Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study.

PURPOSE: Although the prevalence of drug-drug interactions (DDIs) in elderly outpatients is high, many potential DDIs do not have any actual clinical effect, and data on the occurrence of DDI-related adverse drug reactions (ADRs) in elderly outpatients are scarce. This study aimed to determine the incidence and characteristics of DDI-related ADRs among elderly outpatients as well as the factors associated with these reactions. METHODS: A prospective cohort study was conducted between 1 November 2010 and 31 November 2011 in the primary public health system of the Ourinhos micro-region, Brazil. Patients aged ≥60 years with at least one potential DDI were eligible for inclusion. Causality, severity, and preventability of the DDI-related ADRs were assessed independently by four clinicians using validated methods; data were analysed using descriptive analysis and multiple logistic regression. RESULTS: A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6 % (n = 30). Warfarin was the most commonly involved drug (37 % cases), followed by acetylsalicylic acid (17 %), digoxin (17 %), and spironolactone (17 %). Gastrointestinal bleeding occurred in 37 % of the DDI-related ADR cases, followed by hyperkalemia (17 %) and myopathy (13 %). The multiple logistic regression showed that age ≥80 years [odds ratio (OR) 4.4; 95 % confidence interval (CI) 3.0-6.1, p < 0.01], a Charlson comorbidity index ≥4 (OR 1.3; 95 % CI 1.1-1.8, p < 0.01), consumption of five or more drugs (OR 2.7; 95 % CI 1.9-3.1, p < 0.01), and the use of warfarin (OR 1.7; 95 % CI1.1-1.9, p < 0.01) were associated with the occurrence of DDI-related ADRs. With regard to severity, approximately 37 % of the DDI-related ADRs detected in our cohort necessitated hospital admission. All DDI-related ADRs could have been avoided (87 % were ameliorable and 13 % were preventable). The incidence of ADRs not related to DDIs was 10 % (n = 44). CONCLUSIONS: The incidence of DDI-related ADRs in elderly outpatients is high; most events presented important clinical consequences and were preventable or ameliorable.

Prevalence and predictors of potential drug-drug interactions in the elderly: a cross-sectional study in the brazilian primary public health system.

PURPOSE: The primary objective of this study was to investigate the prevalence of clinically important potential drug-drug interactions (DDIs) in elderly patients attending the public primary health care system in Brazil. The secondary objective was to investigate possible predictors of potential DDIs. METHODS: A cross-sectional study was carried out in 5 Brazilian cities located in the Ourinhos Micro-region, Sao Paulo State, between November 2010 and April 2011. The selected sample was divided according to the presence (exposed) or absence (unexposed) of one or more potential DDIs (defined as the presence of a minimum 5-day overlap in supply of an interacting drug pair). Data were collected from medical prescriptions and patients' medical records. Potential DDIs (rated major or moderate) were identified using 4 DDI-checker programs. Logistic regression analysis was used to study potential DDI predictors. RESULTS: The prevalence of clinically important potential DDIs found during the study period was 47.4%. Female sex (OR = 2.49 [95% CI 2.29-2.75]), diagnosis of ≥ 3 diseases (OR = 6.43 [95% CI 3.25-12.44]), and diagnosis of hypertension (OR = 1.68 [95% CI 1.23-2.41]) were associated with potential DDIs. The adjusted OR increased from 0.90 [95% CI 0.82-1.03] in patients aged 60 - 64 years to 4.03 [95% CI 3.79 - 4.28] in those aged 75 years or older. Drug therapy regimens involving ≥ 2 prescribers (OR = 1.39 [95% CI 1.17-1.67]), ≥ 3 drugs (OR = 3.21 [95% CI 2.78-3.59]), ≥ 2 ATC codes (OR = 1.19 [95% CI 1.12-1.29]), ≥ 2 drugs acting on cytochrome P450 (OR = 2.24 [95% CI 2.07-2.46]), and ATC codes B (OR = 1.89 [95% CI 1.05-2.08]) and C (OR = 4.01 [95% CI 3.55-4.57]) were associated with potential DDIs. CONCLUSION: Special care should be taken with the prescription and therapeutic follow-up of patients who present characteristics identified as predictors. Knowledge of potential DDI predictors could aid in developing preventive practices and policies that allow public health services to better manage this situation.

Incidence and predictors of adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study.

PURPOSE: The primary objective of this study was to investigate the incidence of drug-drug interactions (DDIs) related to adverse drug reactions (ADRs) in elderly outpatients who attended public primary healthcare units in a southeastern region of Brazil. The secondary objective was to investigate the possible predictors of DDI-related ADRs. METHODS: A prospective cohort study was conducted between November 1, 2010, and November 31, 2011, in the primary public healthcare system in the Ourinhos micro-region in Brazil. Patients who were at least 60 years old, with at least one potential DDI, were eligible for inclusion in the study. Eligible patients were assessed by clinical pharmacists for DDI-related ADRs for 4 months. The causality of DDI-related ADRs was assessed independently by four clinicians using three decisional algorithms. The incidence of DDI-related ADRs during the study period was calculated. Logistic regression analysis was used to study DDI-related ADR predictors. RESULTS: A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6.5%. A multivariate analysis indicated that the adjusted odds ratios (ORs) rose from 0.91 (95% confidence interval [CI] = 0.75-1.12, p = 0.06) in patients aged 65-69 years to 4.40 (95% CI = 3.00-6.12, p < 0.01) in patients aged 80 years or older. Patients who presented two to three diagnosed diseases presented lower adjusted ORs (OR = 0.93 [95% CI = 0.68-1.18, p = 0.08]) than patients who presented six or more diseases (OR = 1.12 [95% CI = 1.02-2.01, p < 0.01]). Elderly patients who took five or more drugs had a significantly higher risk of DDI-related ADRs (OR = 2.72 [95% CI = 1.92-3.12, p < 0.01]) than patients who took three to four drugs (OR = 0.93 [95% CI = 0.74-1.11, p = 0.06]). No significant difference was found with regard to sex (OR = 1.08 [95% CI 0.48-2.02, p = 0.44]). CONCLUSION: The incidence of DDI-related ADRs in elderly outpatients was significant, and most of the events presented important clinical consequences. Because clinicians still have difficulty managing this problem, highlighting the factors that increase the risk of DDI-related ADRs is essential. Polypharmacy was found to be a significant predictor of DDI-related ADRs in our sample.

Effect of a 36-month pharmaceutical care program on the coronary heart disease risk in elderly diabetic and hypertensive patients.

PURPOSE: To examine the effect of a pharmaceutical care program on the coronary heart disease risk in elderly diabetic and hypertensive patients. METHODS: A total of 200 elderly (> 60 years) diabetic and/or hypertensive patients were recruited into a randomized, controlled, prospective clinical trial with a 36-month follow-up, developed in a public primary health care unit in a municipality in the Brazilian State of Sao Paulo. A range of clinical measurements were evaluated at the baseline and up to 36 months afterwards. The intervention group patients received pharmaceutical care from a clinical pharmacist, whereas the control group patients received their usual care from the medical and nursing staff. The Framingham scoring method was used to estimate changes in the 10-year coronary heart disease risk scores of all the patients. RESULTS: A total of 194 patients completed the study. Significant reductions (p < 0.05) in the mean values (baseline vs. 36 months) for the systolic blood pressure [156.7 mmHg vs 133.7 mmHg; P < 0.001), diastolic blood pressure (106.6 mmHg vs. 91.6 mmHg; P < 0.001),fasting glucose (135.1 mg/dL vs. 107.9 mg/dL; P < 0.001), hemoglobin A1C (7.7% vs. 7.0%; P <0.001), triglycerides (206.0 mg/dL vs. 152.5 mg/dL; P < 0.001), low-density lipoprotein (LDL)cholesterol (112.4 mg/dL vs. 102.0 mg/dL; P < 0.001), high-density lipoprotein cholesterol (55.5 mg/dL vs. 65.5 mg/dL; P < 0.001), total cholesterol (202.5 mg/dL vs. 185.9 mg/dL; P < 0.001), body mass index (26.2 kg/m2 vs. 26.1 kg/m2; P < 0.001), and abdominal circumference (103.2 cm vs. 102.5 cm; P= 0.001) were observed in the intervention group, whereas no significant changes were verified in the control group. The mean Framingham risk prediction score in the intervention group was 6.8% at baseline and decreased to 4.5%; P < 0.001) after 36 months, but remained unchanged in the control group. CONCLUSION: The pharmaceutical care program resulted in better clinical measurements and reduced the cardiovascular risk scores in elderly diabetic and hypertensive patients over a 36-month period.

Prevalence of potential drug-drug interactions and its associated factors in a Brazilian teaching hospital.

PURPOSE: The hazards of prescribing many drugs, including side-effects, drug-drug interactions (DDI) and difficulties of compliance have long been recognized as particular problems when prescribing. This study estimates the rate and factors associated with potential DDI in prescriptions from wards of a Brazilian teaching hospital. METHODS: Data were retrieved from wards of a teaching hospital (300 beds) handwritten prescription, once a week during a period of 4 months in 2004. Potential DDI were identified using DrugReax system. Patient's age and gender, number of prescribers; number of drugs and therapeutic drug classes on prescriptions were explored as associated factors to DDI. RESULTS: The overall frequency of potential DDI was 49.7%. The frequency of the potentially major DDI was 3.4%, with digoxin-hydrochlorothiazide as the most common interacting pair. The rate of potential DDI was significantly associated to in-patients' gender [woman, Odds ratio (OR)=1.23 (P=0.035)], age=55 years old [OR=1.5 (P=0.0008)], number of therapeutic drug class (ATC code, level 1)=4 [OR=5.5 (P=0.0000), cardiology patients [OR=7.87 (P=0.0000)] hospitalized at weekends [OR=1.24 (P=0.039)] and having digoxin prescribed [OR=16.79 (P=0.0000)]. A positive correlation was found between DDI, patient's age, number of drugs and therapeutic action ATC codes were significant, controlling for gender (Pearson's r=0.628, P=0.001). CONCLUSIONS: Cardiology women inpatients, age more then 55 years old, 7 or more drugs prescribed (including digoxin) and hospitalized at weekends should be closely monitored for adverse outcomes from DDI. A collaborative approach toward drug selection is strongly recommended, as well as electronic prescribing and development of pharmaceutical care in Brazilian hospitals.

A pharmacoepidemiologic study of drug interactions in a Brazilian teaching hospital.

PURPOSE: Although drug-drug interactions constitute only a small proportion of adverse drug reactions, they are often predictable and therefore avoidable or manageable. There are few studies on drug-drug interactions from Brazil. This study aimed to assess the frequency of drug-drug interactions in prescriptions and their potential clinical significance in patients of a Brazilian teaching hospital. METHODS: From January to April 2004, a sample of 1785 drug prescriptions was drawn from a total of 11,250. Drug-drug interactions were identified by using Micromedex DrugReax System. Patients'records with major drug-drug interactions were reviewed by a pharmacist and a medical doctor looking for signs, symptoms, and lab tests that could indicate adverse drug reactions due to such interactions. RESULTS: From the 1785 prescriptions examined, 1089 (61%) were from the male adult ward. Patients' average age was 52.7 years (SD = 18.9; range, 12-98). The median number of drugs in each prescription was 7 (range, 2-26). At least 1 drug-drug interactions was present in 887 (49.7%) prescriptions. Regarding the severity of the clinical result, the interactions were classified as minor (20; 2.3%), moderate (184; 20.7%), major (30; 3.4%), and undetermined because of an incidence of more than 1 interaction in a single patient (653; 73.6%). From the 30 patients with major interactions, 17 (56.7%) presented adverse drug reactions induced by exposure to a major drug-drug interaction. CONCLUSIONS: Patients did suffer adverse drug reactions from major drug-drug interactions. Many physicians may be unaware of drug-drug interactions. Education, computerized prescribing systems and drug information, collaborative drug selection, and pharmaceutical care are strongly encouraged for physicians and pharmacists.

Effect of a 36-month pharmaceutical care program on pharmacotherapy adherence in elderly diabetic and hypertensive patients.

OBJECTIVE: The primary objective of this study was to evaluate the effect of a pharmaceutical care program on pharmacotherapy adherence in elderly diabetic and hypertensive patients. The clinical outcomes of this pharmacotherapy adherence approach were the secondary objective of the study. SETTING: Public Primary Health Care Unit in a municipality in the Brazilian State of Sao Paulo. METHOD: A 36-month randomized, controlled, prospective clinical trial was carried out with 200 patients divided into two groups: control (n = 100) and intervention (n = 100). The control group received the usual care offered by the Primary Health Care Unit (medical and nurse consultancies). The patients randomized into the intervention group received pharmaceutical care intervention besides the usual care offered. MAIN OUTCOME MEASURE: Pharmacotherapy adherence (Morisky-Green test translated into Portuguese and computerized dispensed medication history) and clinical measurements (blood pressure, fasting glucose, A1C hemoglobin, triglycerides and total cholesterol) were evaluated at the baseline and up to 36 months. A P value <0.05 was considered statistically significant. RESULTS: A total of 97 patients from the intervention group and 97 patients from the control group completed the study (n = 194). Significant improvements in the pharmacotherapy adherence were verified for the intervention group according to the Morisky-Green test (50.5% of adherent patients at baseline vs. 83.5% of adherent patients after 36 months; P < 0.001) and the computerized dispensed medication history (52.6% of adherent patients at baseline vs. 83.5% of adherent patients after 36 months; P < 0.001); no significant changes were verified in the control group. Significant improvements in the number of patients reaching adequate values for their blood pressure (26.8% at baseline vs. 86.6% after 36-months; P < 0.001), fasting glucose (29.9% at baseline vs. 70.1% after 36 months; P < 0.001), A1C hemoglobin (3.3% at baseline vs. 63.3% after 36 months; P < 0.001), triglycerides (47.4% at baseline vs. 74.2% after 36 months; P < 0.001) and total cholesterol (59.8% at baseline vs. 80.4% after 36 months; P = 0.002) were verified in the intervention group, but remained unchanged in the control group. CONCLUSION: These results indicated the effectiveness of pharmaceutical care in improving pharmacotherapy adherence, with positive effects in the clinical outcomes of the patients studied.

Avaliação de prescrições medicamentosas de um hospital universitário brasileiro / Evaluation of prescription data of a Brazilian teaching hospital

A prescrição é o ponto de partida para a utilização de medicamentos. O objetivo deste trabalho foi identificar a qualidade das informações presentes nas prescrições das enfermarias de um hospital universitário brasileiro. Foram coletadas 1.785 prescrições medicamentosas de pacientes maiores de 12 anos, de ambos os sexos, internados em enfermaria de 1º de janeiro a 30 de abril de 2004. A amostragem foi feita coletando-se todas as prescrições emitidas em um dia de cada semana durante o período de estudo, observando-se o intervalo de seis dias entre cada coleta. Foram avaliados dados relativos à identificação do paciente, do medicamento e do prescritor. Em 230 (12,9 por cento) prescrições não havia a idade do paciente. Em 224 (12 por cento) prescrições não constava à assinatura do prescritor. Em 16 por cento dos medicamentos prescritos foi detectada afalta de pelo menos uma informação relativa à posologia (dose, forma farmacêutica, via e/ou intervalo entre doses). Afalta destas informações é um obstáculo ao uso seguro de medicamentos, podendo levar ao uso inadequado e a reações adversas. Sugerimos intervenções educativas junto aos profissionais que lidam com o medicamento (desde a prescrição até sua utilização) e a implantação de monitoramento farmacoterapêutico dos pacientes. A participação mais ativa do farmacêutico na equipe de saúde também pode proporcionar tratamentos mais efetivos, seguros e convenientes aos pacientes hospitalizados. A assistência farmacêutica e a utilização de medicamentos em hospitais brasileiros precisam ser mais estudadas.

Prescription is the starting point for medicine use. The objective of this work was to identify the quality of the information contained in the prescriptions of a Brazilian university hospital. During the period January 1 to April 30,2004,1.785 drug prescriptions for inpatients older than 12 years were collected. The sample consisted of the total of prescriptions emitted on one day of each week during the study period, observing an interval of 6 days between each collection. Characteristics of the patient, the drug and the prescriber were evaluated. In 230 (12.9 percent) prescriptions the age of the patient was no mentioned. In 224 (12 percent) cases the prescriber had not signed the prescription. In 16 percent of prescriptions at least one item of the information regarding dosage (dosage, pharmaceutical form, route and/or time interval between doses) was missing. The lack of such information represents an obstacle for safe use of medicines and can lead to misuse and adverse reactions. We suggest educative interventions for the professionals who deal with medicines and pharmacotherapeutic monitoring of patients. The participation of the pharmacist in the health team can also contribute to more effective, safe and convenient therapies for the hospitalized patients. Pharmaceutical care and medicine use in Brazilian hospitals need further studies.

A pharmacoepidemiologic study of drug interactions in a Brazilian teaching hospital / Um estudo farmacoepidemiológico de interações medicamentosas em um hospital universitário brasileiro

PURPOSE: Although drug-drug interactions constitute only a small proportion of adverse drug reactions, they are often predictable and therefore avoidable or manageable. There are few studies on drug-drug interactions from Brazil. This study aimed to assess the frequency of drug-drug interactions in prescriptions and their potential clinical significance in patients of a Brazilian teaching hospital. METHODS: From January to April 2004, a sample of 1785 drug prescriptions was drawn from a total of 11,250. Drug-drug interactions were identified by using Micromedex® DrugReax® System. Patients'records with major drug-drug interactions were reviewed by a pharmacist and a medical doctor looking for signs, symptoms, and lab tests that could indicate adverse drug reactions due to such interactions. RESULTS: From the 1785 prescriptions examined, 1089 (61 percent) were from the male adult ward. Patients' average age was 52.7 years (SD = 18.9; range, 12-98). The median number of drugs in each prescription was 7 (range, 2-26). At least 1 drug-drug interactions was present in 887 (49.7 percent) prescriptions. Regarding the severity of the clinical result, the interactions were classified as minor (20; 2.3 percent), moderate (184; 20.7 percent), major (30; 3.4 percent), and undetermined because of an incidence of more than 1 interaction in a single patient (653; 73.6 percent). From the 30 patients with major interactions, 17 (56.7 percent) presented adverse drug reactions induced by exposure to a major drug-drug interaction. CONCLUSIONS: Patients did suffer adverse drug reactions from major drug-drug interactions. Many physicians may be unaware of drug-drug interactions. Education, computerized prescribing systems and drug information, collaborative drug selection, and pharmaceutical care are strongly encouraged for physicians and pharmacists.

INTRODUÇÃO: Embora as interações medicamentosas constituam uma pequena parcela das reações adversas a medicamentos, elas geralmente são previsíveis e às vezes podem ser evitadas. As prevalências de interações medicamentosas em hospitais são escassas no Brasil. OBJETIVO: Avaliar a prevalência de interações medicamentosas em prescrições hospitalares e seu significado clínico em pacientes de um hospital universitário brasileiro. MÉTODOS: Uma amostra de 1785 prescrições de enfermaria de adultos foi coletada de um total de 11.250 aviadas no período de janeiro a abril de 2004. As interações medicamentosas foram identificadas pelo Micromedex. Prontuários de pacientes com interações medicamentosas graves foram examinados por um médico e uma farmacêutica a busca de resultados laboratoriais que confirmassem a ocorrência da interação medicamentosa. RESULTADOS: As prescrições eram de pacientes masculinos (1089; 61 por cento) em sua maioria. A idade média dos pacientes foi de 52,7 anos (DP=18,9; variação de 12 a 98 anos). Cada paciente recebeu em média 7 medicamentos (variando de 2 a 26). Ao menos 887 (49,7 por cento) das prescrições continham interação medicamentosa. As prescrições continham interação medicamentosa classificadas como leve (55; 3.1 por cento), moderada (421; 23.6 por cento) e grave (90; 5.0 por cento). Em 321 (17.9 por cento) prescrições foram encontradas mais de uma interação medicamentosa, cujo resultado clínico é desconhecido. Uma amostra de 33 prontuários com interações medicamentosas graves foram avaliadas, destes, 17 (51.5 por cento) apresentaram reações adversas a medicamentos induzida por uma interação medicamentosa grave. CONCLUSÃO: Um grande número de pacientes sofre reações adversas a medicamentos como resultado de interações medicamentosas graves. Acreditamos que a maioria dos médicos desconheça a ocorrência de interações medicamentosas. Educação continuada, sistema computadorizado para prescrição, seleção de medicamentos em parceria com farmacêuticos...