Outpatient subcutaneous injection therapy : drug use problems with low-molecular-weight heparins and impact of pharmaceutical care

Arterial and venous thromboses are important diseases associated with significant morbidity, mortality, and costs. To date, the orally taken vitamin K antagonists are, together with the parenterally administered heparins, still the most frequently used anticoagulants. Pre-filled syringes constitute one of the fastest growing markets in the drug delivery sectors. Reasons for handling difficulties and drug use problems are diverse and may lead to dosing errors or non-compliance. Pharmaceutical care aims to develop an individualized, patient-centered, and goal-oriented treatment plan to optimize safety and effectiveness. Poor compliance shows a high prevalence of about 50%, leading to poor clinical outcomes, mortality, and increased health-care costs.
The objective of project A was to investigate one single handling difficulty that, to our knowledge, had not been reported in the literature so far. We aimed at comparing subjectively (self-assessment by a study population; observer’s assessment) and objectively measured pull-off forces required to remove the needle shield of commercial low-molecular-weight heparin (LMWH) pre-filled syringes. The removal of the needle shield was not possible in 5 of 204 cases, involving four subjects and two brands. Significant differences between the visual analog scale scores were detected. The observer’s results confirmed these findings, as did the mechanical cap-pull-off tests: they showed a large range of median forces (13.6─29.9 Newtons), with the highest forces needed for Fraxiparine and the old Clexane device. Significant differences between different lots of the same brand were detected with Fraxiparine.
A literature search failed to find any studies on application problems pertaining to the self-injection of LMWH in a heterogeneous outpatient population under daily-life conditions. In project B, we therefore designed a prospective cross-sectional study using pharmacy customers with the aim of recording drug use problems, patient satisfaction, compliance, problems arising from the injection site (abdomen vs. thigh), and residual drug volumes in used pre-filled syringes. Data were collected by means of structured questionnaire-based telephone interviews that were carried out at the beginning and the end of the LMWH treatment. Of the 213 patients enrolled, 15.5% had their injections administered by a third person. The rate of self-reported non-compliance was 17.1%. At least one relevant problem was recorded in 85.0% of the cases. At the end of the treatment, 38.9% of the patients stated self-administration of the injections required some effort. An overall mean residual drug volume ≥10.0% was detected for 3.9% of the patients. If residual drug was present, a median of 11.2% (IQR 8.6─17.6%) of the total drug volume had not been injected. Patients injecting into the thigh showed a higher risk of leaving residual medication (odds ratio 2.16, 95% confidence interval 1.04─4.51).
The effectiveness of community-pharmacy-based interventions in preventing problems that arise during subcutaneous (s.c.) self-injections of LMWH was unknown. Therefore, in project C, we aimed: (1) to develop a standard operating procedure (SOP) for the first instruction in the s.c. injection technique given by a community pharmacist and the subsequent pharmaceutical care provided during outpatient therapy; and (2) to compare intensive pharmaceutical care vs. standard care in both a clinical setting under study conditions (patient recruitment in hospital wards) and a daily life setting (patient recruitment in community pharmacies). Interventions were offered according to patient needs. Data were collected by means of a monitored self-injection at home and structured questionnaire-based telephone interviews at the beginning and the end of the LMWH treatment. Interventions resulted in improved s.c. injection technique (p<0.01) and knowledge (p=0.03). Oral instructions were pivotal for improving patients’ injection technique. Patients’ compliance rate was high (95.8%) as were their baseline skills, with the lowest score being 0.86 on a range of −2.00 to +2.00 making further improvement difficult.
In conclusion this thesis showed that:
- The pull-off forces required to remove the needle shields of LMWH pre-filled syringes correspond roughly to the force needed to hold a narrow-neck plastic flask containing 1─3 l of water by pinching the neck between a finger and thumb
- Drug use problems with outpatient s.c. injection therapies are very prevalent, diverse, and complex. They may be associated with the injection itself or with the handling of the injection-device. No associations with any factors studied were observed with non-compliance, the injection site (beside residual drug), and discomfort or effort required (beside prior injection use)
- The overall mean residual drug volume was negligible, but the total injection volume seemed to have an influence. If residual drug was present, however, it tended to be of pharmacological relevance
- From a patient’s point of view, injections require some effort. Patients have concerns with pre-filled syringes, but are aware of their need. Further research should investigate whether compliance is not only disease- and time-dependent, but also device-dependent
- The provided SOP for pharmacist interventions was of good quality, adequate, appreciated by the patients, and feasible in the daily life of community pharmacies. Patients are capable of managing s.c. injection therapies in a satisfactory way and with high compliance if adequate assistance is provided
- We confirmed our hypothesis that intensive pharmaceutical care for outpatients self-injecting LMWH resulted in more safety, but we had to reject our assumptions of improved compliance, more satisfaction, and fewer complications