ABSTRACT
During the pandemic caused by the SARS-CoV-2 virus, pharmacy services have had to adapt their service portfolio, and yet ensure efficient, equitable and quality pharmaceutical care. Given the limited scientific evidence available, most drugs have been used off-label or in the context of clinical trials, which should be the preferred option in order to create new evidence. Among kind different situations we have faced are the increase in workload, the expansion of coverage to new wards and ICUs and shortages, which have caused the use of alternative drugs and even other routes of administration. Given that covid-19 affects elderly population with greater severity and many of them are polymedicated, great effort have been focused on monitoring interactions, both pharmacokinetic and pharmacodynamic (specially prolongation of the QT interval), monitoring correct concentrations of electrolytes, nutritional support, adaptation of chemotherapy treatment protocols and anticoagulant management, among others. The use of personal protective equipment added difficulty for nursing work and some measures had been taken to minimize the number of entries into the rooms. Eventually, team's split to guarantee care, the challenge of teleworking, remote validation, telemedicine and telepharmacy for communication between professionals and patients, as well as training in this pandemic situation have been a challenge for our profession. These difficulties have risen up new learning opportunities we hope will be useful to us in the event we have to face similar situations in the future.
La pandemia ocasionada por el virus SARS-CoV-2 ha hecho que los servicios de farmacia hayan tenido que adaptar su cartera de servicios, y sin embargo asegurar una atención farmacéutica eficiente, equitativa y de calidad. Dada la escasa evidencia científica disponible, la mayoría de los medicamentos se han empleado fuera de indicación o en el contexto de ensayos clínicos, que debería ser la opción preferente para generar nueva evidencia. Entre las diversas situaciones que se han tenido que afrontar se encuentran el incremento de trabajo asistencial, la ampliación de la cobertura a nuevas salas y unidades de cuidados intensivos y los desabastecimientos, que han ocasionado el uso de fármacos alternativos e incluso otras vías de administración. Dado que la COVID-19 afecta con mayor gravedad a población de edad avanzada, muchos de ellos polimedicados, se ha tenido que dedicar un gran esfuerzo al seguimiento de interacciones, tanto farmacocinéticas como farmacodinámicas (en especial, prolongación del intervalo QT), monitorización de concentraciones correctas de electrolitos, soporte nutricional, adaptación de pautas de quimioterapia y manejo e los anticoagulantes, entre otros. La dificultad adicional para enfermería de la administración de medicamentos con equipos de protección individual ha supuesto la adaptación de formas de administración para minimizar el número de entradas en las habitaciones. Por último, el fraccionamiento del equipo para garantizar la atención, el reto del teletrabajo, la validación en remoto, la telemedicina y la telefarmacia para la comunicación entre profesionales y pacientes, así como la formación en esta situación de pandemia, han supuesto un reto para nuestra profesión. Estos desafíos han creado nuevas oportunidades de aprendizaje que esperemos nos puedan ser de utilidad en el caso de que tuviéramos que afrontar situaciones semejantes en el futuro.
Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Inpatients , Pandemics , Pharmacy Service, Hospital/organization & administration , Pneumonia, Viral/drug therapy , Aftercare , COVID-19 , Communication , Comorbidity , Cross Infection/prevention & control , Drug Administration Routes , Drug Interactions , Drug Monitoring , Forecasting , Health Personnel/education , Health Services Needs and Demand , Humans , Infection Control/methods , Infection Control/organization & administration , Off-Label Use , Patient Education as Topic , Patient Safety , Personal Protective Equipment , Pharmacovigilance , Professional-Patient Relations , SARS-CoV-2 , Telemedicine , COVID-19 Drug TreatmentABSTRACT
La pandemia ocasionada por el virus SARS-CoV-2 ha hecho que los ser-vicios de farmacia hayan tenido que adaptar su cartera de servicios, y sin embargo asegurar una atención farmacéutica eficiente, equitativa y de calidad. Dada la escasa evidencia científica disponible, la mayoría de los medicamentos se han empleado fuera de indicación o en el contexto de ensayos clínicos, que debería ser la opción preferente para generar nueva evidencia. Entre las diversas situaciones que se han tenido que afrontar se encuentran el incremento de trabajo asistencial, la ampliación de la cobertura a nuevas salas y unidades de cuidados intensivos y los desabastecimientos, que han ocasionado el uso de fármacos alternativos e incluso otras vías de administración. Dado que la COVID-19 afecta con mayor gravedad a población de edad avanzada, muchos de ellos polimedicados, se ha tenido que dedicar un gran esfuerzo al seguimiento de interacciones, tanto farmacocinéticas como farmacodinámicas (en especial, prolongación del intervalo QT), monitorización de concentraciones correctas de electrolitos, soporte nutricional, adaptación de pautas de quimioterapia y manejo de los anticoagulantes, entre otros. La dificultad adicional para enfermería de la administración de medicamentos con equipos de protección individual ha supuesto la adaptación de formas de administración para minimizar el número de entradas en las habitaciones. Por último, el fraccionamiento del equipo para garantizar la atención, el reto del teletrabajo, la validación en remoto, la telemedicina y la telefarmacia para la comunicación entre profesionales y pacientes, así como la formación en esta situación de pandemia, han supuesto un reto para nuestra profesión. Estos desafíos han creado nuevas oportunidades de aprendizaje que esperemos nos puedan ser de utilidad en el caso de que tuviéramos que afrontar situaciones semejantes en el futuro
During the pandemic caused by the SARS-CoV-2 virus, pharmacy ser-vices have had to adapt their service portfolio, and yet ensure efficient, equitable and quality pharmaceutical care. Given the limited scientific evidence available, most drugs have been used off-label or in the context of clinical trials, which should be the preferred option in order to create new evidence. Among kind different situations we have faced are the increase in workload, the expansion of coverage to new wards and ICUs and shortages, which have caused the use of alternative drugs and even other routes of administration. Given that covid-19 affects elderly population with greater severity and many of them are polymedicated, great effort have been focused on monitoring interactions, both pharmacokinetic and pharmacodynamic (specially prolongation of the QT interval), monito-ring correct concentrations of electrolytes, nutritional support, adaptation of chemotherapy treatment protocols and anticoagulant management, among others. The use of personal protective equipment added difficulty for nursing work and some measures had been taken to minimize the number of entries into the rooms. Eventually, team's split to guarantee care, the challenge of teleworking, remote validation, telemedicine and telepharmacy for com-munication between professionals and patients, as well as training in this pandemic situation have been a challenge for our profession. These difficulties have risen up new learning opportunities we hope will be useful to us in the event we have to face similar situations in the future
Subject(s)
Humans , Betacoronavirus , Coronavirus Infections/drug therapy , Inpatients , Pandemics , Pneumonia, Viral/drug therapy , Pharmacy Service, Hospital/organization & administration , Aftercare , Communication , Comorbidity , Cross Infection/prevention & control , Drug Administration Routes , Drug Interactions , Forecasting , Health Personnel/education , Infection Control/methods , PharmacovigilanceABSTRACT
AIM: The incidence of adverse drug events (ADEs) in surgical and non-surgical patients may differ. This individual patient data meta-analysis (IPDMA) identifies patient characteristics and types of medication most associated with patients experiencing ADEs and suggests target areas for reducing harm and implementing focused interventions. METHODS: Authors of eligible studies on preventable ADEs (pADEs) were approached for collaboration. For assessment of differences among (non-)surgical patients and identification of associated factors descriptive statistics, Pearson chi-square, Poisson and logistic regression analyses were performed. For identification of high risk drugs (HRDs), a model was developed based on frequency, severity and preventability of medication related to ADEs. RESULTS: Included were 5367 patients from four studies. Patients aged ≥ 77 years experienced more ADEs and pADEs compared with patients aged ≤ 52 years (odds ratios (OR) 2.12 (95% CI 1.70, 2.65) and 2.55 (95% CI 1.70, 3.84), respectively, both P < 0.05). Polypharmacy on admission also increased the risk of ADEs (OR 1.21 (95% CI 1.03, 1.44), P < 0.05) and pADEs (OR 1.85 (95% CI 1.34, 2.56), P < 0.05). pADEs were associated with more severe harm than non-preventable ADEs (54% vs. 32%, P < 0.05). The top five HRDs were antibiotics, sedatives, anticoagulants, diuretics and antihypertensives. Events associated with HRDs included diarrhoea or constipation, abnormal liver function test and central nervous system events. Most pADEs resulted from prescribing errors (90%). CONCLUSION: Elderly patients with polypharmacy on admission and receiving antibiotics, sedatives, anticoagulants, diuretics or antihypertensives were more prone to experiencing ADEs. Efficiency in prevention of ADEs may be improved by targeted vigilance systems for alertness of physicians and pharmacists.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Elective Surgical Procedures , Polypharmacy , Age Factors , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Elective Surgical Procedures/adverse effects , Elective Surgical Procedures/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Logistic ModelsABSTRACT
BACKGROUND: To study endometrial receptivity in terms of osteopontin (OPN) and αvß3 integrin expression and co-expression in infertile women with early stages of endometriosis. METHODS: We investigated the immunohistochemical expression and co-expression of OPN and αvß3 integrin in the endometrium of 20 infertile patients with Stage I or II endometriosis as the only detectable cause of infertility, 20 infertile patients with unexplained infertility and 20 fertile women undergoing tubal sterilization. Two endometrial biopsies were performed during a single menstrual cycle (postovulatory Day +7 to +8 and 4 days later) in each subject. RESULTS: No statistically significant differences regarding OPN and αvß3 integrin expression were found between infertile patients with endometriosis and the two control groups. There was no significant correlation between OPN and αvß3 integrin staining intensity in the mid-luteal phase biopsies in any of the groups studied. CONCLUSIONS: Endometrial OPN and αvß3 integrin expression or co-expression is not impaired during the window of implantation in patients with Stage I-II endometriosis. Further studies are needed to determine whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with these markers of implantation.
Subject(s)
Embryo Implantation , Endometriosis/metabolism , Endometrium/metabolism , Infertility, Female/metabolism , Integrin alphaVbeta3/metabolism , Osteopontin/metabolism , Endometriosis/complications , Female , Humans , Infertility, Female/complicationsABSTRACT
Raltegravir es el primer inhibidor de la integrasa aprobado para tratar la infección por el virus de la inmunodeficiencia humana de tipo 1 en pacientes adultos con evidencia de replicación viral a pesar de estar recibiendo terapia antirretroviral. Se administra por vía oral a una dosis de 400 mg cada 12 h, con o sin alimentos. Se elimina mayoritariamente por glucuronidación mediante la UGT1A1 y no tiene efecto inhibidor ni inductor en las principales isoenzimas del citocromo P450 hepático, por lo que presenta escaso riesgo de interacciones farmacológicas con la mayoría de los fármacos de uso habitual, como metadona, antifúngicos azólicos o fármacos para tratar la disfunción eréctil. Los estudios de interacción con otros antirretrovirales demuestran que raltegravir puede emplearse en combinación con tenofovir, efavirenz, atazanavir, ritonavir o tipranavir/ritonavir sin que se requiera ajuste de dosis. En combinación con rifampicina se recomienda valorar el aumento de dosis de raltegravir a 800 mg/12 h. Los inhibidores de la bomba de protones aumentan las concentraciones plasmáticas de raltegravir (exposición o área bajo la curva 3 veces mayor), por lo que se recomienda evitar, en lo posible, su uso combinado. Raltegravir es un fármaco bien tolerado y no requiere ajuste de dosis en pacientes con insuficiencia renal grave ni en pacientes con insuficiencia hepática leve a moderada. No hay estudios en pacientes con insuficiencia hepática grave(AU)
Raltegravir is the first integrase inhibitor approved for the treatment of HIV-1 infection in pretreated adults with evidence of viral replication despite receiving antiretroviral therapy. Raltegravir is administered orally at a dose of 400 mg every 12 hours, with or without food. This drug is mainly eliminated through UGT1A1-mediated glucuronidation and is not an inhibitor or inducer of the main liver cytochrome P450 isoenzymes; consequently there is virtually no risk of pharmacological interactions with most commonly used drugs such as methadone, azole antifungal agents or drugs used to treat erectile dysfunction. Studies of interaction with other antiretroviral agents show that raltegravir can be used in combination with tenofovir, efavirenz, atazanavir, ritonavir or tipranavir/ritonavir without the need for dose adjustments. When combined with rifampicin, the dose of raltegravir should be increased to 800 mg/12 h. Proton pump inhibitors increase plasma levels of raltegravir (a 3- fold increase in exposure or AUC levels), and consequently their combined use should be avoided as far as posible. Raltegravir is well tolerated and does not require dose adjustments in patients with severe renal impairment or mild-to-moderate liver impairment. There are no studies in patients with severe liver impairment(AU)
Subject(s)
Humans , HIV Integrase Inhibitors/pharmacokinetics , HIV Infections/drug therapy , Anti-Retroviral Agents/pharmacokinetics , Drug Interactions , Cytochrome P-450 Enzyme SystemABSTRACT
Raltegravir es el primer inhibidor de la integrasa aprobado para tratar la infección por el virus de la inmunodeficiencia humana de tipo 1 en pacientes adultos con evidencia de replicación viral a pesar de estar recibiendo terapia antirretroviral. Se administra por vía oral a una dosis de 400 mg cada 12 h, con o sin alimentos. Se elimina mayoritariamente por glucuronidación mediante la UGT1A1 y no tiene efecto inhibidor ni inductor en las principales isoenzimas del citocromo P450 hepático, por lo que presenta escaso riesgo de interacciones farmacológicas con la mayoría de los fármacos de uso habitual, como metadona, antifúngicos azólicos o fármacos para tratar la disfunción eréctil. Los estudios de interacción con otros antirretrovirales demuestran que raltegravir puede emplearse en combinación con tenofovir, efavirenz, atazanavir, ritonavir o tipranavir/ritonavir sin que se requiera ajuste de dosis. En combinación con rifampicina se recomienda valorar el aumento de dosis de raltegravir a 800 mg/12 h. Los inhibidores de la bomba de protones aumentan las concentraciones plasmáticas de raltegravir (exposición o área bajo la curva 3 veces mayor), por lo que se recomienda evitar, en lo posible, su uso combinado. Raltegravir es un fármaco bien tolerado y no requiere ajuste de dosis en pacientes con insuficiencia renal grave ni en pacientes con insuficiencia hepática leve a moderada. No hay estudios en pacientes con insuficiencia hepática grave
Raltegravir is the first integrase inhibitor approved for the treatment of HIV-1 infection in pretreated adults with evidence of viral replication despite receiving antiretroviral therapy. Raltegravir is administered orally at a dose of 400 mg every 12 hours, with or without food. This drug is mainly eliminated through UGT1A1-mediated glucuronidation and is not an inhibitor or inducer of the main liver cytochrome P450 isoenzymes; consequently there is virtually no risk of pharmacological interactions with most commonly used drugs such as methadone, azole antifungal agents or drugs used to treat erectile dysfunction. Studies of interaction with other antiretroviral agents show that raltegravir can be used in combination with tenofovir, efavirenz, atazanavir, ritonavir or tipranavir/ritonavir without the need for dose adjustments. When combined with rifampicin, the dose of raltegravir should be increased to 800 mg/12 h. Proton pump inhibitors increase plasma levels of raltegravir (a 3- fold increase in exposure or AUC levels), and consequently their combined use should be avoided as far as posible. Raltegravir is well tolerated and does not require dose adjustments in patients with severe renal impairment or mild-to-moderate liver impairment. There are no studies in patients with severe liver impairment (AU)
Subject(s)
Humans , HIV Integrase Inhibitors/pharmacokinetics , HIV , HIV Infections/drug therapy , Anti-HIV Agents/pharmacokinetics , Drug Interactions , Anti-Retroviral Agents/pharmacokinetics , Proton Pumps/antagonists & inhibitorsABSTRACT
Raltegravir is the first integrase inhibitor approved for the treatment of HIV-1 infection in pretreated adults with evidence of viral replication despite receiving antiretroviral therapy. Raltegravir is administered orally at a dose of 400 mg every 12 hours, with or without food. This drug is mainly eliminated through UGT1A1-mediated glucuronidation and is not an inhibitor or inducer of the main liver cytochrome P450 isoenzymes; consequently there is virtually no risk of pharmacological interactions with most commonly used drugs such as methadone, azole antifungal agents or drugs used to treat erectile dysfunction. Studies of interaction with other antiretroviral agents show that raltegravir can be used in combination with tenofovir, efavirenz, atazanavir, ritonavir or tipranavir/ritonavir without the need for dose adjustments. When combined with rifampicin, the dose of raltegravir should be increased to 800 mg/12 h. Proton pump inhibitors increase plasma levels of raltegravir (a 3-fold increase in exposure or AUC levels), and consequently their combined use should be avoided as far as posible. Raltegravir is well tolerated and does not require dose adjustments in patients with severe renal impairment or mild-to-moderate liver impairment. There are no studies in patients with severe liver impairment.
Subject(s)
HIV Infections/drug therapy , HIV Integrase Inhibitors/pharmacology , Pyrrolidinones/pharmacology , Adult , Aged , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Child , Clinical Trials as Topic , Cytochrome P-450 Enzyme System/metabolism , Drug Interactions , Fasting , Female , Food-Drug Interactions , Glucuronosyltransferase/genetics , Glucuronosyltransferase/metabolism , HIV Integrase Inhibitors/administration & dosage , HIV Integrase Inhibitors/adverse effects , HIV Integrase Inhibitors/pharmacokinetics , HIV Integrase Inhibitors/therapeutic use , Humans , Inactivation, Metabolic , Intestinal Absorption , Male , Microsomes, Liver/enzymology , Polypharmacy , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pyrrolidinones/administration & dosage , Pyrrolidinones/adverse effects , Pyrrolidinones/pharmacokinetics , Pyrrolidinones/therapeutic use , Raltegravir PotassiumABSTRACT
En este artículo se revisan las principales interacciones de los antirretrovirales con fármacos de otras familias que pueden comprometer la eficacia virológica. Tanto los inhibidores de la proteasa como los no nucleósidos presentan un elevado metabolismo hepático, por lo que los fármacos que actúan como inductores enzimáticos pueden reducir sus concentraciones plasmáticas. Los principales inductores son los antiepilépticos carbamacepina, fenitoína, fenobarbital; los antituberculosos rifampicina y rifabutina; los propios antirretrovirales nevirapina y efavirenz y algunos productos naturales, como la hierba de San Juan (Hypericum). Otro tipo de interacciones afecta a la absorción, y destaca la que se produce entre atazanavir y antiácidos, antihistamínicos H2 e inhibidores de la bomba de protones. La mayoría de estas interacciones se puede prevenir evitando la asociación o ajustando las dosis adecuadamente. Dada la elevada variabilidad interindividual, en algunos casos puede ser útil el seguimiento de las concentraciones plasmáticas
The present article reviews the main interactions of antiretroviral drugs with those from other families that can compromise virological efficacy. Both protease and non-nucleoside inhibitors are mainly metabolized in the liver and consequently drugs that act as enzyme inducers can reduce plasma levels of these antiretroviral agents. The main inducers are the antiepileptic drugs carbamazepine, phenytoin, and phenobarbital, the tuberculostatic agents, rifampicin and rifabutin, the antiretroviral agents nevirapine and efavirenz, and some natural products such as St. John's wort (Hypericum). Another type of interaction affects drug absorption. Notable among these is that produced between atazanavir and antacids H2-antihistamines and protein pump inhibitors. Most of these interactions can be prevented by avoiding the association or by adequately adjusting the dosage. Given that there is wide interindividual variability, monitoring plasma levels can be useful in some individuals