One of my earliest lessons as a pharmacist working in the “real world” was that customers didn’t always act the way I expected. Parents of sick children frequently fell into this category — and the typical vignette went like this for me:

Parent has determined that their child is sick, and needs some sort of over-the-counter medicine. Parent asks pharmacist for advice selecting a product from the dozens on the shelves. Pharmacist uses the opportunity to provide science-based advice, and assures parent that no drug therapy is necessary. Parent directly questions the validity of this advice, and may ask about the merits of a specific product they have already identified. Pharmacist explains efficacy and risk of the product, and provides general non-drug symptom management suggestions. Parent thanks pharmacist, selects product despite advice, and walks to the front of the store to pay.

In many ways, a pharmacy purchase mirrors the patient-physician interaction that ends with a prescription being written — it’s what feels like the logical end to the consultation, and without it, feels incomplete. It’s something that I’m observing more and more frequently when advising parents about cough and cold products for children.

My Beautiful Baby is Sick!

New parents discover quickly that their child can instantly turn into a pint-sized “Patient Zero“, attracting what can feel like years of continuous cold symptoms. It’s true, kids get about six to eight colds per year, on average, and each can last up to two weeks. Compared to adults, colds are different in children. Runny noses are the most common symptom, and fever is frequent, too. Other common symptoms include sore throat, cough, difficulty sleeping and reduced appetite. Ear complaints are also common.

The Treatments — and the Science

While there are hundreds of cough and cold products available, there’s actually very few differences between brands. Each manufacturer puts together their own concoction based on a small number of approved ingredients. The main differences between Benylin, Triaminic, or Dimetapp are packaging, flavouring, and marketing — the chemical ingredients are usually the same. For example, dextromethorphan is the typical cough suppressant. So a “DM” cough syrup is pretty much the same, no matter who makes it.

Cough and cold products have been sold for decades, long before rigorous proof of efficacy was required for regulatory approval. Consequently, clinical studies that support these drugs are (in general) of poor quality. When we look for studies of treatments specifically in children, the data are even more limited. Research results are complicated by different age groups, irregular dosing, lack of placebo control, and very small patient numbers.1 It turns out that the current recommended dosage for children, typically determined during clinical trials, is based mainly on expert opinion. When these products were originally approved, it was assumed that children were just “small adults” and that research in adults could be applied to children. Dosages were estimated based on ages — not weight, which would be more relevant.1

But children are definitely not small adults. Differences exist in how children absorb drugs (e.g., stomach pH) and where the drug distributes in the body (e.g., body fat percentage). Their ability to metabolize drugs can differ, too. Consequently, drugs can behave in different and unpredictable ways, compared to adults. Few studies have examined how cough and cold products behave in children, so their absorption, distribution, metabolism and elimination are poorly understood. An FDA expert advisory panel commented that it was inappropriate to extrapolate data from adults to children.2

The data may be summed up by their absence — there’s very little evidence to demonstrate these products are effective in children, and there’s some evidence to suggest that they are probably ineffective. Yet cough and cold products have a long history of use in children, with very rare reports of toxicity, usually due to inappropriate (excessive) dosing.3 In general, these drugs have a wide “therapeutic window,” meaning that large overdoses are required before serious side effects are expected.

But when you’re treating a mild, self-limiting condition with ineffective or unproven products that have a remote (but possible) risk of harm, the appropriate question should be “Why medicate?” And that’s the questions regulators around the world have been asking.

Regulatory Actions

Depending on a particular government’s policies on self-medication, and their own interpretation of the data, evaluations can differ, which I’ve pointed out before. In the case of cough and cold products in children, major regulators have all taken action to discourage their use:

In 2008, a Food and Drug Administration (FDA) advisory panel concluded that cough and cold products in children were ineffective and potentially hazardous. The committee recommended that they should be relabelled to indicate “do not use” in children under the age of six. Following this announcement, product manufacturers voluntarily relabelled their products to state “do not use” in children under the age of four.

Health Canada determined that cough and cold products should be relabelled to caution against use in children under the age of six. Products developed for this age group are no longer permitted.

In Australia, cough and cold products are now labelled “do not use” for those under the age of 2, and are available only with a prescription. They continue to be marketed and sold with labelling for children aged 2–12.

In the United Kingdom, products for children under the age of six are withdrawn. Medication for children aged 6–12 will continue to be available, with new warnings on the label.

(For those interested, here is a nice summary of actions taken by the TGA and other regulatory agencies regarding cough and cold medicines in the treatment of children.)

Remarkably, the restriction of these products may already be having an effect. A paper published this week in Pediatrics draws a relationship between the restriction of cough and cold products, and a decrease in emergency room visits for adverse events from their ingredients.

The Market Reacts

As someone who wears both a “pharmacist” hat and a “sleep-deprived parent of sick child” hat, I recognize the sense of urgency: a sick child is no fun for the parent or the child. Parents want to do something, anything, to help their child sleep/breath/stop coughing — so they head to the pharmacy with the intention of finding something to help. But what happens now that the traditional products are restricted, or otherwise labelled to caution against use?

The supplement/natural health product industry has responded quickly, bringing products to market that take advantage of regulatory double standards. In the USA, it’s the Dietary Supplement Health and Education Act (DSHEA). In Canada, it’s the Natural Health Products Regulations. As I’ve pointed out here before, these regulations reduce product safety standards, and all but eliminate the requirement to demonstrate that a product actually works. So what’s filling in the empty shelf space in pharmacies? Herbal, homeopathic and other “alternative” and “natural” cough and cold products for kids. And they’re being positioned as safe and effective alternatives for children. The Globe and Mail noticed:

When Health Canada ruled in 2008 that children under age 6 should not be given over-the-counter cough and cold remedies, it probably didn’t realize it was creating a whole new market for medications aimed at kids. Companies that use certain active ingredients in over-the-counter medications, such as dextromethorphan (used in cough remedies) and brompheniramine maleate (used in cold meds), now must carry labels indicating they are not to be given to children under age 6. But the recent ruling, made because there is little proof that these products work in children and evidence they can cause rare side effects or lead to overdose, doesn’t apply to makers of natural or homeopathic medicine. Now, many of those companies are rushing to fill the void and attract a following from confused parents looking for ways to help their sick children in the wake of Health Canada’s restrictions on traditional remedies.

It’s the homeopathic remedy manufacturers that seem to be making the biggest inroads:

Boiron Canada, part of an international homeopathic company, has begun promoting several products it says can relieve cold and flu symptoms and aren’t included in Health Canada’s restrictions on cough and cold medications. Hyland’s Homeopathic Canada, a division of U.S.-based Standard Homeopathic Co., sells a flu-care kit that it says can relieve fever, chills, aches, congestion and other symptoms in kids. Companies selling natural or homeopathic cold and flu medications for children highlight that they offer safe alternatives to over-the-counter medications that have been restricted for use in children by Health Canada.

Boiron makes Oscillococcinum, a product of fermented duck’s heart and liver that has been diluted so dramatically (1 part in 100, 200 times in a row), that in order to consume even a single molecule of the original fermented duck, patients would have to swallow a volume of tablets greater that the mass of the entire universe. The chance of effectiveness, or side effects, with these sugar tablets is equally remote. Boiron has several other products, including Stodal, a “toxin-free” homeopathic cough syrup without any demonstrated evidence of efficacy, either.

Hyland’s Homeopathics is the company that recently announced a recall of their teething tablets — it seems they didn’t dilute the ingredients enough, and some children displayed signs of belladonna poisoning. Hyland’s offers a variety of homeopathic products intended for children — again, all without any objective evidence of effectiveness.

Conclusion

Despite a long history of reasonably safe use, there’s no evidence that traditional cough and cold products have any effectiveness in children. Mild side effects are not uncommon, and fatal side effects are exceptionally rare, but possible. Given that colds are generally mild and resolve on their own, and that no product has ever been demonstrated to have a meaningful effect on the duration of a cold, over-the-counter products, “natural” or not, are unnecessary for children. Rest, adequate fluid intake, and acetaminophen or ibuprofen for the feverish child, may be all that is required.

Homeopathic and other “natural” remedies have emerged as the only marketed alternative — not because they are effective, but because of regulatory double standards and loopholes allow the sale of these products without demonstrated efficacy (or even any medicinal ingredients at all). With the medicinal products pulled off the shelf, they’re the only game in town now. And while homeopathy is admittedly safer than restricted products, given there’s no medicinal ingredients, and they’re not effective, all you can expect are placebo effects. Are parents aware the substitute remedies are just sugar and water?

Pharmacists have some challenges to manage. They may be concerned that the “traditional” products they’ve recommended for years are gone, and embrace the new remedies, without pausing to look for the evidence. Others may rely on marketing, anectodal reports of efficacy, or just read the parent’s desire to have a product – any product, as justification for selling them. And in some cases, they may just recommend these products because it’s profitable to do so. As a pharmacist, I admit that it’s more time consuming and less profitable to reassure an anxious parent that the cough and cold product they’re seeking isn’t necessary. But it’s far more ethically acceptable to me than to sell a homeopathic nostrum or unproven “natural” remedy that has no demonstrated evidence of efficacy, just so parents have the illusion they’re doing something to ease their children’s symptoms.

References