Cross-sectional survey of off-label and unlicensed prescribing for inpatients at a paediatric teaching hospital in Western Australia.

OBJECTIVES: To evaluate the prevalence of off-label and unlicensed prescribing in inpatients at a major paediatric teaching hospital in Western Australia and to identify which drugs are commonly prescribed off-label or unlicensed, including factors influencing such prescribing. METHODS: A retrospective cross-sectional study was conducted in June, 2013. Patient and prescribing data were collected from 190 inpatient medication chart records which had been randomly selected from all admissions during the second week of February 2013. Drugs were categorised as licensed, off-label or unlicensed, according to their approved Australian registration product information (PI). All drugs were classified according to the Anatomical Therapeutic Chemical (ATC) code. RESULTS: There were 120 male and 70 female inpatients. The average age was 6.0 years (± 4.7). The study included 1160 prescribed drugs suitable for analysis. The number of drugs prescribed per patient ranged from 1 to 25 with an average of 6.1 (± 4.3). More than half (54%) were prescribed off-label. Oxycodone, clonidine, parecoxib and midazolam were always prescribed off-label. The most common off-label drugs were ondansetron (18.5%), fentanyl (12.9%), oxycodone (8.8%) and paracetamol (6.1%). Many ATC classifications included high off-label proportions especially the genitourinary system and sex hormones, respiratory system drugs, systemic hormonal preparations and alimentary tract and metabolism drugs. CONCLUSIONS: This study highlights that prescribing of paediatric drugs needs to be better supported by existing and new evidence. Incentives should be established to foster the conduct of evidence-based studies in the paediatric population. The current level of off-label prescribing raises issues of unexpected toxicity and adverse drug effects in children that are in some cases severely ill.

Clinical setting influences off-label and unlicensed prescribing in a paediatric teaching hospital.

PURPOSE: To estimate the prevalence of off-label and unlicensed prescribing during 2008 at a major paediatric teaching hospital in Western Australia. METHODS: A 12-month retrospective study was conducted at Princess Margaret Hospital using medication chart records randomly selected from 145,550 patient encounters from the Emergency Department, Inpatient Wards and Outpatient Clinics. Patient and prescribing data were collected. Drugs were classified as off-label or unlicensed based on Australian registration data. A hierarchical system of age, indication, route of administration and dosage was used. Drugs were classified according to the Anatomical Therapeutic Chemical Code. RESULTS: A total of 1,037 paediatric patients were selected where 2,654 prescriptions for 330 different drugs were prescribed to 699 patients (67.4%). Most off-label drugs (n = 295; 43.3%) were from the nervous system; a majority of unlicensed drugs were systemic hormonal preparations excluding sex hormones (n = 22, 32.4%). Inpatients were prescribed more off-label drugs than outpatients or Emergency Department patients (p < 0.0001). Most off-label prescribing occurred in infants and children (31.7% and 35.9% respectively) and the highest percentage of unlicensed prescribing (7.2%) occurred in infants (p < 0.0001). There were 25.7% of off-label and 2.6% of unlicensed medications prescribed across all three settings. Common reasons for off-label prescribing were dosage (47.4%) and age (43.2%). CONCLUSION: This study confirmed off-label and unlicensed use of drugs remains common. Further, that prevalence of both is influenced by the clinical setting, which has implications in regards to medication misadventure, and the need to have systems in place to minimise medication errors. Further, there remains a need for changes in the regulatory system in Australia to ensure that manufacturers incorporate, as it becomes available, evidence regarding efficacy and safety of their drugs in children in the official product information.

Lacosamide as adjunctive therapy in treatment-resistant epilepsy in childhood.

AIMS: Lacosamide (LCM) is a novel anti-epileptic drug (AED) that enhances the slow inactivation of voltage-gated sodium channels. Its efficacy as adjunctive therapy for focal seizures is confirmed in adult placebo controlled trials with >50% reduction in seizure frequency in up to 50% patients. There is paucity of data on its efficacy and tolerance in treatment-resistant epilepsy in childhood (TREC). This study aims to assess efficacy and tolerance of LCM as adjunct therapy in TREC. METHODS: Audit of medical records and seizure diaries in children with TREC on LCM. A response (RR) was defined as ≥50% reduction in seizure frequency. RESULTS: Forty children (age range: 2-19 years) with TREC received LCM as add-on therapy. All had abnormal electroencephalograms, and 36 had abnormal neuroimaging. All children failed >2 AED trials, nine had trialled the ketogenic diet, five had failed the vagal nerve stimulator and 11 had failed resective epilepsy surgery. Median dose and duration of LCM therapy were 5.7 mg/kg/day and 10.5 months, respectively. RR was seen in 20% with persistence of RR in 8/36, 8/30 and 8/26 children on LCM at 3-, 6- and 9-month follow-up. Two children became seizure free. Retention on LCM was 65% at 9 months. LCM was well tolerated with minor side effects in seven children; no child discontinued LCM because of side effects. CONCLUSION: LCM is a well-tolerated AED with RR in 20%: in 5%, it resulted in seizure freedom. LCM may be useful even in TREC when seizures have not responded to intervention with multiple modalities.

Topical rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: follow up of a pilot study and promising future directions.

One of the most visible and potentially disfiguring cutaneous manifestations of tuberous sclerosis complex is the development of multiple facial angiofibromas, present in over 80% of patients. Topical rapamycin has been shown in many reports to be a safe and effective treatment for facial angiofibromas. In February 2012 we reported the results of a pilot study of four patients undertaken at a paediatric tertiary hospital in Australia. Since then, we have continued to refine the optimal formulation and concentration of topical rapamycin and expanded our selection of patients. We present an update on our current cohort of treated patients, discuss the optimal formulation of topical rapamycin and include a literature review on all published cases to date. Although topical rapamycin is not a curative treatment, we have demonstrated that its early institution significantly reduces both the vascularity and palpability of angiofibromas and prevents their progression with age. It is well tolerated and now a cost effective option.

Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients.

Tuberous sclerosis complex (TSC) is an autosomal dominant genodermatosis characterised by the development of hamartomatous tumours in multiple organs including the brain, skin, kidneys, heart and lungs. Facial angiofibromas are the most visible and unsightly of the cutaneous manifestations of TSC, often resulting in stigmatisation for both the affected individuals and their families. Current treatments include vascular laser, ablative lasers and other destructive techniques such as shave excision and electrodessication. For the best outcome these treatments have to be repeated throughout childhood and teenage years, necessitating multiple general anaesthetics. We report a pilot study of topical rapamycin in four children with TSC and facial angiofibromas. Two patients were trialled on 0.1% rapamycin in petrolatum and the other two patients with 0.1% rapamycin solution (Rapamune) applied topically. Both preparations were rapidly and equally effective, however the 0.1% in petrolatum was much better tolerated. Younger patients with smaller angiofibromas had the best response with near complete clearance. Both preparations were more cost effective than pulsed dye laser under general anaesthesia. Although larger studies are needed, this treatment shows a potential to be a first-line management for facial angiofibromas in TSC and appears safe to start in early childhood.

Sterile abscess formation associated with depot leuprorelin acetate therapy for central precocious puberty.

We describe a case of an 8 year old girl with central precocious puberty. She was commenced on 3 monthly intramuscular depot Leuprorelin acetate therapy, as a result of which she developed sterile abscesses. She was converted to daily subcutaneous Leuprorelin acetate therapy with no recurrence of the abscesses. The possible mechanisms for this reaction are described in the article.