4 SYSTEMATIC REVIEW
4.4 Results
4.4.2 Study Characteristics
Table 2 Study characteristics of the 27 studies included in this systematic review.
Authors Study title
Caregivers report Tastes bad: 4.9% (n=4/81).
(Tucker et al.,
Neither group of patients agreed that they dislike taking their medicines because they tasted bad or may make them sick. Neither group agreed that swallowing was an issue due to tablet size either.
Among both groups, perceived characteristics of their medication regimen, including pill size, pill taste and medication complexity, were found to have significantly low to moderate associations with medication adherence.
17% reported taste as a reason for non-adherence 2% reported ‘hard to swallow.’
Those who identified ‘‘hate
the taste’’ as a barrier missed more doses, z = -2.4, p = 0.02 (average ranks 39.81 vs.
25.36) and took more doses late, z = -2.7, p = 0.007 (average ranks 40.44 vs. 24.61).
Authors Study title
75%, (n = 41) faced some kind of problem or difficulty when dealing
with oral chemotherapy:
Unpleasant taste of the liquid (n=10)
Capsules dispensed were too big to swallow (n=1).
Approximately one quarter of parents (24%, n = 10) had at least at some point during treatment crushed tablets prior to administration and evidence of dosage form manipulation was evident in responses to open-ended questions.
Breaking capsules in to ice-cream and crushing tablets on cornflakes were described by two fathers in the study.
Hate the taste: 10.8% (all reported by Crohn’s patients) Hard to swallow: 10.8% (all reported by Crohn’s patients).
‘Children resisting, refusing, spitting out drugs (because of bad taste?) (32%).’
Taste was reported as a barrier for taking oral antibiotics. Children with CF also identified difficulty swallowing solid dosage forms as a key barrier to taking oral medications (like oral antibiotics and enzymes).
Barriers to oral enzymes:
CF Children reports swallowing (13%)
CF Parent reports of oppositional behaviours (11%) Barriers to Nutrition medicines:
Authors Study title
Too many medicines/tablets to take: 36%
Difficulty swallowing: 32%
Bad taste: 24%
Child resists/refuses/spits out medicine 32% (unknown reason).
Barriers to adherence, reasons for missing medicines in previous month:
Child: Taste, can’t get it down, or keep it down (pill or liquid) (18%), Child refused (20%) Too much medication (9%).
Adult reports (also reported in bar chart:
Taste, can’t get it down, or keep it down (pill or liquid) (8%), Child refused (12%), Too much medication (2%).
Significant agreement between child and caregiver reports on the barrier of taste/cannot get it down as a barrier, based on a kappa statistical test, k = 0.44, (P<0.001).
In response to specific questions, caregivers reported as barriers to adherence: taste (10%), volume of medicine (10%).
Strategies related to improving taste or taking away unpleasant aftertaste were somewhat more frequently reported (29% and 24%, respectively).
Authors Study title
Caregivers evaluated the following factors as entailing moderate to high difficulties for correct adherence:
number of drugs in the antiretroviral combination, organoleptic properties (smell, taste) of protease inhibitors (PI), related deglutition problems, and PI-related immediate gastrointestinal adverse events.
These factors may be considered potential obstacles for adequate adherence to antiretroviral therapy in paediatric patients.
Grading of organoleptic difficulties based on average values of scores of carers:
Syrups and Liquids reverse transcriptase inhibitor, protease inhibitor: taste: 0.3, 4.5 smell: 0.3,2.1 deglutition: 0.1, 2.3
Solid pharmaceutical forms: taste:0.3, 1.6 deglutition:
0.75, 1.8
Mentions texture. The only factor assessed as high adherence difficulty was the flavour of the protease inhibitors in liquid form. For solid dosage forms, the aspects with a highest score (within that none of them reached the score corresponding to moderate difficulty), were the flavour and the difficulties in swallowing of the PI.
6 caregivers reported barriers to adherence.
Taste (n=3/20) Child refuses (n=4/20).
Authors Study title
10 changes were made because of patient preference or poor adherence.
Primary reasons for medicine change included medications not being palatable or patient’s inability to swallow pills or capsules.
(Hammami et
Almost all caregivers mentioned a history of opposition from their child as a result of bad taste and side effects.
Adherent patients demonstrated creativity in solving such problems. One parent discussed offering “nice tasting things” at the same time as administering the medicine to facilitate child acceptance of the medicine.
(Leprevost et
9/24 (38%) of caregivers commented that taste of medications had been a problem for their children during the study.
Authors Study title
Barriers to adherence endorsed: Pills are too big to swallow (n=5)
Medication tastes bad (n=5) Child isn’t able to swallow pills (n=1) Too many pills (n=3)
Child doesn’t drink all the medicines (n=1).
Described difficulties experienced by a caregiver when preparing a solution. However no more details were reported.
Medication related factors that influence adherence are mainly associated with side effects, size of tablets, Palatability and tablet regime.
Crying because of the ‘bitter taste of the medicines’
was reported by a caregiver of a non-adherent child.
“It was difficult to break the tablets into exact doses.
Once they prescribed 1/3rd of the tablet but it is difficult to give. For this, syrup would have been better. I feel it is difficult because we are unable to break the tablet correctly. I have the feeling that I am not giving the correct dosage.”
(Plipat et al., Evaluation of a Siriraj Antiretroviral <7-14y 137 PACTG adherence One hundred and thirty-seven (85%) caregivers
Authors Study title
Problems when administering medicines to children:
Swallowing (29.5%), Bad taste (20.5%), Child resists/refuses/spits out (25%), Too many medicines/
pills (34%). List of main problems reported:
Less than 6 years
1. Taking medicines at school or out of home 2. Child resists/refuses/spits out, 2. Child complains of bad taste, 2. Food interactions, 2. Vomiting
From 6 to 10 years 1. Difficulty swallowing pills 2. Too many medicines/pills
3. Child complains of bad taste, 3. Food interactions, 3.
Change in routine (holidays, weekend) More than 10 years
1. Too many medicines/pills 2. Food interactions 3. Difficulty swallowing pills
4. Taking medicines at school or out of home, 4.
Running out of medicines.
As soon as I put them in my mouth, they dissolve and taste nasty.”
“When you put them in your mouth . . . it tastes all nasty.”
“It’s hard because they’re too big for me. Because when it goes down like this, it goes ‘dush, dush, dush.’
It hurts my throat.”
“He started having problems taking it, like if he looks at it or smells it, then he’s just coughing and gagging...”
Some guardians reported giving their children various foods or beverages (e.g., pudding) to make the
The mothers did not present taste a central difficulty, but rather as a challenge to be mastered.
32% of the mothers described the ways they made the medication palatable as part of the process
Authors Study title
“At the first visit, all thirty caregivers answered that the child had never missed any antiretroviral medicine dose and that they did not experience problems with administering the medicine on time every day.”
However, during the interview, most caregivers reported that the child disliked taking antiretroviral medicines because of the bitter taste especially generic AZT syrup, 3TC syrup, ddI powder, NVP crushed tablet and EFV opened capsule.
At the final visit, caregivers gave the same answers for the PACTG adherence questionnaire with no reported problems or occurrence of poor adherence.
From the interview, 24 caregivers reported that, after using FLAVORx, their children had an easier time taking antiretroviral medicines with FLAVORx.
FLAVORx did not affect adherence as full adherence was reported in all children despite the problem of bitter antiretroviral medicines. after 3 months of treatment to assess experience with giving medication and self-reported adherence (PACTG with open-ended questions element)
Experience with giving medication:
Poor palatability of medication was the most common problem (21.8% of caregivers), 68% of these attributed to ritonavir.
Authors Study title
Study
Setting Medication type Age of children
Reasons why a child had difficulty taking medicines were given by caregivers of 65 children and could be divided into 2 main groups: comments on taste/
palatability/volume of drug(s); and social situations.
The largest number of responses (n _ 48) was in the first group and included comments on taste/flavour/
smell, size of tablets, consistency of medicine, causing vomiting/nausea and difficulty in swallowing.
“Difficulties with unpleasant flavor”; “Taste causes nausea”; “Hates the taste and smell”; “Child vomits due to taste”; “Bad smell and a big tablet” (referring to NFV); and “Difficulties with quantities.”
(Goode et al., difficulties with administering medicines were due to:
Taste (44%)
Procedural factors (i.e. mixing and preparation) (reported by 28% of respondents).
0-18y 119 children Chart review
Cross-sectional survey of physicians caring for the children
Ritonavir was the least palatable drug compared with other antiretroviral medicines (p = 0.01); 50% of children have refused its consumption because of poor taste, and in 27% of children, drug change was required.
Authors suggested adding FLAVORx to opened capsules to improve palatability.
Seven key studies are highlighted in bold font.
Drug names in Bunupuradah and co-workers (2006) AZT= zidovudine, 3TC= lamivudine, ddI= didanosine, NVP= nevirapine, EFV= efavirenz.
Authors Study title
Study
Setting Medication type Age of children
Better tasting medicines were rated ‘very helpful’ by 81% of caregivers.
Reasons for difficulty in administration were primarily the size of the nelfinavir pill, taste and consistency of nelfinavir powder and the taste of both the pill and liquid form of ritonavir.
The main reasons stated for non-adherence were taste (16%) and child refuses (16%) for ritonavir and taste (9%) for nelfinavir.
‘The large volume and unusual texture of the nelfinavir powder is particularly challenging for parents to administer.’