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Abstract: |
In Germany, community pharmacists supply patients with medicine pursuant to a totally pharmaceutical care concept. This means that, in contrast to many other countries, they are allowed to produce and supply, for example, parenteral drugs for oncology outpatients. Yet, because only a few community pharmacists run a clean-air laboratory and thus lack the necessary equipment, skills and knowledge to produce sterile medication, outpatients will often be supplied by more than one pharmacy. Typically, the specialized pharmacy provides the parenteral preparation; while the community pharmacy ensures the availability of all other medications, see Figure 1. Usually, more than one discipline is involved in the care for one patient. Thus, community pharmacies are a critical interface. Community physicians have an overview of the whole medication prescribed by different physicians as well as over-thecounter products and drugs supplied by the specialized pharmacy.
*Figure 1 pending to upload.
Therefore, a main assignment of the community pharmacy is the control of whole medication with regard to drug–drug interactions. Moreover, they are involved in providing advice to patients and relatives concerning the correct use, effects and side effects of drugs and enteral nutrition, common medical devices and other healthcare material, e.g. incontinence support. They also produce individual prescriptions such as mucositis solution or dermatological prescriptions.
Approximately 300 community pharmacies run a good manufacturing practice—like clean air laboratory for compounding IV chemotherapy, individual parenteral nutrition, see Figure 2; antibiotics, antiemetics, antiviral drugs and analgesic solutions for personal controlled analgesia devices (PCA). Further, they provide medical technology as nutrition- and PCA-infusion pumps, see Figure 3. To supply patients at home, extensive services are necessary, surpassing normal manufacturing, see Figure 4.
*Figures 2, 3 and 4 pending to upload.
Drug–drug interactions (DDIs) have been identified as a relevant problem for pharmacotherapy with a significant impact on morbidity and mortality [1, 2]. Fatal medication errors occurring in the outpatient setting have increased substantially in recent years [3]. The provision of oral cytotoxic drugs demands an increased awareness of DDI due to their potentially hazardous and lethal side effects.
Prescriptions of medications by different specialists for the same patient represent a central difficulty. Physicians do not always know the prescriptions that their colleagues have written, see Figure 5.
*Figure 5 pending to upload.
Hence, community pharmacies automatically check their patient’s medication for DDIs. In the past, databases classified DDIs according to their pharmacological severity, e.g. ‘major’, ‘moderate’ or ‘minor’, but with the lack of concise recommendations of management. Generating long lists of theoretically possible interactions can lead to lists that are ignored (alert-fatigue) [4]. Therefore, the new DDI software and the ABDA database that is used by all community pharmacies in Germany identify possible DDIs according to the new OpeRational ClassificAtion of drug interaction (ORCA) classification [5]. This classification focuses on the clinical relevance of the DDI [6]. In the past, databases classified DDIs according to their pharmacological severity, but with the lack of concise recommendations of management. Generating long lists of theoretical possible interactions leads to ignoring interaction warnings of database or clinical relevance [4]. According to recommended therapeutic consequences, six classes of DDIs are defined, see Table 1. The database is updated twice a month.
*Table 1 pending to upload.
During the drug-dispensing process in a pharmacy, actual and former medication, maintained over a defined period will be controlled—retrospective analysis. Over-the-counter medicines bought in the same common pharmacy will also be included in the assessment. In case of a potential drug interaction, the pharmacist receives a warning message combined with clear instructions, see Figures 6 and 7.
*Figures 6 and 7 pending to upload.
For many years, palliative care has been recommended in addition to anticancer therapy [7]. Recent studies have even reported a survival benefit of cancer patients due to early palliative care [8, 9]. Therefore, oncology specialists as well as community pharmacists have to acquire knowledge concerning palliative care medications. Palliative patients form an individual patient group that requires special attention for potential DDIs of the established therapeutic palliative regimes. In two recent studies of specialized palliative care, physicians and community pharmacists examined potential DDIs in a palliative care inpatient ward and in hospices; and provided concise recommendations about how to avoid DDIs.
Furthermore, the authors concluded that pharmacists should be an essential part of palliative care teams [10, 11]. Due to the developments described above, even pharmacists in palliative care have to acquire knowledge about oral cytotoxic drugs, e.g. tyrosine-kinase inhibitors; since they are being increasingly used in far-advanced stages of the disease and even at home or in the palliative care/hospice setting [12].
Pharmacists need to be aware of DDIs between especially oral, cytotoxic agents and drugs used merely for the management of symptom control, e.g. opioids. A typical example of DDIs with oral cytotoxic drugs in an advanced stage of cancer disease is the combined administration of tyrosine-kinase inhibitors and carbamazepine for neuropathic pain; azole-antimycotics, macrolide antibiotics, or fluoropyrimidines and sorivudine, brivudine for zoster neuralgia. DDIs in palliative care concern drugs interacting via histamine, acetylcholine or dopamine receptors and non steroidal anti-inflammatory drugs such as scopolamine, metoclopramide, dimenhydrinate, cyclizine, haloperidol, amitriptyline, levomethadon. Further on, surveillance of side effects of cytotoxic drugs in palliative care is an indispensable part of pharmaceutical care. A specialized education programme ‘pharmacy in palliative care’ for clinical and community pharmacists was established in 2008 throughout Germany [13] enabling community pharmacists to care about the special needs of patients with far advanced diseases staying at home.
DDI-checks are only possible when receiving medication lists in the same pharmacy. Yet, hospital teams, different physicians and pharmacies often lack the awareness of potential hazards associated with DDIs. One possible solution could be the ‘electronic health insurance card’, which provides all relevant information, for example, about medication, diseases, allergies, on a memory chip for each patient. Every healthcare professional will be able to receive all required medication information to avoid DDIs. Unfortunately, in Germany, the implementation of such a system is some way off due to concerns about data security and hardware problems, as well as the high costs of fitting out all pharmacies and physicians with card-reader equipment and software systems.
As with IV chemotherapy, oral chemotherapeutic agents may be hazardous, and correct application often requires complex individualized therapeutic regimes. The occurrence of potentially life-threatening side effects and DDIs must be considered. For this and other reasons, oncology patients who are receiving oral chemotherapy need specialized pharmaceutical advice. But in contrast to IV chemotherapy, oral chemotherapy is provided in Germany by all pharmacies. Thus, for the safe provision of oral chemotherapeutics, community pharmacists require new, additional knowledge. In general, different pharmacies may supply the same patient. Improving the level of awareness and pharmaceutical care skills for this patient group is essential for all community pharmacists. Therefore, DGOP has successfully implemented a national pilot programme ‘Oral chemotherapy—safe and effective’. This programme has five goals for oncology patients [14]:
There is a need for immediate availability of individual mixtures for individual outpatients. For example, topical analgesic and antiphlogistic solutions are required to reduce the symptom burden of patients with mucositis or stomatitis. By production of such topical preparations (morphine ointment, anaesthetic solutions) and individual oral preparations (especially pediatric patients) pharmacists often seek unorthodox solutions to reduce the burden of palliative care patients. This is particularly true for the treatment of odynophagia or impossibility of enteric drug administration. Moreover, community pharmacists adopt the physician’s prescription according to patient needs, priorities and capabilities. Thus, they prepare individual mixtures and educate patients and relatives concerning the correct use of these medications.
For example, an emergency analgesic and sedative medication, containing fentanyl, midazolam and s-ketamine, was needed for a six-year-old girl with an advanced, incurable hepatoblastoma and multiple lung metastases in case of severe dyspnoea or life-threatening bleeding [15]. Her parents wanted to fulfill their daughter´s wish to die at home but the girl lived more than 1.5 hours away from the hospital where she was being treated and her palliative care team, so emergency support was not available. Her parents were not able to administer parenteral drugs. Hence, community pharmacists established an emergency kit, containing individual nasal and rectal preparations of fentanyl, midazolam and s-ketamine, see Figure 8. They also trained the parents to use the kit. The girl died a few weeks later at home, in the presence of her family and without apparent suffering after the emergency kit was used because of acute and massive blood vomiting and dyspnoea during the dying phase.
*Figure 8 pending to upload.
Community pharmacists make an indispensable contribution to drug safety concepts for oncology and palliative care patients. The surveillance of medication, prescribed by different physicians, avoidance of DDIs, pharmaceutical care of patients with oral cytotoxic drug therapy, pharmaceutical palliative care at home and preparation of individual mixtures are important assignments that are routinely fulfilled by community pharmacists. As a new development, community pharmacists are currently: (i) increasingly providing oral outpatient chemotherapy; (ii) concerned with the necessary patient (and family) advice and surveillance that is associated with these therapeutic regimens; and (iii) providing specialized pharmaceutical palliative care support. For this, inter-professional education programmes such as the DGOP project ‘Oral chemotherapy—safe and effective’ and the education programme ‘Pharmacy in palliative care’ can effectively support pharmacists in the challenging task of increased drug safety and advanced symptom control.
Dr rer medic Klaus Ruberg
Pharmacist
Dr rer nat Andrea Tasar
Pharmacist
Kronen Pharmacy
Hospital and Community Pharmacy
82 Kronenweg
DE-50389 Wesseling, Germany
Associate Professor Dr med Jan Gaertner
Department of Palliative Care
University Hospital Cologne
DE-50924 Cologne, Germany
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