Rational prescribing and dispensing of oral dosage forms of medicines to children: an observational study

Introduction

The WHO defines the rational use of medicine (RUM) as ‘patients receiving medications appropriate to their needs, in doses that meet their requirements, for an adequate period and at the lowest cost to them and their community’.1 The RUM needs rational prescribing, rational dispensing and RUMs.1 Irrational use of medicines is the use of medicines that are not as per the above definition. Irrational use of medications is prevalent across the globe, and about half of the medications prescribed and dispensed are found to be inappropriate.2

The irrational use of medicines resulted in several problems for the healthcare system in many aspects and caused economic losses.3 Therefore, it is mandatory to promote RUMs; for this, the WHO develops core policies to promote rational use of medicines. However, before the promotion, it is critical to identify the type and degree of irrational use of medications.1 The irrational use of medications may be higher in children compared with adults, as they usually do not have access to age-appropriate dosage forms.4–9 Prescribers and pharmacists face various challenges when it comes to rational prescribing and dispensing of medicines due to a lack of appropriate dosage forms for children.10

The limited availability of suitable or age-appropriate oral dosage forms (ODFs) for children resulted in the practice of prescribing and dispensing adult ODFs to the children. As a result, manipulation of dosage forms like crushing, splitting tablets, splitting suppositories, dissolution of tablets, and so on are considered and practiced in the course of prescribing and dispensing medicines.4 6 Several factors influence ODF manipulation, including whether the tablet is scored or unscored, tablet hardness and friability, whether the prescription dose is much lower than the administered formulation, and so on. These manipulated dosage forms have issues with the safety, efficacy, palatability and acceptability of ODFs.4 11–13

The RUMs was extensively researched using WHO core drug use indicators, a well-established tool for assessing irrational medication use.14 However, because the indicators are generic, they will not assess rational medication use in unique populations such as paediatrics.15 The RUMs in the paediatric population is not well studied in a manner that addresses specific issues related to them. This study was aimed at assessing the rational prescribing and dispensing of ODFs of medicines to children at ambulatory clinics using newly developed validated indicators.15

Methods

Results

Discussions

The RUMs in children and adults has been extensively studied using the WHO core indicators. Many studies assess the broad issues of RUM using generic indicators; these indicators may not address some issues specific to the paediatric population. There are few studies conducted that have used these paediatric-specific indicators. In this study, rational prescribing and dispensing of paediatric dosage forms were assessed. The average number of drugs per child was 1.33±0.62. This is lower than the ideal value, which is less than 2, or 1.6–1.8. When the average number of drugs per child is above the ideal value, it suggests the presence of polypharmacy.22 The lower value in this study may be due to the limited number of drugs available in the setting, which in turn may affect the prescribing pattern.

The percentage of ODFs of medicines prescribed in a dose appropriate for the weight was 150 (16.1%), 95% CI: 14% to 18.4%. This is one of the newly developed indicators to support the WHO core drug use indicators, which was aimed at assessing the tendency of prescribers to use a weight-based dosing approach.15 In this study, the percentage of ODFs appropriate for the weight was slightly lower than in a study done in Sri Lanka (23.7%).16 This may be due to the fact that, in the majority of prescriptions, weights were not recorded at 701 (75.3%, 95% CI: 72.6% to 78%). Even though there were balances in paediatric ambulatory and follow-up clinics, weights are usually not recorded. The result needs to be interpreted cautiously, as the majority of prescriptions’ weights were not recorded. Such a type of problem was reported in a similar study done previously.16

The percentage of solid ODFs prescribed was 56.3% (524) (95% CI: 53.2% to 59.5%) of 931 total ODFs. This is an indicator that shows the tendency of the prescribers to prescribe solid ODFs to children. As we can see here, more than half of the children have been prescribed solid ODFs. The percentage of solid ODFs prescribed was higher than a similar study that was done in Sri Lanka (33%).11 In addition, solid ODFs prescribed for infants and toddlers account for 8.9% of prescribed solid ODFs. Generally, solid ODFs are not acceptable for infants and toddlers.4 20 This high percentage of solid ODFs prescriptions may be in part due to the unavailability of paediatric-specific dosage forms in resource-limited settings. In the pharmacies for chronic follow-up care, more than 90% of medications prescribed for children were tablets. Even though the term solid ODFs includes granules, powders, tablets, capsules, pellets and others, almost all of the solid ODFs prescribed in this study were tablets, 51.3% of the total 56.3% of the prescribed solid ODFs; the rest were capsules. Tablets and capsules have minimum dose flexibility, particularly for those with weight-based dosing, compared with liquid ODFs. It is better to procure liquid ODFs of medicines for paediatrics which have optimal dose flexibility.

One of the newly developed indicators was the percentage of ODFs suitable for the age, which was 92.9% (859) (95% CI: 91.2% to 94.4%). This finding was in harmony with a study done in Sri Lanka, in which 90% of the total dosage forms prescribed were suitable for age.11 But higher than in a study done in the Netherlands (67% in ICU and 85% in non-ICU),23 This variation is mainly due to the variability of criteria for suitability, as they used the European Medicine Agency matrix.24 The proportion of ODFs not suitable for age accounted for 7.1% (66) (95% CI: 5.6% to 8.8%). We considered that solid ODFs are not suitable for children ≤2 years.15 However, the term ‘age suitability’ is a broad term and has variable cut points in different studies; some say starting from 3 years and some say 6 years.4 10 The European Medicine Agency sets a variable tablet size for ages 3–18 years.25

The mean number of tablets prescribed per child per day was 1.13±1.44 (median 1 (0–2)). Whereas, the mean number of tablets prescribed in the chronic care pharmacy is 1.6±1.54, and 0.43±0.99 in the OPD pharmacy. The higher mean in the chronic care pharmacy was because more than 90% of the prescribed medications in this dispensary were tablets. The mean volume of liquid prescribed per child per day was 6.05 mL±9.79 mL. The mean volume of liquid prescribed in the OPD pharmacy was 13±11.38 mL. This figure is much higher than the maximum daily dose recommended by the European Medicine Agency, which was 5 mL for 0–3 years and 10 mL for 4–12 years.25 Exposing the children to high amounts of liquid dosage forms will expose them to high amounts of excipients. The mean volume of liquid medications in the chronic care pharmacy was 0.8±2.59 mL. The higher mean value of liquid dosage forms was due to the fact that most liquid ODFs were prescribed in the OPD pharmacy.

The number of instances in which alternative ODFs were dispensed was 1% (95% CI: 0.3% to 2%). This was in line with the study done in Sri Lanka, which was 0.9%. According to WHO standards, the number of instances in which alternative dosage forms are dispensed should be 0.11 21 However, due to the limited supply of medications in resource-limited settings, the prescribed medications may not be available and may be a major contributor.

The number of ODFs dispensed with adequate labels was 0.8% (95% CI: 0% to 1.8%) both in the OPD and the chronic care pharmacy. This is in harmony with some studies done in Ethiopia, Egypt and Pakistan with the three facilities, which range from 0% to 0.3%.23 26–28 However, this is much lower than many other studies conducted in Ethiopia and India, which range from 3% to 100%.29–32 According to the WHO, adequate labelling means that, at least the patient’s name, drug name and when to take the drug should be included. Many of the dispensed medications have labels that may indicate when to take the drug and/or the drug name. In addition, high patient loads and not having proper labelling materials are also some of the many problems.

In our study, 0.8% (95% CI: 0% to 4%) of ODFs were dispensed with adequate advice on storage conditions. In another study done in Sri Lanka, 10% of drugs were dispensed with adequate advice on storage conditions; this result was much higher compared with the other study done in Sri Lanka.11 In our setting, there was very poor practice of advising patients on the storage conditions of drugs. Advice on the storage conditions was not common unless the dosage form type needed special storage conditions. If drugs are not properly stored, they may be exposed to light, humidity and extreme temperatures, making them less effective.

From the 400 ODFs dispensed by the pharmacists, 81 (39.7%) (95% CI: 33.7% to 47.1%) of drugs needed manipulation before being administered as a single unit. From this, the chronic care pharmacy accounts for 95.1% (77) of drugs that needed manipulation. The types of dosage forms of dispensed drugs that needed manipulation were immediate release, sustained release/controlled release and enteric-coated with 38.4%, 0.5% and 1%, respectively. The majority of tablets that needed manipulation before being administered as a single dose were unscored at 68 (84.0%), and about 12 (14.8%) tablets that needed manipulation were scored into two. Generally, unscored tablets, as well as controlled or sustained-release tablets, are not suitable for manipulation.33

The percentage of ODFs that needed manipulation before being administered as a single unit was 81 (39.7%) (95% CI: 33.74% to 47.3%). This was in agreement with a study done in Germany (37%),34 but slightly higher than many other studies done in Sri Lanka, China and Sweden (22%, 20% and 14%, respectively).11 35 This variation with German may be due to the fact that the German study was conducted in paediatric wards rather than OPD pharmacies. Being in a limited resource setting might impact the availability of paediatric-specific dosage forms; due to this, there is a need to manipulate adult dosage forms. In addition, most adult dosage forms are tablets or capsules, which have the least dose flexibility among different pharmaceutical dosage forms. Moreover, most paediatric medication dosage regimens use weight-based dosing; usually, the calculated dose may not be easily tailored for the children, which may lead to manipulation of dosage forms. The most important point in the manipulation of dosage forms is the quality of the manipulated dosage forms; many of the dosage forms are not suitable to practice the ‘best practice of tablet splitting’.33 36 For example, most of the dispensed tablets that needed manipulatioin in this study were unscored tablets 68 (84%); more than 90% of tablets had standard shapes (convex), sustained release or controlled release (0.5%) and were enteric-coated (1%). These types of dosage forms are not generally suitable for splitting or manipulation. Manipulating such types of ODFs is considered an off-label manipulation; most of the manipulations of dosage form practices were off-label.34 35 These factors highly affect the delivery of appropriate doses to the children and the pharmacotherapy of the children as well. Furthermore, this has been confirmed by many previous studies: more than 50% of individuals faced problems during splitting,37 and inadvisable manipulation was 20%.35 In a study done in Sweden, most active pharmaceutical ingredients have limited solubility and are sensitive to formulation changes.10 A focus should be given to the provision of paediatric-specific dosage forms to the children.

Conclusion

The practice of rational prescribing and dispensing was assessed. The proportion of the prescribed medications that were adequate for the weight of the child was low; despite this, the majority of the prescriptions’ weight was not recorded. Therefore, it needs cautious interpretation. ODFs not suitable for children were prescribed. The majority of the dispensed ODFs were not adequately labelled. The proportion of medications that need manipulation before administering a single unit was high, especially in the chronic care pharmacy. Emphasis needs to be given to improving rational prescribing and dispensing of ODFs to children who have chronic follow-up.

Limitations

The study was a single-centred study, and the findings may not be generalisable outside of the institution. Conducting a multicentre study may increase the generalisability of the study findings. It would be better if the administration practices of ODFs for children were assessed, as this may assess the RUMs at the patient level.