|Year : 2014 | Volume
| Issue : 1 | Page : 35-39
Prescribing pattern of medicines in chronic kidney disease with emphasis on phosphate binders
Chaitali S Bajait, Sonali A Pimpalkhute, Smita D Sontakke, Kavita M Jaiswal, Amruta V Dawri
Department of Pharmacology, Government Medical College, Nagpur, Maharashtra, India
|Date of Submission||07-Aug-2012|
|Date of Decision||11-May-2013|
|Date of Acceptance||11-Nov-2013|
|Date of Web Publication||16-Jan-2014|
Chaitali S Bajait
Department of Pharmacology, Government Medical College, Nagpur, Maharashtra
Source of Support: None, Conflict of Interest: None
Objectives: Patients with chronic kidney disease (CKD) suffer with multiple comorbidities and complications like secondary hyperparathyroidism and hyperphosphotemia. Altered mineral metabolism contributes to bone disease and cardiovascular disease. In patients of CKD, despite dietary phosphorus restriction, phosphate binders (PBs) are recommended to control phosphorous level. No studies about the utilization pattern of PBs in CKD patients have been reported from India. This study analyses the current prescribing trends in the management of CKD patients undergoing tertiary care with focus on PBs.
Materials and Methods: This cross-sectional, observational study was conducted in nephrology department of a government super speciality hospital over 8-month period from January to August 2011. Demographic, clinical, and medication details were collected in a specially designed proforma.
Results: A total 111 prescriptions were included in the study. Average number of drugs per prescription was 9.47. About 41.53% of the prescribed drugs were from the World Health Organization essential medicines list. Out of total prescribed drugs (1052), most commonly prescribed were vitamins and minerals (24.71%), cardiovascular drugs, (22.14%), and hematopoietic agents (20.15%). Considering individual drugs, five most commonly prescribed drugs were multivitamins (14.82%), iron (8.65%), folic acid (8.55%), calcium carbonate (8.17%), and calcitriol (5.60%). A total of 11.02% of prescribed drug were PBs. Among PBs, calcium carbonate was the most frequently prescribed and sevelamer was the least prescribed PB. No patient was prescribed lanthanum carbonate.
Conclusion: This study identified a wide variety of drug classes including PBs prescribed in CKD patients. Although sevelamer hydrochloride has less side effects as compared to calcium salts, it was less prescribed since it is costlier.
Keywords: Calcium acetate, calcium carbonate, drug utilization study, lanthanum carbonate, sevelamer hydrochloride
|How to cite this article:|
Bajait CS, Pimpalkhute SA, Sontakke SD, Jaiswal KM, Dawri AV. Prescribing pattern of medicines in chronic kidney disease with emphasis on phosphate binders. Indian J Pharmacol 2014;46:35-9
|How to cite this URL:|
Bajait CS, Pimpalkhute SA, Sontakke SD, Jaiswal KM, Dawri AV. Prescribing pattern of medicines in chronic kidney disease with emphasis on phosphate binders. Indian J Pharmacol [serial online] 2014 [cited 2016 Aug 30];46:35-9. Available from: http://www.ijp-online.com/text.asp?2014/46/1/35/125163
| » Introduction|| |
Chronic kidney disease (CKD) is a global threat to health in general and for developing countries in particular because of an increasing incidence, poor outcome, and high cost of treatment. It is a general term for heterogeneous disorders affecting kidney structure and function.  The Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation (NKF) defines CKD as either kidney damage or a decreased glomerular filtration rate of less than 60 mL/min/1.73 m 2 for 3 or more months.  CKD is known to be associated with various complications and comorbidities. Secondary hyperparathyroidism and the associated homeostatic control of serum calcium, phosphate, and vitamin D is a critical issue in patients with CKD. Altered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in these patients.  Results of the Dialysis Outcomes and Practice Patterns Study clearly demonstrated that uncontrolled serum concentrations of phosphorus, calcium, and intact parathyroid hormone (iPTH) were associated with all-cause mortality as well as cardiovascular mortality. , Patients with serum phosphate levels above 6.5 mg/dL have a 27% higher risk of death compared with those with levels between 2.4 and 6.5 mg/dL. For this reason, one of the main goals in CKD patients is to maintain serum phosphate in the range recommended in different guidelines.  In CKD patients, if phosphorus or intact PTH levels cannot be controlled within the target range, despite dietary phosphorus restriction, phosphate binders (PBs) should be prescribed.  Use of the oldest, aluminium-based PBs is currently restricted because of concerns about tissue accumulation and associated toxic effects of aluminium. Hence, calcium carbonate and calcium acetate became the most widely used agents. With recent concern about soft-tissue calcification, which may be worsened by calcium-based PBs, newer non calcium, nonaluminium binders, particularly sevelamer hydrochloride and lanthanum carbonate, are being used more frequently? These PBs represent a significant expense for patients and healthcare systems, and the cost of equally effective binder doses may vary by as much as 140%. , Patients of CKD are at higher risk of drug-related problems since they need complex therapeutic regimens that require frequent monitoring and dosage adjustment. In India, there is no clear picture of overall medication profile in CKD patients. Moreover, reports of drug utilisation studies of PBs in these patients are lacking. The study of prescribing patterns is a component of medical audit that monitors and evaluates prescribing practices, and recommends necessary modifications to achieve rational drug use.  Hence, this study was planned to analyze current prescribing trends in the management of CKD patients with focus on PBs and to suggest ways to rationalize drug use, minimise medication error, and improve therapeutic outcome.
| » Materials and Methods|| |
This prospective, cross-sectional, observational study was conducted in nephrology department of a government super speciality hospital over 8-month period from January to August 2011. Study was approved by institutional ethics committee and written informed consent was obtained from each patient before enrolment. All CKD patients diagnosed by consultant nephrologists, undergoing treatment in the nephrology unit were included and their prescriptions analyzed. Demographic details, necessary clinical data, and medication details were collected in a specially designed proforma. Drugs were classified into different groups based on Anatomic Therapeutic Chemical (ATC) classification. World Health Organization (WHO) recommends this classification system developed by European Association for Pharmaceutical Market and International group. In the ATC classification system, drugs are divided into different groups according to the organ system on which they act and/or therapeutic and chemical characteristics.  Data on utilization of different classes as well as individual drugs were subjected to descriptive analysis.
| » Results|| |
Total 111 prescriptions of patients with age 51.40 ±14.29 years (mean ± standard deviation) suffering from CKD were included in the study. Demographic characteristics of patients are shown in [Table 1]. When enquired, all patients stated that they were strictly adherent to dietary modification as advised by nephrologists. The results of analysis of prescriptions for rationality are mentioned in [Table 2]. A total number of drugs prescribed were 1052. Out of 111 prescriptions analyzed, average number of drugs per prescription was 9.47. On the basis of first anatomical level of ATC classification most commonly prescribed were drugs for gastrointestinal tract and metabolism (44.86%) followed by drugs for cardiovascular system (22.05%) and those for treatment of disorders of blood and blood forming organs (21.38%) [Table 3]. Vitamins and minerals were the most frequently prescribed drugs (24.71%), followed by cardiovascular drugs (22.14%), hematopoietic agents (20.15 %), and PBs (11.02 %.) [Table 4]. The five most commonly prescribed drugs were multivitamins (14.82%), iron (8.65%), folic acid (8.55%), calcium carbonate (8.17%), and calcitriol. (5.60%). [Figure 1] represents utilization pattern of PBs. Out of total 111 prescriptions PBs were prescribed in 110. Some prescriptions had more than one PB. Most commonly prescribed PB was calcium carbonate (79.27%), followed by sevelamer hydrochloride (17.11%) and calcium acetate (9.9%).
|Table 1: Demographic characteristics of patients suffering from chronic kidney disease (n = 111)|
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|Table 3: Distribution of drugs prescribed for chronic kidney disease in different categories according to Anatomic Therapeutic Chemical classification|
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|Table 4: Pattern of drug utilization in patients suffering from chronic kidney disease|
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|Figure 1: Utilisation pattern of phosphate binders in patients with chronic kidney disease|
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| » Discussion|| |
The gender distribution and mean age of patients in our study was similar to that reported in an earlier study.  Average number of drugs per prescription was 9.47. Practice of polypharmacy is a common finding in similar studies in CKD patients with average number of drugs per prescription varying from 8  to 12.3.  Polypharmacy is defined as prescription of five or more medications to one patient at one time.  However, considering the necessity of polypharmacy in CKD, it may not be considered as polypharmacy.  Hence, some experts have even advised redefining polypharmacy as nine or more medications, rather than five or more. , In this study, only the prescribed medicines were considered. But it is well-known that over-the-counter use of medicines is common in this country. This further increases the chances of drug interactions and ADRs.
In our study, no drug was prescribed by its generic name, showing that prescribing by brand name is the norm, which needs to be discouraged. Encouraging prescription of drugs by generic names is always recommended by various national and international bodies to promote rational use of medicines. But implementation of this practice is never satisfactory and requires motivation of prescribers and strong regulatory interventions.
Only 41.53% of the prescribed drugs were from the WHO essential medicines list. So making these drugs freely available in public health facilities is less likely. Majority of the patients attending these facilities cannot afford to purchase these drugs from private pharmacies. Hence, whether the patients are actually consuming all the prescribed drugs or not is a matter of great concern.
Out of total prescribed drugs (1052), most commonly prescribed were vitamins and minerals (24.71%), cardiovascular drugs, (22.14%), and hematopoietic agents (20.15%). Considering individual drugs, the five most commonly prescribed drugs were multivitamins (14.82%), iron (8.65%), folic acid (8.55%), calcium carbonate (8.17%), and calcitrioln (5.60%). These findings are similar to most of the earlier reported studies where calcium carbonate, multivitamin, folic acid, and ferrous sulphate were the most commonly prescribed drugs for CKD patients. ,
Out of all the drugs prescribed, 11.02% were PBs. Among PBs, calcium carbonate was the most frequently prescribed and sevelamer was the least prescribed. These findings are similar to those reported in an earlier study using data from contributors to the European practice database.  But even in the said study which analyzed data from five different countries, higher use of sevelamer was reported in Greece. Similarly a study from Brazil also reported a large percentage of prescriptions of sevelamer among patients on maintenance hemodialysis despite the high cost of the medication and absence of contraindications for PB with calcium salts.  Though calcium salts are inexpensive, they are associated with increased risk of metastatic calcification. Sevelamer hydrochloride is an ion exchange resin, nonabsorbable, and the first PB that is not a source of aluminium or calcium. Sevelamer, besides its effect on phosphate, has been associated with reduction of coronary and aortic calcification.  But it is more expensive than either calcium acetate or calcium carbonate which may be the reason for its underutilization. Advantages and drawbacks of using sevelamer hydrochloride and lanthanum carbonate, as first choice of PB yet remains debatable. , In this study, sevelamer hydrochloride was prescribed in combination with calcium carbonate to four patients and with calcium acetate to two patients. Even guidelines recommend that no single binder is effective and acceptable to every patient and a combination of binders needs to be considered for many patients so as tominimize the potential adverse effects of any specific binder. 
In contrast to previous study,  wherein calcium channel blockers (CCBs) were most frequently prescribed antihypertensive drugs, in our study diuretics (9.50%) were found to be most frequently prescribed followed by CCBs (5.89%). In chronic renal failure or end stage renal disease, hyperkalemia is more likely to develop when Angiotensin converting enzyme (ACE) inhibitors or Angiotensin receptor blockers (ARBs) are prescribed. Also, unlike CCBs, most of the ACE inhibitors need dose modification in renal failure. So the choice of CCBs and diuretics seems to be logical.
Out of 34 patients suffering with diabetes mellitus, antidiabetics were prescribed in only 19 patients with preference for insulin (12) over oral hypoglycaemic drugs (7). In diabetic patients, rigorous glycaemic control decreases the rate and progression of micro-albuminuria. However, during the phase of deteriorating renal function, insulin requirement falls because the kidney is a site of insulin degradation and this might be reason for the remarkable number of patients not receiving any antidiabetic agent, similar to previous study. 
In contrast to previous studies,  antimicrobials were less prescribed in this study in spite of high risk of infection seen in patients on hemodialysis and peritoneal dialysis a fact which needs to be noted. Most of the CKD patients are anemic. Underutilization of erythropoietin in the present study is surprising despite recommendations for its use. The high cost of erythropoietin may be the reason for its underuse since most patients visiting this government hospital are economically backward. The low prescription rate of erythropoietin indicates lacunae of current treatment practices and signals an opportunity for improvement in prescribing practices in CKD patients. 
We found that prescribing herbal drugs was a routine practice. This has not been reported in any previous study. Obtaining details about the contents of these preparations was, however, beyond the scope of our study.
There are several limitations to this study. First, the sample size may not be adequate to reflect the exact picture of prescribing patterns in general and PB in particular. Similarly, data from multiple centres need to be collected to get a broader yet more comprehensive idea of use of PB and to analyze the reasons for underuse of these drugs. Another shortcoming of the study is the point prevalence nature of the medication-related data. It cannot be assumed that the prescription characteristics of a particular medication for a given patient remains unchanged over the course of follow-up of these patients. In spite of these lacunae, this study certainly provides an insight into the problems associated with the use of drugs in CKD patients.
To conclude, this study identified a wide variety of drug classes prescribed in a cohort of CKD patients indicative of prevailing morbidity. It provides a framework for continuous prescription audit in a hospital setting and suggests possible improvement in prescription practices in patients suffering from CKD.
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[Table 1], [Table 2], [Table 3], [Table 4]