This audit has shown that the guidelines are being followed but the paediatric dosing of vancomycin requires modification to achieve therapeutic levels. Limitations of the audit included low patient numbers, standard 1 and 3 could not be assessed and an assumption was made that all the levels documented were taken at the correct time, unless stated. Not enough data were collected to make suggestions based on different ages. An option would be to follow recommendation that frequency of dosing is changed from three to four times a day.1 A continuous infusion of vancomycin could also be considered.
BackgroundBrincidofovir (BCV) is an antiviral drug currently undergoing stage 2 clinical trials in America. BCV is released only on direct application with subsequent approval from the manufacturer; Chimerix. It is currently available via the Named Patient Program (NPP); an open-label, non-randomised, multi- centre expanded access program that provides access to BCV for patients that are not currently enrolled in a BCV clinical trial. It has previously been approved for use in Adenovirus treatment, with requests for use in other indications being denied.On day +33 post bone marrow transplant (BMT), our patient began suffering from gut graft versus host disease (GVHD). According to Trust protocol, he was started on methylprednisolone intravenously(IV), then budesonide orally (PO). He received subsequent courses of infliximab(IV), basiliximab (IV), and ruxolitinib (PO). During treatment with ruxolitinib the patient was diagnosed with Adenovirus. This is not routinely treated in otherwise well patients, however due to severe immunosuppression following BMT and high dose steroids for GVHD, cidofovir was started. No improvement was seen, and viral load continued to increase (from 7290 copies/mL on day +74 to 9 53 000 copies on D+83) alongside cidofovir related renal toxicity.Pharmacist contributionsAfter a discussion with the MDT since BCV is experimental and unlicensed, the specialist pharmacist (SP) contacted Chimerix to begin the application process alongside the Lead Consultant; providing detailed clinical information for panel approval. The Chief Pharmacist was contacted to ensure correct paperwork was in place, ensuring import of an unlicensed medication from America would be both financially sound and approved for use within the Trust. The SP then contacted the Trust pharmacy purchasing department and created a new line form on the Trust’s dispensing programme ready to receive the product; shipping and delivery arrangements were organised with the company. Finally the SP contacted the pharmacy Quality Assurance/Quality Control department to agree any further verification before use in a patient at the Trust.Treatment began at 2 mg/kg twice weekly on day +90 post transplant. The SP explained the key information in the pharmacy manual and individualised treatment plan for the patient to the MDT, and ensured the product did not interact with current BMT regimen. A major side effect identified during clinical trials was diarrhoea, which due to pre-existing GVHD was difficult to distinguish so the patient was closely monitored with regular stool charts and fluid balance review.OutcomeThe patient significantly improved, with adenovirus load becoming undetectable (<50 copies/mL) after 9 doses of BCV. Two negative blood polymerase chain reaction (PCR) results were received before stopping treatment on day +119.Lessons learnedBCV has been shown to be a useful agent to use to treat Adenovirus in the paediatric bone marrow transplant population, however more experience of its use is needed to ensure efficacy across this pa...
BackgroundTMA is a life threatening complication with a high mortality rate in SCT patients.1 The pathophysiology involves damage of the endothelial lining via over activation of the complement system which forms part of the innate immune system.2 Complications include; kidney damage, pulmonary hypertension and possible multi organ failure.1 Eculizumab is an agent that exhibits activity by inhibiting the complement system however dosing and effects in the paediatric population are lacking.1,2 An 18 year old patient was admitted to the paediatric SCT unit for a sibling haploidentical SCT. On day +48 she developed worsening acute kidney injury, hypertension and confusion. She was diagnosed with TMA confirmed via fragments on the blood film, blood in the urinalysis and an elevated lactate dehydrogenase (LDH).Summary of the problem encounteredThe use of eculizumab is limited in paediatric centres. Furthermore there is limited dosing and monitoring information available for paediatric patients for the unlicensed indication of TMA. The urgent nature of the request of this medication due to the rapid deterioration of the patient meant there was no time to submit a non- formulary drug application or develop local protocol guidance. However when presented with a drug request for an unfamiliar drug several # had to be taken to ensure the safe and effective use of this drug.Pharmacy contributionsThe first step involved determining an appropriate dosing regimen. A literature search was conducted alongside the attending consultant to determine this. Consequently the pharmaceutical company was contacted requesting a supply of the drug and required paperwork completed including a certificate of vaccination form. The next step involved calculating the total anticipated treatment cost as eculizumab is an extremely expensive drug. As this was non formulary and off label, the attending consultant took clinical responsibility and approval was sought from the Chief of Service and Chief Pharmacist. A prescription and administration proforma was designed which also included monitoring information and pre-medication required. Monitoring parameters to determine clinical efficacy were closely observed, this mainly included LDH and CH50 levels.OutcomeThe patient clinically improved and eculizumab was stopped on day +222, the treatment course was longer than originally anticipated however CH50 levels were suppressed to <25%.Lessons learnedAlthough unlicensed eculizumab was effective against TMA complications experienced post SCT. This is however a high cost drug with complex monitoring requirements, also requiring a vast amount of support from pharmacy services.Procedures are underway to develop local guidance for its use and also individual funding requests to be completed before treatment in order to gain funding for individual cases for this off label condition.ReferencesJodele S, Fakuda T, Vinks A, et al. Eculizumab therapy in children with severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Biol Blood M...
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