Pharmaceutical care issues identified by pharmacists in patients with diabetes, hypertension or hyperlipidaemia in primary care settings

This study was part of a large controlled trial called the Cardiovascular Risk Factors Intervention Strategies (CORFIS) trial. The CORFIS trial was a community-based, multicentre trial which compared the impact of collaborative intervention by various healthcare professionals (GPs, pharmacists, dietitians and nurses) to usual standard care on patients with diabetes, hypertension or hyperlipidaemia. All the patients in the intervention group of the CORFIS trial were included in this part of the study. Patients in the control group were not included in this part of the study because under the usual healthcare practice in Malaysia, patients who seek treatment in GP clinics obtained their medications from the clinic itself and do not have to see a pharmacist. The study was approved by the Medical Research Ethics Committee of the Ministry of Health Malaysia.

Participants were recruited from 44 GP clinics in the Klang Valley, Malaysia from January to June 2008. The Klang Valley encompasses Kuala Lumpur and its vicinity which constitutes the main commercial and administrative centre in Malaysia. Inclusion criteria of patients were: participants aged 18 and above, with at least one of the following diseases: diabetes mellitus, hypertension or hyperlipidaemia, and currently managed with at least one medication. Exclusion criteria were those who did not provide written consent, were pregnant or breast-feeding, had history of unstable angina, heart failure, acute myocardial infarction, clinically significant valvular heart disease, stroke, coronary revascularization procedure, or who had serum creatinine of more than 150 mmol/L in the preceeding 6 months, or were not able to visit the clinics for monthly follow-up sessions. Written informed consent for participation in the study was obtained from all participants.

The study involved a group of pharmacists, dietitians and nurses. Each participant was interviewed and counselled by one of the pharmacists, dietitians and nurses at the GP clinic where the participant was recruited (Figure 1). Each participant spent about 30 to 60 min with each of the healthcare providers. In this study, the term PCIs was used instead of DRPs to cover a wider spectrum of issues and also because pharmaceutical care was provided by service pharmacists to the participants. During the 24-week follow-up assessments, the pharmacist reviewed the participants’ medications and counselled the participants every 4 weeks, noted any PCIs encountered by the participants and helped to resolve the PCIs. If required, the pharmacist would contact the GP concerned to alert, discuss and if possible, to resolve the PCIs which could affect the participants’ clinical outcomes. Whereas, the dietitians provided dietary advice while the nurses advised the patients on general healthcare such as foot care.

The primary outcome was the types of PCIs encountered by the participants, as identified by the pharmacists. The secondary outcomes were the causes and clinical significance of the PCIs, and outcome of the interventions made by the pharmacists.

Of the 477 participants, 53.7% (256 participants) had at least one PCI, giving a total of 706 issues. Details of the PCIs encountered by the participants are shown in Table 2.

Non-adherence to medications was the most common drug-use problem (146 of 235 issues, 62.1%). Other drug-use problems involved participants administrating their medications at incorrect doses or frequencies or incorrect timing with respect to meals. For example, metformin and aspirin were taken before meals and sulphonylureas were taken at bedtime.

PCIs classified under “insufficient awareness or knowledge” included 47 issues pertaining to the misconception of participants concerning the use of medications and participants’ lack of knowledge and queries about their medications and also their disease states. Fifteen issues were related to participants’ undue worries about the side effects and complications related to their medications and another 82 issues of unclear complaints concerning some health problems which may be related to patients’ medications were also included in this category.

Adverse drug reactions (ADRs) included side effects of medications as reported by the participants. Examples of these side effects are as shown in Table 2. Hypoglycaemia was related to the use of antidiabetic agents. Gastrointestinal disturbances included gastritis due to non-steroidal anti-inflammatory drugs (NSAIDs) and diarrhoea associated with the use of metformin (6 cases each). Another 12 participants complained of dry cough attributed to the use of angiotensin-converting enzyme inhibitors while 10 participants complained of muscle aches and cramps after using statins. ADRs classified as “Others” included dermatological reactions such as eczema, rashes and itch; weight gain; frequent urination; hair loss; bradycardia; bleeding from the anus; blocked nose and flushing.

Therapy failure was assumed when participants’ blood pressure (BP), blood glucose levels or lipid levels were not at target levels despite being on pharmacological treatment. Whereas, drug choice problem in this study involved participants who had been seen by the GPs but still with high BP, high blood glucose or high cholesterol level and were not on any medications. Inappropriate duplication of therapeutic group or active ingredient involved two participants who were given both glimepiride and gliclazide, another participant was given gliclazide 80 mg (Diamicron®) and modified-release gliclazide 30 mg (Diamicron MR®) while another participant was given irbesartan (Approvel®) and a combination of irbesartan and hydrochlorothiazide (Co-Approvel®). In addition, one participant was on both loratadine and desloratadine. The only case of contraindication encountered in this study involved a woman planning to get pregnant but was prescribed a combination of irbesartan and hydrochlorothiazide (Co-Approvel®) [23].

Dosing problems included doses and frequencies of medications prescribed which were either too high or too low. Two cases with problems in the duration of treatment involved a participant given a statin for only a week and another who was still prescribed a statin even though his cholesterol level was only 2.9 mmol/L and his low-density lipoprotein (LDL) was 1.3 mmol/L.

Dispensing issues involved incorrect labeling of the dosage or frequency of antidiabetic drugs. There were two cases where the strength of enalapril was wrongly stated on the label. Another case involved atorvastatin (Storvas®) being labeled as simvastatin. In addition, a participant was prescribed irbesartan (Approvel®) but was dispensed irbesartan and hydrochlorothiazide (Co-Approvel®). Another participant was dispensed 40 mg of atorvastatin although was prescribed only 10 mg. This subclass of PCIs also included two cases of inappropriate storage of medication. Glyceryl trinitrate (GTN) was dispensed in a plastic envelope instead of its original bottle. Atovarstatin was kept in a plastic envelope and the colour of the tablets had changed. These PCIs were brought to the attention of the GPs or clinic staff concerned to prevent repetition of such issues.

Potential drug interactions included the use of enalapril with allopurinol which may increase the risk of leucopenia and hypersensitivity induced by allopurinol; fenofibrate and atorvastatin which may increase the risk of myopathy, and the use of atorvastatin with alcohol which may increase the risk of liver problems [23, 24].

The eight cases of lifestyle modifications included participants who were current smokers and were counselled on smoking cessation. There were several cases where participants asked about diet and exercise but these were referred to the dietitian and not considered as PCIs. Monitoring of side effects included alerting the doctors to monitor participants’ liver function for those on statins and blood glucose level in a patient suspected to have diabetes.

Causes of PCIs are as shown in Table 3. Non-adherence to medications was attributed to forgetfulness or to participants having doubts or misconception about the purpose and effectiveness of their medications. Some participants reported that they were not clear regarding the dosage and use of their medications while others were unwilling to take their medications due to fear of side effects.

The most common intervention made by the pharmacists was the counselling of patients on their medications (38.8%), followed by the referral of patients to the prescribers (20.8%), educating patients concerning their disease states (12.0%), recommending a change in the dose or frequency of the medications or to add another medication (5.8%) and to monitor the patient’s condition (5.0%).

The outcome of pharmacist intervention is as shown in Table 4. If the PCIs with “unknown outcomes” and “no change required” categories were excluded, then 87.3% (295 out of 338) of changes were made as recommended by the pharmacist. No change was made when the prescriber or patient preferred to continue monitoring the patient’s condition or to wait until the next clinic appointment before making any changes. Majority of pharmacist interventions were directed at the patients (496 of 702; 70.9%) with only 29.1% (204 of 702) that involved the medical doctors. One of the PCIs required action to be taken by the caregiver and another by the clinic staff. If “unknown outcomes” and “no change required” were excluded, 77.9% of changes recommended by the pharmacists were accepted by the doctors. However, 91.5% of changes recommended by the pharmacists were carried out by the patients.