|Year : 2020 | Volume
| Issue : 2 | Page : 136-142
Assessment of knowledge and practice of Sudanese renal transplant recipients about tacrolimus usage: A cross-sectional study
Tsabeih Osman Idress1, Safaa Badi2, Bashir Alsiddig Yousef3
1 Department of Clinical Pharmacy, University of Khartoum, Khartoum, Sudan
2 Department of Clinical Pharmacy, Faculty of Pharmacy, Omdurman Islamic University, Khartoum, Sudan
3 Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan
|Date of Submission||26-Nov-2019|
|Date of Decision||10-Feb-2020|
|Date of Acceptance||02-Mar-2020|
|Date of Web Publication||9-Apr-2020|
Bashir Alsiddig Yousef
Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Al-Qasr Ave, Khartoum 11111
Source of Support: None, Conflict of Interest: None
BACKGROUND: Tacrolimus is an immunosuppressive drug used for the prevention of rejection in kidney transplant recipients (KTRs). There are many factors that can affect tacrolimus blood levels, include nonadherence, blood sampling time, food effect, and co-medication. This study aimed to assess Sudanese KTRs knowledge and practice about tacrolimus use.
MATERIALS AND METHODS: This was a descriptive cross-sectional hospital-based study. The study population was Sudanese KTRs under tacrolimus-based therapy attending the renal transplant outpatient clinic in Khartoum renal dialysis and transplantation center from April to July 2018. A total of 190 KTRs were interviewed. The collected data were manually scored, coded, and then analyzed using SPSS.
RESULTS: Regarding overall knowledge, approximately 46% of enrolled KTRs have a low level of knowledge about tacrolimus therapy, and there is a significant association between KTRs knowledge and their level of education. There is a variation between the knowledge about tacrolimus monitoring and KTRs' practice. The primary source of information for the KTRs was doctors, and more than half of them never forget to take the tacrolimus. Only 32.1% of KTRs have nonadherence problems. The association between KTRs knowledge and their level of education and the transplantation period was statistically significant. Regarding tacrolimus side effects, 50% of KTRs said they have been informed or read about the drug side effects.
CONCLUSION: Knowledge of the Sudanese KTRs enrolled in this study was inadequate, and the behavior of them when suffering from a new complaint was relatively good. Great efforts are needed to improve their knowledge, to maintain graft function, and to prevent graft loss.
Keywords: Adherence, kidney transplant recipients, knowledge and practice, tacrolimus
|How to cite this article:|
Idress TO, Badi S, Yousef BA. Assessment of knowledge and practice of Sudanese renal transplant recipients about tacrolimus usage: A cross-sectional study. Int J Health Allied Sci 2020;9:136-42
|How to cite this URL:|
Idress TO, Badi S, Yousef BA. Assessment of knowledge and practice of Sudanese renal transplant recipients about tacrolimus usage: A cross-sectional study. Int J Health Allied Sci [serial online] 2020 [cited 2020 Aug 8];9:136-42. Available from: http://www.ijhas.in/text.asp?2020/9/2/136/282129
| Introduction|| |
Renal transplantation is considered a life-saving, although high-cost treatment for patients with end-stage kidney disease. It can maintain patients indefinitely and prolong life with increase the survival of patients with stage-five chronic kidney disease significantly when compared with other therapeutic options. Following renal transplantation, immunosuppressive therapy will be administered to kidney transplant recipients (KTRs) to prevent acute graft rejection and subsequent graft loss. The most common immunosuppressive regimens use a combination of two or three immunosuppressive drugs with different mechanisms of action to maximize efficacy and minimizing the toxicity of each drug.
Tacrolimus is one of these immunosuppressive drugs used to prevent transplantation rejection. It is prescribed as a part of the posttransplant cocktail, including steroid, mycophenolate, and IL-2 receptor inhibitor. Oral tacrolimus is slowly absorbed from the gastrointestinal tract, with total bioavailability of 20%–25%, and the highest blood plasma concentration (Cmax) reached after 1–3 h. Taking the drug together with a meal rich in fat slows down reabsorption and reduces bioavailability., Therefore, it is recommended to take the drug at the same time, either 1-h before or 2-h after food. After absorption, tacrolimus is well distributed and then metabolized in the liver through CYP3A, and in the intestinal wall., Many factors, including age, liver diseases, genetic factors, food, and concomitant medications, are influencing tacrolimus blood levels by affecting its metabolism., Tacrolimus is associated with many and various side effects include; baldness, anemia, loss of appetite, diarrhea, high blood pressure, high concentration of potassium in blood, nausea, vomiting, itching, tingling sensation in the extremities, high blood sugar concentration, abdominal pain, infection, kidney injury, and blurred vision.
The patient used tacrolimus need to know some information about the drug, such as why it is prescribed, dosing and administration, drug indications, what is precaution should follow, side effects of the drug, drugs that having interaction with tacrolimus and monitoring of drug levels., It is a useful tool used in the clinical evaluation of rejection or toxicity episodes, dose adjustment, and in the assessment of patient compliance. Among these factors, compliance with immunosuppressant drugs is one of the main factors that may lead to graft losses. Therefore, Kidney Disease: Improving Global Outcomes 2009 recommended providing all KTRs and family members with education, prevention, and treatment measures to minimize nonadherence to immunosuppressive medications.
From the researcher's close contact with some Sudanese KTRs, it seems there is a problem in the frequency of doing tacrolimus blood level test on the scheduled time and their knowledge about the effect of food, diseases, and other medications used on the test. Of course, decreased knowledge about tacrolimus therapy can negatively affect the practice of KTRs, their behavior, and subsequently, on graft survival. Therefore, our study aimed to assess the Sudanese KTRs knowledge and practice about tacrolimus use.
| Materials and Methods|| |
A descriptive cross-sectional hospital-based study was used. The study was conducted at the renal transplant outpatient clinic in Khartoum renal dialysis and transplantation center. The study population was Sudanese renal transplant patients under tacrolimus-based therapy attending the center. The study duration was from April to July 2018.
Inclusion and exclusion criteria
All Sudanese KTRs under tacrolimus-based immunosuppressive therapy regularly attending the outpatient clinic in Khartoum renal dialysis and transplantation center during the study were included in the study. For exclusion criteria, KTRs who refused to participate in this study, and all questionnaires with missing data were excluded from the study.
Sampling method and sample size
A convenient sample was taken from the population of KTRs on tacrolimus-based therapy attending transplant clinic in Khartoum renal dialysis and transplant center. The total number of Sudanese KTRs on tacrolimus therapy attending the center was 384, according to the report from the center. From the target population, 190 KTRs who came for their routine follow-up during the study were eligible and consented to participate in the study were selected, they represented the final sample which was calculated by the Slovin's Formula, the sample size will be (n = 196).
Where, N = total target population attending the center. n = sample size. e = margin of error (0.05) at 95% confidence level.
We excluded six KTR patients because they refused to participate and fill the questionnaire, and we found that there were missed data in some questionnaires, so the final sample size was 190 KTRs.
Data collection method
Data were collected using a questionnaire designed by the researcher based on the literature and patient-oriented inserted tacrolimus package leaflet. The questionnaire was prepared in English and translated into the Arabic language to respondents. It consisted of four sections – demographic characteristics of the KTRs, knowledge (23 questions), attitude (3 questions), and practice (3 questions). The collected data were checked for completeness, manually scored and finally coded before the analysis, for each question in the knowledge section, a score of one was given for a correct answer, whereas a zero score was given for incorrect and (I do not know) responses. Questions were rated, and a total score was obtained. The median score was then computed, therefore, those with a total score below the median (score = 0–11) were classified as having a low level of knowledge, whereas those equal to or above the median (score = 12–23) were considered having a high level of knowledge.
Data were entered for the analysis using the International Business Machines (IBM). Statistical Package for Social Sciences (SPSS) for Windows, Version 23.0 software (Armonk, NY, USA: IBM Corp). The results were present in terms of descriptive statistics (tables as percentage) and inferential statistics. Chi-square test was applied to check the significant difference between categorical variables. P < 0.05 was considered statistically significant.
The ethical clearance (FPEC-03-2018) was obtained from the Ethical Committee of the Faculty of Pharmacy, University of Khartoum. Informed consent was obtained from each participant. All questionnaires were coded with ensuring confidentiality throughout the study.
| Results|| |
Of 190 KTRs enrolled in the present study, 51% were male. The residence inside Khartoum was 35.6%, and the rest live outside Khartoum. 49.5% were doing their transplantation inside Sudan while in the rest, the transplantations were done abroad. Regarding the educational status, about 30% of the KTRs were university graduates. Around 40% of the KTRs were transplanted within the previous year of the study duration. About two-thirds of them were taking prednisolone, tacrolimus, and azathioprine, while the rest were taking prednisolone, tacrolimus, and mycophenolic mofetil [Table 1].
|Table 1: Demographic and clinical data of the Sudanese kidney transplant recipients (n=190)|
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As shown in [Table 2], 42.6% of KTRs enrolled in the study knew that the tacrolimus blood level test need to be done every 2–3 months, and they do the test every 2–3 months, while 37% stated that the test should be done weekly. Regarding the drug's interaction with tacrolimus, 76% of then recognized that amlodipine affecting the tacrolimus level. Interestingly, 77% of KTRs knew that the tacrolimus level might fluctuate, and 64% of them reported that doctors need to make an appropriate dose adjustment according to the test results. While 42.1% of them reported that re-measuring of tacrolimus level should be carried within 1 week after the dose adjustment. Regarding knowledge about food interaction, 71% of KTRs recognized that grapefruit might affect the tacrolimus level. About the tacrolimus adverse effects, 37%, 21% of them recognized that tacrolimus might induce hypertension or diabetes, respectively [Table 2].
|Table 2: Sudanese kidney transplant recipients knowledge toward tacrolimus (n=190)|
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After measuring the overall knowledge score, approximately 46% of enrolled KTRs have inadequate knowledge about tacrolimus therapy. Chi-square was applied to test the associations between the overall knowledge and sociodemographic data; knowledge was significantly associated with the transplantation period (P = 0.02). Furthermore, there is a highly significant association between the level of education and overall knowledge (P = 0.001). On the other hand, there was no significant association between overall knowledge and KTRs gender, age, and transplantation country (P < 0.05).
Regarding the attitude of Sudanese KTRs about forgetting tacrolimus dose, 34% stated they would wait until the time of the next dose, while 19% reported that they would take it as soon as they remember [Table 3]. In case of suffering from a new complaint, the majority of them said they go to the transplant clinic for treating these new complaints. Moreover, 96.7% do not use any other medications unless they consult their nephrologists. After prescribing new drugs, 34% of them stated that they take the new drugs before referring to their doctor, while 7% reported that they read about interaction between tacrolimus and other drugs [Table 3].
|Table 3: Sudanese kidney transplant recipients attitude toward tacrolimus (n=190)|
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In response to the questions about the adherence and practice to the medication, 52% said that they never forget taking tacrolimus, while 32.1% stated they sometimes forget or delay taking it from the scheduled time [Table 4]. About the adverse effects of tacrolimus, 34% of them experienced infection, and 21% suffered from tremors. On the other hand, the majority of KTRs mentioned that their doctors represent their main source of information about tacrolimus therapy [Table 4].
|Table 4: Sudanese kidney transplant recipients practice toward tacrolimus (n=190)|
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| Discussion|| |
Tacrolimus is the immunosuppressant of choice in kidney transplantation, and its monitoring based on pharmacokinetics and pharmacogenetics profiles is critical for optimizing treatment and improving long-term outcomes for treated patients., This descriptive study recruited 190 Sudanese KTRs under tacrolimus therapy. A high percentage (49.5%) of transplantation was done in Sudan due to the low cost of the surgery in comparison to other countries., Regarding tacrolimus monitoring, although the majority of respondents knew the correct frequency, only one-half of the study samples said they do it every 2–3 months as recommended by most national transplant clinics after the 1st year of transplantation. This may due to the nonavailability and the high cost of the test, particularly for those coming from outside Khartoum state. Furthermore, the determination of tacrolimus blood concentration should be done 2–3 days after any dose adjustment., Adherence is an essential factor that is important to maintain tacrolimus levels, and the long-term success of any organ transplantation depends on adherence to the immunosuppressive regimen. One-quarter of the KTRs has a problem of forgetting some doses, which indicated the low adherence for them. These findings are similar to the results of a study conducted in Germany to determine the noncompliance in organ transplants and another study done in the United States that evaluated the nonadherence to medications among KTRs and its effect in clinical outcomes.,
Explaining the interaction between food and tacrolimus is a responsibility of the multidisciplinary team such as nutrition specialists, pharmacists dispensing tacrolimus, and finally, the outpatient transplant clinics. Herbs and grapefruit can change tacrolimus levels, grapefruit and its juice can increase bioavailability up and strongly elevated trough levels., In the current study, about one-third of KTRs interviewed have no information about the interaction of gripe fruit juice with tacrolimus. Furthermore, two-thirds the KTRs go to the renal transplant clinic when they have a new complaint, there was a group from KTRs said they treat themselves by taking traditional medicines such as herbs because they believe that traditional medicines are safer, which may affect the tacrolimus levels. Thus, KTRs need to know the fact that herbs and traditional medicines can affect tacrolimus therapy.,
The majority (95.8%) of the Sudanese KTRs enrolled in the study were having chronic diseases, and they received drugs besides immunosuppressive therapy. In this study, we found the majority (77%) do not know about the possible interaction between the chronic medications and tacrolimus, which may affect the therapeutic monitoring of tacrolimus, particularly when prescribing a new drug. Similar studies in Switzerland and Myanmar and showed the benefits of therapeutic drug monitoring of tacrolimus in renal transplant patients., Furthermore, tacrolimus can cause different side effects;, here, we found that more than one-half of them have no idea about tacrolimus side effects. There were four side effects mentioned by most of the KTRs such as tremors, hypertension, infection, and diabetes; furthermore, it was noticed that the same side effects were experienced among them. These results in accordance with a report from Jordanian KTRs.
Regarding the source of information, doctors were the main source of information in this study. Unfortunately, in this study, the pharmacist who dispenses tacrolimus was not providing any information about tacrolimus therapy. In the proper situation, the pharmacist has a crucial role in providing information and patient care to KTRs to avoid, detect and/or treat the side effects and drug/or food interactions with immunosuppressant drugs. Moreover, the pharmacist also provides pre- and post-transplant education to KTRs to enhance adherence and hence, reduce readmission to hospitals and emergency departments. A small proportion (17.4%) of the participants were able to read the drug leaflet; they were attending morning educating lectures during the hospitalization period immediately after transplantation and receiving booklets or brochures at discharge or take information from the nurses.
| Conclusion|| |
Knowledge of the Sudanese KTRs enrolled in the study was inadequate, and the behavior of them when suffering from a new complaint was relatively good by consulting the doctors in the transplant clinic. There were associations between KTRs knowledge and their level of education, and the transplantation period. Great efforts are needed to improve their knowledge, to increase adherence and maintain graft function, and preventing graft loss.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Morris P, Knechtle SJ. Kidney Transplantation: Principles and Practice. Philadelphia, United States: Elsevier Health Sciences; 2008.
Colaneri J. An overview of transplant immunosuppression-history, principles, and current practices in kidney transplantation. Nephrol Nurs J 2014;41:549-60.
Hariharan S, McBride MA, Cherikh WS, Tolleris CB, Bresnahan BA, Johnson CP. Post-transplant renal function in the first year predicts long-term kidney transplant survival. Kidney Int 2002;62:311-8.
Wallemacq PE, Verbeeck RK. Comparative clinical pharmacokinetics of tacrolimus in paediatric and adult patients. Clin Pharmacokinet 2001;40:283-95.
Lindholm A. Factors influencing the pharmacokinetics of cyclosporine in man. Ther Drug Monit 1991;13:465-77.
Gupta SK, Benet LZ. High-fat meals increase the clearance of cyclosporine. Pharm Res 1990;7:46-8.
Hebert MF. Contributions of hepatic and intestinal metabolism and P-glycoprotein to cyclosporine and tacrolimus oral drug delivery. Adv Drug Deliv Rev 1997;27:201-14.
Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet 2004;43:623-53.
Vanhove T, Annaert P, Kuypers DR. Clinical determinants of calcineurin inhibitor disposition: A mechanistic review. Drug Metab Rev 2016;48:88-112.
Ptachcinski RJ, Venkataramanan R, Rosenthal JT, Burckart GJ, Taylor RJ, Hakala TR. Cyclosporine kinetics in renal transplantation. Clin Pharmacol Ther 1985;38:296-300.
Myers BD, Ross J, Newton L, Luetscher J, Perlroth M. Cyclosporine-associated chronic nephropathy. N
Engl J Med 1984;311:699-705.
Oellerich M, Armstrong VW. The role of therapeutic drug monitoring in individualizing immunosuppressive drug therapy: Recent developments. Ther Drug Monit 2006;28:719-25.
McMaster P, Mirza DF, Ismail T, Vennarecci G, Patapis P, Mayer AD. Therapeutic drug monitoring of tacrolimus in clinical transplantation. Ther Drug Monit 1995;17:602-5.
Bunzel B, Laederach-Hofman K. Noncompliance in organ transplant recipients: A literature review. Gen Hosp Psychiatry 2000;112:423-40.
Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, et al
. Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012:2:1-138.
Galero-Tejero E. A Simplified Approach to Thesis and Dissertation Writing. Mandaluyong City: National Book Store; 2011. p. 43-4.
Tsunoda SM, Aweeka FT. The use of therapeutic drug monitoring to optimise immunosuppressive therapy. Clin Pharmacokinet 1996;30:107-40.
Brunet M, van Gelder T, Šsberg A, Haufroid V, Hesselink DA, Langman L, et al
. Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy: Second Consensus Report. Ther Drug Monit 2019;41:261-307.
Elsharif ME, Elsharif EG, Gadour WH. Costs of hemodialysis and kidney transplantation in Sudan: A single center experience. Iran J Kidney Dis 2010;4:282-4.
Abdelwahab HH, Shigidi MM, Ibrahim LS, El-Tohami AK. Barriers to kidney transplantation among adult Sudanese patients on maintenance hemodialysis in dialysis units in Khartoum State. Saudi J Kidney Dis Transpl 2013;24:1044-9.
] [Full text]
Kälble T, Lucan M, Nicita G, Sells R, Burgos Revilla FJ, Wiesel M, et al
. EAU guidelines on renal transplantation. Eur Urol 2005;47:156-66.
Voora S, Adey DB. Management of kidney transplant recipients by general nephrologists: Core curriculum 2019. Am J Kidney Dis 2019;73:866-79.
Hucker A, Bunn F, Carpenter L, Lawrence C, Farrington K, Sharma S. Non-adherence to immunosuppressants following renal transplantation: A protocol for a systematic review. BMJ Open 2017;7:e015411.
Wacke R, Rohde B, Engel G, Kundt G, Hehl EM, Bast R, et al
. Comparison of several approaches of therapeutic drug monitoring of cyclosporin A based on individual pharmacokinetics. Eur J Clin Pharmacol 2000;56:43-8.
Patzer RE, Serper M, Reese PP, Przytula K, Koval R, Ladner DP, et al
. Medication understanding, non-adherence, and clinical outcomes among adult kidney transplant recipients. Clin Transplant 2016;30:1294-305.
Devaney A. Role of hospital clinical pharmacist in transplantation and generic immunosuppressive therapies. GaBI J 2014;3:958.
Liu C, Shang YF, Zhang XF, Zhang XG, Wang B, Wu Z, et al
. Co-administration of grapefruit juice increases bioavailability of tacrolimus in liver transplant patients: A prospective study. Eur J Clin Pharmacol 2009;65:881-5.
Yarnell E, Abascal K. Herbs and immunosuppressive drugs: Calcineurin inhibitors. Altern Complement Ther 2013;19:315-22.
Izzo AA. Interactions between herbs and conventional drugs: Overview of the clinical data. Med Princ Pract 2012;21:404-28.
Posfay-Barbe KM, Baudet H, McLin VA, Parvex P, Chehade H, Combescure C, et al
. Immunosuppressant therapeutic drug monitoring and trough level stabilisation after paediatric liver or kidney transplantation. Swiss Med Wkly 2019;149:w20156.
Htun YY, Swe HK. Therapeutic drug monitoring of cyclosporine and tacrolimus in Myanmar kidney transplant patients. Transplantation Reports 2019;4:(3):100031.
Mihatsch MJ, Kyo M, Morozumi K, Yamaguchi Y, Nickeleit V, Ryffel B. The side-effects of ciclosporine-A and tacrolimus. Clin Nephrol 1998;49:356-63.
Bulatova N, Yousef AM, Al-Khayyat G, Qosa H. Adverse effects of tacrolimus in renal transplant patients from living donors. Curr Drug Saf 2011;6:3-11.
Sam S, Guérin A, Rieutord A, Belaiche S, Bussières JF. Roles and impacts of the transplant pharmacist: A systematic review. Can J Hosp Pharm 2018;71:324-37.
Wiegel JJ, Olyaei AJ. The role of the pharmacist in the management of kidney transplant recipients. Indian J Urol 2016;32:192-8.
] [Full text]
[Table 1], [Table 2], [Table 3], [Table 4]