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It’s the time of year where if you’re not sick, someone you know probably is. The influenza season in the Northern hemisphere started out slowly, but seems to be accelerating and hasn’t peaked yet. Add that to cold viruses circulating, and you get the peak purchasing period for cough and cold remedies. John Snyder gave a nice summary of the evidence base for the common treatments a few weeks ago. In short, despite all the advertising, there is little evidence to suggest that most of the “tried and true” products we’ve used for decades have any effect on our symptoms. One of the most sensible developments that’s occurred over the past few years has been the discontinuation or relabeling (depending on your country) of cough and cold products for children. The rationale to pull these products is compelling: Cough and cold remedies have a long history of use, and were sold without prescriptions before current regulatory standards were in place. They were effectively grandfathered onto the marketplace. When it comes to their use in children, the data are even more limited. There are few published trials and the results are complicated by different age groups, irregular dosing, lack of placebo control, and very small patient numbers. What’s even harder to believe was that doses were based mainly on expert opinion, not data, and generally didn’t consider that children don’t handle drugs the way adults do. So why withdraw them from pediatric use, but not adult use? Like most regulation, it comes down to risk and benefit. Both are troubling for pediatric use.

One of the earliest lessons you’ll gain from a pharmacokinetics course (which studies drug behavior in the body) is that children are not small adults. It’s not just their size, it’s their physiology. The stomach acidity can differ, changing how drugs are absorbed. Body-fat-proportion differences affect how drugs are distributed in the body. And the body’s pathways for metabolism are not fully mature, which means drugs can behave in different and often unpredictable ways. Given the lack of data showing how the major cough and cold ingredients behave in children, and a lack of evidence showing that they have any meaningful effects, it comes down to a question of safety. While these products had long histories of safe use, harms and deaths have been linked to cough and cold product use in children. Fatal side effects are exceptionally rare, but can occur. Risks are greater in the younger child, and particularly in infants. In light of the potential for harm and the lack of benefit, there is no justification to keep them in the market, and most regulators around the world eventually acted to reduce the risk that they will be used in children. Like many other health professionals, I was happy to see them go. Today’s treatment guidelines don’t recommend drug therapy.

The Cough Suppressant and Pharmacologic Protussive Therapy : ACCP Evidence-Based Clinical Practice Guidelines (2006) make the following recommendations about cough suppressants and expectorants:

In patients with acute cough due to the common cold, preparations containing zinc are not recommended. Level of evidence, good; benefit, none; grade of recommendation, D

Level of evidence, good; benefit, none; grade of recommendation, D In patients with acute cough due to the common cold, over the counter combination cold medications, with the exception of an older antihistamine-decongestant, are not recommended until randomized controlled trials prove that they are effective cough suppressants. Level of evidence, fair; benefit, none; grade of recommendation, D

Level of evidence, fair; benefit, none; grade of recommendation, D In patients with cough due to URI [upper respiratory infection], central cough suppressants (i.e., codeine and dextromethorphan) have limited efficacy for symptomatic relief and are not recommended for this use. Level of evidence, good; benefit, none; grade of recommendation, D

The British Thoracic Society Cough Guideline Group in its recommendations for the assessment and management of cough in children (2007) notes the following:

Over-the-counter medications are as effective as placebo for acute cough with head colds in children. A systematic review of six RCTs and a further recent RCT found that over-the-counter antitussives, antihistamines and antihistamine-decongestant combinations were as effective as placebo with the potential for causing side effects.

Evidence is one thing. Reassuring parents that they don’t need to give any medication is another matter entirely – especially since many of us grew up taking cold remedies. Once these products disappeared from the shelves, their absence made my dialogue with patients easier. I could explain the rationale for no treatment, why the traditional treatments had been relabeled or removed from sale, and discuss the self-limiting nature of colds. I’d also suggest products that actually do work, like analgesics such as Tylenol, and sometimes saline (drug-free) nasal sprays for treating congestion. And that’s pretty much it. Once you break the habit of reaching for a bottle of syrup each time your kid gets sick, you adapt. Give fluids, lots of rest, and lots of TLC. And don’t worry about giving cold remedies.

The shelves didn’t stay bare for too long. As John Snyder pointed out, a stunning 10% of children are given a cough and cold remedy every week. The demand is huge. That’s an enormous market that manufacturers couldn’t ignore. There are several new remedies that you’ll see on the shelf – most of them marketed at infants and children, and they’re advertised as “natural” products that really work. The enabler is weak regulation. In the USA, it’s the Dietary Supplement Health and Education Act ( DSHEA ). In Canada, it’s the Natural Health Products Regulations. Different regulatory frameworks, but with the same intent – to allow “natural” products and supplements to be sold without actually requiring those products to be backed by good evidence of safety or effectiveness. It’s the easiest way for a new product to be approved – describe it as “natural” (if you’re in Canada) or a supplement (in the USA), and you bypass the strict regulatory requirements required if you called it a “drug” instead. It’s simply not possible to keep up with all of the new products appearing – here’s the evidence for some of the products that I’ve seen appear on pharmacy shelves:

Homeopathic remedies

The first products that appeared after the traditional cough and cold products disappeared were the homeopathic remedies. Even pharmacies that don’t tend to sell much homeopathy now seem to offer homeopathy for children, suggesting pharmacies are prioritizing sales ahead of scientific evidence – because as pseudoscience goes, there is no product so demonstrably useless as homeopathy. Based on the idea that “like cures like” (which is magical thinking) and the concept that water has a memory (also magical thinking), homeopathic remedies look like medicine – but don’t have any medicine in them. Various substances are taken and diluted – not just herbs but products like “Berlin Wall”, “Stonehenge” and even “Rabbit Anus” are considered potential “remedies”. The net effect is that while there are hundreds of homeopathic products sold, it’s effectively all the same thing – an inert placebo. The granddaddy of the homeopathic cold remedies is 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, you would have to swallow a volume of tablets greater that the mass of the entire universe. The chance of effectiveness or side effects with this product is equally remote. Boiron, the manufacturer, has several other cough and cold products, including Stodal, a “toxin-free” homeopathic cough syrup without any demonstrated evidence of efficacy, either. There are other manufacturers on the market now, directly targeting the children’s market. Homeocan now has an entire line of “cough and cold” “remedies” that are marketed under the banner “Kids 0-9 All Natural Medicine” which were created by “a pharmacist and professional homeopath”. The cough and cold product is labelled “Helps relieve dry cough, congestion, mucus build-up and reduce pain and fever.” when the bottle actually contains no medicinal ingredients. There’s also NatraBio, which is advertised to be useful in children as young as 4 months, and it’s claimed:

Treating children with homeopathy utilizes nature’s medicines to gently relieve symptoms and promote healing. Homeopathic medicine is a safe treatment for most minor ailments. Precise levels of homeopathic ingredients work safely and without side effects. All natural ingredients

No side effects

No sugar

No drowsiness

Made in accordance with the U.S. Homeopathic Pharmacopoeia.

If you didn’t know better, you could easily be fooled into thinking Natrabio is a product with medicine in it. The ingredient list, like all homeopathic remedies, is deliberately deceiving:

Active Ingredients: Aconitum Napellus (Monkshood) 3X, 6X, 12X, 30X (Aconite), Echinacea Angustifolia (Coneflower) 3x (Coneflower), Allium Cepa (Red Onion) 6X (Red Onion), Hydrastis Canadensis 6X (Golden Seal), Euphrasia Officinalis (Eyebright) 6X (Eyebright), Gelsemium Sempervirens 6X (Yellow Jessamine), Sanguinaria Canadensis (Blood Root) (Blood Root), Sticta Pulmonaria (Lungwort) 6X (Lungwort)

3X is a 1:1000 dilution. 6X is a 1:1,000,000 dilution. While there may be a few molecules of monkshood or red onion in the final dilution, it is all for intents and purposes inert, as these ingredients would not have any medicinal effects.

Zarbee’s

Not all the new cough and cold remedies are completely inert. Pediatrician Zack Zarbock created the honey-based cough syrup Zarbee’s, which is marketed as claiming it “maintains immune function” but actually contains:

Per teaspoon (5mL) Honey 4.15 mL

Vitamin C 34 mg

Zinc 1.65 mg

Zarbee’s is effectively diluted honey, with a few vitamins added. Zarbee’s claims it is “clinically proven” but there are no trials in Pubmed using the product or its combination of ingredients. There are a few trials that show plain honey may be equivalent or superior to dextromethorphan (which is more than likely ineffective) and may be better than placebo or no treatment. So while it’s possible that pure honey may offer a modest effect on cough, the same can’t be said (with certainty) for Zarbee’s, as there are no studies with this particular product. Moreover, there is no evidence that vitamin C provides any meaningful effects in children with coughs and cold. And while there is some promising but conflicting evidence studying zinc lozenges for colds in adults, its use in children has not been established as effective. And there’s no evidence at all to suggest that zinc supplied as a syrup has any meaningful effects. The bottom line is that Zarbee’s doesn’t offer any demonstrable advantage over pure honey. Zarbee’s also markets a cough syrup for infants (aged 2-12 months) that contains agave nectar instead of honey. There is no published evidence to suggest that agave is effective for the treatment of cough in infants. And Zarbee’s also markets a “mucus relief” version which is honey and ivy (Hedera helix), the evidence for which is summarized below.

Helixia

Helixia is a new (to North America) line of cough and cold remedies that are marketed for children as young as 1-year old (and younger, “with consultation”). The active ingredient is English ivy leaf extract (Hedera helix). Leaves are purported to have expectorant and antispasmodic properties owing to irritation of the gastric mucosa, a mechanism of action which is unproven. The manufacturer claims the product is “clinically proven” but there’s no information on the website to support this claim. An enquiry to the manufacturer (Pendopharm) for evidence resulted in a link to Fazio S et al., “Tolerance, safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: a prospective, open, multicenter postmarketing study in 9657 patients“. The title tells you all you need to know about this study’s quality – it was an open label survey that asked about effectiveness and safety in children with inflammatory lung disease – not colds. When I pressed the manufacturer further, they provided me with the citation “Efficacy and tolerability of ivy-containing cough remedies, a study in children with recurrent obstructive airway disease”. It’s published in a German journal, dated 1996, and doesn’t appear to be in Pubmed or available online. It’s poorly written and missing most of the signs of a quality study. The researchers looks at airway function in children aged 6-15 with obstructive airway disease (not children with the common cold) and reported improvements in pulmonary function – not measures related to colds. Another irrelevant study. A search on my own was more instructive:

“Systematic Review of Clinical Trials Assessing the Effectiveness of Ivy Leaf (Hedera helix) for Acute Upper Respiratory Tract Infections” seems to provide the best overview, which is probably why the manufacturer was reluctant to provide it or mention it. Most of the relevant trials were published in Germany which makes reviewing the original trials difficult. Of the ten trials published, the authors noted that only one was considered high quality, and that trial excluded children from the study. The authors did not identify any trials that compared ivy leaf alone (the composition of Helixia Prospan) with placebo, which is the comparison we’re looking for. The authors concluded:

Although all studies report that ivy extracts are effective to reduce symptoms of URTI, there is no convincing evidence due to serious methodological flaws and lack of placebo controls. The combination of ivy and thyme might be more effective but needs confirmation.

That’s the conclusion that other groups have reached. The Natural Medicines Comprehensive Database says there is insufficient evidence to evaluate the effectiveness or safety of ivy. The Natural Standard, another publication, gives it a “C” (unclear or conflicting) rating for childhood asthma and obstructive lung disease, and no rating at all for coughs and colds. The manufacturer claims there are no drug interactions, but there is no evidence this has been systematically studied. In short, Helixa Cough Prospan is a poorly studied herbal remedy with no convincing evidence of effectiveness for the treatment of coughs or colds, in either adults or children.

Conclusion

It’s not possible to keep up with all of the new cough and cold products for children appearing on the market. But it is easy to understand the current state of the evidence, and the current treatment guidelines. There is little convincing evidence that the marketed cough and cold products for children have meaningful effects. Consequently, medicating children is generally unnecessary and sometimes inadvisable. It needs to be emphasized that coughs and colds are self-limiting illnesses – children will recover, with or without treatment. Manufacturers of cough and cold remedies are actively trying to convince consumers otherwise, and they’ve been aided by weak regulatory standards that are permitting products to be sold, often without any convincing evidence that they work. The result is a marketplace that’s reminiscent of where we were, with ineffective and unnecessary treatments crowding pharmacy shelves.