Background Brincidofovir (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 contributions After 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.
Outcome The 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 learned BCV 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 patient cohort. Access to BCV is only through the NPP scheme until completion of on-going clinical trials. Close monitoring for severe side effects remains essential.
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