Consultation psychiatry in COVID-19 patients: Lopinavir/ritonavir interactions with main psychiatric drugs.
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ABSTRACT:
SUBMITTER: Marcatili M
PROVIDER: S-EPMC8014835 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69-85%) patients, and in 33 (26%, 95% CI 19-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10-731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.
| S-EPMC7708981 | biostudies-literature
Project description:ObjectiveTo develop a population pharmacokinetic model for lopinavir boosted by ritonavir in coronavirus disease 2019 (Covid-19) patients.MethodsConcentrations of lopinavir/ritonavir were assayed by an accredited LC-MS/MS method. The population pharmacokinetics of lopinavir was described using non-linear mixed-effects modeling (NONMEM version 7.4). After determination of the base model that better described the data set, the influence of covariates (age, body weight, height, body mass index (BMI), gender, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), C reactive protein (CRP), and trough ritonavir concentrations) was tested on the model.ResultsFrom 13 hospitalized patients (4 females, 9 males, age?=?64?±?16 years), 70 lopinavir/ritonavir plasma concentrations were available for analysis. The data were best described by a one-compartment model with a first-order input (KA). Among the covariates tested on the PK parameters, only the ritonavir trough concentrations had a significant effect on CL/F and improved the fit. Model-based simulations with the final parameter estimates under a regimen lopinavir/ritonavir 400/100 mg b.i.d. showed a high variability with median concentration between 20 and 30 mg/L (Cmin/Cmax) and the 90% prediction intervals within the range 1-100 mg/L.ConclusionAccording to the estimated 50% effective concentration of lopinavir against SARS-CoV-2 virus in Vero E6 cells (16.7 mg/L), our model showed that at steady state, a dose of 400 mg b.i.d. led to 40% of patients below the minimum effective concentration while a dose of 1200 mg b.i.d. will reduce this proportion to 22%.
| S-EPMC7552959 | biostudies-literature
Project description:No specific treatment against SARS-CoV-2 is available after 6 months of COVID-19 worldwide outbreak Antivirals could decrease the viral load and reduce direct and indirect damages of SARSCoV-2 infection Ritonavir-bosted lopinavir is effective against SARS-CoV-2 in vitro Sequential virological and pharmacological monitoring helped to understand the efficacy of ritonavir-boosted lopinavir in a SARS-CoV-2 infected patient Ritonavir-boosted lopinavir could be proposed as early treatment for SARS-CoV-2 infection.
| S-EPMC7251410 | biostudies-literature
Project description:Highlights•Two cases of Serotonin syndrome (SS) in COVID-19 patients are presented.•Lopinavir/ritonavir (LPV/r) have been widely used during the COVID-19 pandemic.•LPV/r with duloxetine and lithium triggered SS in patient 1.•LPV/r with risperidone, and probably also morphine, triggered SS in patient 2.•A Video of patient 2 shows myoclonus and ocular clonus in the context of SS.
| S-EPMC7255189 | biostudies-literature
Project description:Following the first case of Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov-2), in Wuhan, China, in December 2019, it has spread worldwide. An outbreak in Japan occurred on a cruise ship, and this was followed by community-acquired COVID-19. Herein, we report three cases of COVID-19 that presented pneumonia following admission to Kitasato University Hospital. Patients were admitted based on the positive result of real-time reverse transcriptase–polymerase chain reaction (RT-PCR) tests for COVID-19 nucleic acid. All patients were diagnosed as suffering from non-severe COVID-19 pneumonia and were successfully treated with Lopinavir/Ritonavir (LPV/r). LPV/r could be an option for treating non-severe COVID-19 pneumonia in general and even in elderly patients.
| S-EPMC7248319 | biostudies-literature
Project description:BACKGROUND:No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS:We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS:A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS:In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).
| S-EPMC7121492 | biostudies-literature
Project description:Currently, there is no specific antiviral treatment for COVID-19. However, drugs previously developed to treat other viral infections are being tested to verify if they might also be effective against SARS-CoV-2, the virus that causes COVID-19. Twenty years ago, the F.D.A. approved Lopinavir/ritonavir (LPV/r) to treat HIV infection. LPV and ritonavir were initially purposed to inhibit 3-chymotrypsin-like protease (3CLpro) of SARS-CoV and MERS-CoV and preliminary promising data on its efficacy for treating people infected with those viruses were available. Therefore, due to the high genetic similarities among those viruses and SARS-CoV-2, early during COVID-19 pandemic LPV/r was also proposed as one emergency treatment. We reviewed data from the literature about LPV/r treatment and SARS-CoV-2 infection, mainly focused on the efficacy and safety of this drugs for COVID-19 treatment. We can conclude that although up to date no clear benefit has been observed with the LPV/r treatment beyond standard care, its efficacy against SARS-COV-2 infection deserves further evaluations, particularly during the very early phase of the disease.
| S-EPMC7654234 | biostudies-literature
Project description:The COVID-19 outbreak is now one of the most critical crises to manage for most of national healthcare systems in the world. The situation is complicated by the absence of vaccines and authorized pharmacological treatments, except for remdesivir. In this context, many medicaments, including different Ebola and HIV antivirals, are used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Authorized medicaments manipulation is sometimes necessary because they are not always formulated to be administered to non-cooperative patients or they are in shortage. It is this the case of the fixed combination of lopinavir/ritonavir, which was extensively used in the first phase of the outbreak inducing a shortage of the oral solution available in the EU market. This work provides data on size distribution, osmolarity other than drug chemical stability of a lopinavir/ritonavir extemporaneous preparation made by using the solid dosage form (i.e., tablet) available on the market as drug source. The reported data indicate that such preparation is suitable to be delivered through a nasogastric tube, and enough stable for two weeks from the preparation at room temperature.
| S-EPMC7582040 | biostudies-literature
Project description:BackgroundMental health problems are commonly encountered in primary care, with primary care providers (PCPs) experiencing challenges referring patients to specialty mental health care. Electronic consultation (eConsult) is one model that has been shown to improve timely access to subspecialty care in a number of medical subspecialties. eConsults generally involve a PCP-initiated referral for specialty consultation for a clinical question that is outside their expertise but may not require an in-person evaluation.ObjectiveOur aim was to describe the implementation of eConsults for psychiatry in a large academic health system.MethodsWe performed a content analysis of the first 50 eConsults to psychiatry after program implementation. For each question and response, we coded consults as pertaining to diagnosis and/or management as well as categories of medication choice, drug side effects or interactions, and queries about referrals and navigating the health care system. We also performed a chart review to evaluate the timeliness of psychiatrist responses and PCP implementation of recommendations.ResultsDepression was the most common consult template selected by PCPs (20/50, 40%), followed by the generic template (12/50, 24%) and anxiety (8/50, 16%). Most questions (49/50, 98%) pertained primarily to management, particularly for medications. Psychiatrists commented on both diagnosis (28/50, 56%) and management (50/50, 100%), responded in an average of 1.4 days, and recommended in-person consultation for 26% (13/50) of patients. PCPs implemented psychiatrist recommendations 76% (38/50) of the time.ConclusionsFor the majority of patients, psychiatrists provided strategies for ongoing management in primary care without an in-person evaluation, and PCPs implemented most psychiatrist recommendations. eConsults show promise as one means of supporting PCPs to deliver mental health care to patients with common psychiatric disorders.
| S-EPMC5562932 | biostudies-literature
Project description:BackgroundCOVID-19 infection is the most serious global public health crisis of the century. With no approved treatments against it, investigational treatments are being used despite limited safety data. Besides being at higher risk of complications of COVID-19 infection, patients with underlying cardiovascular disease are more likely to develop cardiac-related side effects of treatment. We present a case of sinus arrest with junctional escape related to lopinavir-ritonavir.Case summaryA 67-year-old man, with underlying stable ischaemic heart disease, acquired COVID-19 infection. He had a prolonged duration of fever and cough. He subsequently developed acute respiratory distress and required intensive care unit (ICU) care. Given his severe infection, he was started on lopinavir-ritonavir. Hydroxychloroquine was not used as he had a prolonged QTc interval. During observation in the ICU, the patient developed recurrent episodes of sinus arrest with junctional escape. Initial concerns were of myocarditis, but he had no ST-segment changes on ECG, with mild elevations of highly sensitive troponin I and a normal transthoracic echocardiogram. A multidisciplinary team discussion involving the intensivist, infectious disease physicians, and cardiologist; the decision was made to stop treatment with lopinavir-ritonavir. Within 48 h, the bradyarrhythmia resolved. The patient did not require transvenous and permanent pacemaker insertion.ConclusionCurrent efficacy and safety evidence of lopinavir-ritonavir as a treatment in COVID-19 patients is limited. Although uncommonly reported, those with underlying cardiovascular disease are at increased risk of bradyarrhythmia-related adverse effects of lopinavir-ritonavir. When initiating investigational therapies, especially in patients with cardiovascular conditions, adequate counselling and close monitoring are required.
| S-EPMC7337728 | biostudies-literature