The Hospice Clinician Blog

The FDA is currently reviewing recent reports of children who developed serious adverse effects or died after taking codeine for post-surgical pain relief. Three children died and one child developed life-threatening respiratory depression after taking codeine. All four children used codeine for pain after having their tonsils and/or adenoids removed for treatment of obstructive sleep apnea. The children were given appropriate doses of codeine, but were found upon genetic testing to be “ultra-rapid metabolizers” of codeine, which resulted in overdose.

Codeine is not active as an analgesic until it is converted to morphine in the liver. The enzyme that converts codeine to morphine is called cytochrome P450 2D6 (CYP2D6). There is a wide genetic variation in the level of activity of CYP2D6. Some people have fairly inactive CYP2D6 enzymes, so they don’t get much pain relief from codeine (they are called “poor metabolizers”). Others, like the children described above, have extremely active CYP2D6 enzymes, so they may be prescribed an appropriate dose of codeine, but end up with much higher levels of morphine in their blood – and overdose can result. It is hypothesized that these particular children, with a history of sleep apnea, were already at a higher risk of fatal respiratory depression from opioids.

Ethnicity is a factor in CYP2D6 variability. In most populations, 1-7% of people are ultra-rapid metabolizers of codeine. But in Africans, as much as 29% of the population are ultra-rapid metabolizers. On the flip side, approximately 6-10% of Caucasians are poor metabolizers; the percentage is slightly higher in African-Americans and slightly lower in Asians.

The FDA is reviewing the safety reports about codeine, and looking at the use of codeine in other patients and other settings, and said it will provide a public update when the process is complete. In the meantime, healthcare professionals should be aware of the risks of using codeine in children, and should perhaps consider other drugs instead of codeine. If prescribing codeine-containing drugs, the lowest effective dose for the shortest period of time should be used on an as-needed basis (i.e., not scheduled around the clock). Parents and caregivers who observe unusual sleepiness, confusion, or difficult or noisy breathing in their child should seek medical attention immediately, as these are signs of overdose.

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A huge challenge facing parents, caregivers and healthcare professionals who take care of ill children is getting those children to take their medicine. When children won’t take their medicine, optimal care is obviously challenged, whether in a chronically ill child who must take routine medicine to control their disease or in an acutely ill child who must take an as-needed medication to control symptoms. In this article, I’d like to present some strategies, which can be employed by anyone caring for an ill child, for getting kids to take medications.

Dealing with Bad Flavor

Medicines, especially liquids, are notorious for tasting bad. When flavor is an issue, try the following:

• Use the cheek pocket. To avoid the tongue as much as possible, place the medicine between the cheek and lower jaw, toward the back of the mouth. From there, liquid medicine will glide straight down the throat, avoiding the taste buds.
• Offer a “spoonful of sugar”. Combine the medicine with a little sweet-tasting food or drink to mask the bitterness, or offer a “chaser”. Always check with a pharmacist before mixing medicines with food or drink to make sure it is OK, and make sure the child is able to consume the entire food or drink so he or she gets the full dose.
• Ask about FlavoRx. FlavoRx is an FDA-approved medication flavoring system available at many pharmacies, including all Walgreens, Rite-Aid, CVS, Target and Walmart pharmacies. The child’s medicine can be customized with one of 18 available flavors. They also offer “Pill Glide”, which is a flavored spray designed to make pills easier to swallow.
• Rerigerate. Liquid meds are usually more palatable when served cold. Check with the pharmacist first.
• Ask about alternatives. Sometimes another delivery device, formulation, route of administration or brand will be more acceptable to the child.
• Try a pacifier medicine dispenser. This nifty device, which retails for about $5, includes a pacifier equipped with a medication dispensing reservoir inside. The medication is slowly dispensed as the infant or child sucks on the pacifier.

Strategies for Toddlers and Older Kids

Like most things with toddlers and older kids, medicine-taking can quickly become a turf war, resulting in a lot of stress and fighting. To avoid getting to that point, try these strategies:

• Make medicine more enticing and fun. Add food coloring, decorate their medication cup, or have a medication “tea party.”
• Create a routine and reward successes. Toddlers and young children thrive on routine. Create a routine surrounding medications and a designated spot in the house. Use the reward system to recognize each success.
• Explain yourself. Explain how medicine helps kids get well, in terms they will understand, such as "This medicine will help you feel better so you can go back to the playground.“ or "You didn't wake up at all last night. That's because the medicine took your pain away."
• Offer choices whenever you can. Taking medicine is not optional, but some aspects of taking medication can be. For example, ask a child “Would you like apple juice or orange juice with your medicine?” Giving them a choice in any aspect you can will help them feel that they have some control in the process.
• Avoid physical struggles. Sometimes, you may have no choice, but try to avoid physical struggles at all costs. If medicine-taking is associated with a negative experience in the child’s mind, that will only make it that much more difficult the next time around.
• Watch your own demeanor. Children reflect the attitude of the adults around them. So if you treat medicine-taking as a horrible thing, changes are the child will too.

With all children, anticipate and prevent side effects as much as possible. Children make strong and fast associations, so even one negative experience may create a difficult situation where the child no longer wants to take the medicine.

What strategies have you found useful in getting children to take their medicine?

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Currently, pediatric acetaminophen is available in two liquid concentrations: 160 mg per 5 mL (usually labeled as “children’s”) and 160 mg per 1.6 mL (usually labeled as “infants’”, as it is given in drop form).  The availability of two concentrations has resulted in confusion and dosing errors, and has been a long-standing source of concern.

In May of this year, the Consumer Healthcare Products Association (CHPA) announced an industry-wide transition to a single pediatric acetaminophen concentration. Companies are voluntarily shifting to the 160 mg per 5 mL concentration. Eventually, the more concentrated infants’ drops will no longer be available. This shift is consistent with an FDA Advisory Committee recommendation made in 2009.

Pediatric acetaminophen dosing remains 10-15 mg/kg/dose.

Dosing chart for liquid pediatric acetaminophen products 

Outcome Resources is a pharmacy partner exclusively for hospices with experienced pediatric palliative care pharmacists on staff and available for consultation to our hospice clients. If you are interested in learning more about how a partnership with Outcome Resources can benefit your hospice, including your pediatric palliative care program, Contact Us today.

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This final article in our pediatric series will focus on the management of some of the most common non-pain symptoms encountered in pediatric palliative care. Research is notoriously lacking in this area, so much of what is done in pediatric palliative care is derived from the general pediatric population, from adult palliative care, or simply from clinical experience.

Specific symptom complexes that are addressed include: anxiety & depression, agitation, insomnia, anorexia-cachexia, nausea-vomiting, constipation, and dyspnea. Specific medication strategies will be presented for managing each of these troubling symptoms in pediatric hospice patients. 

Download the complete copy of Part 3 of our Pediatric Palliative Care Series: Pediatric Palliative Symptom Management. This article includes common non-pain symptoms such as depression, agitation, and dyspnea.

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