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1.
Drugs Aging ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646509

RESUMO

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) are often elderly, with comorbidities, and receiving polypharmacy, all of which are known factors for potentially severe drug-drug interactions (DDIs) and the prescription of potentially inappropriate medications (PIMs). OBJECTIVE: The aim of this study was to assess the risk of DDIs and PIMs in COVID-19 patients at hospital discharge. METHOD: Patients with a proven diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were hospitalized between 21 February and 30 April 2020, treated with at least two drugs, and with available information regarding pharmacological treatments upon admission and at discharge were considered. The appropriateness of drug prescriptions was assessed using INTERcheck®. RESULTS: A significant increase in the prescription of proton pump inhibitors and heparins was found when comparing admission with hospital discharge (from 24 to 33% [p < 0.05] and from 1 to 17% [p < 0.01], respectively). The increased prescription of heparins at discharge resulted in a highly significant increase in the potentially severe DDIs mediated by this class of drugs. 51% of COVID-19 patients aged > 65 years had at least one PIM upon admission, with an insignificant increment at discharge (58%). CONCLUSION: An increased number of prescribed drugs was observed in COVID-19 patients discharged from our hospital. The addition of heparins is appropriate according to the current literature, while the use of proton pump inhibitors is more controversial. Particular attention should be paid to the risk of bleeding complications linked to heparin-based DDIs.

5.
HIV Med ; 2020 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-33368966

RESUMO

OBJECTIVES: A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID-19 pandemic. Clinical data on patients co-infected with HIV and SARS-CoV-2 are still scarce. METHODS: This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID-19 in people living with HIV (PLWH), infected with SARS-CoV-2 in three countries in different clinical settings. COVID-19 was clinically classified as to be mild-to-moderate or severe. RESULTS: Of 175 patients, 49 (28%) had severe COVID-19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID-19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/µl, current CD4+ T cells < 350/µl and the presence of at least one comorbidity were significantly associated with severity of COVID-19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS-defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID-19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2.85, 95% confidence interval 1.26-6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir. CONCLUSIONS: In PLWH, immune deficiency is a possible risk factor for severe COVID-19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide.

7.
Clin Pharmacokinet ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180272

RESUMO

BACKGROUND AND OBJECTIVE: According to the drug label, linezolid dosage adjustments are not needed in geriatric patients. Nevertheless, clinical evidence suggests that elderly patients may benefit from the use of reduced linezolid doses to limit drug overexposure. Here, we aimed to describe the results of the last 5 years of therapeutic drug monitoring of linezolid in our institution with a special focus on elderly patients. METHODS: Linezolid therapeutic drug monitoring requests collected between January 2016 and June 2020 were considered. Linezolid trough concentrations were considered both as a continuous variable and as a categorical variable, clustering data according to the therapeutic range proposed by available literature (< 2, 2-8, and > 8 mg/L, respectively). Patients' age and sex were considered as categorical variables. Comparisons of linezolid trough concentrations between groups of patients stratified according to age were performed using an analysis of variance; comparisons in the frequency distributions were performed using the chi-squared test. RESULTS: From 2016 to 2020, we collected 3250 linezolid TDM requests. A highly significant, progressive increment in the linezolid trough concentrations was observed moving from patients aged < 50 years (5.8 ± 5.6 mg/L) to those aged > 90 years (16.6 ± 10.0 mg/L), with an overall increment of 30% per decade of age. Nearly 30%, 50%, and 65% of patients aged < 65 years, 65-80 years, and > 80 years, respectively, had supra-therapeutic linezolid trough concentrations at the first therapeutic drug monitoring assessment. This trend did not change significantly moving from 2016 to 2020. CONCLUSIONS: Elderly patients given linezolid at the conventional 600-mg twice-daily dose might be at a high risk of being overexposed to treatment, eventually increasing their risk to experience drug-related hematological toxicity. Reduced linezolid dosing schemes should be potentially considered in elderly patients at a low risk of treatment failure, ideally guided by therapeutic drug monitoring.

8.
Drugs Aging ; 37(12): 925-933, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33150470

RESUMO

BACKGROUND: Patients hospitalised with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2; coronavirus 2019 disease (COVID-19)] infection are frequently older with co-morbidities and receiving polypharmacy, all of which are known risk factors for drug-drug interactions (DDIs). The pharmacological burden may be further aggravated by the addition of treatments for COVID-19. OBJECTIVE: The aim of this study was to assess the risk of potential DDIs upon admission and during hospitalisation in patients with COVID-19 treated at our hospital. METHODS: We retrospectively analysed 502 patients with COVID-19 (mean age 61 ± 16 years, range 15-99) treated at our hospital with a proven diagnosis of SARS-CoV-2 infection hospitalised between 21 February and 30 April 2020 and treated with at least two drugs. RESULTS: Overall, 68% of our patients with COVID-19 were exposed to at least one potential DDI, and 55% were exposed to at least one potentially severe DDI. The proportion of patients experiencing potentially severe DDIs increased from 22% upon admission to 80% during hospitalisation. Furosemide, amiodarone and quetiapine were the main drivers of potentially severe DDIs upon admission, and hydroxychloroquine and particularly lopinavir/ritonavir were the main drivers during hospitalisation. The majority of potentially severe DDIs carried an increased risk of cardiotoxicity. No potentially severe DDIs were identified in relation to tocilizumab and remdesivir. CONCLUSIONS: Among hospitalised patients with COVID-19, concomitant treatment with lopinavir/ritonavir and hydroxychloroquine led to a dramatic increase in the number of potentially severe DDIs. Given the high risk of cardiotoxicity and the scant and conflicting data concerning their efficacy in treating SARS-CoV-2 infection, the use of lopinavir/ritonavir and hydroxychloroquine in patients with COVID-19 with polypharmacy needs to be carefully considered.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33106270

RESUMO

Four pre-exposure prophylaxis (PrEP) users with gastro-intestinal disorders (sleeve gastrectomy, terminal ileitis, celiac disease or chronic diarrhea) and receiving oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) were included. Despite a self-reported high adherence, trough plasma tenofovir concentrations (after a supervised intake) were significantly lower than those observed in PrEP recipients without gastrointestinal disorders [21 (±9.1) vs. 138 (±85) ng/mL]. PrEP users with gastrointestinal disorders may need increased TDF doses or alternative prophylactic measures.

12.
Clin Pharmacokinet ; 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32737820

RESUMO

BACKGROUND: People living with human immunodeficiency virus are ageing under combination antiretroviral treatments but data on drug exposure in serum and cerebrospinal fluid are limited. Dolutegravir is a widely used second-generation integrase strand transfer inhibitor: conflicting data suggest that neuropsychiatric side effects may present at a higher frequency in patients with higher dolutegravir serum concentrations. METHODS: We performed a retrospective analysis of our therapeutic drug monitoring registry identifying patients receiving once-daily dolutegravir without concomitant interacting drugs and significant clinical conditions. Data were analysed stratifying time after drug dose intake (maximum concentration 0.5-4 and trough concentration 21-27 h). Cerebrospinal fluid samples from patients enrolled in neurological studies and receiving dolutegravir were analysed for dolutegravir cerebrospinal fluid concentrations and cerebrospinal fluid-to-plasma ratios. Serum and cerebrospinal fluid concentrations were measured through validated chromatographic methods. RESULTS: We included 207 (providing 457 serum samples) and 41 patients (providing 41 cerebrospinal fluid samples). Participants were mostly male (68.2-72.8%) of median age of 50 years (50-53 years). Non-significant changes in dolutegravir maximum concentration and trough concentration were observed with age at Spearman's test (p values > 0.05); linear logistic regression showed a significant effect of age on dolutegravir trough concentration (p = 0.0013) (Fig. 1). Dolutegravir maximum concentration [3830 ng/mL (2311-5057) vs 4230 ng/mL (2919-5272), p = 0.311] and trough concentration [838 ng/mL (362-1587) vs 966 ng/mL (460-2085), p = 0.056] were non-significantly or borderline higher in patients aged > 50 years. Cerebrospinal dolutegravir concentrations were associated with plasma concentrations (ρ = 0.374, p = 0.016) and age (ρ = 0.537, p = 0.003); cerebrospinal fluid dolutegravir concentrations (13.8 vs 7.3 ng/mL, p = 0.015) and cerebrospinal fluid-to-plasma ratios (0.57 vs 0.32%, p = 0.017] were higher in participants aged > 50 years. CONCLUSIONS: We observed an increase in dolutegravir exposure in serum and in cerebrospinal fluid in older patients living with human immunodeficiency virus.

14.
J Med Virol ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32776534

RESUMO

As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.

15.
Int J STD AIDS ; 31(10): 1008-1010, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32693738

RESUMO

We report here the case of a 32-year-old male with recent diagnosis of HIV that, 45 days after starting a single tablet regimen co-formulated with bictegravir, emtricitabine and tenofovir alafenamide (BIC/FTC/TAF), experienced severe epigastric pain radiating to the back, nausea, episodes of non-bloody non-bilious vomiting and anorexia. Laboratory examination showed a rise in lipase with no alterations in serum transaminases. Abdominal ultrasound revealed a non-homogeneous structure of the pancreatic parenchyma. A diagnosis of mild drug-related acute pancreatitis was made and BIC/FTC/TAF was immediately stopped. The association between the episode of acute pancreatitis and BIC/FTC/TAF was scored as probable according to the Naranjo causality scale.

16.
Int J Cardiol ; 318: 160-164, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32610153

RESUMO

The novel coronavirus disease, affecting ~9 million people in the past five months and causing >460,000 deaths worldwide, is completely new to mankind. More than 2,000 research projects registered at ClinTrials.gov are aiming at finding effective treatments for rapid transfer to clinical practice. Unfortunately, just few studies have a sufficiently valid design to provide reliable information for clinical practice.


Assuntos
Antivirais/farmacologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus , Reposicionamento de Medicamentos/métodos , Pandemias , Pneumonia Viral , Terapias em Estudo/métodos , Betacoronavirus , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/organização & administração , Ensaios Clínicos como Assunto/normas , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Itália , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pesquisa , Projetos de Pesquisa
17.
Ther Drug Monit ; 42(4): 643-647, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32701254

RESUMO

BACKGROUND: There is extensive evidence to show that pre-exposure prophylaxis (PrEP) using tenofovir disoproxil fumarate (TDF)-based formulations dramatically reduces the risk of HIV acquisition among individuals without HIV infection. Here, the authors aim to compare tenofovir plasma predose concentrations in subjects taking PrEP daily versus on demand and using different TDF-based generic formulations. METHODS: Subjects providing informed signed consent for the measurement of tenofovir plasma levels were included in the study. Predose drug concentrations were stratified according to PrEP administration and the type of TDF-based formulation. The control group consisted of patients with HIV infection who were matched for renal function and were administered branded TDF that was not combined with boosted-antiretroviral drugs. RESULTS: The study consisted of 100 subjects (mean age, 39 ± 10 years; body weight, 77 ± 11 kg). A wide distribution in tenofovir predose concentrations was observed, with values ranging from 17 to 297 ng/mL (coefficient of variation 77%). No significant differences were noted in tenofovir predose concentrations between subjects who were administered PrEP daily (n = 75) or on demand (n = 25) [94 (35-255) versus 104 (37-287) ng/mL; P = 0.476]. Comparable tenofovir predose concentrations were found between patients with HIV infection (n = 220) who were administered branded TDF and those without HIV infection who were treated with 5 different generic TDF-based formulations with generics-to-branded ratios. These were always within the range of 80%-125% and were used to define bioequivalence. CONCLUSIONS: The marketed generic formulations of TDF delivered tenofovir plasma predose concentrations comparable with those delivered by branded formulations.

19.
Clin Infect Dis ; 71(16): 2276-2278, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32407467

RESUMO

Little is known about the clinical outcomes of patients with human immunodeficiency virus infected with SARS-CoV-2. We describe 47 patients referred to our hospital between 21 February and 16 April 2020 with proven/probable COVID-19, 45 (96%) of whom fully recovered and 2 who died.

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