appreciate the use of the Nm/R during the Omicron wave and among vaccinated persons.


Subject(s)
COVID-19 , Pulmonary Embolism , Humans , Male , SARS-CoV-2 , Ritonavir/adverse effects , Pulmonary Embolism/chemically induced , Acute Disease
2.
Obstet Gynecol ; 140(3): 447-449, 2022 Sep 01.
Article in English | MEDLINE | ID: covidwho-2018210

ABSTRACT

This is a descriptive study of pregnant patients who received nirmatrelvir-ritonavir therapy from April 16, 2022, through May 18, 2022. Patients were eligible to receive nirmatrelvir-ritonavir if they were diagnosed with mild-to-moderate coronavirus disease 2019 (COVID-19) with symptom onset within 5 days, did not require oxygen therapy or hospital admission, and had no contraindications to nirmatrelvir-ritonavir. During the study time frame, 11 patients were identified as candidates for nirmatrelvir-ritonavir treatment. All patients agreed to nirmatrelvir-ritonavir treatment after a telehealth consultation; seven patients completed the treatment. All patients who received nirmatrelvir-ritonavir experienced symptom resolution without the need for additional care. All but one patient tolerated nirmatrelvir-ritonavir without immediate adverse effects, and no adverse fetal or neonatal effects were observed.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Infant, Newborn , Pregnancy , Humans , Ritonavir/therapeutic use , Ritonavir/adverse effects , COVID-19/drug therapy , Lopinavir/therapeutic use , SARS-CoV-2 , Pregnancy Outcome , Antiviral Agents/therapeutic use , Drug Combinations , Pregnancy Complications, Infectious/drug therapy
5.
Ann Pharm Fr ; 80(4): 531-542, 2022 Jul.
Article in French | MEDLINE | ID: covidwho-1977718

ABSTRACT

OBJECTIVES: The aim of the study is to provide an overview of Drug-drug Interactions (DDIs) and adverse effects caused by drugs used in SARS-CoV-2 infection during the first epidemic wave. METHODS: We retrospectively analyzed patients treated by drugs used in SARS-CoV-2 infection (Azithromycin, Hydroxychloroquine and/or Lopinavir/ritonavir) between 15th March 2020 to 17th April 2020. A review of adverse events and DDI-risky drug association on medical record was conducted for each patient. Each adverse events was analyzed by the Centre régional de pharmacovigilance (CRPV) to assess causality of drugs used in SARS-CoV-2 infection. RESULTS: A total of 312 precriptions were analyzed during the period, of which 110 prescriptions had 157 drug association at risk of DDIs; 26 adverse events were reported. Causality assessment by CRPV concluded that 10 (35,7 %) adverse effects were possibly related to SARS-CoV-2 drugs with only 2 (7,1 %) related to DDIs. CONCLUSIONS: Despite risk of adverse drug reactions and DDIs related to drugs used in SARS-CoV-2 infection, few iatrogenics diseases were found.


Subject(s)
COVID-19 , Antiviral Agents/adverse effects , COVID-19/drug therapy , Drug Interactions , Humans , Hydroxychloroquine/adverse effects , Retrospective Studies , Ritonavir/adverse effects , SARS-CoV-2
6.
Viruses ; 14(8)2022 08 02.
Article in English | MEDLINE | ID: covidwho-1969513

ABSTRACT

This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06-0.96; p = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06-0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03-0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46-0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting.


Subject(s)
COVID-19 , Antiviral Agents/adverse effects , COVID-19/drug therapy , Disease Progression , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic , Ritonavir/adverse effects , Treatment Outcome
9.
Clin Pharmacol Ther ; 112(4): 892-900, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1894584

ABSTRACT

Nirmatrelvir coadministered with ritonavir is highly efficacious in reducing the risk of coronavirus disease 2019 (COVID-19) adverse outcomes among patients at increased risk of progression to severe disease, including patients with chronic kidney disease. Because nirmatrelvir is eliminated by the kidneys when given with ritonavir, this phase I study evaluated the effects of renal impairment on pharmacokinetics, safety, and tolerability of nirmatrelvir/ritonavir. Participants with normal renal function (n = 10) or mild, moderate, or severe renal impairment (n = 8 each) were administered a single 100-mg nirmatrelvir dose with 100 mg ritonavir given 12 hours before, together with and 12 and 24 hours after the nirmatrelvir dose. Systemic nirmatrelvir exposure increased with increasing renal impairment, with mild, moderate, and severe renal impairment groups having respective adjusted geometric mean ratio areas under the plasma concentration-time profile from time 0 extrapolated to infinite time of 124%, 187%, and 304% vs. the normal renal function group. Corresponding ratios for maximum plasma concentration were 130%, 138%, and 148%. Apparent clearance was positively correlated with estimated glomerular filtration rate, and geometric mean renal clearance values were particularly lower for the moderate (47% decrease) and severe (80% decrease) renal impairment groups vs. the normal renal function group. Nirmatrelvir/ritonavir exhibited an acceptable safety profile; treatment-related adverse events were mild in severity, and there were no significant findings regarding laboratory measurements, vital signs, or electrocardiogram assessments. These findings led to a dose reduction recommendation for nirmatrelvir/ritonavir in patients with moderate renal impairment (150/100 mg nirmatrelvir/ritonavir instead of 300/100 mg twice daily for 5 days). NCT04909853.


Subject(s)
COVID-19 , Renal Insufficiency , Antiviral Agents/adverse effects , COVID-19/drug therapy , Enzyme Inhibitors , Humans , Protease Inhibitors , Ritonavir/adverse effects
10.
Transplant Proc ; 54(6): 1557-1560, 2022.
Article in English | MEDLINE | ID: covidwho-1852177

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a significant impact on communities and health systems. New antiviral medications against this disease have not been properly tested yet, and their efficiency, side effects, and drug-drug interactions are not entirely known. Organ transplant recipients receive immunosuppressive medications such as tacrolimus to prevent graft rejection. Tacrolimus is metabolized by the cytochrome P450 3A4 enzyme system. Many medications can either induce or inhibit this enzyme and affect the level. Awareness of possible drug-drug interactions is vital because tacrolimus levels should be kept within a specific narrow range determined by the recipient's immunologic risk. Underexposure increases the risk of graft rejection, whereas overexposure may lead to adverse effects. Paxlovid, a novel antiviral medication approved for emergency use to treat SARS-CoV-2, is a combination of nirmatrelvir and ritonavir, a cytochrome P450 34A inhibitor. In this case report, we present a case of a kidney transplant patient receiving tacrolimus treated with Paxlovid, leading to an abruptly high tacrolimus level, significant symptoms, treatment interruption, and acute kidney injury. We conclude that the drug-drug interaction between Paxlovid and tacrolimus is indeed robust and noteworthy and leads to high tacrolimus levels and its metabolites, adverse effects, and acute kidney injury. Physicians managing immunocompromised patients receiving tacrolimus should be aware of this significant drug-drug interaction and consider other options or reduction of daily tacrolimus dose during treatment in addition to timely monitoring of both tacrolimus levels and serum creatinine. Consulting with the transplant pharmacist is foremost in alerting for these interactions.


Subject(s)
Acute Kidney Injury , COVID-19 , Kidney Transplantation , Acute Kidney Injury/chemically induced , Antiviral Agents/adverse effects , COVID-19/drug therapy , Creatinine , Drug Combinations , Drug Interactions , Graft Rejection/drug therapy , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Lactams , Leucine , Nitriles , Proline , Ritonavir/adverse effects , SARS-CoV-2 , Tacrolimus/adverse effects
11.
BMJ Open ; 12(3): e048502, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1822067

ABSTRACT

BACKGROUND: To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19. METHODS: We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach. RESULTS: We included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference (RD) 8 fewer per 1000, 95% CI 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of cardiac toxicity (RD 10 more per 1000, 95% CI 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI 23 more to 110 more) compared with standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI 100 more to 210 more) compared with standard care or placebo. DISCUSSION: Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.


Subject(s)
Adenosine Monophosphate/adverse effects , Alanine/adverse effects , COVID-19 , Hydroxychloroquine , Lopinavir/adverse effects , Ritonavir/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Drug Combinations , Humans , Hydroxychloroquine/adverse effects , Randomized Controlled Trials as Topic , SARS-CoV-2
12.
J Laryngol Otol ; 135(9): 755-758, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1747302

ABSTRACT

BACKGROUND: There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing's syndrome. METHOD: All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted. RESULTS: A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019. CONCLUSION: The use of potent steroids metabolised via CYP3A4, such as fluticasone and budesonide, are not recommended for patients taking ritonavir or cobicistat. Mometasone should be used cautiously with ritonavir because of pharmacokinetic similarities to fluticasone. There was a delayed onset of symptoms in many cases, most likely due to the relatively lower systemic bioavailability of intranasal fluticasone.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Cushing Syndrome/chemically induced , HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , HIV , Administration, Intranasal , Adrenal Cortex Hormones/administration & dosage , Adult , Cobicistat/administration & dosage , Cobicistat/adverse effects , Drug Interactions , Fluticasone/administration & dosage , Fluticasone/adverse effects , HIV Protease Inhibitors/administration & dosage , Humans , Male , Ritonavir/administration & dosage , Ritonavir/adverse effects
14.
J Med Virol ; 94(4): 1513-1522, 2022 04.
Article in English | MEDLINE | ID: covidwho-1718397

ABSTRACT

OBJECTIVES: To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method. METHODS: The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19. RESULTS: The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. CONCLUSIONS: Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Indoles/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Sulfides/therapeutic use , COVID-19/mortality , Drug Combinations , Humans , Indoles/adverse effects , Lopinavir/adverse effects , Ritonavir/adverse effects , SARS-CoV-2/drug effects , Sulfides/adverse effects , Treatment Outcome
15.
N Engl J Med ; 386(15): 1397-1408, 2022 04 14.
Article in English | MEDLINE | ID: covidwho-1692474

ABSTRACT

BACKGROUND: Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (Mpro) inhibitor with potent pan-human-coronavirus activity in vitro. METHODS: We conducted a phase 2-3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19-related hospitalization or death from any cause through day 28, viral load, and safety were evaluated. RESULTS: A total of 2246 patients underwent randomization; 1120 patients received nirmatrelvir plus ritonavir (nirmatrelvir group) and 1126 received placebo (placebo group). In the planned interim analysis of patients treated within 3 days after symptom onset (modified intention-to treat population, comprising 774 of the 1361 patients in the full analysis population), the incidence of Covid-19-related hospitalization or death by day 28 was lower in the nirmatrelvir group than in the placebo group by 6.32 percentage points (95% confidence interval [CI], -9.04 to -3.59; P<0.001; relative risk reduction, 89.1%); the incidence was 0.77% (3 of 389 patients) in the nirmatrelvir group, with 0 deaths, as compared with 7.01% (27 of 385 patients) in the placebo group, with 7 deaths. Efficacy was maintained in the final analysis involving the 1379 patients in the modified intention-to-treat population, with a difference of -5.81 percentage points (95% CI, -7.78 to -3.84; P<0.001; relative risk reduction, 88.9%). All 13 deaths occurred in the placebo group. The viral load was lower with nirmatrelvir plus ritonavir than with placebo at day 5 of treatment, with an adjusted mean difference of -0.868 log10 copies per milliliter when treatment was initiated within 3 days after the onset of symptoms. The incidence of adverse events that emerged during the treatment period was similar in the two groups (any adverse event, 22.6% with nirmatrelvir plus ritonavir vs. 23.9% with placebo; serious adverse events, 1.6% vs. 6.6%; and adverse events leading to discontinuation of the drugs or placebo, 2.1% vs. 4.2%). Dysgeusia (5.6% vs. 0.3%) and diarrhea (3.1% vs. 1.6%) occurred more frequently with nirmatrelvir plus ritonavir than with placebo. CONCLUSIONS: Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns. (Supported by Pfizer; ClinicalTrials.gov number, NCT04960202.).


Subject(s)
Antiviral Agents , COVID-19 , Lactams , Leucine , Nitriles , Proline , Ritonavir , Administration, Oral , Adult , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Disease Progression , Double-Blind Method , Hospitalization , Humans , Lactams/administration & dosage , Lactams/adverse effects , Lactams/therapeutic use , Leucine/administration & dosage , Leucine/adverse effects , Leucine/therapeutic use , Nitriles/administration & dosage , Nitriles/adverse effects , Nitriles/therapeutic use , Proline/administration & dosage , Proline/adverse effects , Proline/therapeutic use , Ritonavir/administration & dosage , Ritonavir/adverse effects , Ritonavir/therapeutic use , SARS-CoV-2 , Treatment Outcome , Vaccination , Viral Load/drug effects , Viral Protease Inhibitors/administration & dosage , Viral Protease Inhibitors/adverse effects , Viral Protease Inhibitors/therapeutic use
17.
Zhonghua Nei Ke Za Zhi ; 59(8): 605-609, 2020 Aug 01.
Article in Chinese | MEDLINE | ID: covidwho-1556260

ABSTRACT

Objective: To evaluate the efficacy and safety of lopinavir/ritonavir (LPV/r) and arbidol in treating patients with coronavirus disease 2019 (COVID-19) in the real world. Methods: The clinical data of 178 patients diagnosed with COVID-19 admitted to Guangzhou Eighth People's Hospital from January 20 to February 10, 2020 were retrospectively analyzed. According to patient's antiviral treatment regimens, 178 patients were divided into 4 groups including LPV/r group (59 patients), arbidol group (36 patients), LPV/r plus arbidol combination group (25 patients) and the supportive care group without any antiviral treatment (58 patients). The primary end point was the negative conversion time of nucleic acid of 2019 novel coronavirus (2019-nCoV) by pharyngeal swab. Results: The baseline parameters of 4 groups before treatment was comparable. The negative conversion time of viral nucleic acid was (10.20±3.49), (10.11±4.68), (10.86±4.74), (8.44±3.51) days in LPV/r group, arbidol group, combination group, and supportive care group respectively (F=2.556, P=0.058). There was also no significant difference in negative conversion rate of 2019-nCoV nucleic acid, the improvement of clinical symptoms, and the improvement of pulmonary infections by CT scan (P>0.05). However, a statistically significant difference was found in the changing rates from mild/moderate to severe/critical type at day 7 (χ(2)=9.311, P=0.017), which were 24%(6/25) in combination group, 16.7%(6/36) in arbidol group, 5.4%(3/56) in LPV/r group and 5.2%(3/58) in supportive care group. Moreover, the incidence of adverse reactions in three antiviral groups was significantly higher than that in supportive care group (χ(2)=14.875, P=0.002). Conclusions: Antiviral treatment including LPV/r or arbidol or combination does not shorten the negative conversion time of 2019-nCoV nucleic acid nor improve clinical symptoms. Moreover, these antiviral drugs cause more adverse reactions which should be paid careful attention during the treatment.


Subject(s)
HIV Infections , HIV Infections/drug therapy , Humans , Indoles , Lopinavir/adverse effects , Retrospective Studies , Ritonavir/adverse effects , SARS-CoV-2
18.
Trials ; 22(1): 869, 2021 Dec 04.
Article in English | MEDLINE | ID: covidwho-1551220

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in Wuhan, Hubei, China, in December 2019. It was recognized as a pandemic by the World Health Organization on 11 March 2020. Outbreak forecasting and mathematical modelling suggest that these numbers will continue to rise. Early identification of effective remedies that can shorten the duration and severity of illness is critical for Lagos State, which is the epi-centre of the disease in Nigeria. METHODS: This is a multi-centre, randomized, double-blind placebo-controlled superiority trial. The study investigates the efficacy of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir added on to standard of care compared to standard of care only in patients with COVID-19 disease. The primary outcome is the clinical status of patients measured using a 7-point ordinal scale at day 15. Research participants and clinicians will be blinded to the allocated intervention. Outcome measures will be directly assessed by clinicians. Statistical analysis will be done by a team blinded to the identity and allocation of research participants. Data analysis will follow intention-to-treat methods, using R software. DISCUSSION: The current study is of strategic importance for Lagos State in potentially curbing the health, social and economic burden of COVID-19 disease. Should the current study demonstrate that either of the three intervention drugs is more efficacious than standard therapy alone, the State Ministry of Health will develop an evidence-based guideline for the management of COVID-19 in Lagos State. The findings will also be shared nationally and with other states which may lead to a standardized national guideline for the treatment of COVID-19 in Nigeria. TRIAL REGISTRATION: Pan African Clinical Trials Register PACTR202004801273802 . Registered prospectively on April 2, 2020.


Subject(s)
COVID-19 , Hydroxychloroquine , COVID-19/drug therapy , Chloroquine/analogs & derivatives , Humans , Hydroxychloroquine/adverse effects , Lopinavir/adverse effects , Multicenter Studies as Topic , Nigeria , Randomized Controlled Trials as Topic , Ritonavir/adverse effects , SARS-CoV-2
19.
J Clin Pharmacol ; 62(5): 646-655, 2022 05.
Article in English | MEDLINE | ID: covidwho-1525452

ABSTRACT

This study aimed to characterize adverse drug reactions (ADRs) to hydroxychloroquine in the setting of COVID-19, occurring in Italy in the period March to May 2020. The analysis of the combination therapy with azithromycin or/and lopinavir/ritonavir as well as a comparison with ADRs reported throughout 2019 was performed. ADRs collected by the Italian National Network of Pharmacovigilance were analyzed for their incidence, seriousness, outcome, coadministered drugs, and Medical Dictionary for Regulatory Activities classification. A total of 306 reports were gathered for the quarter of 2020: 54% nonserious and 46% serious, and half of the latter required either the hospitalization or its prolongation. However, most of them were either completely recovered (26%) or in the process of recovery (45%), except for 9 fatal cases. Throughout 2019, 38 reports were collected, 53% nonserious and 47% serious, but no deaths had been reported. Diarrhea, prolonged QT interval, and hypertransaminasemia were the most frequently ADRs reported in 2020, significantly higher than 2019 and specific for COVID-19 subjects treated with hydroxychloroquine. The logistic regression analyses demonstrated that the likelihood of serious ADRs, QT prolongation, and diarrhea significantly increased with hydroxychloroquine dosage. Coadministration of lopinavir/ritonavir and hydroxychloroquine showed a positive correlation with diarrhea and hypertransaminasemia and a negative relationship with the ADR seriousness. The combination therapy with azithromycin was another independent predictor of a serious ADR. Off-label use of hydroxychloroquine for COVID-19, alone or in combination regimens, was associated with increased incidence and/or seriousness of specific ADRs in patients with additional risk factors caused by the infection.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Long QT Syndrome , Azithromycin/adverse effects , COVID-19/drug therapy , Diarrhea/chemically induced , Humans , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Lopinavir/adverse effects , Off-Label Use , Pharmacovigilance , Ritonavir/adverse effects
20.
Medicine (Baltimore) ; 100(28): e26538, 2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1494086

ABSTRACT

ABSTRACT: Corrected QT (QTc) interval prolongation has been associated with poor patient prognosis. In this study, we assessed the effects of different drugs and cardiac injury on QTc interval prolongation in patients with coronavirus disease 2019 (COVID-19).The study cohort consisted of 395 confirmed COVID-19 cases from the Wuhan Union Hospital West Campus. All hospitalized patients were treated with chloroquine/hydroxychloroquine (CQ/HCQ), lopinavir/ritonavir (LPV/r), quinolones, interferon, Arbidol, or Qingfei Paidu decoction (QPD) and received at least 1 electrocardiogram after drug administration.Fifty one (12.9%) patients exhibited QTc prolongation (QTc ≥ 470 ms). QTc interval prolongation was associated with COVID-19 severity and mortality (both P < .001). Administration of CQ/HCQ (odds ratio [OR], 2.759; 95% confidence interval [CI], 1.318-5.775; P = .007), LPV/r (OR, 2.342; 95% CI, 1.152-4.760; P = .019), and quinolones (OR, 2.268; 95% CI, 1.171-4.392; P = .015) increased the risk of QTc prolongation. In contrast, the administration of Arbidol, interferon, or QPD did not increase the risk of QTc prolongation. Notably, patients treated with QPD had a shorter QTc duration than those without QPD treatment (412.10 [384.39-433.77] vs 420.86 [388.19-459.58]; P = .042). The QTc interval was positively correlated with the levels of cardiac biomarkers (creatine kinase-MB fraction [rho = 0.14, P = .016], high-sensitivity troponin I [rho = .22, P < .001], and B-type natriuretic peptide [rho = 0.27, P < .001]).In conclusion, QTc prolongation was associated with COVID-19 severity and mortality. The risk of QTc prolongation was higher in patients receiving CQ/HCQ, LPV/r, and quinolones. QPD had less significant effects on QTc prolongation than other antiviral agents.


Subject(s)
Antiviral Agents/adverse effects , COVID-19/drug therapy , COVID-19/mortality , Long QT Syndrome/mortality , SARS-CoV-2 , Aged , COVID-19/virology , Chloroquine/adverse effects , Drug Therapy, Combination , Drugs, Chinese Herbal/adverse effects , Electrocardiography , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/adverse effects , Indoles/adverse effects , Interferons/adverse effects , Long QT Syndrome/chemically induced , Lopinavir/adverse effects , Male , Middle Aged , Odds Ratio , Quinolones/adverse effects , Retrospective Studies , Ritonavir/adverse effects , Severity of Illness Index
SELECTION OF CITATIONS
SEARCH DETAIL