According to the World Health Organization, patients may not be taking 50% of their medications as prescribed by providers, and this omission of therapy can lead to negative health-related outcomes (including but not limited to treatment failures, hospital admissions, and increased costs).1 Whether patients are prescribed medications for acute or chronic illnesses, their adherence (or ability to fill prescriptions and then take as directed for the duration of treatment) can be influenced by numerous social, economic, and logistic factors.1-3 One element that can influence adherence is drug formulation, and via hypothetical cases, we will highlight relevant advantages and disadvantages of oral liquid medications in pediatric and geriatric populations.4
Our ability to take oral dosage forms continuously changes with age.4 Generally, in the neonatal and infant populations, most medications are prescribed as oral liquids (e.g., solutions, suspensions, syrups), while most young children and adolescents can take chewable or whole tablets.4 Most adults can swallow whole tablets or capsules, but with older age and/or declining physical/cognitive functions, alternate routes of administration become necessary (e.g., patch).4
Hypothetical Case #1
AB is a 5-year-old female with a body weight of 41 pounds, and she has a history of asthma and a skin rash from penicillin and cephalexin. Her pediatrician prescribed clindamycin 30 mg/kg/day to be taken three times per day for 5 days for an acute otitis media infection and prednisolone 1 mg/kg/day for 5 days for an asthma exacerbation. The community pharmacist received a prescription for “clindamycin oral solution 2.5 mL po tid” and “prednisolone 15 mg/5 mL oral solution: 6 mL po daily with food,” in which she dispensed a reconstituted 100-mL bottle of clindamycin 75 mg/mL oral suspension, a 30-mL bottle of prednisolone 15 mg/5 mL oral solution, and two oral syringes. During the medication-counseling session, AB’s father was informed to keep the clindamycin suspension at room temperature (i.e., do not refrigerate) and discard after 14 days, and to keep the prednisolone oral solution in the refrigerator. He additionally requested to enhance palatability (e.g., with grape flavor) so that his daughter would be more willing to take it, which was an additional fee atop the copayment. After 5 days, AB’s symptoms for otitis media were not fully resolved, and her pediatrician determined that clindamycin was actually given once daily because it still tasted bad and caused AB to have an upset stomach. Clindamycin was inadvertently kept in the refrigerator for a few hours on the fourth day of treatment. AB was able to take 4 days of prednisolone with improvement via decreased wheezing.
Advantages: In the pediatric population, oral liquid medications have flexible dosing and can be swallowed more easily.4 Palatability (i.e., taste and smell) can sometimes be improved via sweetener (e.g., sucrose), flavor (e.g., chocolate), refrigeration (per prescribing information), and/or admixture with food/juice (per prescribing information).5-9 Smaller volumes are also better tolerated with oral liquid medications with palatability issues, unless dilution would help with the taste.4,10
Additional methods to improve adherence and reduce administration errors in pediatric patients include simplifying the frequency (e.g., once-daily dosing, if possible), providing medication syringes for dose measurements (i.e., avoiding household spoons), and reviewing educational materials with the parents (to minimize incorrect handling and to set expectations about side effects).4,5
For this pediatric patient, palatability was enhanced with flavoring, one of her medications (prednisolone) was dosed once a day, the volume amount of the medications was appropriate for her age, and oral syringes were provided for accurate dosing of medications.
Disadvantages: Certain issues can arise with oral liquid medications in pediatric patients. Medications with negative palatability can have a negative influence on adherence, as children may spit out or vomit doses.9 Clindamycin oral solution is known for children refusing to take it.11 Prednisolone oral solution contains preservatives, which can be bitter and make the medication unfavorable to take as well. 8 Besides preservatives, prednisolone oral solution contains sweeteners, fruit flavors, and is alcohol-free.8 Certain excipients, such as alcohol, propylene glycol, and parabens, should be avoided when possible in the pediatric population, especially in neonates and young children due to possibly affecting their growth and development.12
Frequency of administering the dose also affects adherence. Once-daily or twice-daily drug administrations are associated with compliance rates greater that 70%.5 Unfortunately, clindamycin oral suspension is dosed every 6 to 8 hours, whereas prednisolone can be dosed once or twice a day.8
Prednisolone oral solution is available in concentrations of 15 mg/5 mL and 5 mg/5 mL, which can be kept at room temperature or refrigerated, depending on manufacturer product.8 Doses can potentially be confused with the volume (e.g., administering 5 mL, instead of 15 mL) or the volume can be confused for frequency/duration (e.g., administering 3 mL three times daily, instead of once daily for 3 days).8,13 Such intricate details highlight the need for clear instructions, precise measurement devices, and thorough medication counseling to ensure proper medication adherence.
This pediatric case study did not incorporate any dispensing errors, but adherence to clindamycin was found to be influenced by its palatability (despite the addition of flavoring), dose frequency, and tolerability of gastrointestinal side effects, which led to a decrease in the number of doses given to the patient and resulted in failure to treat the infection. Another adherence barrier is noted when the patient only completed 4 out of 5 days of the prednisolone course because she was feeling better.
Hypothetical Case #2
YZ is a 67-year-old male receiving chemotherapy with 3-week cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for diffuse large B-cell lymphoma (DLBCL). For preventing viral reactivations, he was taking acyclovir 400 mg twice daily and entecavir 0.5 mg daily. His past medical history was also notable for hypertension (on nifedipine XL 30 mg daily), atrial fibrillation (on metoprolol XL 25 mg daily, apixaban 5 mg twice daily), and benign prostatic hypertrophy (on finasteride 5 mg daily, tamsulosin 0.4 mg daily). His most recent cycle of R-CHOP was complicated by neutropenic fever and severe hypoxia requiring intubation, which was managed in an ICU. After being weaned off mechanical ventilation, he was transferred to a stepdown unit with a nasogastric tube (NG) in place. To facilitate NG administration, notable changes to his medications included switching nifedipine to amlodipine, switching metoprolol succinate to tartrate salt, switching tamsulosin to doxazosin, and stopping finasteride. He was eventually discharged from the hospital and back on all his usual medications, and he had family support at home to assist with medication administration. At the next clinic visit, he mentioned some difficulties with swallowing.
Advantages: For older adults who are unable to swallow whole solid dosage forms (whether due to choking, gagging, and/or vomiting sensations), drug or formulation modifications may be indicated.14 For certain immediate-release oral solid dosage forms, there may exist data in prescribing information to open, break, crush, chew, dissolve, and/or switch to an oral liquid dosage form.8 These interventions mitigate interruptions in treatment and promote medication adherence.14 In our patient who is having swallowing difficulties after hospitalization, we could theoretically switch the medications to the following: acyclovir tablet to suspension, entecavir tablet to solution, nifedipine tablet to amlodipine suspension, metoprolol succinate to the tartrate salt (and crushed), tamsulosin to low-dose doxazosin (and crush), and crushed apixaban.8
Disadvantages: The Institute for Safe Medication Practices maintains a list of oral dosage forms that should not be crushed.15 In general, most drugs that should not be crushed have modified release mechanisms (e.g., enteric coated, film coated, slow release), mucous membrane irritant potential, and/or antineoplastic/cytotoxic properties.15,16 Pharmacokinetic parameters (e.g., absorption, onset of action, peak concentration) are important factors to consider before switching to an oral liquid dosage form.8 Immediate-release drugs may need to be administered multiple times per day to match the expected efficacy/outcomes of extended-release formulations.8 In older patients who have dysphagia, oral liquid dosage forms may increase the risk of aspiration events, particularly if the resultant solution/suspension has low viscosity.4 Options to improve palatability are also limited, as some oral liquid medications are not coformulated with flavoring agents and administration instructions in product information may not directly address interventions for untoward flavor or smell.8,17
Overall, medication adherence is influenced by a number of factors, such as palatability and swallowing capability, in which there are distinct advantages and disadvantages to using oral liquid medications in select situations. There exists limited and mixed literature that directly compares adherence rates between oral solid and liquid dosage forms of the same drug. Inpatient and community pharmacists alike should continue recommending and selecting the most optimal dosage forms for their patient population, as well as provide comprehensive medication counseling that emphasizes safe administration practices and realistic expectations.
1. World Health Organization. Adherence to Long-Term Therapies. https://apps.who.int/iris/bitstream/handle/10665/42682/9241545992.pdf. Accessed September 8, 2021.
2. Ho PM, Bryson CL, Rumsfeld JS. Medication adherence: its importance in cardiovascular outcomes. Circulation. 2009;119(23):3028-3035.
3. Adams AJ, Stolpe SF. Defining and measuring primary medication nonadherence: development of a quality measure. J Manag Care Spec Pharm. 2016;22(5):516-523.
4. Liu F, Ranmal S, Batchelor HK, et al. Patient-centered pharmaceutical design to improve acceptability of medicines: similarities and differences in paediatric and geriatric populations. Drugs. 2014;74(16):1871-1889.
5. Gardiner P, Dvorkin L. Promoting medication adherence in children. Am Fam Physician. 2006;74(5):793-798.
6. Al Humaid J. Sweetener content and cariogenic potential of pediatric oral medications: A literature. Int J Health Sci (Qassim). 2018;12(3):75-82.
7. Walgreens. FLAVORx: Favorable Flavors. www.walgreens.com/images/IN2163/favorable_flavors.pdf. Accessed September 8, 2021.
8. Lexicomp Online. Waltham, MA. https://online.lexi.com. Accessed September 8, 2021.
9. El-Rachidi S, LaRochelle JM, Morgan JA. Pharmacists and pediatric medication adherence: bridging the gap. Hosp Pharm. 2017;52(2):124-131.
10. European Medicines Agency. Guideline on Pharmaceutical Development of Medicines for Paediatric Use. EMA/CHMP/QWP/805880/2012 Rev. 2 Committee for Medicinal Products for Human Use (CHMP) Paediatric Committee (PDCO) 2013. www.ema.europa.eu/en/documents/scientific-guideline/guideline-pharmaceutical-development-medicines-paediatric-use_en.pdf. Accessed September 8, 2021.
11. Zajicek A, Fossler MJ, Barrett JS, et al. A report from the pediatric formulations task force: perspectives on the state of child-friendly oral dosage forms. AAPS J. 2013;15(4):1072-1081.
12. Batchelor HK, Marriott JF. Formulations for children: problems and solutions. Br J Clin Pharmacol. 2015;79(3):405-418.
13. Robinson J, McKenzie C, MacLeod D. Paediatric dosing errors with oral prednisolone mixture. Aust Prescr. 2016;39(5):176.
14. Schiele JT, Schneider H, Quinzler R, et al. Two techniques to make swallowing pills easier. Ann Fam Med. 2014;12(6):550-552.
15. Institute for Safe Medication Practices. List of oral dosage forms that should not be crushed. www.ismp.org/recommendations/do-not-crush. Accessed September 8, 2021.
16. Spencer SH, Menard SM, Labedz MZ, et al. Enteral tube administration of oral chemotherapy drugs. J Oncol Pharm Pract. 2020;26(3):703-717.
17. Belissa E, Vallet T, Laribe-Caget S, et al. Acceptability of oral liquid pharmaceutical products in older adults: palatability and swallowability issues. BMC Geriatr. 2019;19(1):344.
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