Background: This review describes the safety of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX) and combined therapy in young patients less than 25 yr of age with haemoglobinopathies. Methods: Searches in electronic literature databases were performed. Studies reporting adverse events associated with iron chelation therapy were included. Study and reporting quality was assessed using AHRQ Risk of Bias Assessment Tool and McMaster Quality Assessment Scale of Harms. Prospective clinical studies were pooled in a random-effects meta-analysis of proportions. Results: Safety data of 2040 patients from 34 studies were included. Ninety-two case reports of 246 patients were identified. DFX (937 patients) and DFP (667 patients) possess the largest published safety evidence. Fewer studies on combination regimens are available. Increased transaminases were seen in all regimens (3.9-31.3%) and gastrointestinal disorders with DFP and DFX (3.7-18.4% and 5.8-18.8%, respectively). Therapy discontinuations due to adverse events were low (0-4.1%). Reporting quality was selective and poor in most of the studies. Conclusion: Iron chelation therapy is generally safe in young patients, and published data correspond to summary of product characteristics. Each iron chelation regimen has its specific safety risks. DFO seems not to be associated with serious adverse effects in recommended doses. In DFP and DFX, rare, but serious, adverse reactions can occur. Data on combined therapy are scarce, but it seems equally safe compared to monotherapy.

Pharmacotherapy of neonates is complex and marked to a large extent of off-label use. The implementation of the Paediatric Regulation (2007) gave hope for a change in the safety and efficacy for drugs used in neonatal intensive care units (NICU). This study investigates drug utilisation patterns and off-label use in a German neonatal intensive care unit (NICU) in 2014. A 12-months retrospective, observational cohort study was performed at the NICU of the University Children’s Hospital Erlangen, Germany. Licensing status was determined using the Summary of Product Characteristics (SmPC). Results are compared with a similar study conducted 10 years earlier. The study included 204 patients (57.8% male) (2004: 183) and 2274 drug prescriptions were recorded (2004: 1978). The drugs that were mostly prescribed were drugs for the nervous system (2004: 22.6%; 2014: 26.9%) and anti-infectives for systemic use (2004: 26.0%; 2014: 24.9%);34.3% (2004) and 39.2% (2014) of all prescriptions were off-label;62.7% of all patients received at least one off-label or unlicensed drug (2004: 70%). For 13 drugs, the licensing status changed either from off-label to label (n = 9) or vice versa (n = 4). Overall, there was no significant change neither in terms of the drugs used nor regarding their licensing status. Further studies are needed to validate these findings in a European context.

Key points• Use of analgesic and anti-inflammatory drugs was in line with local recommendations and WHO guidelines • Oral paracetamol and oral ibuprofen are the most commonly used analgesic drugs on general paediatric wards • Differences regarding dose and frequency of ibuprofen and paracetamol use were observed, indicating that safety concerns for individual drugs are perceived differently among countries BOTZENHARDT et al. 2/1 2016-09-16 ABSTRACT AimAnalgesic and anti-inflammatory drugs are frequently prescribed in paediatrics. Prescribing and dosing patterns in hospitalised children are not well known. This study explores analgesic drug utilisation on five paediatric wards and discusses its findings in comparison with WHO guidelines. MethodA sub-analysis of a prospective, multi-centre, observational cohort study was undertaken. Prescription data of children aged up to ≤18 years were collected between October 2008 and December 2009 on paediatric general medical wards in five hospitals in Australia, Germany, the United Kingdom (UK), Hong Kong (HK) and Malaysia. Analgesic drug prescriptions were analysed for prescribing patterns in terms of dosing, frequency and route of administration. Dosing data were compared with local recommendations and WHO guidelines for children. ResultsIn the study cohort 56.8% (726/1,278) of paediatric patients received at least one analgesic drug prescription (1,227 prescriptions). Median age of patients with analgesics was 2.2 years (IQR 0.8-7.3) and median number of prescriptions per patient was 1 (IQR 1-2). Most commonly prescribed drugs were oral paracetamol (45.9%, 563/1,227) and oral ibuprofen (19.9%, 244/1,227). Daily doses of paracetamol ranged from 30 mg/kg/day in Germany to 67-68 mg/kg/day in UK and HK (p<0.05). For ibuprofen, single doses ranged from 5-6 mg/kg in HK and UK to 10 mg/kg in GER and AUS (p<0.001). Opioid use prevalence was statistically different between the centres and ranged from 0% to 17.6% (p<0.001). ConclusionThis study provides a comprehensive overview of analgesic drug use of hospitalised children. Similar to primary care data, paracetamol is the most commonly used analgesic. As recommended by WHO guidelines, oral medication was favoured and opioids used in addition to paracetamol and ibuprofen. Overall drug utilisation was in line with local recommendations and WHO guidelines. Differences in use of paracetamol and ibuprofen among countries was seen indicating that safety concerns are perceived differently. More large-scale safety studies are needed. BOTZENHARDT et al.

• Half of the identified ADRs related to deferiprone therapy occurred during the first three months of treatment. • A relatively high incidence of agranulocytosis and neutropenia. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy.