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OBJECTIVES: To describe the management of haematological patients experiencing prolonged SARS-CoV-2 viral shedding, as the optimal management strategy for this condition remains undetermined. METHODS: We conducted a retrospective evaluation of our prospectively followed cohort of haematological patients treated with remdesivir for more than 10 days. Starting January 2023, upon COVID-19 diagnosis, the treatment strategy was based on symptoms and PCR cycle threshold (Ct) as follows: (i) when Ct was 25 or less or if the patient had symptoms, a course of remdesivir for at least 10 days, nirmatrelvir/ritonavir for 5 days (whenever possible) and convalescent plasma was administered; and (ii) when the patient was asymptomatic and had a PCR Ct of more than 25, when possible, a course of 5 days of nirmatrelvir/ritonavir was administered. The patient was considered to have achieved viral clearance and, thus, remdesivir was stopped, in either of these cases: (i) PCR negativity, or (ii) subgenomic RNA negativity. RESULTS: From January to November 2023, 18 patients benefited from a safe extended remdesivir administration, resulting in detection of SARS-CoV-2 viral clearance in a median time of 3.5 weeks (IQR 2.6-3.9) (min-max 1.6-8.0). No clinical or biological side effects were detected. No patient died or needed further treatment for their COVID-19 episode. CONCLUSIONS: The extended course of remdesivir, combined with other active therapies for COVID-19 infection, was well tolerated. Cure and virus negativity were obtained in all these high-risk patients.
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BACKGROUND: Drug-drug interactions between antiretroviral treatment (ART) and cytostatics may have a negative impact in the prognosis of people with HIV (PWH) and cancer. OBJECTIVE: The objective of this study is to evaluate the impact of the implementation of interdisciplinary management and the type of ART in PWH diagnosed with lymphoid neoplasms. METHODS: This is a multicentric, retrospective observational cohort study including PWH diagnosed with lymphoid neoplasm who started first-line chemotherapy between 2008 and 2020. Demographic, clinical and therapeutic variables were obtained from the electronic medical records and associated with 5-year progression-free survival (PFS) and overall survival (OS) using Cox proportional hazard models. RESULTS: A total of 118 individuals were included. Boosted ART was being used in 55 (46.6%) cases at the time of neoplasm diagnosis. The Infectious Diseases or the Pharmacy Department was consulted before starting chemotherapy in 79/118 (66.9%) cases. Interdisciplinary management resulted in fewer subjects taking boosted ART (17.7% versus 71.8%, Pâ<â0.001) and more subjects using unboosted integrase strand transfer inhibitor-based ART (74.7% versus 7.7%, Pâ<â0.001). The use of boosted ART with chemotherapy was associated with worse 5-year PFS (Pâ=â0.003) and 5-year OS (Pâ=â0.016). There was a trend towards better 5-year PFS and OS when interdisciplinary management was implemented, with significant differences for individuals receiving boosted ART at neoplasm diagnosis (Pâ=â0.0246 and Pâ=â0.0329, respectively). CONCLUSIONS: Our findings underscore the significant impact of the type of ART on the prognosis of PWH undergoing chemotherapy. Encouraging collaborative management between oncologists, pharmacists and HIV teams for these patients enhances PFS and OS rates.
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BACKGROUND: We aimed to describe a cohort of hematologic patients with COVID-19 treated with antivirals early. METHODS: Non-interventional chart review study. Comparison of baseline characteristics and outcomes in high-risk hematologic patients treated with remdesivir between December 2021 and April 2022 versus those treated with nirmatrelvir/ritonavir between May and August 2022. RESULTS: Eighty-three patients were analyzed. Forty-two received remdesivir, and 41 nirmatrelvir/ritonavir. Patients with remdesivir were younger, vaccinated with lower number of doses, and received prior corticosteroids less frequently and sotrovimab, hyperimmune plasma and corticosteroids more often. Viral shedding median (IQR) duration was 18 (13-23) and 11 (8-21) days in the remdesivir and nirmatrelvir/ritonavir groups, respectively (p = 0.004). Median (IQR) Ct values before treatment were similar in both groups. Within 5 days of treatment, median (IQR) Ct values were 26 (23-29) and 33 (30-37) in the remdesivir and nirmatrelvir/ritonavir groups, respectively (p < 0.0001). All patients were hospitalized for remdesivir administration and only four (9.8%) in the nirmatrelvir/ritonavir group. The overall outcomes in this cohort of COVID-19 patients with Omicron variant was good, as no patient needed oxygen or ICU admission. One patient in remdesivir group died from septic shock. No severe adverse event was recorded in both treatment groups. CONCLUSIONS: Patients with hematologic malignancies and non-severe COVID-19 who received nirmatrelvir/ritonavir experienced faster decrease in viral load and shorter viral shedding. Furthermore, besides the advantage of oral administration, nirmatrelvir/ritonavir administration reduced the need of hospital admission.
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COVID-19 , Neoplasias Hematológicas , Lactamas , Leucina , Nitrilos , Prolina , Humanos , Ritonavir/uso terapéutico , SARS-CoV-2 , Corticoesteroides , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19RESUMEN
INTRODUCTION: The objective was to characterize real-world outcomes of drug-drug interactions (DDIs) between antiretrovirals (ARVs) and other drugs, including over-the-counter medications (OTC), and treatment outcomes in clinical practice. METHODS: www.clinicalcasesDDIs.com is an open-access website for healthcare providers to consult and briefly describe real-world clinical cases on DDI with ARVs. We reviewed all the clinical cases reported to the website between March 2019 and May 2023. RESULTS: A total of 139 cases were reported, mostly involving ritonavir or cobicistat (boosters; 74 cases), unboosted integrase inhibitors (InSTI; 29 cases), and non-nucleoside reverse transcriptase inhibitors (NNRTI; 23 cases). Central nervous system drugs (29 cases) and cardiovascular drugs (19 cases) were the most frequently described co-medications. Notably, OTC medications were implicated in 27 cases, including mineral supplements (11 cases), herbals (8 cases), weight loss drugs (4 cases), anabolic steroids (3 cases), and recreational drugs (1 case). OTC acted as the perpetrator drug in 21 cases, leading to loss of ARV efficacy in 17 instances (mineral supplements in 10 cases, weight loss drugs in 4 cases, herbals in 3 cases). Additionally, toxicity was reported in 4 out of 6 cases where OTC was considered the victim drug of the DDI (anabolic steroids in 3 cases, MDMA in 1 case). CONCLUSIONS: Frequent unwanted outcomes resulting from DDIs between ARVs and OTC medications underscore the importance of integrating non-prescription drugs into medication reconciliation. The real-world data available through www.clinicalcasesDDIs.com serves as a valuable resource for assessing the clinical relevance of DDIs.
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AIM: To analyze trends in the prescription of COVID-19 treatments for hospitalized patients during the pandemic. METHODS: Multicenter, ecological, time-series study of aggregate data for all adult patients with COVID-19 treated in five acute-care hospitals in Barcelona, Spain, between March 2020 and May 2021. Trends in the monthly prevalence of drugs used against COVID-19 were analyzed by the Mantel-Haenszel test. RESULTS: The participating hospitals admitted 22,277 patients with COVID-19 during the study period, reporting an overall mortality of 10.8%. In the first months of the pandemic, lopinavir/ritonavir and hydroxychloroquine were the most frequently used antivirals, but these fell into disuse and were replaced by remdesivir in July 2020. By contrast, the trend in tocilizumab use varied, first peaking in April and May 2020, declining until January 2021, and showing a discrete upward trend thereafter. Regarding corticosteroid use, we observed a notable upward trend in the use of dexamethasone 6 mg per day from July 2020. Finally, there was a high prevalence of antibiotics use, especially azithromycin, in the first three months, but this decreased thereafter. CONCLUSIONS: Treatment for patients hospitalized with COVID-19 evolved with the changing scientific evidence during the pandemic. Initially, multiple drugs were empirically used that subsequently could not demonstrate clinical benefit. In future pandemics, stakeholders should strive to promote the early implementation of adaptive randomized clinical trials.
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BACKGROUND: Antimicrobial resistance killed 1.27 million people in 2019, so urgent actions are desperately needed. Antimicrobial stewardship programmes (ASPs) are essential to optimize antimicrobial use. The objective was to acknowledge the current role of clinical pharmacists engaged in ASP activities in Catalonia. METHODS: This was a cross-sectional survey shared through the Catalan Infection Control Programme (VINCat). The survey consisted of four sections and was sent by e-mail. RESULTS: A total of 69.0% of the centres answered. Pharmacists dedicated a median of 5.0 h per week (2.1 h/week/100 acute care beds), representing 0.15 full time equivalents. The ASP lacked information technology (IT) support, as only 16.3% of centres automatically calculated defined daily doses and days of therapy. Those with less than 15% of their time available for ASPs conducted fewer clinical activities, especially prospective audits and feedback. Those without official infectious diseases training also performed fewer clinical activities, but training was less determinant than IT support or time. Pharmacists performed interventions mostly through annotation in the medical records. CONCLUSIONS: Clinical pharmacists from Catalonia dedicated to ASPs present an important lack of time and IT support to perform clinical activities. Pharmacists should also improve their clinical skills and try to conduct clinical advice to prescribers, either by phone or face-to-face.
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INTRODUCTION: Real-life data about cefiderocol use to treat extensively drug-resistant bacteria are scarce. We aim to report our early experience in patients with difficult-to-treat infections and limited therapeutic options. METHODS: Patients treated with cefiderocol from March 2018 to April 2022 in a tertiary-care hospital in Spain were included. Demographic, clinical, and microbiological data were collected up to 90 days after the end of treatment or until death. Survival status was recorded at 30 and 90 days. RESULTS: Ten patients were included, seven of them critically ill. Ventilator-associated pneumonia (40%) and bacteremia (40%) were the main infections. Multidrug-resistant or extensively drug-resistant P. aeruginosa was the most frequently isolated pathogen (70%, of which six patients were infected with bacteria with difficult-to-treat resistance), followed by A. baumannii, E. coli, and A. xylosoxidans (10% each). Seven patients received combination therapy. Clinical and microbiological cures were achieved in 90% and 80% of patients, respectively. Two previously susceptible strains (20%) developed resistance to cefiderocol. Overall, 30-day and 90-day mortality rates were 10% and 50%, respectively, although two out of five patients died due to the infection. No serious adverse events were reported, except for one patient who developed thrombocytopenia. CONCLUSION: Cefiderocol seems to be an effective and safe rescue therapy for patients infected with difficult-to-treat pathogens, although there is a definite risk of the emergence of resistance.
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OBJECTIVES: To review the drug-drug interactions between tacrolimus and lopinavir/ritonavir in 23 patients who received solid organ transplant during the first wave of COVID-19 and to determine the efficacy as well as safety of prednisone monotherapy. METHODS: Observational study performed between March and June 2020 in solid organ transplant recipients admitted with an established diagnosis of SARS-CoV-2 infection who received lopinavir/ritonavir (≥2 doses). Once lopinavir/ritonavir therapy was initiated, calcineurin inhibitor treatment was temporarily switched to prednisone monotherapy (15-20 mg/d) to avoid drug-drug interactions and toxicity. After lopinavir/ritonavir treatment completion, immunosuppressive treatment was restarted with reduced doses of prednisone-tacrolimus (target minimum blood concentration -C0- approximately 5 ng/mL). Patients were observed for 3 months to confirm the absence of rejection. RESULTS: The median time from discontinuation of tacrolimus to initiation of lopinavir/ritonavir was 14 hours (interquartile range [IQR], 12-15) and from discontinuation of lopinavir/ritonavir to resumption of tacrolimus 58 hours (IQR, 47-81). The duration of lopinavir/ritonavir treatment was 7 days (IQR, 5-7). Nine of the 21 (42.8%) patients on tacrolimus treatment had C0 above the cutoff point after lopinavir/ritonavir initiation, despite having been substituted with prednisone before lopinavir/ritonavir initiation. Three patients had very high concentrations (>40 ng/mL) and developed toxicity. No episodes of acute rejection were diagnosed. DISCUSSION: We did not observe toxicity in patients for whom tacrolimus was discontinued 24 hours before starting lopinavir/ritonavir and reintroduced at half dose 48 to 72 hours after lopinavir/ritonavir discontinuation. Prednisone monotherapy during lopinavir/ritonavir therapy was safe with no episodes of acute rejection. Experience with lopinavir/ritonavir may be applicable to the use of nirmatrelvir/ritonavir, but larger multicentre studies are needed to confirm these findings.
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COVID-19 , Trasplante de Órganos , Humanos , Ritonavir/efectos adversos , Lopinavir/efectos adversos , SARS-CoV-2 , Inhibidores de Proteasas , Tacrolimus/efectos adversos , Prednisona/efectos adversos , Tratamiento Farmacológico de COVID-19 , Interacciones Farmacológicas , Receptores de TrasplantesRESUMEN
BACKGROUND: There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. METHODS: We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. RESULTS: A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission. CONCLUSIONS: Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.
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COVID-19 , Humanos , ARN Subgenómico , SARS-CoV-2 , Tiempo de Internación , Tratamiento Farmacológico de COVID-19 , Antivirales/uso terapéuticoRESUMEN
INTRODUCTION: Increased mortality has been reported in the Latin American population. The objective is to compare the clinical characteristics and outcome of Latin American and Spanish populations in a cohort of patients hospitalized with COVID-19 during the first year of the pandemic. METHODS: We retrospectively analysed all the Latin American patients (born in South or Central America) hospitalized in our centre from February 2020 to February 2021 and compared them with an age- and gender-matched group of Spanish subjects. Variables included were demographics, co-morbidities, clinical and analytical parameters at admission and treatment received. The primary outcomes were ICU admission and mortality at 60 days. A conditional regression analysis was performed to evaluate the independent baseline predictors of both outcomes. RESULTS: From the 3216 patients in the whole cohort, 216 pairs of case-controls (Latin American and Spanish patients, respectively) with same age and gender were analysed. COPD was more frequent in the Spanish group, while HIV was more prevalent in the Latin American group. Other co-morbidities showed no significant difference. Both groups presented with similar numbers of days from symptom onset, but the Latin American population had a higher respiratory rate (21 vs. 20 bpm, P = 0.041), CRP (9.13 vs. 6.22 mg/dl, P = 0.001), ferritin (571 vs. 383 ng/ml, P = 0.012) and procalcitonin (0.10 vs. 0.07 ng/ml, P = 0.020) at admission and lower cycle threshold of PCR (27 vs. 28.8, P = 0.045). While ICU admission and IVM were higher in the Latin American group (17.1% vs. 13% and 9.7% vs. 5.1%, respectively), this was not statistically significant. Latin American patients received remdesivir and anti-inflammatory therapies more often, and no difference in the 60-day mortality rate was found (3.2% for both groups). CONCLUSION: Latin American patients with COVID-19 have more severe disease than Spanish patients, requiring ICU admission, antiviral and anti-inflammatory therapies more frequently. However, the mortality rate was similar in both groups.
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Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein.
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Anticuerpos Monoclonales Humanizados , Proteína C-Reactiva , Tratamiento Farmacológico de COVID-19 , Dexametasona , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Proteína C-Reactiva/metabolismo , Dexametasona/uso terapéutico , Femenino , Humanos , Masculino , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. METHODS: Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. RESULTS: In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54-77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4-6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218-0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days). CONCLUSIONS: Patients with ≤3 days and 4-6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.
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Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/análogos & derivados , Anciano , Alanina/análogos & derivados , Antivirales/uso terapéutico , Humanos , Masculino , Respiración Artificial , Estudios Retrospectivos , SARS-CoV-2RESUMEN
PURPOSE: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. METHODS: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. RESULTS: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. CONCLUSIONS: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.
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Deprescripciones , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Infecciones por VIH/tratamiento farmacológico , Prescripción Inadecuada/prevención & control , Medicamentos bajo Prescripción/uso terapéutico , Interacciones Farmacológicas , Humanos , Esperanza de VidaRESUMEN
Objective: Comorbidities associated with the ageing of the HIV+ population may require chronic treatment. Our aim is to determine the degree of polypharmacy and the number of potential drug-drug interactions, as well as the relationship between both variables in a HIV-infected population over the age of 65. Methods: Descriptive transversal study targeting HIV+ patients aged ≥65, attended in a Spanish hospital in 2014. The prevalence of polypharmacy (≥5 drugs) and potential drug-drug interactions were assessed, and also risk factors associated with such. Results: 265 subjects aged ≥65 years were identified, 197 of whom were on antiretroviral treatment and had data about their electronic prescription. 93% were polymedicated. The patients whose antiretroviral treatment included a non-nucleoside reverse transcriptase inhibitor (NNRTI) demonstrated a fourfold probability of being polymedicated. 65% of the patients showed at least one potential drug-drug interaction and 6.6% a severe potential drug-drug interaction. The risk of interaction was significantly associated with the number of prescribed drugs (incidence rate ratio per prescribed drug, CI 95%: 1.18 (1.14;1.22; p<0.0001) and with the use of protease inhibitors (PI) (incidence rate ratio, CI 95%: 1.65 (1.28;2.11; p=0.0001)). Conclusion: Polypharmacy has a high prevalence and is more common in patients treated with NNRTI. The number of potential drug-drug interactions increase with the number of prescribed drugs and is higher in those patients on PI (AU)
Objetivo: Las comorbilidades asociadas al envejecimiento de la población VIH+ pueden requerir tratamientos crónicos. Nuestro objetivo es determinar el grado de polifarmacia y el número de interacciones farmacológicas potenciales, así como la relación entre ambas variables en un grupo de población VIH+ mayor de 65 años. Métodos: Estudio descriptivo transversal en pacientes VIH+≥65 años atendidos en un hospital español en 2014. Se evaluó la prevalencia de polimedicación (≥5 fármacos) y se analizaron las interacciones farmacológicas potenciales y los factores de riesgo asociados a ellas. Resultados: Se identificaron 265 sujetos ≥65 años, de los cuales 197 recibían tratamiento antirretroviral y tenían datos en la receta electrónica. El 93% estaban polimedicados. Los pacientes cuyo tratamiento antirretroviral incluía un inhibidor de la transcriptasa inversa no nucleósido (ITINN) presentaban una probabilidad cuatro veces mayor de estar polimedicados. El 65% de los pacientes presentó al menos una interacción potencial y el 6,6% una interacción potencial grave. El riesgo de interacciones se asoció significativamente al número de fármacos prescritos (razón de tasas de incidencia por fármaco prescrito con IC 95%: 1,18 (1,14;1,22; p<0.0001)) y a los inhibidores de la proteasa (IP) (razón de tasas de incidencia IC 95%: 1,65 (1,28;2,11; p=0,0001)). Conclusión: La prevalencia de la polifarmacia es muy alta y más frecuente en los pacientes tratados con ITINN. El número de interacciones farmacológicas potenciales aumenta con el número de fármacos prescritos y es mayor en los pacientes tratados con IP (AU)
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Humanos , Anciano , Polifarmacia , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Infecciones por VIH/complicaciones , Enfermedad Crónica/epidemiología , Interacciones Farmacológicas , Antirretrovirales/uso terapéutico , EnvejecimientoRESUMEN
OBJECTIVE: Comorbidities associated with the ageing of the HIV+ population may require chronic treatment. Our aim is to determine the degree of polypharmacy and the number of potential drug-drug interactions, as well as the relationship between both variables in a HIV-infected population over the age of 65. METHODS: Descriptive transversal study targeting HIV+ patients aged ≥65, attended in a Spanish hospital in 2014. The prevalence of polypharmacy (≥5 drugs) and potential drug-drug interactions were assessed, and also risk factors associated with such. RESULTS: 265 subjects aged ≥65 years were identified, 197 of whom were on antiretroviral treatment and had data about their electronic prescription. 93% were polymedicated. The patients whose antiretroviral treatment included a non-nucleoside reverse transcriptase inhibitor (NNRTI) demonstrated a fourfold probability of being polymedicated. 65% of the patients showed at least one potential drug-drug interaction and 6.6% a severe potential drug-drug interaction. The risk of interaction was significantly associated with the number of prescribed drugs (incidence rate ratio per prescribed drug, CI 95%: 1.18 (1.14;1.22; p<0.0001) and with the use of protease inhibitors (PI) (incidence rate ratio, CI 95%: 1.65 (1.28;2.11; p=0.0001)). CONCLUSION: Polypharmacy has a high prevalence and is more common in patients treated with NNRTI. The number of potential drug-drug interactions increase with the number of prescribed drugs and is higher in those patients on PI.
Objetivo: Las comorbilidades asociadas al envejecimiento de la población VIH+ pueden requerir tratamientos crónicos. Nuestro objetivo es determinar el grado de polifarmacia y el número de interacciones farmacológicas potenciales, así como la relación entre ambas variables en un grupo de población VIH+ mayor de 65 años.Métodos: Estudio descriptivo transversal en pacientes VIH+≥65 años atendidos en un hospital español en 2014. Se evaluó la prevalencia de polimedicación (≥5 fármacos) y se analizaron las interacciones farmacológicas potenciales y los factores de riesgo asociados a ellas.Resultados: Se identificaron 265 sujetos ≥65 años, de los cuales 197 recibían tratamiento antirretroviral y tenían datos en la receta electrónica. El 93% estaban polimedicados. Los pacientes cuyo tratamiento antirretroviral incluía un inhibidor de la transcriptasa inversa no nucleósido (ITINN) presentaban una probabilidad cuatro veces mayor de estar polimedicados. El 65% de los pacientes presentó al menos una interacción potencial y el 6,6% una interacción potencial grave. El riesgo de interacciones se asoció significativamente al número de fármacos prescritos (razón de tasas de incidencia por fármaco prescrito con IC 95%: 1,18 (1,14;1,22; p<0.0001)) y a los inhibidores de la proteasa (IP) (razón de tasas de incidencia IC 95%: 1,65 (1,28;2,11; p=0,0001)).Conclusión: La prevalencia de la polifarmacia es muy alta y más frecuente en los pacientes tratados con ITINN. El número de interacciones farmacológicas potenciales aumenta con el número de fármacos prescritos y es mayor en los pacientes tratados con IP.
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Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Polifarmacia , Anciano , Anciano de 80 o más Años , Estudios Transversales , Combinación de Medicamentos , Interacciones Farmacológicas , Utilización de Medicamentos , Femenino , Infecciones por VIH/complicaciones , Humanos , MasculinoAsunto(s)
Fármacos Anti-VIH/uso terapéutico , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/etiología , Cobicistat/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Voriconazol/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Antifúngicos/administración & dosificación , Terapia Antirretroviral Altamente Activa , Aspergilosis/diagnóstico , Cobicistat/administración & dosificación , Sinergismo Farmacológico , Infecciones por VIH/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Voriconazol/administración & dosificaciónRESUMEN
INTRODUCTION: Drugs like statins may induce rhabdomyolysis. Simvastatin and lovastatin have a high hepatic metabolism and their potential toxicity could be increased by interactions with other drugs that reduce their metabolism. PATIENTS AND METHODS: A case-report is presented of an HIV-infected patient treated with antiretroviral drugs who developed a rhabdomyolysis-induced renal failure and liver toxicity when simvastatin was substituted for atorvastatin. A literature review is also presented. RESULTS: The patient required hospital admission and showed a favorable response after hydration and urine alkalinization. There were 4 additional cases published of which there was one death. CONCLUSIONS: Drug-drug interactions can increase the risk of statin induced rhabdomyolysis. In order to evaluate them properly, physicians at all levels of clinical care should be aware of all drugs prescribed to their patients and the contraindicated combinations.
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Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Inhibidores del Citocromo P-450 CYP3A/efectos adversos , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Rabdomiólisis/inducido químicamente , Ritonavir/efectos adversos , Simvastatina/efectos adversos , Terapia Antirretroviral Altamente Activa , Atorvastatina/economía , Atorvastatina/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Comorbilidad , Contraindicaciones , Análisis Costo-Beneficio , Inhibidores del Citocromo P-450 CYP3A/farmacología , Sustitución de Medicamentos/efectos adversos , Sinergismo Farmacológico , Dislipidemias/inducido químicamente , Dislipidemias/tratamiento farmacológico , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/farmacología , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/economía , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Necrosis Tubular Aguda/inducido químicamente , Persona de Mediana Edad , Rabdomiólisis/prevención & control , Ritonavir/farmacología , Ritonavir/uso terapéutico , Simvastatina/economía , Simvastatina/farmacología , Simvastatina/uso terapéuticoRESUMEN
INTRODUCTION: In recent years, the number of oral antitumoral agents has considerably increased. Oral administration increases the risk of interactions, because most oral anticancer drugs are taken on a daily basis. Interactions can increase exposure to antitumoral agents or cause treatment failure. Many antitumoral drugs undergo enzymatic metabolism by cytochrome P450. As some act as inducers or inhibitors of one or more isoenzymes, they can lead to decreases or increases in plasma concentrations of concomitant drugs. Hence, cytostatic drugs can act not only as victims but also as perpetrators. P-glycoprotein, an efflux transporter, can also be involved in pharmacokinetic interactions. AREAS COVERED: A Medline search was performed to summarize the available evidence of the most clinically relevant interactions between oral chemotherapy agents and other drugs. The search covered the period from 1966 until August 2012 for each antitumoral drug using the medical subject headings 'Drug Interactions' OR 'Pharmacokinetics'. While the present review is not exhaustive, it aims to increase clinicians' awareness of potential drug-drug interactions. EXPERT OPINION: As cancer patients are often polymedicated and treated by different physicians, the risk of drug interactions between antitumoral agents and other medications is high. More clinical interaction studies are encouraged to ensure appropriate antineoplastic pharmacokinetics in clinical practice.
Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Administración Oral , Sistema Enzimático del Citocromo P-450/metabolismo , Interacciones Farmacológicas , HumanosRESUMEN
As of November 2010, a total of 22 antiretroviral agents are marketed in Spain. These agents are divided into 6 classes according to their mechanism of action: 1) nucleos(t)ide reverse transcriptase inhibitors (NRTI) (abacavir, didanosine, emtricitabine, stavudine, lamivudine, zidovudine, and tenofovir), 2) non-nucleoside reverse transcriptase inhibitors (NNRTI) (efavirenz, etravirine, and nevirapine), 3) protease inhibitors (PI) (atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir), 4) entry inhibitors (enfuvirtide), 5) coreceptor CCR5 inhibitors (maraviroc), and 6) integrase inhibitors (raltegravir). All 22 agents are indicated for the treatment of HIV-1 infection in combination with other antiretroviral drugs. Most have also proven to be active against HIV-2 (except the NNRTIs, enfuvirtide, and maraviroc) and some are active against hepatitis B virus (lamivudine, emtricitabine, and tenofovir). The present article reviews the main characteristics of the different antiretroviral agents and classes, namely, commercial presentations, paediatric and adult dosages, dose adjustments in renal and hepatic insufficiency, pharmacokinetics and interactions, mechanism of action, treatment indications, resistance, adverse effects, and safety during pregnancy and breastfeeding. Some of the characteristics of antiretrovirals are class-specific and common to other agents of the same class, and others are individual and different from those of other drugs in the same class. Knowledge of these characteristics enables us to prepare efficacious therapeutic regimens according to the specific requirements of the patient (tolerability, simplicity, adaptability to lifestyle) and clinical setting (naive, simplification, rescue, resistance).