Variations in captopril formulations used to treat children with heart failure: a survey in the United kingdom

Background and objective

Different liquid formulations of a drug prepared for use in children cannot be assumed to have therapeutic equivalence. The objective of this study was to ascertain the interhospital constancy of unlicensed liquid captopril formulations used to treat children with heart failure in the UK.

Design

A questionnaire‐based telephone survey.

Setting

13 tertiary paediatric cardiac centres in the UK and 13 large hospitals referring patients to these centres.

Participants

The study included pharmacists responsible for providing the pharmaceutical input to children with congenital heart disease or a pharmacist designated to cover paediatric services. Technical staff employed by “specials” manufacturers also participated.

Results

Four hospitals dispensed captopril tablets for crushing and dissolving in water before administration; the remaining 22 used nine different liquid formulations of captopril. Only three cardiac centres and their referring hospitals were found to be using the same liquid captopril formulations; 10 centres and their referring hospitals were using completely different captopril formulations.

Conclusions

This survey shows that paediatric cardiac centres and their referring hospitals use a variety of unlicensed liquid captopril formulations interchangeably. This degree of inconsistency raises issues about optimal captopril dosing and potential toxicity, such that its use may influence paediatric cardiac surgical and interventional outcomes.Captopril is a common and well‐established pharmacological treatment for managing children with heart failure. However, its use in this patient group is largely founded on drug efficacy and safety data from studies involving adults with acquired heart disease.^1,2 Although clinicians do not doubt the efficacy and utility of captopril in managing children with heart failure, concerns exist about optimal dosing schedules and toxicity.^1,2 One parameter that may cause significant variation in ensuring optimal dosing and minimal toxicity is its formulation.³ Currently, licensed captopril is available only in tablet form; many children are either unable or unwilling to swallow tablets. At our institution, we use an unlicensed liquid captopril preparation obtained from a “specials” manufacturer. Such manufacturers operate under a specials manufacturing licence, although their medicines do not undergo formal clinical studies and are therefore not licensed with any regulatory authority. Thus, as with many other pharmaceutical formulations obtained from “specials” manufacturers, liquid captopril does not have any supporting bioequivalence data.Although our institution is a regional congenital heart centre, we have no control over the type of formulation dispensed by other hospital pharmacies or even community pharmacies that serve children whose care is co‐ordinated in our institution. Although it is difficult to quantify the clinical effect this has, we have noticed large interpatient variability in the duration of time needed to optimise the dose of captopril (with the resulting inconvenience for the patient and family of spending more time in hospital). The variation in the type of liquid captopril formulation dispensed to children in our service raises relevant issues about optimal dosing and toxicity. To determine whether this was a local or national issue, we performed a national survey of all pharmacies linked to a congenital heart service and of neighbouring hospital pharmacies.     

Fanconi-Bickel syndrome

We present here the first case of Fanconi-Bickel syndrome, a rare type of glycogen storage disease, from India. A 17-month-old female child presented with severe growth retardation and abdominal distention. Clinical examination revealed a "doll-like" face, massive hepatomegaly, and rickets. Laboratory investigations confirmed severe hypophosphatemic rickets and proximal renal tubular dysfunction. Liver biopsy showed glycogen accumulation in the hepatocytes.     

Esophageal reconstruction with larynx preservation using forearm-free flap

Surgery for cervical esophageal malignancy frequently involves comcomitant total laryngectomy carried out because of either oncologic or functional concerns. Though uncommon, preservation of the larynx has, in recent years, been described in patients undergoing cervical esophagectomy with reconstruction of the resulting circumferential esophageal defect achieved using either free jejunal flaps or gastric pullup procedures. The use of tubed-free cutaneous flaps for circumferential cervical esophageal reconstruction, however, has been rarely described in situations where the larynx has been preserved. We describe successful use of a tubed radial forearm-free flap for reconstruction of a circumferential cervical esophageal defect with preservation of the larynx. Use of the radial forearm flap in this situation resulted in minimal donor site-related morbidity, avoided the need for laparotomy and excellent voice and swallowing function were maintained. As such, use of tubed cutaneous free flaps can be considered an option for cervical esophageal reconstruction when the larynx has been preserved.     

Unifocal, subconjunctival twin cysticercosis cysts

We report a case of multiple, unifocal, subconjunctival cysticercosis in an 8-year-old boy. Two cysts, each with a scolex, were in the subconjunctival space. They were removed surgically, and histopathologically proven to be Cysticercus cellulosae. This is only the second report of twin cysticercus in the literature, to the best of our knowledge.     

Subdural empyema in a case of Gaucher disease: a rare presentation

Subdural empyema is a surgical emergency; if not recognized and managed early, it may prove fatal. In most of the cases, condition is preceded by paranasal sinusitis, otitis media or trauma. The authors report a previously undescribed case of spontaneous subdural empyema associated with Gaucher disease that had a good outcome following burr hole evacuation of subdural empyema and parenteral antibiotics. Patients with Gaucher disease may be vulnerable to severe bacterial infections, due to defective function of phagocytic cells and hypersplenism.