Cough and Cold Products for Children: Risk and No Benefit

Prior Science-Based Pharmacy posts have examined some of the most appalling examples of quackery found in the pharmacy – products like homeopathy and detox kits. It’s time to turn our attention to a group of “conventional” pharmacy items – cough and cold products for children. After being on the market for decades, they’re suddenly in the news. Many countries are banning them or relabeling them to warn against use in children. What’s happened to cause these changes?

Recent Actions

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.

Around the same time, Health Canada announced that cough and cold products will be relabelled to caution against use in children under the age of six. Products developed just for this age group will be no longer be sold. This extends an earlier decision to remove any products intended for children under the age of two.

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In the United Kingdom, products for children under the age of six are currently being withdrawn.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

So depending on where you live, certain products may or may not be sold, and dosing instructions for children may vary dramatically. Given the average household has four to eight over-the-counter cold medications, efficacy and safety questions are highly relevant to most consumers. So  how did four different countries arrive at different conclusions? Is any decision the right one? This review will focus on the evidence base supporting cough and cold products for children.

The Nature of Colds in Children[1]

Colds are viral infections, caused by a variety of respiratory viruses. Children get the most colds (6­ – 8 per year), and they tend to last longer – up to two weeks each time. Adults contract 2 – 4 colds annually, and then tend to last 7 days on average.  Cold symptoms experienced by children differ from adults. Runny noses are the most common sign, and fever is common in the first three days. Other common symptoms include sore throat, cough, difficulty sleeping and reduced appetite. Ear complaints are also common.

Treatments[1]

There is no cure for the common cold, and treatments are intended to reduce symptoms. The most common drugs in non-prescription cough and cold products are antihistamines, decongestants, cough suppressants, and expectorants. Each manufacturer puts together their own concoction, with either single-ingredient or multi-ingredient formulas. The main features that distinguish a product like Benilyn from Triaminic or Dimetapp are packaging, flavouring, and marketing – the ingredients are typically identical within each category.

Fever reducing drugs (i.e,, Tylenol or Tempra (acetaminophen); Advil or Motrin (ibuprofen)) are used to treat fever and pain from colds. Fever reduction is acceptable but not essential when treating a cold. Both acetaminophen and ibuprofen effectively reduce fever and are safe when used as directed. No countries have recommended restricting their use in children.

Examining Efficacy in Children

Cough and cold products have been sold for decades, and were approved for sale long before rigorous proof of efficacy was required. Consequently, clinical studies that support these drugs are (in general) of poor quality.

When we look at studies 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. [2] 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. [2]

But children are definitely NOT small adults. Differences exist in how children absorb drugs (amount of stomach acid) and where the drug goes in the body (body fat percentage). Their ability to metabolize drugs may differ, due to an immature liver. Consequently, drugs can behave in different and unpredictable ways, compared to adults.

Few studies have examined how cough and cold products behave in children. Consequently, their absorption, distribution, metabolism and elimination are poorly understood. The FDA expert advisory panel indicated that it was inappropriate to extrapolate data from adults to children.[3]

Despite the lack of direct research, cough and cold products have a long history of use in children with very rare reports of toxicity, usually due to inappropriate (excessive) dosing. [4] In general, these drugs have a wide “therapeutic window”, meaning that large overdoses are required before serious side effects are expected.

So let’s consider the evidence to support their use.  Literature searches have identified only a handful of clinical trials studying children, with few trials demonstrating efficacy.

Antihistamines

Antihistamines are usually used for seasonal allergies, and don’t have many meaningful effects in colds.  “First generation” antihistamines  – e.g., diphenhydramine (Benadryl), chlorpheniramine (Chlor-Tripolon) are often added to “night-time” versions of adult cough and cold products, where the side effect of drowsiness provides the only meaningful effect. A Cochrane review, the gold standard of evidence reviews, concluded that there  is no evidence to demonstrate that these products, when used on their own, have any beneficial effects at reducing cough or cold symptoms in adults or children.[5] Side effects have been reported, however, and include sedation and hallucinations. Some children experience a paradoxical excitation reaction, instead of sedation. In some circumstances, deaths have been reported.

“Second generation” antihistamines, sometimes called “nonsedating” antihistamines, are not useful for cold symptoms.  Examples include cetirizine (Reactine, Zyrtec) and loratidine (Claritin). They are not subject to the current warnings about cough and cold products, as they continue to be used for the treatment of allergies.

Decongestants – pseudoephedrine (Sudafed), phenylephrine

Decongestants cause blood vessel constriction in the nasal passages, reducing runny noses and opening up airways. Oral and nasal spray versions are available, but only the oral forms are used in children. In adults, oral decongestants have been demonstrated to have some positive effects. Pseudoephedrine, in particular, has been demonstrated to be effective in adults to reduce congestion, and it’s considered reasonable to use for a few days. [1]

There is no evidence that decongestants have any positive effects in children under the age of 12. Side effects associated with use include heart palpitations, nervousness, agitation, and elevated blood pressure. Serious toxic effects, including death, have been attributed to oral decongestant use in children. [1]

In 2001 data emerged suggesting that the decongestant phenylpropanolamine is associated with a very slight increase of stroke. Consequently, the ingredient was removed from cough and cold products in the US, Canada and most other countries. It may still be available in some countries—and should be avoided.

Antitussives (Cough Suppressants) – Dextromethorphan (DM)

Cough suppressants are commonly used to reduce dry, hacking coughs. They’re not usually recommended for productive coughs (i.e., phlegm) Dextromethorphan is the usual cough suppressant in non-prescription products.

There is no persuasive evidence that cough suppressants are effective in children under the age of 12. [6] A Cochrane review concluded that there is no good evidence for or against the effectiveness of cough suppressants. [7] This advice is also supported by the American College of Chest Physicians, who do not recommend cough suppressants for coughs. [8]

Expectorants

Expectorants are used to loosen phlegm and ease its elimination through coughing. The most commonly used ingredient is guaifenesin. There’s no persuasive evidence (either positive or negative) that can help us assess if expectorants have any beneficial effects in children. [7]

Expert Opinion

When there is insufficient data from clinical trials, it is reasonable to consult expert opinion for guidance. The following organizations have made statements:

• The Canadian Pediatric Society (CPS) provides advice consistent with Health Canada, recommending against treatment with cough and cold products in children under the age of six. The only acceptable exception are fever-reducing drugs (ibuprofen and acetaminophen).
• The American Academy of Pediatrics has concluded that there is sufficient evidence to conclude that cough and cold products are ineffective in children under 6 years old. It has regularly criticized multi-ingredient products as well as the lack of data to support the recommended dosages.
• The American College of Chest Physicians has concluded that the published data does not support the efficacy of cough and cold products in the paediatric age group.

Summary of the Evidence

• There is little convincing evidence that these products are effective in children up to about age 18.
• Serious side effects are rare, and usually associated with high doses, typically the consequence of administration errors.
• Parents and caregivers may be unaware of the risks of excessive doses.
• Excessive doses may be accidentally caused by the use of multiple products at the same time.
• Evidence-based dosing guidelines are problematic due to the lack of good quality evidence.

Two years, four years, six years, twelve years – When is it safe to give these products?

Despite concluding that there is a lack of evidence in all pediatric age groups, Health Canada concluded that age 6 was an appropriate cutoff for these products. Their rationale was:

• National and international recommendations
• Body weight variation can be significant. Some children aged 2-6 could be smaller than those under the age of 2. Drugs for children under the age of 2 have already been withdrawn.
• Children under the age of six generally have more colds compared to older children, so their exposure to any health risk from these products would be greater
• Younger children are less likely to be able to communicate a potential problem with a cough or cold product, or ask for help, the way an older child can.

Is age 6 appropriate? It’s reasonable but completely arbitrary. There is nothing magical about age six.  Restricting sale, however, is reasonable, given effectiveness has not been demonstrated and risks are real.

Summary

Despite a long history of reasonably safe use, we must hold cough and cold products to the same standard that we would apply to any other unproven therapy. Despite the presence of a drug, and in some cases, demonstrated efficacy in adults, it’s not clear that cough and cold products have any effectiveness in children. While most children tolerate these products well, mild side effects are not uncommon. Fatal side effects are exceptionally rare, but possible. Risks are greater in the younger child, and particularly in infants. We know that colds are generally mild and resolve on their own, and that no product has been demonstrated to have a meaningful effect on the duration of the cold. Rest, adequate fluid intake, and acetaminophen or ibuprofen for the feverish child may be all that is required. Steam humidification and saline nasal sprays may also offer some modest relief of clogged nasal passages.[1]

Until evidence emerges to demonstrate that these drugs are effective, the risk-benefit calculation tilts well away from a decision to use these drugs in children. The science-based bottom line: Cough and cold products in children offer no benefit, yet carry real risks. There is no compelling reason to use these products. If they are not already restricted, they have no place in the science-based pharmacy.

References

[1]Pappas DE. The common cold in children. Hendley JO (Ed). In UpToDate,
Waltham, MA, 2009 (Subscription required to view).

[2] Sime S. The Safety and efficacy of cough and cold medicines for use in children. New Zealand Medicines and Medical Devices Safety Authority. Report for the 13 December 2007 MARC meeting. Available here: [doc]

[3] Nonprescription Drugs and Pediatric Advisory Committee Meeting. Minutes from October 18-19, 2007. Dated October 31, 2007. Available here: [PDF]

[4] Health Canada’s Decision on Cough and Cold Medicines. Health Canada. December 2008.

[5]De Sutter AIM, Lemiengre M, Campbell H. Antihistamines for the common cold. Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD001267. DOI: 10.1002/14651858.CD001267

[6] Simasek M, Blandino DA. Treatment of the Common Cold. American Family Physician 2007; 75(4):515-20.

[7] Smith SM, Schroeder K, Fahey T. Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD001831. DOI: 10.1002/14651858.CD001831.pub3.

[8]Bolser DC. Cough suppressant and pharmacologic protussive therapy. Chest 2006; 129:238S-249S.

For More Information
For the treatment of fever in children: Up To Date

For the treatment of colds in children: Up To Date

For the treatment of colds in adults: Up to Date

The Canadian Pediatric Society’s guidelines on kids and colds.

For more information about the treatment of colds and the flu in adults, I recommend the excellent Natural Medicines Comprehensive Database, which provides a thorough, evidence-based overview of the efficacy of different “natural” products.