BackgroundThe extended use of rituximab for off-label indications accentuates the need for creating standardised protocols to speed up both the administrative processes and the supply to the patient.PurposeTo analyse rituximab’s off-label indications as well as the treatment schedule used to evaluate the degree of compliance with the Royal Decree which regulates the use of medicines under special circumstances.Material and methodsAn observational retrospective study was carried out in 2015, in which all patients treated with rituximab, both exclusively or in combination with other drugs, were included. For data collection, the oncologic treatment management tool, Onconfarm, and the electronic clinic history programme, Selene, were used: age, gender, diagnosis, treatment schedule received, off-label indication or not, and, if affirmative, whether it was processed and authorised by the medical board at the hospital.Results74 patients were included, 38 women and 36 men, with an average age of 69 years (20–90). A total of 103 treatments were applied, the following being the most frequent: follicular lymphoma (23%), giant cell lymphoma (13.5%) and chronic lymphocytic leukaemia (CLL) (12%). The most used treatment schedules were: R-CHOP (22%), rituximab every 2 months (13.5%) and rituximab quarterly (12.5). Of all treatments applied, 48 (47%) did not comply with the indications in the technical data sheet. The most frequent indications were: membranous glomerular nephropathy (14.5%), CLL as maintenance treatment (12.5%) and Mantle cell lymphoma and Waldenström’s macroglobulinaemia (10.5%). Of all the off-label treatments, 58% were processed following the procedures related to the use of medicines under special circumstances and authorised to be applied, while the remaining 42% were applied without being administratively processed.ConclusionPrescribing Rituximab for off-label indications is very frequent in hospitals. These situations should be registered under some therapeutic protocols, mandatory for physicians, and in which regulation by the Pharmaceutical and Therapeutical Commission should be actively engaged and involved.References and/or acknowledgementsGarcía-Sabina A, Rabunal Rey R, Martínez-Pacheco R. Review of use of drugs for conditions not included in product characteristics. Farmhosp (Internet). 2016 (mentioned 10 Oct 2016); 2011;35:264–77. Available at European Assessment Report, de la European Medicines Agency. Procedure No. EMEA/H/C/165/II/0060. Available at , mentioned 10 Oct 2016No conflict of interest

BackgroundThe incidence of factor IX inhibitor development in congenital haemophilia B is low (3–5% depending on the population) and usually occurs in the first days of treatment. Guidelines suggest that, after 150 days exposed to the drug (ED), testing is only required if clinically indicated. But we detected two cases in which the inhibitors developed on long term treatments.PurposeTo describe all worldwide reported cases in which patients developed inhibitors when they were treated with Nonacog alfa. We focused on the time it took to develop the inhibitors since the treatment started.Material and methodsWe searched on VigiBase and FEDRA (global and Spanish pharmacovigilance databases, respectively), including all spontaneous reports in patients with Nonacog alfa who developed inhibitors in the past 20 years. All patients who did not have laboratory confirmation were excluded. Age, gender, reporting country, Nonacog alfa treatment starting date, EDs and confirmation inhibitor testing date were recorded.Results52 cases of inhibitor development were reported globally: 29 in the USA, 8 in Japan and 15 in Europe. They were primarily in men (45/52) and gender was unknown in 5 cases. Their ages ranged from 9 months to 50 years (age was unknown in 19 cases). It was not possible to confirm the EDs in any of the cases. Half of the notifications (26/52) did not correctly record the chronology of inhibitor development. Of the remainder, 19 notifications were made in the first year of treatment (12 in the first 100 days), 2 notifications between the first and second year, 1 notification between the second and third year, 1 notification between the third and fourth year, 2 notifications between the fourth and fifth year and 1 notification between the sixth and seventh year.ConclusionThese results show that patients treated for several years are also susceptible, although to a lesser extent, to developing inhibitors. Despite the major limitations of this study, it is not wrong to think that patients with longer treatments have been exposed to more doses which might even exceed 150 ED. Hence it is important to monitor all haemophilia B patients throughout all of their treatment.No conflict of interest

BackgroundSpironolactone is widely used in paediatrics for cardiovascular disease despite being an off-label treatment. After detecting a case of severe gynaecomastia in a 4-month-old child with spironolactone and no other likely causes, it was decided to make a more thorough review of the cases globally reported.PurposeTo describe worldwide reported cases in which the paediatric population developed breast disorders (BD) associated with spironolactone treatment. We focused on the time it took to develop the disorder since the treatment started. We also focused on whether there was another reason which could have induced the condition.Material and methodsA search was conducted on Vigibase and FEDRA (Global and Spanish Pharmacovigilance Database, respectively), including all spontaneous reports performed in patients >18 years of age with BD treated with spironolactone. We calculated how long the BD appeared after treatment had started. We also checked the product information to determine if concomitant medication could produce this adverse drug reaction (ADR). We included as BD: gynaecomastia, breast enlargement, galactorrhoea and nipple pain. Age, gender, reporting country, spironolactone treatment starting date, date of diagnosis of BD and list of concomitant medications were recorded.Results14 cases of BD were reported globally: 7 in Asia, 5 in Europe, 1 in Australia and 1 in the USA. They were 11 boys and 3 girls. Median age was 2 years (21 days–17 years). 7 cases developed BD early (in the first month of treatment), 2 cases developed it late (more than 4 years after treatment) and in the other cases (5) the time it took for BD to appear could not be correctly identified. Regarding possible causes of BD, 10 cases could be attributed to spironolactone and 4 cases to concomitant medication. The drugs involved were digoxin, ramipril and domperidone.ConclusionReported cases occurred after a few days of treatment with spironolactone, especially in infants. Despite the off-label use, this draws attention to the low incidence of notifications in a drug widely used in paediatrics. This may be because this ADR is well known, and ADR notifications in paediatrics is generally low.No conflict of interest

BackgroundIn order to improve the quality of assistance and to promote rational use of drugs in patients who come to the emergency department (ED), a new drug kit dispensation programme was launched.PurposeTo assess the viability of the drug kit dispensation programme in ED patients after discharge. To analyse the impact on the prescription of these drugs.Material and methodsA retrospective experimental observational study was conducted from June to December 2015. 5 kits (ibuprofen, omeprazole, metamizol, paracetamol and butylscopolamine) were dispensed for the most common diagnoses in ED, containing the right medication to treat them. The kits were properly identified, packed and contained written information. All dispensations were registered by the ED physician in charge through the computer tool Selene, and the kits were given to the patients together with the discharge report. The registered variables were: number of patients, number and type of dispensed kits, prescriptions given by the correspondent ED, direct costs, percentage difference in expenditure compared with previous year, bearing in mind the trend in the first semester of 2015.ResultsOver the period of this study, 4320 kits (710 omeprazole, 1620 ibuprofen, 930 metamizole, 820 paracetamol and 240 butylscopolamine) were dispensed. Only 20% of the dispensations were registered, and therefore it was impossible to monitor these patients and analyse the results. In terms of expenditure on prescriptions, there was a drop in paracetamol (5.17%), in metamizole (18.64%) and in ibuprofen (9.14%); and there was an increase in omeprazole (2.97%). Butylscopolamine was not taken into consideration due to its erratic fluctuation. The cost of the kits, passed on to the hospital pharmacy service, was €287.82 for paracetamol, €184.14 for metamizole, €112.32 for butylscopolamine, €70.30 for omeprazole and €335.34 for ibuprofen. The estimated potential savings were: €4743 for paracetamol, €1485 for metamizol, €139 for butylscopolamine, €4509 for omeprazole and €3133 for ibuprofen.ConclusionMedication kits after discharge can be a good strategy to ensure compliance with the treatment, to promote rational use of drugs and to reduce the costs in ED as far as traceability can be totally ensured.No conflict of interest