Background A male infant was admitted to the neonatal unit with respiratory distress, following delivery by emergency caesarean section at 36/40 for maternal illness (viraemia). The patient’s condition deteriorated with disseminated intravascular coagulation (DIC), abnormal liver function, ascites and pleural effusions. Enteroviral sepsis was diagnosed following positive enterovirus PCR on lumbar puncture and stool sample.

Summary of problem There are no commercially available treatments for enterovirus in the UK. Following an extensive literature search, the neonatology consultant became aware of an experimental treatment with potential action against enterovirus.^{1 2} Pocapavir is an investigational drug candidate developed for poliovirus indications, but also has antiviral activity against nonpolio enteroviruses. The consultant was keen to exhaust every option, so reached out to the company in the US. The company (Virodefense) offered to provide the drug on a compassionate use/open label trial basis, asking that regular pharmacokinetics tests be carried out as part of the agreement to supply.

Pharmacy contribution Following the initial contact with Virodefense, there were several challenges for the specialist pharmacist and pharmacy procurement team. Working with IDIS and Virodefense, arrangements were made for shipment of the medication to the pharmacy department. This was complicated by the urgency of the situation and the time differences involved. Pocapavir is in phase 2 clinical trial which required the MHRA to be notified to approve the importing of the drug into the country. The MHRA were quick to give a positive decision which allowed the product to be delivered direct to the hospital while IDIS handled the importing documentation. The advised dose was 25mg/kg daily, the drug came as 500 mg capsules containing 200mg of pocapavir (with 300 mg excipients).

The patient (2.7 kg) required 67.5 mg daily. The pharmacy manufacturing unit packed down 170 mg capsule contents (68 mg active ingredient) into individual pots for the neonatal unit to administer. Doses were mixed with EBM and given daily for 14 days.

Outcome The patient recovered from the acute sepsis episode. The patient was also treated with immunoglobulin and standard supportive care so it is impossible to know how much can be attributed to the pocapavir. Pharmacokinetic samples were taken as agreed. After recovering from the initial acute sepsis the patient developed hypoglycaemia between feeds. These were investigated and metabolic causes were excluded. The working diagnosis was a response to the large hit to the liver during the septic episode, although an adverse effect of pocapavir cannot be excluded. Hypoglycaemic episodes continued and the patient was still fed 3 hourly on discharge. The patient is growing and developing well, tolerating longer fasts of 6 hours without hypoglycaemia and reducing risk in the provision of parenteral nutrition for effects that could occur due to opioid toxicity. The patient has been discharged from neonatal follow up.

Lessons to be learned Where there’s a will there’s a way! There were many barriers to overcome including regulatory, logistical and practical complications but thanks to a concerted effort from a wide variety of teams, co-ordinated by pharmacy, the patient received this treatment. Although the contribution of this experimental drug is unclear the positive outcome for a very unwell infant should be celebrated.

References

1. Modlin JF. Treatment of Neonatal Enterovirus Infections. J Pediatric Infect Dis Soc 2016;5:63–64

2. Torres-Torres S, Myers AL, Klatte M, et al. First Use of Investigational Antiviral Drug Pocapavir (V-073) for Treating Neonatal Enteroviral Sepsis. Pediatr Infect Dis J 2015;34:52–54.