BackgroundSevere neonatal autosomal-dominant polycystic kidney disease (ADPKD) is rare and easily confused with recessive PKD. Managing such infants is difficult and often unsuccessful.Case diagnosis/treatmentA female infant with massive renal enlargement, respiratory compromise and hyponatraemia was treated with the arginine vasopressin receptor 2 antagonist tolvaptan. This resolved hyponatraemia, and there was no further increase in renal size.ConclusionTolvaptan may be a useful treatment for severe neonatal PKD.
BackgroundUnlicensed medications are used all the time in the management of diseases in childhood. Tolvaptan (Jinarc®) is a vasopressin V2-receptor antagonist licensed for use to slow the progression of cyst development and renal insufficiency of ADPKD in adults with CKD stage 1 to 3 with evidence of rapidly progressing disease. Studies of animal models implicate the antidiuretic hormone arginine vasopressin and its messenger cyclic adenosine monophosphate (cAMP) as promoters of kidney-cyst cell proliferation and luminal fluid secretion. The suppression of vasopressin release by means of high water intake, genetic elimination of vasopressin, and vasopressin V2-receptor blockade all reduce the cyst burden and protect kidney function1 A Phase 3 trial showed that Tolvaptan, as compared with placebo, slowed down the increase in total kidney volume and decline in kidney function in adults (average 39 yrs) with ADPKD over a 3-year period.2 ADPKD is the most common form of polycystic kidney disease (PKD) typically late in onset and results from mutation of either of two genes: PKD1 and PKD2. Autosomal recessive polycystic kidney (ARPKD), the other form of PKD, is 20 times less common, presents primarily in infancy and childhood, is typically more severe, and commonly associated with hypertension. ARPKD results from mutation of PKHD1. In spite of these differences, there is growing evidence to suggest that ADPKD and ARPKD are more related than previously suspected.3 Bilineal inheritance of PKD1 abnormalities has been reported to cause extremely severe disease resembling ARPKD.4 The use of Tolvaptan in the management of PKD in children is therefore expected to become more important.AimTo describe the first known UK use of Tolvaptan in a neonate with severe ADPKD and the role of the hospital pharmacist in facilitating the use.MethodThe role descriptor of hospital pharmacists produced by the World Health Organisation (WHO) was adapted and used to map the pharmaceutical challenges of using Tolvaptan in this child. The descriptor include: (i) Promotion of rational prescribing of drugs, (ii) Use of specialist pharmacists networks to gain greater expertise; (iii) Monitor compliance and therapeutic response and report adverse drug reactions; (iv) ensure supply of high quality products; (v) partake in planning and implementation of clinical trials.ResultsThe use of Tolvaptan for indication other than hyponatraemia and other endocrine uses are not routinely commissioned by NHS England. In view of the exceptionality of this case – a severe neonatal form of ADPKD with estimated prevalence of the order of 1 in tens of millions, an Individual Funding Request (IFR) application was made and was approved. The application was supported by financial information provided by the hospital pharmacist who facilitated the application process. Using available information and formulation knowledge, a suspension was eventually recommended and was well tolerated. This resulted in approximately 85% reduction in the cost of treatment over six months. T...
Introduction/aimThe European Medicines Agency (EMA) reviewed the use of domperidone containing medicines in March 2014, due to concerns about cardiac abnormalities. The Medicines and Healthcare products Regulatory Agency (MHRA) then responded and issued a drug safety update in May 2014,1 which listed new restricted indications, dosing, duration and contraindications for domperidone.In May 2015 the Neonatal and Paediatric Pharmacists Group (NPPG) released a statement on the use of domperidone.2 This was a highly significant document in child health, and empowered paediatric pharmacists to react to national alerts and implement changes locally. The aim of the audit was to collect information on the current prescribing of domperidone in paediatric patients in a hospital setting, and to evaluate the effects of the alerts on prescribing.MethodPatients aged 0–18 years were retrospectively identified within a children’s hospital (n=60) as having domperidone prescribed between the 1 st of January 2014 and the 31 st of July 2015 using electronic prescribing records. For each patient, data was collected regarding domperidone dose, indication, duration, monitoring and non-pharmacological interventions for gastro-oesophageal reflux disease (GORD).ResultsA total of 60 patients were included in the audit, of which 10 (17%) were prescribed domperidone after the publication of the NPPG alert.In terms of dosing, 43/50 (86%) achieved the standard before the NPPG alert; for duration 6/50 (12%), for indication 9/50 (18%); for ECG monitoring in high risk patients 12/33 (36%) and for the trial of non-pharmacological treatment in GORD 11/17 (64%).For the patients post implementation, these figures were 10/10 (100%), 1/10 (10%), 1/10 (10%), 0/4 (0%) and 2/3 (66%) respectively.ConclusionIn conclusion, this audit has shown that the drug safety updates have been received and acted upon within a secondary care setting, and hospital teams are following the new domperidone prescribing guidelines. Whilst many of the children audited were still receiving domperidone off-licence and long-term to improve gastric motility, this is to be expected as there are currently no licensed paediatric medicines for the management of these conditions.After the NPPG alert no patients received unsafe doses or interacting medicines, and the number of patients trialling non-pharmacological treatment for GORD increased. However, there remains a concern that cardiac monitoring is not being undertaken in patients at risk of cardiac defects. It is important to educate healthcare professionals on the cardiac risks of domperidone, and suggest appropriate monitoring in patients with underlying cardiac disease and those receiving concomitant drugs that prolong the QT interval. Clear national guidance, and the introduction of local protocols that recommend which patients need to be monitored and how often may improve domperidone prescribing.ReferencesMHRA. Drug safety update: Domperidone: Risks of cardiac side effects. Gov.uk [Internet]. https://www.gov.uk/drug-safety-upda...
BackgroundClonidine is an alpha-2 agonist acting in the central nervous system (CNS) and licensed for use in all grades of hypertension, prophylactic management of migraine or recurrent vascular headache and management of vasomotor conditions.1 In paediatrics, clonidine has been used for a variety of indications which include use as pre-medication, as analgesia adjuvant, for sedation in paediatric intensive care units (PICU), treatment of spasticity and dystonias, prevention of emergency agitation and in hypertension.2 Oral clonidine has a short half-life of 12 to 16 hours and is associated with peaks and troughs in drug concentration resulting in 2 to 8 hourly dosing intervals. Long-term intravenous clonidine is unviable for a variety of reasons which includes intravenous (IV) access, infection risks and complex ongoing management. Clonidine transdermal patches, approved for use in 1984, provide approximately constant therapeutic drug level for 7 days3 and may represent a viable option for paediatric patients on long-term clonidine.AimTo describe the strategies adopted in converting four paediatric patients to clonidine transdermal patches from either enteral or parenteral clonidine; the benefits and challenges of the conversion.MethodThe intrinsic characteristics of clonidine transdermal patches4 and the therapeutic/clinical goal for each patient informed the switch strategy. Evaluation of the effect of switch was done at least three months after switch through consented open interviews with stakeholders, and evaluation of clinical symptoms.ResultsThe switch strategy to clonidine patch is complex and different for each patient. The factors to consider include: (i) clinical/therapeutic goal for the patient; (ii) the characteristics of the patch (iii) patient’s characteristics – weight and surface area; (iv) detailed counselling of patients and carers; (v) individualised prescription; (vi) ongoing review of supply and patch effectiveness. All patients were switched to patches and achieved approximately equivalent clinical effects, although one child required further dose adjustment. One parent considered the switch to patches to be very good:‘We struggled....we employed the services of night carers four times a week...and we were too exhausted. (The change) has a massive impact on everyone’s quality of life...it has been brilliant’.Another parent observed that the application of patches was not difficult and that the change has been good:‘The nurse gives me the patch, I label them and make three lines on the child’s skin and rotate the patch, so there is always a space spare for 2 weeks before re-applying there again. It is not difficult’.In a clinic letter for another child who was switched to patches, the clinician noted:‘Since he changed to the patches there was no change in his dystonia (and) he has tolerated well. According to mother the main trigger for his dystonic episodes is heat’.One of the nurses looking after another child considered the switch overall to be poor to fair:‘(Using patches) is good in general as they (children) are not attached to pump and easy to move them around...(however) for him (this child), he was too sweaty and patch will fall off...his skin is really dry/red around the cover patches. It would be better if you didn’t have as many as nine patches to apply. It is difficult to wash him with so many patches. He responded better with IV clonidine but we were able to get him off infusion to patches. Education on what to do when it (the patch) falls off will be really useful’.ConclusionThe use of clonidine transdermal patches is a viable option for children needing long-term clonidine. This option has the potential to offer significant cost saving to the National Health Service (NHS) and improved quality of life of children and their carers; especially in those cared for at home. The strategy for conversion is complex and requires taking a number of factors into account. Switch to transdermal patches will not be suitable for all patients and criteria for selecting suitable patients and a generalised framework for switching are yet to be fully described.ReferencesSPC. Clonidine 25 mg tablets BP. Summary of Product Charcteristics 2015. Retrieved June 27, 2019, from Electronic Medicines Compendium: https://www.medicines.org.ukBasker S, Singh G, Jacob R. Clonidine in paediatrics - a review. Indian J Anaesth 2009;53:270–80.SPC. Catapres-TTS. Summary of Product Charcteristics 2016. Retrieved June 27, 2019, from https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Catapres%20TTS/CatapresTTS.pdfSica DA, Grubbs R. Transdermal clonidine: therapeutic considerations. The Journal of Clinical Hypertension 2005;7:558–562.
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