Medicines and children

Probably my favourite tip is try and administer the medication with something cold. So like a mouthful of ice cream. The idea behind it is that it numbs the taste buds. So the coldness makes it less likely to cause taste disturbances.

[Music] Welcome to the Australian Prescriber Podcast, Australian Prescriber, independent, peer-reviewed and free.

I'm Dhineli Perera, your host for this episode and it's a pleasure to be speaking to Lucinda Smith today. Lucinda is a senior medicines information pharmacist at the Women's and Children's Hospital in Adelaide. Lucinda and her team tackle the perennial challenge of getting children to take medicines with practical advice and considerations for prescribers and health professionals.

Lucinda, welcome to the program.

Thank you for having me.

Can you start us off by discussing the challenge of convincing children to take medicines. Why has it been so difficult for so long to develop suitable paediatric formulations of medicines?

Yeah, it's a bit of a challenge even to think about. We think it's a bit of a multifactorial issue where children often are referred to as the therapeutic orphan. So this is due to the underdevelopment of treatments that are tailored just for paediatrics. And it's commonly just because they're not commonly studied in clinical trials. So paediatrics are often excluded from the clinical trials. It just means that the drug manufacturers aren't formulating suitable forms of medicines for paediatrics.

Now it is improving, so in both the US and the EU, regulators are now requiring manufacturers to focus on paediatrics and at least have a plan for paediatric formulations. And I think also from a practical point of view, a lot of our formulations for kids need to be oral formulations and they just need additional requirements. So they need to be often liquids, they need to taste good, they need to be easy to administer and they also need to meet that child specifically, which is really difficult because it's timely, it can be expensive, and it's just often one of those things that drug manufacturers just push to the side because it's a bit too hard.

Yeah, and from memory, I feel like along with paeds, the other orphans would be the pregnant and breastfeeding women and the elderly. So the vulnerable I guess in the community are considered to be the least safe to do these trials in and so they're all popped in the too hard basket. "Let's get it out onto market quicker by testing in those healthy average age adults." Right?

Yeah, exactly. So it's that big group of people that often need to use medications but we just don't study them. Rather than relying on clinical and literature evidence, we have to rely on anecdotal evidence, which is not the easiest to find and not the easiest to evaluate either.

So I think you've kind of answered my next question, which was really about the important considerations around selecting a medicine for a child. So you mentioned taste and ease of administration. Was there anything else that you wanted to add to that list of considerations?

Yeah, I think when selecting a medicine for a child, the number one consideration has to be that child. So you need to consider what does it like, what don't they like, what are their abilities, can they swallow tablets or are they actually willing to swallow tablets or can they be taught to swallow? And it's really vital just to keep that child as your primary focus and also bring in the parents or caregivers and think about what works best for them.

Many cases we have in the children's hospital where we'll send a family home with oral liquids for their child and then the next day the caregiver comes back asking for a tablet because it's actually going to be easier for them to administer. So it's really important actually to bring in the family there as well and just consider what's going to work best for them.

And so each dose form obviously comes with its own set of pros and cons. What would you say would be some of the advantages and risks with oral liquids for children?

Oral liquids are often our preferred formulation for children. It's pretty much just because they're easiest to swallow and we can use them pretty much from birth. We can also do flexible dosing. So unlike tablets which have fixed forms or fixed strengths, oral liquids allow us to base the dose on their age and their weight, which is crucial in paediatric medications. And they can also be easily mixed with different flavours and syrups and cordials to help make them taste better.

But oral liquids also come with a lot of risks. The primary risk is over or under-dosing and it's pretty evident if we're measuring really small volumes. Especially if we are thinking about concentrated liquids or drops, it's easy to cause a tenfold dosing error just by measuring 1 mL instead of 0.1 mL. This can be a dramatic dose change for a small child.

There's also a lot of confusion with oral liquids. They often come in lots of different concentrations, especially propriety products that you can buy over the counter like Panadol or paracetamol. Panadol comes in 24 mg/mL, 48 per mL, 50 per mL, 100 mg/ mL, which you can imagine it's really difficult for a parent who's picking up that bottle to make the correct dose adjustments for that formulation they've chosen. So it's really easy to make mistakes with oral liquids that we don't commonly see with a tablet, which is often just pop one tablet out and that's the dose. So that's the biggest risk. And also we're asking parents or caregivers to pull up doses or draw up a syringe or pour out a dose which adds that extra layer of risk for causing an incorrect dose.

So what about excipients? Can they pose a risk to children? And if so, where can health professionals go for excipient lists and allowable amounts for children?

In all our oral liquids there are excipients, and the literature actually shows that excipients commonly used in adult medicines have been associated with safety problems in children. And this is just because the renal and hepatic clearance of children is completely different to adults. But despite this we have to use excipients in our medications. So we have to balance the risk versus benefit of using those.

You can find a list of what excipients are in the product from the product information, so via MIMS or from the TG or through the drug companies directly. And they will list out the excipients that are in there and the concentrations. But as to find out what the maximum concentration allowed for children, that's not easily found. So they're not often described and the data on this topic is actually been extrapolated from adults so we don't have a lot of data studying excipients in children.

If someone's looking for the safety data on that, what we typically recommend is contacting your pharmacist first to see if they have any information, or contacting a medicines information service as we have a bit more access to that available data. Alternatively, there is an online free database that we'd recommend to health professionals to check out. It's called the step database, so S-T-E-P. And it's a government database which is governed by the European Medicines Agency and it collates all the international guidelines and all the literature on paediatric excipients in one place. So you can evaluate what the appropriate dose of excipients could be.

Fantastic, that's a great resource, thank you for that.

So moving on to solid dose forms, how does a parent know if a child is ready to swallow a tablet? Is there a rule of thumb for age or a test that you recommend?

We don't have a set age, so it's completely dependent on the child themselves. It's dependent on whether they have the ability to listen, the ability to learn and take instructions. So on average what we see happening is children from school age up, so six years up, can be taught how to swallow tablets. However, with some support and training, some children less than six years old can learn. This is especially what we see in children who have to take long-term oral medicines for chronic conditions.

But they don't naturally know how to swallow, it's not going to be something that they know to put a medicine in their mouth and swallow automatically. So we have to teach them. And so there's some good resources out there that can teach and train parents and caregivers on how to train your child to swallow the tablets.

So there's ones from the Royal Children's Hospital, they have a guideline. They all typically start with fun and some relaxed activities that involve cutting up lollies into nice small pieces and then getting them to swallow those. And as they feel more and more comfortable swallowing those small pieces, you slowly increase the size up into a bigger size until you're matching a pretty similar size to the tablet that you're wishing to swallow. And you'd have to see how they go with those. But the whole idea is just making it nice, relaxed, comfortable and if they don't get it the first time, it's, "Okay, we get to come back and try it all again."

Fantastic. That's a great idea. Can you walk us through the solid dose forms that are available, Lucinda? It's not as simple as just tablets, right?

Probably the most common we see in paediatrics is tablets, capsules and oro-dispersible tablets. Tablets range in a wide range of shapes and sizes and they're a bit more accessible than oral liquids. So tablets are often more popular, especially in the adult population. So you'll find a lot more medications come in tablet form. Most of these tablets, however, need to be swallowed whole. But some tablets, depending on what the formulation is, can be crushed, halved, quartered to make it a bit easier to swallow. Generally speaking, we don't like to alter slow-release tablets or cytotoxic medications. So if we're going to be manipulating a tablet, you need to consider what it is.

But the good news with tablets is there's actually a bit of research going on into tablets suitable for paediatrics. So more and more manufacturers are looking at using mini tablets. These are tablets less than 3 mm in diameter and these would be suitable for swallowing in less than six-year-old children. So it's good that they're looking into the research and developing more and more options.

Alternatively, there's capsules. Now capsules are generally in a capsule for a reason and it's generally because the medication tastes really bad. But a lot of people find capsules a lot more easy to swallow. That's because they kind of lubricate as they go down your throat so it's easier to go down. Depending on the capsule, some people actually can open them up and sprinkle them on things, but we give them that warning that there's probably a reason it's in a capsule and it's probably because it's poor tasting.

And then the last one, which is oro-dispersible tablets. So these include tablets, films or wafers which are formulated to disperse pretty quickly when they're placed on the tongue . So they're really useful as they don't need to be swallowed. So you don't need to do all that training of teaching how to swallow. And they also have a reduced opportunity for the child to spit them out because they dissolve and go away pretty quickly. And they also often formulate them to taste pretty nice. There's not a huge amount of medicines available as oro-dispersible tablets, but if they're available, it's definitely something that can be trialled in children.

And, coming back to your capsules, in your article you've mentioned Don't Rush to Crush, which is available via MIMS. It's a S-H-P-A publication that's definitely worth having a look at. And would you say, Lucinda, it's probably one of the most frequently used resources to answer this question about what can be crushed etc? Or are there other references that you like to use to answer that?

That's probably our number one resource we'd refer most people to. It's readily available. Most health professionals have at least heard of it or have access through pharmacists. It explains stuff very nice and clearly as well. So it'll tell you whether or not there's precautions on opening up the capsule or precautions for crushing the tablet, especially if there's any hazardous precautions such as with cytotoxic medications. But definitely the number one go-to resource.

We also have in-house data as well within our hospital that we can utilise to help make those suggestions. So if you can't find the information in MIMS or it's not readily available, often it's helpful to contact your local paediatric hospital as well.

Excellent. So Lucinda's article has a really good do's and don'ts list that is worth checking out. I particularly like your mention of not mixing medicines with essential foods. Do you have tips from this list that you find you are frequently sharing with carers and prescribers or health professionals?

Yeah, definitely. So the essential food one is really important when counselling family or caregivers.

But there are a few other tips that we commonly come back to time and time again when we're counselling parents. Probably a number one is if we're using an oral liquid and you popped it in a syringe, just aiming for the back of the mouth. So trying not to just put it directly on the tongue, trying to aim at the back of the mouth in the inner cheek, which decreases how much it's going to cause taste disturbances. Now that bit of advice is a lot easier to say sitting down talking on a phone than it is for parents when they have a child who's refusing to keep their mouth open. But it is probably one of our frequent tips.

Some of the other things we like to do is recommending mixing the medication, so whether it's been a crushed tablet or the oral liquid, into some strong-flavoured cordial or syrup. It needs to be a small volume, so typically less than a mouthful. You don't really want to mix it with a whole glass of water or whole glass of cordial because then the child would have to drink the entire thing to get the dose. But it's often handy if the child gets to pick out which flavour they want, experiment with a different flavoured cordial or different flavoured syrup for their medication to be mixed in. Alternatively is to have a chaser ready. So once the medication's administered have their favourite drink ready so it can wash down the medication to try and get rid of that bad aftertaste.

And finally, probably my favourite tip is try and administer the medication with something cold. So like a mouthful of ice cream. Probably the reason I like this one is the idea behind it is that it numbs the taste buds. So the coldness makes it less likely to cause taste disturbances. So often we recommend if they're really struggling trying with something nice and cold. So ice cream and ice block to try and numb those taste buds.

And then moving onto something similar, which is around taste and texture. These are such complex and evolving senses for young children. Can you talk us through some of the strategies to address complaints from children about the taste, aftertaste or mouth feel of medicines?

They're some of the hardest things to address. So a lot of the medications we have have a really strong bitter taste. And interesting, the human taste buds have actually evolved to dislike bitter taste. It's actually a safety mechanism for us to try and avoid toxic products. So you can imagine it's really hard for us to try and overcome this mechanism. But as I said before, trying to mix that with a strong flavour to try and combat that taste is probably our number one recommendation. So it could be liquorice, it could be peppermint, it could be pineapple, but it's just a lot of variety that you have to trial.

Number one thing with that is make sure you actually consider what the child likes. Because I mentioned there liquorice and peppermint, they're probably the two flavours that children hate. So make sure you actually bring in what the child likes as well. Not as easily said with aftertaste, often this is just how the medication works and it's not something we can commonly get rid of.

For example, we know roxithromycin initially doesn't taste too bad, so it's got a nice, sweet taste initially, however, the aftertaste is renowned to be as bad as possible. We commonly have children who will accept the first dose, but will flat out refuse any further doses. We recommend trying avoiding the tongue as much as possible, such as with that syringe technique. Alternatively, they can try and take the medicine with a straw, or if possible, change the medication so it's not something that's renownedly bad tasting, or consider swapping to a tablet or capsule.

And lastly, mouth feel. That's pretty much the texture. Now, some kids are really sensitive to texture and often they don't like things that are really viscous or really gritty. Some children don't have any concerns about it, but other ones will be really particular. So to improve the viscosity of the liquid, we often recommend diluting in a small mouthful of water to make it a lot thinner. Alternatively, if you're going to try and combat grittiness, such as when we crush up tablets, we recommend just mixing with something thick. So some foods like jelly, custard. Another common advice we use is if it's going to be gritty or they're going to be able to notice that there's something in there, try and mix it with something like yogurt with seeds, such as passionfruit seeds, so you can't really distinguish between the grittiness of the tablet or the seeds.

Oh, that's a good one. I like that last one. I wouldn't have thought of that at all.

And so when it comes to the actual prescribing of medicines for children, are there any golden rules you'd recommend? Now before you answer that, Lucinda, I wouldn't mind throwing in one of my own questions that I commonly have to field myself at work, which is the age that children will flick from being treated as a paediatric patient to an adult. So if you don't mind incorporating that in your answer, I'd really appreciate it personally. But if there's any other really golden tips that you use for the prescribing of medicines for kids, we'd love to hear it.

Sure. Our number one rule is to, again, consider that child. You have to look at them, you have to look at what their capabilities are, you have to look at their preference as well. So we don't necessarily have a cut-off, apart from the age 18 where they move out of our paediatric hospital, where they start to be considered as an adult or treating as a child. You have some children who are really capable from a young age, and we can start counselling them and giving medications similar to how we treat adults. While alternatively, you can have some children who are in their late teens who we're still giving oral liquids too, and still doing more basic counselling. So it is completely dependent on that child.

I think another, now the golden rule that we like to say is try and avoid those medicines that are renowned for tasting terrible. Now, there's not a nice set list out there. It's coming mostly from anecdotal advice that we get from parents, from nurses or from doctors who've been in the practice for a long time, but trying to avoid medications that are renowned for tasting bad. So this includes things like flucloxacillin, roxithromycin, they're known to taste terrible. So we'd rather you choose a more palatable medicine if appropriate for the indication. So obviously it's highly dependent on what we're treating and what we can use to treat, but we're just trying to avoid those if possible.

We also try and make sure it's nice and easy for dose frequencies. So trying to use something that's twice daily over four times a day is preferred, especially in younger children, it's more likely that you're going to get it into them. This is also really particularly important for school-aged children. If they're in school, it's going to be really hard to organise a school carer or school teacher to administer medicine. So we try and recommend dose frequency that's outside of school hours.

Excellent. And so finally, you have a great list of resources in your article and we've already mentioned Don't Rush to Crush. Are most of these resources freely accessible or do you typically need a subscription to access them?

Nearly all the references and resources that we utilise in the article are freely accessible on the internet. So that is besides the MIMS, which you need a subscription to, which has Don't Rush to Crush. All the other ones are freely available. So that includes the Royal Children Hospital guidelines and patient leaflets and the UK-based Medicines for Children leaflets. They're all freely available to download online.

Fantastic. Well, that's unfortunately all the time we've got for this episode. Thank you so much for joining us today, Lucinda.

Thank you so much for having me.

[Music]

Lucinda's full article is available online. The views of the hosts and guests on the podcasts are their own and may not represent Australian Prescriber or NPS MedicineWise.

I'm Dhineli Perera and thanks for joining us on the Australian Prescriber Podcast.