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- Standing, Joseph F., et al.
(författare)
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Population pharmacokinetics of oral diclofenac for acute pain in children
- 2008
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 66:6, s. 846-853
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Tidskriftsartikel (refereegranskat)abstract
- WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Diclofenac is an effective oral analgesic for acute postoperative pain. In adults 25 mg is half as effective as 50 mg, but 50 mg and 100 mg are similarly effective (ceiling effect). Diclofenac has linear pharmacokinetics in this range.center dot Diclofenac is frequently used 'off-label' in children for acute pain but optimum dosing is unclear (dosing of diclofenac in clinical paediatric studies ranges from 0.5-2.5 mg kg(-1)). There is currently no licensed oral paediatric formulation of diclofenac. WHAT THIS STUDY ADDS center dot Using a new diclofenac oral suspension, a dose of 1 mg kg(-1) in children aged 1 to 12 years gives a similar exposure to 50 mg in adults; paediatric patients are unlikely to benefit from higher doses.To develop a population pharmacokinetic model for a new diclofenac suspension (50 mg 5 ml(-1)) in adult volunteers and paediatric patients, and recommend a dose for acute pain in children.Blood samples were drawn at the start and end of surgery, and on removal of the venous cannula from 70 children (aged 1 to 12 years, weight 9 to 37 kg) who received a preoperative oral 1 mg kg(-1) dose; these were pooled with rich (14 post-dose samples) data from 30 adult volunteers. Population pharmacokinetic modelling was undertaken with NONMEM. The optimum adult dose of diclofenac for acute pain is 50 mg. Simulation from the final model was performed to predict a paediatric dose to achieve a similar AUC to 50 mg in adults.A total of 558 serum diclofenac concentrations from 100 subjects was used in the pooled analysis. A single disposition compartment model with first order elimination and dual absorption compartments was used. The estimates of CL/F and V-D/F were 53.98 l h(-1) 70 kg(-1) and 4.84 l 70 kg(-1) respectively. Allometric size models appeared to predict adequately changes in CL and V-D with age. Of the simulated doses investigated, 1 mg kg(-1) gave paediatric AUC((0,12 h)) to adult 50 mg AUC((0,12 h)) ratios of 1.00, 1.08 and 1.18 for ages 1-3, 4-6 and 7-12 years respectively.This study has shown 1 mg kg(-1) diclofenac to produce similar exposure in children aged 1 to 12 years as 50 mg in adults, and is acceptable for clinical practice; patients are unlikely to obtain further benefit from higher doses.
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| 2. |
- Standing, Joseph F, et al.
(författare)
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Prospective observational study of adverse drug reactions to diclofenac in children
- 2009
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 68:2, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- center dot Diclofenac is frequently used off-label in children for acute pain, but little information is available on diclofenac adverse drug reactions in this population. WHAT THIS STUDY ADDS center dot The common adverse drug reactions of diclofenac for acute pain in children are of a similar type to those seen in adults. center dot Serious adverse reactions occur in < 0.8% of children and the incidence of diclofenac-induced bronchospasm in asthmatic children is < 2.7%. AIM The aim of this study was to investigate the type of common (occurring in > 1% of patients) adverse reactions caused by diclofenac when given to children for acute pain. METHODS A prospective observational study was undertaken on paediatric surgical patents aged < 12 years at Great Ormond Street and University College London Hospitals. All adverse events were recorded, and causality assessment used to judge the likelihood of them being due to diclofenac. Prospective recruitment meant not all patients were prescribed diclofenac, allowing an analysis of utilization. Causality of all serious adverse events was reviewed by an expert panel. RESULTS Children prescribed diclofenac were significantly older, and stayed in hospital for shorter periods than those who were not. Diclofenac was not avoided in asthmatic patients. Data on 380 children showed they suffer similar types of nonserious adverse reactions to adults. The incidence (95% confidence interval) of rash was 0.8% (0.016, 2.3); minor central nervous system disturbance 0.5% (0.06, 1.9); rectal irritation with suppositories 0.3% (0.009, 1.9); and diarrhoea 0.3% (0.007, 1.5). No serious adverse event was judged to be caused by diclofenac, meaning the incidence of serious adverse reactions to diclofenac in children is < 0.8%. CONCLUSION Children given diclofenac for acute pain appeared to suffer similar types of adverse reactions to adults; the incidence of serious adverse reaction is < 0.8%.
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| 3. |
- Standing, Joseph F., et al.
(författare)
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Diclofenac for acute pain in children
- 2009
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Ingår i: Cochrane Database of Systematic Reviews. - 1469-493X .- 1469-493X. ; :4
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Diclofenac is commonly used for acute pain in children, but is not licensed for this indication in all age groups. OBJECTIVES: 1) Assess the efficacy of diclofenac for acute pain in children. 2) Assess the safety of diclofenac for short-term use in children. 3) Identify gaps in the evidence to direct future research. SEARCH STRATEGY: Seventeen databases indexing clinical trial reports were searched in February 2005 (with an update search as part of this first review in May 2008). A hand search of Paediatric Anaesthesia was undertaken and summaries obtained of adverse reaction reports from the UK Yellow Card Scheme and World Health Organization (WHO) Monitoring Centre. The reference lists of included studies were also searched. SELECTION CRITERIA: Any published report, in any language, involving the administration of diclofenac to a patient aged 18 years or younger for acute pain and detailing either monitoring of efficacy or safety. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted the data. Authors were contacted where necessary. Review Manager version 5 was used for analysis. MAIN RESULTS: 1) Efficacy: randomised controlled trials (RCTs) comparing diclofenac with placebo/any other treatment by using pain scores (assessed or reported), or need for rescue analgesia.2) Safety: any type of study seeking adverse events (regardless of cause). An adverse event was defined as any reported adverse or untoward happening to a patient being treated with diclofenac for acute pain.Seven publications on diclofenac efficacy and 79 on safety (74 studies plus five case reports) were included in the final analysis. Compared with placebo/no treatment, diclofenac significantly reduced need for post-operative rescue analgesia (relative risk [RR] 0.6; number needed to treat to benefit [NNT] 3.6; 95% confidence interval [CI] 2.5 to 6.3).Compared with any other non-NSAID, patients receiving diclofenac suffered less nausea or vomiting, or both (RR 0.6; NNT 7.7 [5.3 to 14.3]). There appeared to be no increase in bleeding requiring surgical intervention in patients receiving diclofenac in the peri-operative period. Serious diclofenac adverse reactions occurred in fewer than 0.24% of children treated for acute pain. The types of serious adverse reactions were similar to those reported in adults. AUTHORS' CONCLUSIONS: Diclofenac is an effective analgesic for perioperative acute pain in children. It causes similar types of serious adverse reactions in children as in adults, but these are rare. More research on optimum dosing and safety in asthmatic children is required.
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