Direct-acting antivirals are the recommended treatment for hepatitis C-infected patients. Drug–drug interactions with concomitant treatments can cause lack of effectiveness and/or safety. The objective of this study is to characterise drug–drug interactions of direct-acting antivirals and to analyse their influence both on the effectiveness of antiviral treatment and on the overall safety of pharmacological treatment in hepatitis C-infected patients.
Observational and prospective cohort study for 3 years in the pharmaceutical care outpatient consultation of a general hospital, undertaking detection, evaluation and management of drug–drug interactions by clinical pharmacists and physicians. The main outcome measures were sustained virologic response at week 12 for effectiveness and serious drug-related adverse events for safety. Multivariate statistical analysis applied to: (a) patient basal characteristics related to presence of drug–drug interactions; (b) previous antiviral treatments, viral genotype, cirrhosis, decompensations and presence of drug–drug interactions related to the effectiveness of direct-acting antivirals.
Of a total of 1092 patients, the majority of them were men, around 60 years old and HCV-genotype 1 mono-infected, with a high basal viral load, naive to antiviral treatment, treated with ledipasvir/sofosbuvir and without cirrhosis. 24.5% had drug–drug interactions. Proton pump inhibitors were the concomitant drugs that caused the most drug–drug interactions. Age ≥65 years and direct-acting antivirals based on protease inhibitors were independently related to the presence of drug-drug interactions (p≤0.012). All (100%) of the therapeutic recommendations based on detected drug–drug interactions were implemented; 97.7% of patients with interactions versus 99.0% without them reached sustained virologic failure (p=0.109). The serious adverse events rates were 1.5% and 1.3% in patients with and without drug-drug interactions, respectively (p=0.841).
Drug–drug interactions are frequent among hepatitis C-infected patients receiving treatment with direct-acting antivirals. However, the collaboration between physicians and clinical pharmacists makes it possible to detect, evaluate, avoid or clinically manage these drug–drug interactions, in order to maintain whole treatment therapeutic safety and the effectiveness of direct-acting antivirals.
ObjectivesTo assess the long-term effectiveness of pirfenidone in idiopathic pulmonary fibrosis (IPF) treatment and to establish its adverse effects profile.
MethodsRetrospective observational study in patients with IPF who initiated treatment with pirfenidone between 2011 and 2016. We collected demographic variables (age, sex); date of first and last treatment; reason for discontinuation; pulmonary function measures (forced vital capacity (FVC), carbon monoxide diffusion capacity (DLCO), and 6 min walk test (6MWT)) at treatment initiation (baseline) and at 1, 2 and 3 year follow-up; adherence to pirfenidone treatment; recorded adverse effects; and mortality.
ResultsThirty-one patients treated with pirfenidone were included; mean±SD age was 69±8 years, 74% were men, and 59% had a smoking history. Mean baseline values were: FVC 2.43±0.66 L (61.8±12.1%); DLCO 46.1±19.4%; and 6MWT 334±125 m. Median duration of treatment was 14±13 months, and treatment was discontinued in 58% of patients. The most frequently observed adverse effects were gastrointestinal disturbances and photosensitivity. Twenty (65%) patients were evaluated at 1 year, when mean FVC was 2.41±0.86 L (64.7±20.3%); DLCO 50.8±26.8%; and 6MWT 341±139 m. At 2 years’ follow-up, 11 patients (36%) who were still taking pirfenidone were evaluated. Mean FVC was 2.34±0.79 L (66.2±14.7%); DLCO 50.0±28.3%; and 6MWT 265±121 m. At 3 years, five patients were still taking the treatment. Mean FVC was 2.71±0.84 L (71.0±24.7%); DLCO 52.6±26.7%; and 6MWT 286±139 m. Nineteen per cent of patients were non-adherent to treatment.
ConclusionsPirfenidone seems to be effective for long-term control of IPF despite substantial variability in response among individual patients. The most frequent adverse effects were digestive and cutaneous, prompting in some cases a reduction in dose or even discontinuation of the treatment.
ObjectivesFingolimod is the first oral drug indicated in monotherapy as a modifier of the course of very active relapsing-remitting multiple sclerosis (RRMS). The safety profile of fingolimod is well established in clinical trials and post-marketing studies. Our objective was to study the profile of fingolimod use in our health area.
MethodsA retrospective, observational, descriptive study was performed on the use of fingolimod in adult patients diagnosed with RRMS between January 2015 and February 2017 or until suspension of treatment in a reference hospital in north-western Spain.
ResultsA total of 55 patients were included with a mean±SD time of treatment with fingolimod of 26±14.6 months (range 2–53). Thirteen patients permanently discontinued the treatment (10 due to outbreaks/disease progression and 3 due to adverse effects). No statistically significant differences were found between the percentage of patients who discontinued fingolimod and who had received only one previous treatment and those who had received two or more treatments. No cases of symptomatic bradycardia were reported.
ConclusionsFingolimod is a safe treatment for patients with multiple sclerosis.
Background and objectivePatient medicines helpline services (PMHS) are available from some National Health Service Trusts in the UK to support patients following their discharge from hospital. The aim of this systematic review was to examine the available evidence regarding the characteristics of enquirers and enquiries to PMHS, in order to develop recommendations for service improvement.
MethodsSearches were conducted using Medline, Embase, Cumulative Index of Nursing and Allied Health Literature, Scopus, and Web of Science, on 4 June 2019. Forward and backward citation searches were conducted, and grey literature was searched. Studies were included if they reported any characteristics of enquirers who use PMHS, and/or enquiries received. Study quality was assessed using the Axis tool. A narrative synthesis was conducted, and where appropriate, weighted means (WMs) were calculated. Where possible, outcomes were compared with Hospital Episode Statistics (HES) data for England, to establish whether the profile of helpline users may differ to that of hospital patients.
ResultsNineteen studies were included (~4362 enquiries). Risk of bias from assessed studies was 71%. Enquirers were predominantly female (WM=53%; HES mean=57%), elderly (WM=69 years; HES mean=53 years) and enquired regarding themselves (WM=72%). Out of inpatient and outpatient enquirers, 50% were inpatients and 50% were outpatients (WM). Six of 15 studies reported adverse effects as the main enquiry reason. Two of four studies reported antimicrobial drugs as the main enquiry drug class. From two studies, the main clinical origin of enquiries were general surgery and cardiology. Across six studies, 27% (WM) of enquiries concerned medicines-related errors.
ConclusionsOur findings show that PMHS are often used by elderly patients, which is important since this group may be particularly vulnerable to experiencing medicines-related issues following hospital discharge. Over a quarter of enquiries to PMHS may concern medicines-related errors, suggesting that addressing such errors is an important function of this service. However, our study findings may be limited by a high risk of bias within included studies. Further research could provide a more detailed profile of helpline users (eg, ethnicity, average number of medicines consumed), and we encourage helpline providers to use their enquiry data to conduct local projects to improve hospital services (eg, reducing errors).
PROSPERO registration numberCRD42018116276.