Drug Utilisation Patterns in Children Admitted to a Paediatric General Medical Ward in Five Countries

Overall, systemic anti-infectives (J) were the most frequently prescribed group (n = 1453; 27.1 %), followed by the nervous system group (N) (n = 1272; 23.7 %). This pattern was also shown in each country. However, whereas respiratory system (R) drugs were the third most commonly prescribed group in HK and Malaysia, in the other three countries the alimentary tract and metabolism drugs group (A) was the third most frequently prescribed group (Table 2).

In the total cohort four therapeutic groups accounted for 55.9 % (n = 2999) of all prescriptions; the highest number was systemic antibacterials (n = 1355; 25.2 %), followed by analgesic drugs (n = 903; 16.8 %), drugs for obstructive airway diseases (n = 472; 8.8 %) and anti-inflammatory and antirheumatic products (n = 269; 5.0 %). Similar patterns were seen in each country for the systemic antibacterials and analgesics. Drugs for obstructive airway diseases were significantly more commonly prescribed in Malaysia compared to the other countries (p < 0.001).

Overall, paracetamol was the most frequently prescribed drug (n = 640; 11.9 %), followed by ibuprofen (n = 248; 4.6 %) and salbutamol (n = 226; 4.2 %) (Table 3). A similar pattern was seen in each country for paracetamol prescriptions, except in Germany where ibuprofen (n = 120; 8.9 %) was the most frequently used drug. The second most frequently prescribed drug varied between countries: in the UK it was ibuprofen (n = 108; 5.4 %), in Malaysia cefuroxime (n = 152; 16.8 %), in HK salbutamol (n = 17; 4.8 %), in Australia gentamicin (n = 36; 4.8 %) and in Germany it was metamizole (n = 115; 8.6 %), which was only prescribed in Germany.

Morphine was only prescribed in the UK (53/2010; 2.6 %) and Australia (12/753; 1.6 %); 92.8 % (n = 39/42) of total fluticasone prescribing occurred in Malaysia, where 4.3 % (n = 39/904) of prescriptions were for this medication.

Overall the oral route had the highest percentage of prescriptions (n = 2816/5367; 52.5 %), followed by the parenteral route (n = 1744/5367; 32.5 %) and inhalation (n = 468/5367; 8.7 %). The pattern was similar in each country cohort (Table 4). Topical (n = 149/5367; 2.8 %) and rectal (n = 135/5367; 2.5 %) routes were used less frequently.

Oral and parenteral routes were the most frequently used routes of administration for the five most frequently prescribed therapeutic groups. The majority of systemic antibacterials (n = 979/1355; 72.2 %) were given parenterally, while the majority of analgesics/NSAIDs (n = 922/1172; 78.7 %) were given orally.

Salbutamol was given via both inhalation and parental routes only in the UK (n = 58 and n = 7 prescriptions, respectively).

Of the total rectal prescriptions, 73.3 % (n = 99/135) occurred in Germany, where 7.4 % (n = 99/1343) of prescriptions were for rectal drugs. Of these, 56.6 % (n = 56/99) were paracetamol suppositories and 17.2 % (n = 17/99) were for sorbitol (laxative) administration.

With regard to topical prescriptions, 67.8 % (n = 101/149) occurred in the UK, where 5 % (n = 101/2010) of prescriptions were for a topical medication. Of these, 16.8 % (n = 17/101) were for lidocaine (in combination) as an anaesthetic.

Overall, 65.1 % (n = 742) of the patients received at least one systemic antibacterial (median 1, IQR 1–2, range 1–10). Of the 742 patients, 51.3 % (n = 381) were exposed to one systemic antibacterial, 29.6 % (n = 220) to two different types of antibacterials, and 19 % (n = 141) were prescribed three or more different antibacterials. A similar pattern was shown in most individual countries with the exception of Australia, where the highest percentage was for patients who received three or more different antibacterials (37.6 %; n = 32/85). In Malaysia the number of patients (n = 244/288; 84.7 %) exposed to systemic antibacterials was higher than in the other countries (p < 0.001). Overall, 99.5 % (n = 1348/1355) of the prescriptions for this group were given parenterally (n = 979/1348; 72.6 %) or orally (n = 369/1348; 27.4 %). This pattern of a high percentage of the prescriptions for systemic antibacterials (J01) given parenterally was also shown in the individual countries [Australia 145/189 (76.7 %), Germany 213/291 (73.2 %), UK 252/397 (63.5 %), HK 41/61 (67.2 %) and Malaysia 328/417 (78.7 %)].

At least one analgesic was received by 60.9 % (n = 694) of patients (median 1, IQR 1, range 1–5) and 22.1 % (n = 252) received at least one ‘anti-inflammatory and anti-rheumatic product’ (median 1, IQR 1, range 1–2) (Table 5).

When analgesic and NSAID prescriptions were combined into one group (Analgesics/NSAIDs), the exposure rates varied between 84.2 % in the UK and 35.3 % in HK (p < 0.001). In the overall cohort there was no significant difference within age groups in the number of patients exposed to this combined group (p = 0.899), nor was there in each country.

Overall, 23.6 % (n = 269) of patients received at least one of the ‘drugs for obstructive airway diseases’ (medium 1, IQR 1–2, range 1–6). Overall, there was a significant difference in the exposure rates among age groups (p < 0.05), but this was not the case among age groups within each country.

Also there was a significant difference in the percentage of patients exposed to this therapeutic group between the countries (p < 0.01): highest in Malaysia (n = 97/288; 33.7 %) and lowest in Germany (n = 37/293; 12.6 %) (Table 5).

In our study we found some differences in the route of drug administration; Germany had the highest use of the rectal route. There are cultural and sexual restrictions to consider regarding this route as there is reluctance in some societies to administer drugs via the rectal route [20]. This might be related to child protection concerns, so rectal administration is only used in exceptional situations when the oral route is difficult to use, such as in a vomiting child [20, 21]. A recent review which investigated the reasons for the unpopularity of the rectal route for drug administration to children concluded that more effort needs to be focused on educating parents and care providers on the benefits of this route for drug administration [22].

Also, we found that administration of therapy by inhalation was particularly common in Malaysia. This is probably linked to the high use of drugs for obstructive airway diseases which is higher in Malaysia compared to the other countries.

The topical route was commonly used in the UK mainly for the administration of anaesthetics. It appears that particular caution is paid in the UK to avoid pain and distress when invasive procedures such as inserting a cannula are performed.

In a German study, it was found that antibacterials were the most common drug class used to treat children in hospital [15]. Our study had similar findings. Antibiotics with broad-spectrum activity were most frequently prescribed. The increased use of broad-spectrum antibacterials, compared to those with a narrow spectrum of activity, in primary and secondary care has been recognised in previous studies [23, 24]. Fossum et al.’s study [24] investigated the antibiotic prescription patterns in primary healthcare in Norway, and found that there was an overuse of macrolides and penicillins with an extended spectrum. However, patients admitted to hospital are often severely ill and need immediate antibiotic therapy. Thus empirical antibiotic therapy to treat a broad spectrum of bacteria is usually commenced. Once the antibiogram is available the treatment is adjusted to eliminate the specific bacteria identified for a specific patient.

In our study, 48.7 % of patients treated with systemic antibacterials received two or more different types of antibacterials, which might have led to the high numbers of antibacterial prescriptions in all countries. The fact that different broad-spectrum antibiotics were used in each country may be due to differences in disease patterns and/or variation in guidelines. The high proportion of patients prescribed systemic antibacterial drugs in Malaysia may be because Malaysia is a tropical country and infectious diseases including respiratory tract infections occur with a reported prevalence of 61.3 % [16]. Our study found that the proportion of total prescriptions for antibacterials was much higher in Malaysia than in the other countries; also the proportion of patients with respiratory system disease was high, which supports this proposal.

The variation in the drugs used among the participating countries could be determined by cultural influences, national guidelines, local or regional policy, local resistance patterns, condition for which the child was admitted, knowledge of appropriate antibiotic prescribing and availability of drugs on the market.

Paracetamol was widely used in all countries, but the use of other analgesics varied, e.g. metamizole was only used in Germany, whilst in the UK and Australia morphine was the most frequently prescribed analgesic after paracetamol. This is in line with previous studies from Germany, Australia, the UK, USA and Italy [10, 15, 25‐29]. Though metamizole is a very effective analgesic and antipyretic and can be used in both adults and children, it is not available in some countries, e.g. the UK, because of its association with rare but life-threatening agranulocytosis and aplastic anaemia [30‐32].

Our study shows there are differences between countries in the number of patients exposed to analgesics/NSAIDs, being highest in the UK and lowest in HK. Use of both an analgesic and an anti-inflammatory drug alternatively, e.g. paracetamol and ibuprofen, was seen commonly in some countries such as Germany, but was less frequent in other countries. It was not possible to ascertain the reason(s) for the differences in the prescription patterns of these drugs among the participating countries as we did not investigate the formularies of the participating hospitals nor their guidelines (if any), but a possible explanation could be due to differences in therapeutic practices, availability of drugs or beliefs in each country. Differences in clinical practice and prescribing behaviour between countries and even among healthcare settings within countries have been shown in previous studies [12, 26, 33, 34].

The study provides an interesting finding regarding differences in pain therapy among the participating countries: in the UK up to 90 % of patients received analgesic therapy whereas only 50 % did in some other countries and none of the adolescents in Malaysia received this treatment. However, it has been shown there is often insufficient pain treatment in paediatric patients [35] and our data indicate this may still be the case at some hospitals.

Our study results show a significant difference between countries in the percentage of patients exposed to this drug group, being highest in Malaysia and lowest in Germany. This could be explained by the high percentage of patients with respiratory system diseases and the tropical climate of Malaysia [36]. The use of two routes of administration for some drugs was found in some countries, for example the use of salbutamol via both inhalation and parenteral routes in the UK, but only by inhalation in the other four countries. The use of one drug via two different routes of administration has been shown to increase the risk of adverse drug reactions [16]. One of the reasons for such differences in practice might be related to the severity of the disease being treated or to variations in hospital guidelines.