US Pharm. 2015;40(5):HS6-HS8.

ABSTRACT: Asthma affects approximately one in 10 children in the United States. More than half of these pediatric patients experience an asthma exacerbation each year. Often, the exacerbation requires a short course of oral corticosteroids. Prednisolone, a liquid formulation of prednisone, is commonly prescribed to these children due to its ease of administration. A short course of prednisolone drastically reduces the need for hospitalization and shortens the length of the exacerbation. Poor adherence due to the bitterness or laxative qualities of prednisolone often limits its effectiveness, however, and careful selection must be made between the available forms (prednisolone base versus prednisolone sodium phosphate).

Asthma is the most common cause of hospitalizations and emergency department (ED) visits for pediatric patients in the Unites States.1 These admissions are costly, cause missed school and work days, and utilize healthcare resources.2 Standard therapy with inhaled corticosteroids and short-acting bronchodilators will not prevent episodic viral-induced exacerbations in these patients.3

PATIENT CASE

Presentation

A 3-year-old child is experiencing an asthma exacerbation—her chest is tight, and she is coughing and wheezing with each breath without responding to inhaled albuterol. A short course of oral prednisolone liquid is prescribed to stop the progression of the episode and the need for hospitalization or an emergency department (ED) visit.

Treatment

After picking up the prednisolone from the pharmacy, the mother gives her child the prescribed dose of 5 mL. Almost instantaneously, the child spits out the medicine because of its bitter taste. Her mother tries repeatedly to give the medication, but fails. Two days without successful administration of prednisolone pass before the child’s mother decides to bring her to the ED, where she responds to inhaled bronchodilation and IV methylprednisolone.

Follow-up

A week after the ED visit, the patient is seen by the University of Florida Pediatric Pulmonary Clinic. There they discover that the wrong formulation of prednisolone was dispensed, which was probably responsible for the failure of home therapy. The physician had prescribed the generic for Orapred solution (prednisolone sodium phosphate), but the pharmacist had dispensed the bitter-tasting prednisolone base (generic for Prelone).

Corticosteroids and Asthma

Systemic corticosteroids are an essential treatment option for many disease states, especially asthma. These medications reduce the length and severity of asthma exacerbations and reduce the need for hospitalization or ED visits.4 It is important for asthma patients to receive prednisolone as soon as possible after the onset of symptoms that are bronchodilator-unresponsive to attain these benefits.

Although usually prescribed for a 5- to 7-day period, oral corticosteroids are not without adverse effects. The most common adverse effects are the same for the majority of oral corticosteroids and include increased appetite, weight gain, flushed face, and increased acne in adolescents. Considering that the final amount of prednisolone provided by each formulation is consistent, it would be expected that these adverse effects would be similar for all.

The Bitterness Barrier

The most important physical property of an oral corticosteroid for children is that doses be easily swallowed and retained. Diminished adherence might be due to the type of prednisolone dispensed to the patient. Various formulations are available, each with its own distinguishing characteristics (TABLE 1).5 The differences are in strength (which affects volume required) and excipients (e.g., alcohol to increase solubility or sorbitol to mask bitter taste).

There is, however, a notable difference between prednisolone sodium phosphate (an ester) and prednisolone base. The difference is not in the efficacy of each formulation, but rather in the associated taste. Prednisolone base is much more bitter than prednisolone sodium phosphate (FIGURE 1).5 Children are more sensitive to bitter tastes than adults, owing to the natural rejection of bitter tastes to avoid ingesting toxic substances.6 To improve adherence and palatability of this essential medication, the sodium phosphate ester, available from several generic manufacturers, should be dispensed and not the prednisolone base.

Excipients Matter Too

After eliminating the bitter prednisolone base, the decision needs to be made between three available strengths of prednisolone sodium phosphate—5 mg/5 mL, 15 mg/5 mL, and 25 mg/5 mL. The deciding factor between these products does not reside in the active ingredient, but rather in the inactive ingredients. Sorbitol, a sugar alcohol, is used to increase the palatability of prednisolone sodium phosphate.5 Depending on the dosage, sorbitol can be a potent cathartic. Doses of 5 g have been used in combination with activated charcoal as a treatment of overdose or poisoning. The amount of sorbitol varies with the formulation of prednisolone (TABLE 1).5

The usual dosage of prednisolone for acute asthma exacerbations in the pediatric population is 1 to 2 mg/kg/day, divided 1 to 2 times daily. For a 15-kg child, a 2 mg/kg/day dose of the generic for Pediapred (1 mg/mL) would provide 5.9 g of sorbitol.7 This could lead to an unnecessary ED visit by concerned parents who are unsure of the origin of the child’s catharsis. The high potency Mission Pharmacal product contains corn syrup (fructose), which may also cause diarrhea.8

Increasing Appropriate Dispensing

Appropriate dispensing starts with proactive measures taken by pharmacists. It is recommended that pharmacists dispense the more concentrated prednisolone sodium phosphate (15 mg/5 mL) whenever prednisolone is prescribed. If a physician orders the product by brand name (e.g., Prelone), the pharmacist can call the prescriber and recommend changing the prescription to the generic for Orapred.

If a child refuses the sodium phosphate ester of prednisolone, it is recommended that physicians prescribe a dexamethasone tablet, crushed between two spoons and mixed with sugar-free chocolate pudding. An 0.2 mg/kg dose of dexamethasone is equivalent to 1 mg/kg of prednisolone.9

Conclusion

Asthma continues to be a major health concern among the pediatric population in the U.S. Considering the benefits of short bursts of systemic corticosteroid therapy, it is important to ensure that patients tolerate the drug prescribed. Prednisolone sodium phosphate should be preferentially chosen over prednisone base when prescribing liquid forms of oral corticosteroids.

REFERENCES

1. Chung HS, Hathaway DK, Lew DB. Risk factors associated with hospital readmission in pediatric asthma. J Pediatr Nurs. 2015;30(2): 364-384.
2. Lu S, Kuo DZ. Hospital charges of potentially preventable pediatric hospitalizations. Acad Pediatr. 2012;12(5):436-444.
3. Doull IJ, Lampe FC, Smith S, et al. Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial. BMJ. 1997;315:858-862.
4. Rachelefsky G. Treating exacerbations of asthma in children: the role of systemic corticosteroids. Pediatrics. 2003;112(2):382-397.
5. Hendeles L. Selecting a systemic corticosteroid for acute asthma in young children. J Pediatr. 2003;142(2 suppl):40S-44S.
6. Mennella JA, Spector AC, Reed DR, Coldwell SE. The bad taste of medicines: overview of basic research on bitter taste. Clin Ther. 2013;35(8):1225-1246.
7. National Heart, Lung, and Blood Institute. Asthma care quick reference: diagnosing and managing asthma. Updated June 2012. www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/quick-reference. Accessed April 13, 2015.
8. Escobar MA Jr, Lustig D, Pflugeisen BM, et al. Fructose intolerance/malabsorption and recurrent abdominal pain in children. J Pediatr Gastroenterol Nutr. 2014;58(4):498-501.
9. Derendorf H, Hochhaus G, Möllmann H, et al. Receptor-based pharmacokinetic-pharmacodynamic analysis of corticosteroids. J Clin Pharmacol. 1993;33:115-123.

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