Clinical Pharmacist Role in Increasing the Adherence to Recommendations Among Patients Using Isotretinoin: A Randomized, Controlled Study
Phase: NA
Conditions: Acne Vulgaris
Sponsor: Jordan University of Science and Technology

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Clinical Pharmacist Role in Increasing the Adherence to Recommendations Among 
Patients Using Isotretinoin: a Randomized, Controlled Study 
 
NCT ID not yet assigned (Unique Protocol ID: IsoJordanUST) 
 
Document Date: June 28, 2021 

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Study Protocol 
 Study design and sites: 
A randomized, controlled study will be conducted at the dermatology clinics in several 
Jordanian hospitals: King Abdullah University Hospital (KAUH), Princess Basma Hospital (PBH), 
King Talal Hospital (KTH), Princess Haya Hospital (PHH), Prince Rashid Hospital (PRH) and King 
Hussein Medical Center.  
Patients 
Patients who will come to the clinic to receive isotretinoin medication, with any brand names 
known in Jordan like (ISOSUPRA®, ROACCUTANE®,, CURANCE®,, RUATINE®,) and have 
the following criteria; male or female patients, ≥18 years who are diagnosed for the first time with 
moderate to severe acne vulgaris and receiving standard doses (0.5-1mg/kg/day), are willing to take 
the treatment, and to do follow-ups, will be approached and asked to participate in the study. 
Patient with any contraindication to isotretinoin who cannot take the medication and patients 
who are not willing to participate in the study will be excluded. These contraindications are; age less 
than 12 years, patients having mild acne vulgaris, pregnant women and women who intend to 
become pregnant, breastfeeding women, presence of any renal or hepatic compromise, or any pre-
existing hyperlipidemia. 
A convenience sampling technique will be used to collect the study sample referring to a 
previous study 
 .[
1
]
Also using 30% effect size ( difference in adherence between control (50%) and 
intervention group (80%)), alpha= 0.05, beta=0.8 and enrollment ratio=1 at least 45 patients should 
be enrolled in each group (results from OpenEpi, Version 3, open source calculator—SSCohort/ 
RCT) . To account for loss to follow-up, a minimum of 50 patients will be enrolled in each group.  
After the informed consent (see appendix 1) is taken from each patient who agreed to 
participate in the study, the participants will be randomly assigned to either an intervention group or 
a control group. Intervention group will consist of the patients who will receive the educational 
process (recommendations) about isotretinoin by clinical pharmacists additionally to the usual 
routine care (education about isotretinoin provided by the physician). Control group will consist of 
the patients who will receive the usual routine care. Both patients and physicians are unaware of 
patients’ assignment in both groups. 

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The main task of the clinical pharmacist is to educate patients in intervention group by 
providing them all information about isotretinoin that can serve the patient during the treatment 
period, which includes: the degree of the importance of adherence to the drug and the 
recommendations, the correct method of taking it, the importance, and when, of doing periodic 
laboratory tests (lipid profile, liver enzyme test, and pregnancy test), and explanation of common 
side effects, how to avoid and deal with them, and  what are the cases in which the drug should be 
stopped. The detailed information on the recommendation for managing side effects that will be 
used to educate the patients are provided in Appendix 2.  
Patient's adherence to the recommendations, awareness and side effects managements for 
both groups will be measured through a set of questions adapted from a validated questionnaire after 
one month and three months of isotretinoin initiation (Appendix 3). The validated questionnaire was 
was adopted from a previous study on patients' knowledge about isotretinoin therapy use in Jordan. 
The permission to use the questionnaire was obtained from the researcher. 
The questionnaire is composed of 41 questions related to: demographics, side effects, 
physician and clinical pharmacist practice, recommendations and contraindications according to 
current guidelines, and patients’ commitment. In addition, the Hospital Anxiety and Depression 
Scale (HADS) [22], will be used to evaluate depressive and anxiety symptoms at baseline and during 
the follow up period in each group. Finally, clinical improvement in acne will be evaluated three 
months after initiating the treatment from the view of physicians as well as the patients themselves.  
Location and safety considerations 
The dermatology clinics located in: King Abdullah University Hospital (KAUH), in Princess Basma 
Hospital, (PBH), King Talal Hospital (KTH), Princess Haya Hospital (PHH) and Prince Rashid 
Hospital (PRH) and King Hussein Medical Center will be visited for patients interview and data 
collection. The participants’ privacy will be preserved throughout the study and the participants’ 
answers will be kept strictly confidential and never associated with any personal details. This study 
does not involve any human biological sample. No potential risks will be associated with the 
participation in the current study. No special safety consideration for isotretinoin drug Except those 
mentioned above since it approved from 1982. Consent will be obtained from IRB. 
Data analysis 
After data was collected, the data was entered into Excel worksheets. The responses were coded and 
entered into SPSS (version 23). Descriptive statistics of categorical and continuous variables were 

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calculated. For the categorical variables, the frequency and percentage were calculated, while the 
arithmetic mean and standard deviation were calculated for continuous variables.   
The differences in participants' responses were examined using the Chi-square test (between 
intervention and control groups) and McNamara’s test (between baseline and follow up encounters) for 
categorical dependent variables as appropriate. For continuous dependent variables, One Way Analysis 
of Variance (ANOVA) test, independent samples t-test, and Wilcoxon test were performed when 
applicable. Both Kolmogorov-Smirnov Z and Shapiro-Wilk tests were used to test for normality of 
continuous variables. The statistical significance level was considered at a p-value ≤ 0.05.  
 
Patients Knowledge and Awareness of Isotretinoin: 
The degree of knowledge and awareness of correct practice was calculated as a total score. The patient 
knowledge section consisted of ten different questions/items, and each item had two answers (yes/no). 
Items were coded according to the answer; the correct (adequate) answer was coded as one (1), while 
the wrong (not adequate) answer was coded as zero (0). So, the knowledge score could take the values 
of 0 (no knowledge) to 10 (perfect knowledge).  
Chi square test was used to measure patients’ knowledge regarding isotretinoin use at baseline between 
intervention and control group. It was also used to measure patients’ knowledge regarding isotretinoin 
use at follow-up between intervention and control group. To measure if there was a significant 
difference in the correct patient knowledge regarding isotretinoin use, the percentage of the correct 
response for each question was calculated for both groups in baseline and at follow-up. McNamara’s 
test was performed to test if there was a significant difference in knowledge before the intervention and 
after the intervention in the intervention group, and at if there was a significant difference in knowledge 
between baseline and follow-up in the control group. In addition, independent t-test was used to 
compare the knowledge score differences (knowledge score at follow up – knowledge score at 
baseline) between the intervention group and the control group. Linear regression was conducted to 
evaluate the effect of the educational intervention on the difference in knowledge score adjusting to 
variables that were unbalanced at baseline.  
 
Patients Adherence to the Recommendations 
Similarly, adherence to recommendations for appropriate uses provided by clinical pharmacists for 
correct practice was calculated as a total score for each participant. This section consisted of 10 items 
for all patients, and each item had answers (yes/no). Items were coded according to the answer; the 
correct (adherent) answer was coded as one (1), while the wrong (not adherent) answer was coded as 

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zero (0). The adherence score of patients ’compliance with the recommendations ranged between 0 
(least adherent) to 10 (most adherent). Average score was evaluated across the intervention and control 
groups (using t test). 
 
HADS Scale   
HADS questionnaire was analyzed based on the scoring system; which consists of fourteen items; 
seven items each for the depression and anxiety subscale. The score for each item ranges from 0 to 3, 
and the HADS score ranged from 0 to 21 for depression and the same applied for anxiety. 
Chi square test was used to compare HADS items at baseline between intervention and control group. 
Besides, it was used to compare HADS items at follow-up between intervention and control group. 
Independent t-test was used to compare the HADS score differences (between baseline and at follow 
up) between the intervention group and the control group.  
HADS scores were categorized into three categories based on the abnormality classification; normal 
(less than eight), borderline abnormal (between eight and eleven) and abnormal (above eleven). Chi 
square test was used to evaluate the association between HADS score categories and intervention 
control status at baseline and at follow up. 
 
Patients Adherence to Medication 
The percentages (%) of patients’ adherence to medication and non-pharmacological adherence were 
calculated by dividing the number of adherent patients by the total number of patients in both groups. 
According to the final question, the reasons behind the patient’s non-adherence were themed into three 
distinct groups (forgetfulness, run out, and unavailability of isotretinoin). The frequency (%) of each 
group was calculated by dividing the number of times each category has occurred over the total number 
of patients and multiplying by 100.Chi-square test was conducted to evaluate the association between 
adherence status and patient intervention control status. 

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Results 
1. Baseline Questionnaire Results 
A total of 207 patients using isotretinoin in Jordan were randomly recruited to participate in the 
study. About four patients missed answering the phone in the follow-up phase, so they were 
excluded from the study. The response rate was 96.7% and 203 patients completed the study as 
shown in Figure 1. 
 
Figure 1: Patient recruitment flowchart  
 
1. Demographics of Respondents 
The demographics of the participants are summarized in Table 1.  All baseline demographic and 
clinical characteristics of the study participants were not statistically different between intervention 
and control group except for monthly income with P-value=0.032. Most respondents were female 
(n=179, 88.2%) compared to male (n=24, 11.8%) in both groups. Most of the patients were in the 
age group of 18-25 years, and the mean ± SD of age for the intervention group was 21.68 ± 3.21 and 
21.36 ± 2.6 for the control group. Regarding marital status, 96.9% of the participants were single 

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while the remaining were married (3.1%) for both study groups. The vast majority of participants 
have a bachelor’s degree in both the intervention (85%) and control groups (86%). Most of the 
respondents’ area of the residence for both groups was from the Irbid (77.8%) and the rest were from 
other cities (22.2%). Patients in either intervention or control group had a body mass index (BMI) 
ranged between 18.5 and 24.9 with a percentage of 68.6% and 73%; respectively. 
Regarding health insurance, 96.1% of the intervention group and 98% of the control group were 
insured. For all study participants, the period since starting to use the drug was no more than the first 
four months. More than half of the participants took a daily dose of 40 mg of isotretinoin in both 
intervention (58.3%) and control group (57%). The vast majority of the patients in both study groups 
(99%) had no chronic disease.  
Table 4.1: Baseline demographic and clinical characteristics of the study population 
Characteristics 
Total 
Intervention 
group 
Control group 
P-value 
  
n 
% 
n 
% 
n 
% 
  
Gender 
female 
179 
88.20 
91 88.30 
88 
88 
0.939 
male  
24 
11.80 
12 11.70 
12 
12 
Age (years) 
18-20 
86 
42.40 
41 39.80 
45 
45 
0.628 
21-25 
100 
49.20 
51 49.50 
49 
49 
26-30 
13 
6.40 
7 
6.80 
6 
6 
31-35 
4 
1.90 
4 
3.90 
0 
0 
Marital status 
single 
196 
96.90 
98 95.10 
98 
98 
0.265 
married 
7 
3.10 
5 
4.90 
2 
2 
Educational level  
school 
21 
10.30 
10 
9.70 
11 
11 
0.562 
college 
4 
2 
2 
1.90 
2 
2 
bachelor 
173 
85.20 
87 
85 
86 
86 
postgraduate studies 
5 
2.50 
4 
3.90 
1 
1 
Profession 
student 
146 
71.9 
74 71.80 
72 
72 
0.525 
Unemployed  
25 
12.3 
10 
9.70 
15 
15 
Non-medical 
profession 
16 
7.9 
10 
9.70 
6 
6 
Medical profession 
16 
7.9 
9 
8.70 
7 
7 
Residential area  
Irbid  
158 
77.80 
80 77.70 
78 
78 
0.949 
Alzarqa'a 
3 
1.50 
2 
1.90 
1 
1 
AL Mafraq 
13 
6.40 
7 
6.80 
6 
6 
Amman 
19 
9.40 
9 
8.70 
10 
10 

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Jerash 
4 
2 
2 
1.90 
2 
2 
Ajloun 
5 
2.50 
2 
1.90 
3 
3 
Maan 
1 
0.50 
1 
1 
0 
0 
Monthly income 
below 500 JD 
28 
13.80 
17 16.50 
11 
11 
0.032 
500-100 JD 
111 
54.70 
47 45.60 
64 
64 
above100 JD 
64 
31.50 
39 37.90 
25 
25 
Health insurance 
  
yes 
197 
97 
99 96.10 
98 
98 
0.428 
No 
6 
3 
4 
3.90 
2 
2 
Strength & dose of isotretinoin per a day (mg) 
10 
2 
1 
2 
1.90 
0 
0 
0.612 
20 
55 
27.10 
26 25.20 
29 
29 
30 
26 
12.80 
14 13.65 
12 
12 
40 
117 
57.60 
60 58.30 
57 
57 
60 
3 
1.50 
1 
1 
2 
2 
Period since starting the current isotretinoin course (months): 
newly diagnosed  
42 
20.70 
22 21.40 
20 
20 
0.603 
first month  
42 
20.70 
23 22.30 
19 
19 
second month 
51 
25.10 
26 25.20 
25 
25 
third month 
57 
28.1 
29 28.20 
28 
28 
fourth month 
11 
5.40 
3 
2.90 
8 
8 
Body mass index 
under 18.5 
23 
11.40 
11 10.80 
12 
12 
0.783 
18.5-24.9 
143 
70.40 
70 68.60 
73 
73 
25-29.9 
28 
13.90 
15 14.70 
13 
13 
30-34.9 
7 
3.50 
5 
4.90 
2 
2 
35-39.9 
2 
1 
1 
1 
1 
1 
Total 
203 
100 
103 
50.7 
100 
49.3  
 
2. General Information Regarding Isotretinoin Use 
All patients (100%) were taking isotretinoin based on an authorized prescription. On the other hand, 
10.8% of sampled patients had been taking isotretinoin at least once without a prescription prior to 
current use; 10.7% of intervention group and 11%of control group with P-value  =  0.941. While 
89.2% had never used isotretinoin before without prescription; 89.3% of the intervention group and 
89% of the control group. 59.2% of the intervention group and 67% of the control group did not visit 
a dermatologist for acne problems for the first time but did so several times before starting 
isotretinoin with a P-value=0.251.  
Participants were asked to answer two questions regarding laboratory testing (liver function test and 
lipid profile test), whether these tests were required to be performed, and if they did check them 
before starting treatment. Results showed that 98.1% of intervention group and 98% of control group 

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were required to undergo testing with P-value=0.976, while 97.1% of the intervention group and 
97% of the control group with P-value=0.971 were checked these tests. Approximately 69.5% of 
enrolled patients said that their physicians informed them about the expected side effects of 
isotretinoin and how to manage it; 72.8% of the intervention group and 66% of the control group 
with P-value=0.327.  
During the questionnaire, participants were asked to answer two questions about the impact of 
having acne on their daily, psychological and social life, about the severity of their acne condition, 
and results are summarized in Figure 2 and Figure 3; respectively. 
 
Figure 2: The impact of acne on daily, psychological, and social life. 
 
Figure 3: The severity of acne condition as reported by participants.  
3. 
Patients Knowledge about Isotretinoin Use 
Patients' knowledge about isotretinoin treatment for both groups was assessed at baseline and at the 

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3 months follow-up, and responses of the patients are shown in Table 2 and Table 3; respectively. 
Patients’ average knowledge score at the first meeting before the education process was 6.5 out of 
10. There was no significant  difference in overall knowledge score at baseline between the 
intervention group and the control group with a mean (6.47 for the intervention group vs. 6.57 for 
the control group).. In contrast, the patient's average knowledge score at follow-up (three months 
after the education session) was 8.22 out of 10. The results at follow-up showed a significant 
difference in the knowledge score (P-value>0.001) between the intervention (9.3) and control group 
(7.1). 
 The average difference in the overall knowledge score (before and after the education process) was 
statistically different between the intervention and control group (1.6995±1.589; P-value< 0.001). 
The average difference in overall knowledge score was, 2.835±1.329 for the intervention group and 
0.530±0.784 for the control group. 
Since the monthly income was significantly different between intervention group and control group 
at baseline, results from linear regression showed that the difference in overall knowledge score is 
still significantly different between the intervention and control group after adjustment for income 
status (Coef. = 2.308446); P-value> 0.001 
Table 2: Patients knowledge regarding the use of isotretinoin at baseline 
  
Intervention 
group 
n (%) 
Control group 
n (%) 
P-
value  
knowledge about common side effects 
  
  
  
  
yes  
6 (5.8) 
2 (2) 
0.28 
no 
97 (94.2) 
98 (98) 
We can use isotretinoin during pregnancy* 
yes  
10 (9.7) 
10 (10) 
0.944 
no 
93 (90.3) 
90 (90) 
We can use the drug without prescription* 
yes  
6 (5.8) 
5 (5) 
0.795 
no 
97 (94.2) 
95 (95) 
No need to have laboratory monitoring during isotretinoin use* 
  
yes  
4 (3.9) 
5 (5) 
0.745 
no 
99 (96.1) 
95 (95) 
We should drink water to reduce the dryness 
yes  
  
  
  
99 (96.1) 
98 (98 
0.683 
no 
4 (3.9) 
2 (2) 
We should use sunblock to reduce sensitivity to the sun 
yes  
99 (96.1) 
99 (99) 
0.121 
no 
4 (3.9) 
1 (1) 
It is preferred to take isotretinoin with fatty foods 
yes  
70 (68) 
74 (74) 
0.343 

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no 
33 (32) 
26 (26) 
We can donate blood during isotretinoin* 
yes 
67 (65) 
70 (70) 
0.451 
no 
36 (35) 
30 (30) 
Woman can lactate while using isotretinoin* 
yes 
72 (69.9) 
72 (72) 
0.742 
no 
31 (30.1) 
28 (28) 
We can make laser or wax during isotretinoin* 
yes 
66 (64.1) 
55 (55) 
0.188 
no 
  
  
  
37 (35.9) 
45 (45) 
The correct answer is yes unless otherwise indicated. * The correct answer is no . 
 
Table 3: Patients knowledge regarding the use Isotretinoin at follow-up  
  
Intervention 
group-post 
n (%) 
Control group-
post 
n (%) 
P value 
knowledge about common isotretinoin side effects 
yes  
49 (47.6) 
3 (3) 
< 0.001 
no 
54 (52.85) 
97 (97) 
We can use isotretinoin during pregnancy* 
yes  
0 (0) 
4 (4) 
0.057 
no 
103 (100) 
96 (96) 
We can use the drug without 
prescription* 
  
  
  
  
  
yes  
0 (0) 
5 (5) 
0.028 
no 
103 (100) 
95 (95) 
No need to have laboratory monitoring during isotretinoin use* 
yes  
0 (0) 
5 (5) 
0.028 
no 
103 (100) 
95 (95) 
We should drink water to reduce the dryness 
yes  
100 (97.1) 
98 (98) 
0.675 
no 
3 (2.9) 
2 (2) 
we should use sunblock to reduce sensitivity to the sun 
yes  
103 (100) 
99 (99) 
0.493 
no 
0 (0) 
1 (1) 
It is preferred to take isotretinoin with fatty foods 
yes  
103 (100) 
81 (81) 
< 0.001 
no 
0 (0) 
19 (19) 
We can donate blood during isotretinoin* 
yes 
0 (0) 
57 (57) 
< 0.001 
no 
103 (100) 
43 (43) 
Woman can lactate while using isotretinoin* 
yes 
9 (8.7) 
60 (60) 
< 0.001 
no 
94 (91.3) 
40 (40) 
We can make laser or wax during isotretinoin* 

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yes 
5 (4.9) 
40 (40) 
< 0.001 
no 
98 (95.1) 
60 (60) 
The correct answer is yes unless otherwise indicated. * The correct answer is no . 
 
The percent of correct answers were significantly higher at follow up compared to baseline for most 
of knowledge questions in the intervention group. On the other hand, the percent of correct answers 
were significantly higher at follow up compared to baseline for the five out of the ten knowledge 
questions in the control group as shown in Table 4. 
Table 4: Patient knowledge regarding isotretinoin use at baseline and at follow up.  
  
Intervention 
group-
baseline 
n (%) 
Intervention 
group-
follow up 
n (%) 
P -value 
Control 
group- 
baseline 
n (%) 
Control 
group-
follow up 
n (%) 
P-value 
knowledge about common isotretinoin side effects 
  
6 (5.8) 
49 (47.6) 
< 0.001 
2 (2) 
3 (3) 
0.564 
We can use isotretinoin during pregnancy* 
93 (90.3) 
103 (100) 
0.0016 
90 (90) 
96 (96) 
0.0339 
We can use the drug without prescription* 
97 (94.2) 
103 (100) 
0.0143 
95 (95) 
95 (95) 
0.95 
No need to have laboratory monitoring during isotretinoin use* 
99 (96.1) 
103 (100) 
0.0455 
95 (95) 
95 (95) 
0.95 
We should drink water to reduce the dryness 
  
99 (96.1) 
100 (97.1) 
0.705 
98 (98) 
98 (98) 
0.98 
we should use sunblock to reduce sensitivity to the sun  
  
99 (96.1) 
103 (100) 
0.045 
99 (99) 
99 (99) 
0.317 
It is preferred to take isotretinoin with fatty foods 
70 (68) 
103 (100 
< 0.001 
74 (74) 
81 (81) 
0.0196 
We can donate blood during isotretinoin* 
36 (35) 
103 (100) 
< 0.001 
30 (30) 
43 (43) 
0.0008 
Woman can lactate while using isotretinoin* 
31 (30.1) 
94 (91.3) 
< 0.001 
28 (28) 
40 (40 
0.0027 
we can make laser or wax during isotretinoin* 
37 (35.9) 
98 (95.1) 
<0.001 
45 (45) 
60 (60) 
0.0011 
Frequencies and percentages presented are for correct answers.  
At follow-up, patients were asked if they searched for outside sources for information about the drug 
during their treatment. About 56% of the control group compared to 45% of the intervention group 
said yes with P-value=0.079. 
4. 
Patient’s Adherence to Recommendations About the Proper Use  
The patient’s adherence to recommendations for the proper use of isotretinoin and the adherence to 

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specific instructions on managing side effects provided by the physician or clinical pharmacist at 
follow-up was evaluated. The average recommendation score was 7.601 ±1.358 for all patients, and 
it was significantly different between control and intervention group (the mean for intervention 
group=8.534±0.905 and control group=6.64±1.039) with P-value >0.001. The percentage of 
participants who were adherent to all recommendations (10 out of 10) was 15.5% for the 
intervention group compared to 0% for the control group. 
The frequency and number for patients who were adherent to the recommendations for the 
intervention group and control group are summarized in Table 4.5. Around 59% of the intervention 
group compared to 27% of the control group were adherent to drinking plenty of water (more than 
two liters per day) with P-value<0.001.  
Table 5: Patient’s adherence to recommendations about the proper use at follow-up 
  
Intervention group 
n (%)  
Control group 
n (%) 
P 
value 
I adhere to drink plenty of water during isotretinoin use  
yes  
61 (59.2) 
27 (27) 
< 0.001 
no  
42 (40.8) 
73 (73) 
I adhere to use eye drop during isotretinoin use  
yes  
89 (86.4) 
69 (69) 
0.003 
no  
14 (13.6) 
31 (31) 
I adhere to use lip balm during isotretinoin use  
yes  
101 (98.1) 
98 (98) 
0.90 
no  
2 (1.9) 
2 (2) 
I adhere to use body lotion during isotretinoin use  
yes  
48 (46.6) 
28 (28) 
0.006 
no  
55 (53.4) 
72 (72) 
I adhere to make laboratory monitoring (AST & ALT) during isotretinoin use  
  
yes  
102 (99) 
98 (98) 
0.618 
no 
1 (1) 
2 (2) 
I adhere to make lipid profile test during isotretinoin use  
yes  
102 (99) 
98 (98) 
0.618 
no 
1 (1) 
2 (2) 
I adhere to use sunblock when going out during isotretinoin use  
yes 
98 (95.1) 
91 (91) 
0.244 
no 
5 (4.9) 
9 (9) 
I adhere to take isotretinoin with fatty foods 
yes  
88 (85.4) 
62 (62) 
< 0.001 
no 
15 (14.6) 
38 (38) 
I adhere not to donate blood during isotretinoin use  
yes 
103 (100) 
43 (43) 
< 0.001 
no 
0 (0) 
57 (57) 
I adhere not to make laser or wax during isotretinoin use  

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yes 
87 (84.3) 
51 (51) 
< 0.001 
no 
16 (15.7) 
49 (49) 
Results showed that 86.4% of the intervention group compared to 69% of control group were 
adherent to the use of eye drop, and the difference was statistically significant (P-value=0.003). The 
adherence to using body lotion was higher in the intervention group (46.6%) compared to the control 
group (28%) with a P-value=0.006. On the other hands, there were no significant differences 
between both groups regarding the use of lip balm and sunblock.  
For the two questions about adherence to laboratory monitoring (i.e., the liver function test or the 
lipid profile test), the rate of adherence was high in both group (99% for the intervention group and 
98% for the control group) with no significant statistical difference.  
The results of responses to the last three questions about adherence (taking the medication with or 
after fatty meals, adherence to not donate blood, and not to make laser or wax during treatment) 
were significantly different between the control and intervention group with P-value <0.001. 
5. 
HADS Scale 
 HADS-Anxiety score and HADS-Depression score were tested at baseline and at follow-up after 
three months.  At baseline, the mean HADS-Anxiety score for both groups was 7.8079±4.159, 
which slightly improved to 7.5862±3.28 at follow-up, which was statistically not significant. 
Likewise, the mean HADS-Depression score was 6.773±3.709, while at follow-up it became 
7.0148±3.1029 and it was statistically not significant. The responses for intervention and control 
group at follow-up (intervention vs. control group) are indicated in Table 6. 
Table 6: HADS anxiety and depression score at follow-up  
  
Intervention group 
n (%) 
Control group 
n (%) 
P-
value 
I feel tense or 'wound up.' 
  
most of the time  
  
4 (3.9) 
2 (2) 
0.006 
a lot of the time  
  
20 (19.4) 
7 (7) 
from time to time  
  
54 (52.4) 
75 (75) 
not all time 
  
25 (24.4) 
16 (16) 
I get a sort of frightened feeling like 'butterflies' in the stomach: 
very often 
  
3 (2.9) 
1 (1) 
0.163 
Quite Often 
  
26 (25.2) 
15 (15) 
Occasionally 
  
56 (54.4) 
59 (59) 
not at all  
  
18 (17.5) 
25 (25) 
I get a sort of frightened feeling as if something awful is about to happen 
very definitely and quit badly  
  
10 (9.7) 
5 (5) 
0.577 
yes, but not too badly 
  
30 (29.1) 
27 (27) 
a little, but it does not worry me    
55 (53.4) 
59 (59) 

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not at all  
  
8(7.8) 
9 (9) 
I feel restless as I have to be on the move: 
Very much indeed 
  
2 (1.9) 
0 (0) 
0.362 
Quite a lot 
  
21 (20.4) 
18 (18) 
not very much 
  
57 (55.3) 
64 (64) 
not at all  
  
23 (22.3) 
18 (18) 
Worrying thoughts go through my mind: 
A great deal of the time 
  
9 (8.7) 
4 (4) 
0.432 
A lot of the time 
  
38 (36.9) 
35(35) 
From time to time, but not too 
often 
  
54 (52.4) 
57 (57) 
not occasionally 
  
2 (1.9) 
4(4) 
I get sudden feelings of panic 
Very often indeed 
  
2 (1.9) 
0 (0) 
0.493 
Quite often 
  
6(5.8) 
4 (4) 
Not very often 
  
35 (34) 
34 (34) 
not at all  
  
60(58.3) 
62 (62) 
I can sit at ease and feel relaxed: 
Definitely 
  
12 (11.7) 
11 (11) 
0.674 
usually 
  
47 (45.6) 
54(54) 
Not Often 
  
43 (41.7) 
34 (34) 
not at all  
  
1 (1) 
1(1) 
I feel as if I am slowed down 
Nearly all the time 
  
1 (1) 
1 (1) 
0.871 
very often 
  
19 (18.4) 
15 (15) 
sometimes 
  
73 (70.9) 
76 (76) 
not at all  
  
10 (9.7) 
8 (8) 
I still enjoy the things I used to enjoy: 
definitely as much  
  
17 (16.5) 
12 (12) 
0.33 
not quite so much 
  
43 (41.7) 
54 (54) 
only a little 
  
36 (35) 
30 (30) 
hardly at all 
  
7 (6.8) 
4 (4) 
I have lost interest in my appearance 
Definitely 
  
0 (0) 
1 (1) 
0.269 
I do not take as much care as I 
should 
  
2 (1.9) 
0 (0) 
I may not take quite as much 
care 
  
16 (15.5) 
11 (11) 
I take just as much care as ever 
  
85 (82.5) 
88 (88) 
I can laugh and see the funny side of things: 
As much as I can always could  
  
31 (30.1) 
31 (31) 
0.461 
Not quite so much now 
  
42 (40.8) 
49 (49) 
Definitely not so much now 
  
29 (28.2) 
19 (19) 
not at all  
  
1 (1) 
1 (1) 
I look forward with enjoyment to things: 

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As much as I ever did 
  
36 (35) 
27 (27) 
0.012 
Rather less than I used to 
  
35 (34) 
56 (56) 
Definitely less than I used to 
  
31 (30.1) 
16 (16) 
Hardly at all 
  
1 (1) 
1 (1) 
I feel cheerful: 
  
Most of the time 
  
12 (11.7) 
10 (10) 
0.456 
Sometimes 
  
49 (47.6) 
57 (57) 
Not often 
  
41 (39.8) 
33 (33) 
Not at all  
  
1 (1) 
0 (0) 
I can enjoy a good book or radio or TV program: 
Often 
  
21 (20.4) 
15 (15) 
0.717 
Sometimes 
  
45 (43.7) 
47 (47) 
Not often 
  
25 (24.3) 
28 (28) 
Very seldom 
  
12 (11.7) 
10 (10) 
The average difference in anxiety score (difference between baseline and follow up) was not 
significant between intervention and control group (P-value=0.238) Similarly, the average difference 
in depression score was not significant between intervention and control group (P-value=0.323). 
  HADS score categories for both anxiety and depression subscales were not associated with the 
intervention control status at baseline nor at follow up.  Table 7 summarizes the results for follow-
up. 
Table 7: Comparison between intervention and control groups in HADS percentages at baseline and 
follow-up  
  
HADS-baseline  
(%) 
P- 
value  
HADS-follow up 
(%)  
P- 
value  
  
Intervention 
Control   
Intervention  
Control 
  
Anxiety score 
less than 8 
45.60 
55 
0.283 
49.50 
55 
0.536 
8 _11 
24.30 
24 
26.20 
27 
above 11 
30.10 
21 
24.30 
18 
Depression score 
less than 8 
55.30 
64 
0.108 
58.30 
64 
0.288 
8 _11 
21.40 
24 
20.40 
23 
above 11 
23.30 
12 
21.40 
13 
6. 
Patient Adherence 
7. 
Pharmacological Adherence  
The descriptive results of drug-taking behavior and the adherence at follow-up for all patients are 
presented in Table 8.  
 
Table 8: Descriptive statistics of patient’s answer to adherence questionnaire   
  
Intervention group 
Control group 

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n (%) 
n (%) 
Do you forget taking your medication 
Never 
42 (40.8) 
31 (31) 
Rarely 
51 (49.5) 
51 (51) 
sometimes 
10 (9.7) 
18 (18) 
Usually 
0 (0) 
0 (0) 
Always 
0 (0) 
0 (0) 
Do you stop your medication when you feel better 
Never 
103 (100) 
98 (98) 
Rarely 
0 (0) 
2 (2) 
sometimes 
0 (0) 
0 (0) 
Usually 
0 (0) 
0 (0) 
Always 
0 (0) 
0 (0  
Do you stop your medication when you feel worse 
Never 
103 (100) 
98 (98) 
Rarely 
0 (0) 
2 (2) 
sometimes 
0 (0) 
0 (0) 
Usually 
0 (0)  
0 (0) 
Always 
0 (0 
0 (0) 
Do you run out of your medication  
Never 
67 (65) 
43 (43) 
Rarely 
31 (30.1) 
48 (48) 
sometimes 
5 (4.9) 
9 (9) 
Usually 
0 (0) 
0(0) 
Always 
0 (0) 
0 (0) 
Do you adhere to lifestyle recommendations  
Never 
0 (0) 
1 (1) 
Rarely 
1 (1) 
0 (0) 
sometimes 
2 (1.9) 
1 (1) 
Usually 
51 (45.5) 
78 (78) 
Always 
49 (47.6) 
20 (20) 
Out of the 203 patients in the study, 17.7 % reported that they were non-adherent to isotretinoin 
medication at follow-up (adherence score <4). Patients were grouped into adherent, non-adherent as 
previously indicated in the methodology chapter. Overall, 12.65% of the patients in the intervention 
were non-adherent vs. 23% in the control group (P-value=0.053).  Regarding adherence items, 9.7% 
of intervention group and 18% of the control group said they sometimes, usually or always forget 
taking their medications (non-adherent); with a P-value =0.087. None of the patients in the 
intervention and control group said that they tended to stop taking their medications when they feel 
better or worse.  4.9% of the intervention group and 9% of the control group ran-out of their 
medications before they had the chance to refill them; P- value=0.244. Adherence to lifestyle 
recommendations was reported by 97.5% for all patients in both groups. The difference in non-

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pharmacological level of adherence was not statistically significant between both groups; 98% of the 
control group were adherent and 97.1 % of the intervention group were adherent, as shown in Table 9. 
 
Table 9: Comparison the prevalence of adherence between intervention and control group  
  
Intervention group 
(%) 
Control group 
(%) 
P-value  
Do you forget taking your medication 
adherent 
90.30 
82 
0.087 
non-adherent 
9.70 
18 
Do you stop your medication when you feel better 
adherent 
100 
100 
0.99 
Non-adherent 
0 
0 
Do you stop your medication when you feel worse 
adherent 
100 
100 
 0.99 
non-adherent 
0 
0 
Do you run out of your medication  
adherent 
95.10 
91 
0.244 
non-adherent 
4.90 
9 
total pharmacological score  
adherent 
87.40 
77 
0.053 
non-adherent 
12.65 
23 
Do you adhere to lifestyle recommendations  
adherence  
97.10 
98 
0.675 
non-adherent 
2.90 
2 
The causes of patients' non-adherence to medications are presented in Figure 4.4. Among 203 
patients, the cause for patients not being adherent to their medications was forgetfulness (69%), 
followed by run out of isotretinoin (20%), unavailability of medication (4.5%), and lack of 
motivation (1%). 
 
Figure 4: Causes of patients' non-adherence to medications 
8. 
Miscellaneous 

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In the follow-up questionnaire, multiple additional questions were asked regarding patients’ opinion 
about acne improvement, the impact of side effects on their daily activities, and their satisfaction 
with the provided drug information. There were statistically significant differences in all these three 
dimensions between the intervention and control groups.  
About 47% of the patients who received the educational process from the clinical pharmacist in 
addition to the doctor reported that they had an excellent improvement in their acne conditions 
compared to 30% of the patients who received the educational process from the doctor only, P-value 
=0.048.  Results are shown in Table 10.  
 
Table 10: Patient’s opinions about the improvement of the acne 
 
Intervention group 
n (%) 
Control group 
n (%) 
P value 
In your opinion, how much is the improvement of your acne 
 Excellent 
48 (46.6) 
30 (30) 
0.048 
very good 
50 (48.5) 
56 (56) 
good  
5 (4.9) 
5 (5) 
There was a significant difference between the intervention group and the control group with regards 
to the impact of side effects on daily life and normal activities of the patients, P-value<0.001. 76.6% 
of patients in the intervention group reported no effect or a weak effect on daily activity compared to 
48% of the patients in the control group as indicated in Table 11. 
 
Table 11: Patient’s responses about side effect and their impact on daily activity   
  
Intervention group 
n (%) 
Control group 
n (%) 
P-value 
How does the side effects affect your daily life and your normal activities 
Big impact 
0 (0) 
4 (4) 
< 0.001 
Moderate impact 
24 (23.3) 
48 (48) 
Weak impact 
73 (70.9) 
46 (46) 
There is no impact 
6 (5.8) 
2 (2) 
There are three questions about the patient’s satisfaction with the provided drug information (either 
through the usual care provided by the doctor or the additional care provided by the clinical 
pharmacist in addition to the doctor). There were significant differences between the two groups 
with more satisfaction for the intervention group; 0% of the intervention group compared to 52% of 
the control group said they need more explanation about the drug with P-value<0.001. In addition, 
none of the intervention group compared to 71% of the control group said they need more 

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explanation about the side effects and how to avoid them with P-value<0.001. 17.5% of the 
intervention group compared to 44% of control group reported that they need more follow-up by the 
doctor with P-value<0.001. All the results of responses are presented in Table 12. 
Table 12: Patient’s satisfaction with the drug information 
  
Intervention group 
n (%) 
Control group 
n (%) 
P-value 
Do you think you needed to explain more about the drug in general 
yes  
0 (0) 
52 (52) 
< 0.001 
no 
103 (100) 
48 (48) 
Do you think you need more explanations about the side effects and how to 
avoid it 
yes 
0 (0) 
71 (71) 
< 0.001 
no 
103 (100) 
29 (29) 
Do you think you need more follow-up by the doctor 
yes 
18 (17.5) 
44 (44) 
< 0.001 
no 
85 (82.5) 
56 (56) 
There was an additional question regarding the effect of COVID-19 pandemic on their treatment (as 
the study was conducted during the pandemic), the answer was around 90% of all patients’ treatment 
were not affected, and only 10% affected (either little, medium, or big impact), the distribution of 
responses is presented in Figure 5. 
 
Figure 5: The effect of COVID-19 pandemic on the isotretinoin treatment.  
Furthermore, the analysis of how the treatment was affected during the Corona period was checked 
for the patients and presented in Figure 6. The analysis showed that most of the patients reported an 
effect on their isotretinoin treatments. 70% of the patients were affected by their treatment due to the 
inability to go to monthly visits, and 45% of the patients were affected by the inability to obtain the 
medicine, and 1% of the patients were affected by the inability to make laboratory monitoring test, 
and 1% were affected by the inability to adhere to isotretinoin when they were infected with 
COVID-19 virus. 

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Figure 6:  The effect of treatment with Coronavirus 
9. 
Married Females’ Participants 
Married women received additional questions. There was a total of seven married women who 
participated in the study (5 women in the intervention group and 2 women in the control group. All 
of our sampled married female patients were non-pregnant (100%). Out of them, 71.5% (5 patients); 
60% (3 patients) of the intervention group, and 100% (2 patients) of the control group used one type 
of contraceptive at baseline, after the education process for the intervention group and at follow-up, 
100% of patients were using contraception. Referring to contraceptive use during isotretinoin 
therapy, 0% of the married women in the intervention group and 50% (one patient) in the control 
group used two different contraceptives. In contrast, after the education process for the intervention 
group and at follow-up, 100% of patients were using two methods of contraception. 
Additionally, no one of the participants reported that they had a pregnancy test every month at 
baseline. At follow-up, 60% (3 patients) in the intervention group did the pregnancy test monthly 
compared to no one in the control group. 100% of the participants said that the physician informed 
them about the teratogenicity of isotretinoin, and they signed a pre-approval sheet before starting the 
treatment. 
 

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Informed consent 
 
Appendix 1 
Informed consent 
 
This study aims to determine clinical pharmacist role in increasing adherence to 
recommendations among patients using isotretinoin in Jordan. 
 
You are invited to participate in a research study to measure whether an active 
intervention (educational process) by the clinical pharmacist will increase the patient 
adherence to recommendations related to isotretinoin, awareness about proper use, and 
dealing with the side effects. 
 
Participation in this study is completely voluntary, there are no known risks or 
inconveniences associated with this study. If you choose to be in study, you can 
withdraw at any time without adversely affecting your relationship with anyone at the 
University of Science and Technology. Your responses will be kept strictly confidential, 
and the data will be stored digitally only in secure files on computers. When any report 
on this research is available to the public, it will not include your name or any other 
individual information through which your identity can be identified. 
 
If you have any questions about whether you were treated in an illegal or unethical 
manner, or if you have questions or want a copy or summary of the results of this study, 
you can contact the researcher, Dr Bushra Hijazi at her email bmhijazi3@just.edu.jo or 
Dr. Ruba Al Abdullah, at her  
e-mail: Ruba.yousef1995@gmail.com 
 
 Feel free to take a copy of this approval page to keep it in your records. Choosing the "I 
agree" option below indicates that you are 18 years old or older and indicates your 
agreement to participate in this study. 
 
              I agree                                                                       I disagree                                               
                                                                                                                             
              
                   
 
 
 

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Appendix 2 
Recommendations for managing side effects: 
1- Recommended OTC products for the treatment of common adverse effects 
Dry eyes: artificial tears and eye refreshments.  
Dry mucus membranes and nose: saline nasal spray and Vaseline.  
Dry lips: petroleum lip balm, nonmedicated lip balm. 
 Dry skin; glycerin-based or lactic acid moisturizing lotion or cream. 
 Sunburn: choose sunscreen with SPF15 or higher that doesn’t contain para-aminobenzoic acid    
due to drying effect, [2] , and void excessive exposure to the sun because your skin may become more 
sensitive to sunlight while using the drug, and sunburn may increase [3]. 
 *increase intake of water will decrease the dryness. 
2- Isotretinoin causes an elevation of (AST), (ALT) liver enzyme, and (LDH), Triglyceride (TGA) lipid 
profile, also can lead to pancreatitis. Therefore, monitoring is essential to ensure the safe use of the 
product, so should be checked before treatment, one month after the start of treatment, then 
subsequently at three monthly intervals unless more frequent monitoring is indicated [4].  
*Reduced intake of junk food and alcohol consumption will control the increase in lipid profile.  
3- Female patients must always be informed about the teratogenic risk [5] and required to use two 
forms of contraception, starting one month before therapy and continuing for one-month post 
therapy[6]. Patients should be educated about appropriate forms of birth control since some types are 
unacceptable, such as the female condom and progesterone-only birth control pills (primary forms of 
birth control: tubal sterilization, vasectomy, intrauterine device, and combination hormonal therapy. 
Secondary structures of contraception: condoms, diaphragms, cervical caps, and vaginal sponges 
containing spermicide). 
*they have to make monthly pregnancy test while taking isotretinoin. 

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To reduce fetal exposure to isotretinoin, Clinical pharmacists should encourage the use of 
iPLEDGE, a risk management program to regulate the use of isotretinoin, Available at 
https://www.ipledgeprogram.com/iPledgeUI/home.u, and its goal to ensure that women using 
isotretinoin do not become pregnant and women who are pregnant do not use isotretinoin. 
4- Do not breastfeed while taking isotretinoin and for one month after stopping it. Isotretinoin may pass 
through the milk and harm the baby[7]. 
5- There are important warnings must be mentioned:  
• vitamins :(do not take vitamin A),  
• antibiotics: (Do not take tetracyclines, may increase the pressure in the brain with 
isotretinoin), 
• lenses: (may make irritation), so avoid using it as much as possible 
• blood donation: (It is not possible to donate blood for at least one-month post therapy for fear 
of giving your blood to a pregnant woman, causing congenital diseases in the fetus.), 
• waxing and laser hair removal: may cause pigmentation and skin irritation, so it should be 
avoided during treatment and 6 months after stopping the drug(preferred). 
• Cosmetics: (Do not use cosmetic procedures to smooth your skin; it may increase your 
chance 
of 
scarring 
or 
inflammation 
of 
the 
skin 
from 
these 
procedures). 
https://www.medicines.org.uk/emc/product/3870/pil (isotretinoin leaflet). 
6- Isotretinoin may cause depression, psychosis, and violent behavior; particular care needs to be taken 
in a patient with a history of depression, and all patients should be monitored for signs of depression 
and referred for appropriate treatment if necessary. A further psychiatric or psychological evaluation 
may be necessary. (leaflet) 
7- Take it with food or after food, and it prefers to take with fatty meals, store at room temperature. 
(leaflet) 
8- Isotretinoin may cause pain in the muscles or joints, especially for adolescents who undergo 
vigorous exercise. Painkillers can be taken in this case, such as non-steroidal analgesics or paracetamol. 
(leaflet) 
9- Do not use two doses at one time if you missed the dose (isotretinoin leaflet). 

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10 - Do not share isotretinoin with other people. It can cause congenital disabilities and other serious 
health problems. (leaflet) 
11- Inform the doctor or pharmacist of any medicine that you will take during treatment with 
isotretinoin, because drug interactions may occur. (Leaflet) 
  

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Appendix 3 
A. Baseline questionnaire  
General information 
Age:  
Gender: 
□ female              □ Male 
Marital status: 
□Single    □ Married 
Educational level: 
□ Basic   □ Secondary   □ High school    □ Diploma    □ Bachelor    □ Master   □ PHD 
Residential area: 
         □ Irbid                  □ Amman        □ Al Zarqa             □ Al Mafraq 
         □ Al Balqaa          □ Al Karak      □ others, Mention 
Weight (Kg) 
Hight (cm) 
Profession: 
□ Medical Profession         □ Non-medical profession          
                □ Student                         □   Doesn't work 
Monthly income: 
□ less than 500 JD                        □ 500-1000                                  □ above 1000 
Do you have health insurance ?                  □ yes                                            □ No 
Current dose of isotretinoin medication: 
□ Number of capsules:                 □ number of times:                      □strength: 
Period since the initiation of isotretinoin medication: 
□ Newly diagnosed        □1 month          □ 2 months   
□ 3 months                    □ 4 months, others  
 
Please answer the following questions about your current of isotretinoin: 
1. Do you have chronic diseases? 
 Pressure 
 Diabetes 
 Thyroid gland  

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 Other……… 
2. Have you been asked for the following laboratory tests? 
 Pregnancy test: - yes    - no     -not applicable  
 Liver function test: - yes    -no    
 Lipid profile test: - yes     -no 
3. Did you make liver function test and lipid profile test before starting treatment? 
 Yes  
 No 
4. Have you ever used isotretinoin without prescription even for one time? 
 Yes 
 No 
5. Is it your first visit to a dermatologist to acne? 
 Yes 
 No 
6. Did anyone explain to you about the medicine? 
 Yes 
 No 
                  - Please specify who explained to you about the medicine? 
 Doctor 
 Pharmaceutical 
 The doctor and the pharmacist. 
 Otherwise.  
7. How much does acne affect your daily, psychological and social life? 
 Very big impact.  
 Big impact  
 Medium 
 Weak 
 There's no effect. 
8. What do you think your acne is? 
 Mild < 30 black and white pills 
 Moderate ~ 100 black and white pills 

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 Severe nodules, big, painful red pills.  
 Very severe (there are scar scars, pigments and old raisins) 
 
Please answer the following knowledge questions: 
9. Which of the following is isotretinoin side effect? 
□ Dryness                □ Teratogenicity              □ Abnormal lipid profile 
□ Constipation        □ difficulty in breathing   □ back pain   □ Others 
10. (In case of using isotretinoin based on medical prescription), the physician had 
explained for me isotretinoin side effects and how to manage them: 
 Yes 
 No 
11. Isotretinoin can be used without prescription: 
 
Yes             
 
No 
 
I do not know 
12. Isotretinoin can be used during some periods of pregnancy: 
 
Yes             
 
No 
 
I do not know 
13. There is no need to have laboratory tests during isotretinoin therapy: 
 
Yes             
 
No 
 
I do not know 
14. It is recommended to drink plenty of water during isotretinoin therapy to avoid dryness: 
 
Yes             
 
No 
 
I do not know 
15. It is recommended to use sun block during isotretinoin therapy: 
 
Yes             

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No 
 
I do not know 
16. It is recommended to take isotretinoin after fatty meals: 
 
Yes             
 
No 
 
I do not know 
17. Blood donation is allowed during isotretinoin therapy: 
 
Yes             
 
No 
 
I do not know 
18. Breast feeding is allowed during isotretinoin therapy: 
 
Yes             
 
No 
 
I do not know 
19. wax and laser for hair removal is allowed during isotretinoin therapy: 
 
Yes             
 
No 
 
I do not know 
 
For married female. kindly answer the following questions 
20. Do you use contraception method during your isotretinoin therapy? 
 
Yes             
 
No 
21. Did you have pregnancy test before starting isotretinoin therapy? 
 
Yes             
 
No 
22. Did your doctor explain for you the teratogenicity of isotretinoin? 
 
Yes             
 
No 
23. Did the pharmacist explain for you the teratogenicity of the drug? 
 
Yes             
 
No 
24. Did your doctor request you to sign up consent form which explain to you the 
isotretinoin side effects? 
 
Yes             

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No 
25. (In case of using isotretinoin based on medical prescription), the doctor has explained to 
me the importance of using two contraceptive methods during isotretinoin therapy: 
 
Yes             
 
No 
26. Do you think you needed to explain more about the drug in general? 
 
Yes             
 
No 
27. Do you think you needed to explain more about the drug in terms of the method of use? 
 
Yes             
 
No 
28. Do you think you need edited more explanations about the side effects of the drug and 
how to avoid it? 
 
Yes             
 
No 
29. Do you have any feedback regarding this questionnaire? 
 
Yes ……………………………….           
 
No 
 
Measure of the HADS score: 
I'm frustrated.  
D I feel confused.  
A 
Always  
3 
Always  
3 
Often 
2 
Often 
2 
Sometimes  
1 
Sometimes  
1 
At all  
0 
At all  
0 
I'm scared.  
A I still enjoy the things I used to enjoy.  
D 
Always  
3 
Always  
0 
Often 
2 
Often 
1 
Sometimes  
1 
Sometimes  
2 
At all  
0 
At all  
3 
I lost interest in my appearance.  
D I feel kind of afraid something bad is 
going to happen.  
A 
Always  
3 
Always  
3 
Often 
2 
Often 
2 
Sometimes  
1 
Sometimes  
1 
At all  
0 
At all  
0 
I'd like to have fun and look forward to 
enjoying things.   
D I can laugh and see the funny side of 
things.  
D 
Always  
0 
Always  
0 

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Often 
1 
Often 
1 
Sometimes  
2 
Sometimes  
2 
At all  
3 
At all  
3 
I suddenly feel shaking.  
A Disturbing thoughts are in my mind.  
A 
Always  
3 
Always  
3 
Often 
2 
Often 
2 
Sometimes  
1 
Sometimes  
1 
At all  
0 
At all  
0 
I can enjoy a book or tv show.  
D I feel happy.  
D 
Always  
0 
Always  
0 
Often 
1 
Often 
1 
Sometimes  
2 
Sometimes  
2 
At all  
3 
At all  
3 
I can sit down easily and feel comfortable.  
A I feel unstable.  
A 
Always  
0 
Always  
3 
Often 
1 
Often 
2 
Sometimes  
2 
Sometimes  
1 
At all  
3 
At all  
0 
 
B. Follow-up questionnaire 
1. Have there been any changes in the dose? (Number of tablets / concentrate) 
 Yes 
 No 
2. What are the results of previous tests? 
 LFT: - Normal     - high      - low 
 lipid profile: - normal        -high       -low 
3. Have you been asked to do new tests for this month (after three months of treatment): 
 Pregnancy test: - yes    - no     -not applicable 
 Liver function test: - yes    -no 
 Lipid profile test: - yes     -no 
4. Do you consult your doctor or pharmacist before using any other medications or dietary 
supplement during isotretinoin therapy? 
 Always 100% 
 often 70% 

Deanship of Research © All Rights Reserved                                          32                                                                 عمادة البحث العلمي                        
 
 Sometimes 50% 
 Rarely 20% 
 Never 0% 
5. During your treatment period, did you seek help from outside sources for obtaining 
information about the medication? 
 Yes 
 No 
- What are the sources? 
   Internet 
 Social networking sites 
 Leaflet 
 Relatives or friends 
 Other……….. 
6. Do you have follow-up visits at regular basis with your physician? 
 Yes 
 No 
- If the answer is “Yes” for the previous question. kindly specify follow-up 
period: 
□ every month 
 
 
□ every two months   
 
 
□ every three months  
□ More than three months 
7. In your opinion, how much is the improvement of your disease (acne)? 
 Excellent 
 Very good. 
 It's good. 
 Acceptable 
 Weak 

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Please answer the following knowledge questions: 
8. Which of the following is isotretinoin side effect? 
□ Dryness                □ Teratogenicity              □ Abnormal lipid profile 
□ Constipation        □ difficulty in breathing   □ back pain   □ Others 
9. (In case of using isotretinoin based on medical prescription), the physician had explained for 
me isotretinoin side effects and how to manage them: 
 Yes 
 No 
10. Isotretinoin can be used without prescription: 
 
Yes 
 
No 
 
I do not know 
11. Isotretinoin can be used during some periods of pregnancy: 
 
Yes 
 
No 
 
I do not know 
12. There is no need to have laboratory tests during isotretinoin therapy: 
 
Yes 
 
No 
 
I do not know 
13. It is recommended to drink plenty of water during isotretinoin therapy to avoid dryness: 
 
Yes 
 
No 
 
I do not know 
14. It is recommended to use sun block during isotretinoin therapy: 
 
Yes 
 
No 
 
I do not know 
15. It is recommended to take isotretinoin after fatty meals: 
 
Yes 
 
No 
 
I do not know 
16. Blood donation is allowed during isotretinoin therapy: 
 
Yes 
 
No 
 
I do not know 
17. Breast feeding is allowed during isotretinoin therapy: 

Deanship of Research © All Rights Reserved                                          34                                                                 عمادة البحث العلمي                        
 
 
Yes 
 
No 
 
I do not know 
18. wax and laser for hair removal is allowed during isotretinoin therapy: 
 
Yes 
 
No 
 
I do not know 
 
For married female. kindly answer the following questions 
19. Do you use contraception method during your isotretinoin therapy? 
 
Yes 
 
No 
20. Did you have pregnancy test before starting isotretinoin therapy? 
 
Yes 
 
No 
21. Did your doctor explain for you the teratogenicity of isotretinoin? 
 
Yes 
 
No 
22. Did the pharmacist explain for you the teratogenicity of the drug? 
 
Yes 
 
No 
23. Did your doctor request you to sign up consent form which explain to you the isotretinoin 
side effects? 
 
Yes 
 
No 
24. (In case of using isotretinoin based on medical prescription), the doctor has explained to me 
the importance of using two contraceptive methods during isotretinoin therapy: 
 
Yes 
 
No 
25. How well do you stick to the instructions to avoid medication-related side effects? 
 Excellent 
 Very good. 
 It's good. 
 Acceptable 
 Weak 
26. What is the impact of the side effects on your daily life and your usual activities? 
 Big effect 
 moderate effect 

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 Weak effect 
 There's no effect. 
27. Was the menstrual cycle affected during treatment? 
 Yes 
 No 
- 
If yes, what is the impact? 
 
getting late 
 
getting early 
 
became heavy 
 
became light 
 
its duration became longer 
 
its duration became shorter 
28. Was your treatment affected during the Corona period? 
 Big effect 
 moderate effect 
 Weak effect 
 There's no effect. 
- 
If yes, what is the impact? 
 Getting the medication 
 adherence to medication 
 Going for monthly doctor reviews 
 adherence to periodic tests 
29. Do you think you needed to explain more about the drug in general? 
 
Yes 
 
No 
30. Do you think you needed to explain more about the drug in terms of the method of use? 
 
Yes 
 
No 
31. Do you think you need edited more explanations about the side effects of the drug and how 
to avoid it? 
 
Yes 
 
No 
32. Do you have any feedback regarding this questionnaire? 
 
Yes ………………………………. 

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No 
Please answer the following questions regarding adherence to recommendations 
provided by clinical pharmacist. 
 
yes 
no 
I do not know Not 
applicable  
I adhere to drink 
plenty of water during 
isotretinoin use 
 
 
 
 
I adhere to use eye 
drop during 
isotretinoin use 
 
 
 
 
I adhere to use lip 
balm during 
isotretinoin use 
 
 
 
 
I adhere to use body 
lotion during 
isotretinoin use 
 
 
 
 
I adhere to make 
laboratory monitoring 
(AST & ALT) during 
isotretinoin 
 
 
 
 
I adhere to make lipid 
profile test during 
isotretinoin use 
 
 
 
 
I adhere to use 
sunblock when going 
out during isotretinoin 
use 
 
 
 
 
I adhere to take 
isotretinoin with fatty 
foods 
 
 
 
 
I adhere not to donate 
blood during 
isotretinoin use 
 
 
 
 
I adhere not to make 
laser or wax during 
isotretinoin use 
 
 
 
 
I adhere not to 
breastfeed my child 
during treatment: 
 
 
 
 
 
I adhere to do a 
monthly pregnancy 
test 
 
 
 
 

Deanship of Research © All Rights Reserved                                          37                                                                 عمادة البحث العلمي                        
 
Please answer the following questions regarding adherence to the medication? 
 
At all Rarely 
Sometimes Usually, 
Always 
Do you forget to take your meds? 
 
 
 
 
 
 
Do you skip medication when you 
feel better? 
 
 
 
 
 
 
Do you skip taking medications 
when they're worse after taking 
medications?   
 
 
 
 
 
 
Have you run out of your 
medications? 
 
 
 
 
 
In general, do you adhere to what 
your doctor or pharmacist tells you 
about your lifestyle (food, 
exercise, smoking...) I don't think 
 
 
 
 
 
 
Can you please tell us what are the 
most common reasons for not 
taking your medications? 
 
 
 
Measure of the HADS score: 
I'm frustrated.  
D I feel confused.  
A 
Always  
3 
Always  
3 
Often 
2 
Often 
2 
Sometimes  
1 
Sometimes  
1 
At all  
0 
At all  
0 
I'm scared.  
A I still enjoy the things I used to enjoy.  
D 
Always  
3 
Always  
0 
Often 
2 
Often 
1 
Sometimes  
1 
Sometimes  
2 
At all  
0 
At all  
3 
I lost interest in my appearance.  
D I feel kind of afraid something bad is 
going to happen.  
A 
Always  
3 
Always  
3 
Often 
2 
Often 
2 
Sometimes  
1 
Sometimes  
1 
At all  
0 
At all  
0 
I'd like to have fun and look forward to 
enjoying things.   
D I can laugh and see the funny side of 
things.  
D 
Always  
0 
Always  
0 
Often 
1 
Often 
1 
Sometimes  
2 
Sometimes  
2 
At all  
3 
At all  
3 

Deanship of Research © All Rights Reserved                                          38                                                                 عمادة البحث العلمي                        
 
I suddenly feel shaking.  
A Disturbing thoughts are in my mind.  
A 
Always  
3 
Always  
3 
Often 
2 
Often 
2 
Sometimes  
1 
Sometimes  
1 
At all  
0 
At all  
0 
I can enjoy a book or tv show.  
D I feel happy.  
D 
Always  
0 
Always  
0 
Often 
1 
Often 
1 
Sometimes  
2 
Sometimes  
2 
At all  
3 
At all  
3 
I can sit down easily and feel comfortable.  
A I feel unstable.  
A 
Always  
0 
Always  
3 
Often 
1 
Often 
2 
Sometimes  
2 
Sometimes  
1 
At all  
3 
At all  
0