Prevalence of ethanol and other potentially harmful excipients in pediatric oral medicines: survey of community pharmacies in a Nigerian City

Abstract

Objective Excipients are needed in the formulation of oral liquid medicines intended for children; they have however been reported to trigger safety issues. This study evaluated the concentrations and prevalence of ethanol and other potentially harmful excipients in pediatric formulations marketed in South Eastern Nigeria in line with international labeling guidelines and allowable daily limits (ADL). The study sampled oral pediatric formulations offered for sale in registered pharmacies. Those with accessible information leaflets were assessed for the presence and quantity of previously flagged excipients with potential to harm the pediatric population. Result Of the 380 oral pediatric medicines, 140 provided access to list/quantity of ingredients. 47.9% (67) of the formulations contain at least one of the flagged excipients while the remaining only listed the active ingredients. Ethanol had the highest occurrence (62.7%) and was more in cough/cold medicines. A homeopathic cough and cold remedy had concentration of 90% v/v. Ethanol and sucrose in some formulations exhibited concentrations with a potential of crossing their approved daily intake (ADI) (1–90% v/v and 1.7 g–3.7 g/5 ml respectively). Ethanol use in studied pediatric formulations was quite high, with ethanol-containing formulations being prescribed for children 0–6 years and older. Only 26 (38.8%) completely satisfied the labelling requirements for ethanol containing formulations.

Excipients in the Paediatric Population: A Review

“…Paediatric formulations need excipients to maintain their quality and promote the acceptability of childhood patients [25]. However, just because they are necessary does not mean that they are toxicity-free products; in fact, a study by Georgi and collaborators [26,27] confirms that many of the medicines used in paediatrics contain some toxic or potentially toxic excipient for the paediatric population, with this data being present in two-thirds of new-borns in 21 European countries. Thus, excipients used in paediatric formulations require a thorough assessment of short-term and long-term safety prior to their use in these formulations [28].…”

“…For this reason, permissible maximum limits have been set and, in some countries, non-alcoholic medicines are to be established. It is a very permeable excipient with regard to the blood-brain barrier, and the one most commonly used in oral medicinal products, reaching 63% of cases [26]. It is rapidly absorbed into the gastrointestinal tract and is primarily metabolized in the liver to acetaldehyde, which is oxidized to acetate [29].…”

“…Indeed, Macrel and Bernando's review of liquid formulations in Brazil has furthered our understanding of the high use of ethanol. These researchers demonstrated that ethanol is used in various concentrations and functions: as solvent (main function), co-saver, flavouring agent, preservative and as an extraction solvent in herbal medicines [26,27]. It also has antimicrobial properties and increases the permeability of many preparations [29].…”

“…One of the large prospective studies conducted by Nellis and collaborators [36,37] in hospitalized neonates in Europe described the administration of eight potentially harmful excipients of interest (EOI) (parabens, polysorbate 80, propylene glycol, benzoates, sodium saccharine, sorbitol, ethanol and benzalkonium chloride) and identified risk factors resulting from exposure. Neonates appear to lack the ability to conjugate benzoates with glycine, leading to the accumulation of benzoic acid that can cause metabolic acidosis and neurotoxicity [26,27].…”

<p>Safety and Biopharmaceutical Challenges of Excipients in Off-Label Pediatric Formulations</p>

“…There are severe acute and chronic adverse effects with the use of ethanol-containing medications in the pediatric population. 40 , 41 Acutely, the co-administration of ethanol may alter the drug absorption or metabolism and may result in drug interaction. In addition, ethanol causes severe adverse effects on the central nervous system when its concentration in blood arising in the range of 1–100 mg/100 mL.…”