The ice cream challenge: A favourable extemporaneous Kayexalate formulation improves compliance in paediatric patients

Abstract

We wish to present a challenging case, which required us to “think out of the box.” Its solution is applicable to all children dealing with a similar challenge and may help to significantly improve compliance to a common medication. We present a 4‐year‐old child diagnosed with an autistic spectrum disorder and global developmental delay, limiting his communication skills. In addition, he is very selective to foods—and especially to their texture—and therefore has a very limited and routine diet. The child presented to our hospital with acute kidney injury and anuria following an episode of acute gastroenteritis. After extensive workup, he was diagnosed with atypical hemolytic uremic syndrome, necessitating dialysis, plasmapheresis, and numerous medications— including Eculizumab, anti‐hypertensives, and daily medications to maintain his electrolyte balance (mainly Sevelamer, Calcium carbonate, and Kayexalate). Due to decreased glomerular filtration rate (eGFR) as low as 9 mL/min, the child had persistent hyperkalaemia (levels as high as 5.8 meq/L), requiring daily sodium polystyrene sulfonate (Kayexalate) treatment. Due to its sand‐like texture and the patient s extreme selectivity to foods, this medication was the most difficult for him to take. Various attempts to mix the Kayexalate into different foods did not succeed—the child still noticed the texture and rejected the medication. In such cases, Kayexalate may be administered rectally— but as this experience was very traumatic for him, his parents refused to continue this form of intake. As the patient was oliguric, renal clearance of potassium was impaired, leading to elevated potassium levels which frequently required dialysis. Kayexalate is a cation‐exchange resin well accepted to treat hyperkalaemia. It releases sodium ions from the resin and binds potassium ions within the intestinal lumen, increasing fecal potassium excretion. Although unpredictable and variable, this in vivo exchange capacity is approximately 1 mEq of potassium per 1 g of Kayexalate. Kayexalate can be administered rectally; however, rectal administration is less effective, unpleasant, and even traumatic. Frustrated by the persistent hyperkalaemia, we tasted the drug— and searched for a tasty food that can mask the its texture. Reviewing the patients limited diet, we thought of ice cream—which he loves. The preparation for oral use of Kayexalate requires each dose to be suspended in water or syrup. Any vehicle may be compatible for use in order to improve the taste, except for significant amounts of potassium‐containing products (such as fruit juice) as it may impair the medications action. Usually, sweetened water, any syrup, or sweetened paste (such as jam or honey) are well accepted. In addition, palatability may be improved by cooling the prepared mixture. Kayexalate added into infant formula or expressed breast milk is an acceptable common practice, despite its low water solubility. This extemporaneous formulation should be refrigerated for 60 minutes and used within 24 hours. Moreover, the stability of frozen sodium polystyrene sulfonate at 20°C for at least 6 weeks was demonstrated by Johnson et al as an extemporaneous formulation of sodium polystyrene sulfonate candy (fudge) in order to increase tolerability. The candy is a mixture of Kayexalate with margarine, maple extract (or any other flavoring), cream, and sugar—and may be served frozen (like ice cream). As this formulation is not safe and carries a choking hazard under the age of 5, it was not attempted in this case. Kayexalate should be stored below 30°C, allowing refrigeration. To our knowledge, the sodium polystyrene sulfonate candy is the only evidence in the literature of the stability of the powdered resin in temperatures as low as −20°C (similar to a household freezer). The drugs stability in different vehicles and food ingredients below 30°C as well as under freezing temperatures allowed us to mix it in melted ice cream. We melted the ice cream, mixed it with 15 g of Kayexalate, and froze it again—in order to maintain its texture. Our patient consumed the ice cream in a bowl, once daily. His compliance was amazingly high! It seemed that he did not notice the sand‐like texture of the drug and was able to finish the whole dose of 15 g at one take. Serum potassium levels decreased significantly, as shown in Table 1. Many children have a hard time taking medications in general, and those that are not palatable in particular, making palatability a challenging factor of paediatric formulation development. Palatability—described as the overall acceptance of the taste, flavour, smell, dose, volume or size, and texture of a medication to be administered by mouth or to be swallowed—is essential for adherence in this population and influences the choice of dosage form and its design. As a consequence, caregivers usually attempt to achieve compliance by mixing the dose with different foods or drinks. These manipulations may affect the biopharmaceutical characteristics of the drug—including its chemical stability, solubility, and oral bioavailability —and therefore influence its safety and efficacy. Received: 13 April 2019 Revised: 2 July 2019 Accepted: 5 July 2019