July 2018
clinical initiatives, research and current updates in treatment
Paracetamol safety and risk of inadvertent toxicity Chris Henry, Epic Pharmacy
Paracetamol is the most commonly used over the counter analgesic in the world.1 For the majority of people who use this drug, it is safe and effective.2 However, paracetamol overdose due to accidental paediatric exposures, repeated supra-therapeutic intake (RSI) (i.e. above usual doses required for treatment) and deliberate selfpoisonings can lead to hepatic toxicity and is currently the leading drug responsible for calls to Poisons Information Centres in Australia and New Zealand. 1 Fortunately, due to the availability of an effective antidote, hepatic failure and death are uncommon outcomes. However, paracetamol remains the most important single cause of acute hepatic failure in developed countries. 1 Confusion surrounding the appropriate use and dose in children and infants combined with the availability of numerous paracetamol-containing formulations exposes many patients to the risk of inadvertent overdose. There are currently over 30 different formulations of paracetamol containing products listed on the Australian Register of Therapeutic Goods. 3
The potential for overdose also exists in healthcare facilities. Instances of duplicate orders on multiple drug charts; poorly written or illegible prescriptions and orders for multiple paracetamol containing products or formulations increases the risk of paracetamol toxicity for inpatients. Nurses, doctors and pharmacy staff play important roles in educating patients, carers and parents about the appropriate use, accurate dosing and potential harms of paracetamol both within healthcare facilities and in the community.
the kidneys. 2 However, when taken in larger amounts, the liver is forced to use a different group of enzymes to process paracetamol which results in the accumulation of a toxic metabolite called N-acetyl-p-benzoquinoneimine (NAPQI). 2 NAPQI accumulation results in damage to the liver cells which can progress to liver failure. Current guidelines for the management of paracetamol poisoning define the toxic thresholds for paracetamol ingestion below. 1
Doses considered toxic
Toxicology
Acute Single Ingestion
Despite its long-term use as an analgesic, the precise mechanism of action of paracetamol remains unknown. 2 Paracetamol is rapidly absorbed from the small intestine (after oral administration of the immediate-release tablet) and reaches peak plasma concentration within 1-2 hours (or within 30 minutes for liquid preparations). 1 Elimination half-life is typically 2-3 hours, however, this can be delayed in the elderly, neonates and patients with pre-existing liver disease. 2 At therapeutic doses, paracetamol is processed by liver enzymes to produce predominantly non-toxic metabolites which are excreted by
>200mg/kg or 10g (whichever is less)
Repeated Supra‑Therapeutic Ingestion (RSI) >150mg/kg or 6g (whichever is less) per 24 hours over a 48‑hour period >100mg/kg or 4g (whichever is less) per 24 hours over a period more than 48 hours Continued on page 2
Paracetamol safety and risk of inadvertent toxicity Continued from page 1
However, drug interactions (causing induction of liver enzymes, or a change or reduction in liver metabolism), concurrent medical conditions (Gilbert’s syndrome, diabetes mellitus, obesity, liver disease) and fasting all have the potential to increase paracetamol-induced toxicity or reduce the threshold dose for toxicity. 2
The key factors in any paracetamol toxicity case are the dose ingested (including what formulation and whether staggered or single ingestion), time of ingestion, serum paracetamol level and clinical and laboratory features of liver damage.1 Clinical or biochemical evidence of liver injury may not be apparent for up to 24 hours after an acute paracetamol overdose, or longer for RSI. Serum paracetamol levels are the best surrogate marker for hepatic injury. 1 N-acetylcysteine is an effective antidote and should be administered to all patients deemed to be at risk of developing hepatotoxicity after paracetamol overdose. Administration
Figure 1: Examples of multiple medications containing paracetamol prescribed simultaneously.
within eight hours of exposure guarantees survival in almost all cases. 1
Opportunities for error and recommendations Medication errors in healthcare facilities are common and often occur when patients move between healthcare settings. In fact, half of all hospital medication errors occur on admission, transfer or discharge. 4 Medication histories are often incomplete and nonprescribed medications (such as over the counter paracetamol containing products) are omitted. Many different formulations and brands of products also exist and are often prescribed concurrently (Figure 1). Errors such as these can lead to duplication of therapy and significantly increase the risk of toxicity. A formalised process of medication reconciliation on admission, transfer and discharge has been shown to decrease errors by 5094% 5 and is associated with improved patient outcomes and reduced readmissions. 4 It is important to note that the potential for toxicity also exists at recommended therapeutic doses. Cases of toxicity have been reported
when overweight or obese children have been dosed by their actual body weight. Typically children who are found to be >20% over their ideal body weight should be dosed at their lean body weight in order to avoid this risk. 6 Other factors that increase an individual’s risk of toxicity include malnutrition (e.g. pre-operative fasting) and current febrile illness. The use of intravenous paracetamol in the inpatient setting has been associated with multiple case reports of up to 10-fold dosing errors, most significantly in infants. 7 The New South Wales Therapeutic Advisory Group has since published a set of guidelines for parenteral paracetamol with the goal of minimising risk. This includes ensuring no other formulations of paracetamol are concurrently prescribed or administered and the safe maximum daily dose (from all sources) is not exceeded. 8 Any patients who have suspicion or uncertainty regarding an incident of paracetamol overdose or toxicity should be encouraged to contact their local Poisons Information Centre (13 11 26) for advice. References are available on request.
What’s new Medicinal Cannabis Jamie Jackson (Epic Pharmacy Wesley) and Shan Heynes (Icon Group Pharmacy Practice Unit)
Increasing media attention and international developments in medicinal cannabis access programs, as well as community and advocacy groups, has prompted the Federal Government to fast-track access to medicinal cannabis products for patients in Australia.1 In 2016 the Narcotic Drugs Act 1967 was amended to permit the lawful cultivation and manufacture of cannabis for medicinal and research purposes. Resulting in medicinal cannabis being down scheduled from Schedule 9 to Schedule 8 in the Poisons Standard (refer Table 1). Cannabis sativa has approximately 500 natural components and up to 100 have been classified as cannabinoids. The two main cannabinoids with therapeutic benefits are delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is responsible for the psychoactive effects of cannabis, such as euphoria, drowsiness and loss of inhibition. THC may also be responsible for reduction in nausea, vomiting, pain and muscle spasms, in addition to improvement in sleep and appetite. CBD modulates the euphoric effects of THC. It may be useful in the management of seizures and pain, and may have anxiolytic and antipsychotic effects. 2 Since CBD is not psychoactive, it is included in Schedule 4 when in preparations for therapeutic use containing 2% or less of THC (refer Table 1).
Typically, in Australia, medicinal products for use in patients must meet quality standards set by the Therapeutic Goods Administration (TGA) for inclusion on the Australian Register of Therapeutic Goods (ARTG). The TGA guarantees these products have been manufactured to high standards with supporting evidence regarding their efficacy, safety and quality. Currently there is only one medicinal cannabis product on the ARTG (nabiximols oromucosal spray, Sativex®) but it is not available in Australia. In order to legally prescribe unregistered cannabis medicines and to ensure they meet a quality standard, specialist medical practitioners must seek Commonwealth approval from the TGA, via the Special Access or Authorised Prescriber Schemes. See TGA Access to medicinal cannabis products in Australia: Resource for doctors https://www.tga.gov.au/sites/default/ files/access-medicinal-cannabisproducts-steps-using-accessschemes.pdf
Unregistered medicinal cannabis can also be accessed through clinical trials. For a list of clinical trials underway across Australia, see http:// www.anzctr.org.au. Past clinical trials for medicinal cannabis have had significant limitations. At this stage meaningful clinical trials (such as randomised controlled trials) for most indications are lacking. 3 Refer Table 2. Conventional management should always be tried first and medicinal cannabis only considered when standard treatments have been ineffective or produced intolerable side effects. To support the limited evidence available for the safety and effectiveness of medicinal cannabis, the TGA developed five clinical guidance documents (available at https://www.tga.gov.au/accessmedicinal-cannabis-products) to assist doctors with the prescribing of medicinal cannabis.
Table 1: Current scheduling of medicinal cannabis products
Schedule 4
Schedule 8
Schedule 9
CBD in preparations for therapeutic use containing less than 2% THC (as a percentage of total cannabinoid content)
Cannabis and THC for human therapeutic use, including synthetic products
Cannabis products except those listed in Schedules 4 or 8
Prescription medicine*
Controlled drug*
Prohibited substance
* Scheduling in the Poisons Standard is a national classification system. The adoption of this scheduling and legislation may vary between states and territories. Prescribers must ensure they meet state/territory requirements as well as Commonwealth legislation. See https://www.tga.gov.au/access-medicinal-cannabis-products-steps-using-access-schemes
Medicinal cannabis therapy is continually evolving and public interest is growing.
They cover the following areas related to the current indications for medicinal cannabis: 1. Epilepsy in paediatric and young adult patients 2. Multiple sclerosis 3. Nausea and vomiting 4. Palliative care 5. Chronic non-cancer pain A guidance document for patients has also been developed to help them make informed decisions about treatment with medicinal cannabis (available at https://www.tga.gov.au/ publication/guidance-use-medicinalcannabis-australia-patientinformation).
There are no established or precise dosing schedules for medicinal cannabis and dosing is highly individualised. Doses depend on the type of product, individual variation, development of tolerance, drug interactions and previous exposure to cannabis (recreational or medicinal). It is recommended to “start low and go slow” to maximise therapeutic dose while minimising adverse effects. All starting doses should be administered in the evening to assist the management of side effects. 3 Short term adverse effects include agitation, dizziness, anxiety, hypotension, incoordination and
tachycardia. An estimate of one in ten users may develop dependence. 2 Long term effects from chronic use may include altered brain development, short-term memory loss, compromised judgement and decision-making, and severe anxiety that can manifest as paranoia and psychosis. There is also potential for drug-drug interactions as cannabinoids are mostly metabolised by the liver involving the cytochrome P450 enzyme. 2 When commencing patients on medicinal cannabis, prescribers must take into consideration the facility’s ability to meet regulatory requirements for storage. In addition to Schedule 8 (Controlled Drugs) storage conditions, some products, e.g. Tilray oral solutions and capsules, require cold-chain management (room temperature stability varies between products) 3 thus presenting the additional logistical challenge of secure refrigeration. State/ territory health departments can provide further secure storage recommendations if needed. Where possible, medicinal cannabis products that are stable at room temperature are therefore preferred, e.g. CanniMed® oils. As medicinal cannabis becomes more accessible and prescribed, patients may present to their health care facility with their own supply. As with any S4/S8 medicines, a dispensing
label with the pharmacy’s contact details should be affixed to legallysourced medicinal cannabis. Contacting the prescriber and pharmacist who dispensed the medication would further determine the legal validity of the medication. Hospital and pharmacy staff should not take possession of any prohibited cannabis products brought in by patients or their family. However, if there is a genuine concern that there is a duty of care to not leave prohibited cannabis products in the possession of the patient, or they are otherwise unable to be removed from the facility by the patient’s carer or family, the state/ territory health department should be contacted immediately for advice on the appropriate handling of any such items. Currently, medicinal cannabis is not recommended as first-line therapy for any indication. There is growing evidence for its use in several clinical applications, however further research and trials are necessary to establish the safety and benefits of medicinal cannabis. As medicinal cannabis therapy is continually evolving and public interest is growing, all health care providers need to keep abreast of changing legislation and developments in research to ensure individual patients receive the most appropriate and safe treatment for their condition. References are available on request.
Table 2: Summary of evidence based on a systematic review on cannabinoids for medical use 4 Illness Reduction in pain Spasticity in MS Nausea and vomiting Weight gain in HIV Depression
No. of studies
No. of patients
Strength of evidence
28 (8)
590
Just significant; moderate
14
2280
Just significant; moderate
28 (3)
?
4
225
Mixed results; low Not significant; low
5 (0)
?
Secondary outcomes; low
Anxiety
1
8
Significant; low
Sleep disorders
2
54
Significant; low
Tourette’s
2
36
Significant; low
Glaucoma
1
6
Not significant; low
Psychosis
2
71
Not significant; low
Research from our staff
In 2017 our pharmacy staff conducted a number of research projects. Of these, 5 were presented in various forms at the annual Society of Hospital Pharmacists (SHPA) and the Clinical Oncology Society of Australia (COSA) conferences. We don’t often share this work so we have included 2 of these projects (2 more will follow in the next edition) to give you some understating of our innovations.
Improvement of a clinical pharmacy service in the absence of an onsite pharmacy within a metropolitan day oncology hospital Neil Lam1, Linda Nguyen1, Danielle Queale1, Courtney King2 1 Icon Cancer Care Wesley 2 Icon Group Pharmacy Practice Unit
Background The absence of an on-site pharmacy in a busy metropolitan day oncology hospital provided challenges to the provision of clinical pharmacy services. Limited onsite workspace restricted pharmacy staffing to one full time pharmacist. Nurses were responsible for providing cancer treatment education to patients. Communication with the multidisciplinary team was reliant on email and telephone which created gaps and inefficiencies in the service provided.
Figure 1. Pharmacy KPI Data 100%
82.9
83.8
60%
In May 2017, two new pharmacist roles (Day Unit Pharmacist and Clinical Lead Pharmacist) were implemented at the day oncology hospital (Table 1). Table 1: Summary of Roles and Responsibilities of New Pharmacist Positions For all patients receiving new parenteral cancer treatment:
25.0
0
MMP completion (%)
¬¬ To provide medication counselling on chemotherapy and supportive therapies ¬¬ To obtain best possible medication history via completion of Medication Management Plan (MMP) ¬¬ To provide a Discharge Medication Record (DMR)
DMR provided (%)
¬¬ To collaborate with the Pharmacy Educator to improve clinical pharmacy service ¬¬ To collaborate with the Nurse Consultant to provide training to oncology nurses ¬¬ To respond to consultants’ pharmaceutical queries especially on new drugs ¬¬ To participate in selected initial consults to assist in formulating a pharmaceutical plan
Education provided (%)
May (number of new parenteral cancer treatment = 76) June (number of new parenteral cancer treatment = 74) July (number of new parenteral cancer treatment = 67)
Figure 2. Pharmacy Service - Efficiency 25
21
20
Before implementation After implementation
15 10 5 0
8
5
2
7
1
Excellent
Good
Adequate
Poor
Efficiency Rating
Clinical Lead Pharmacist ¬¬ To provide support to the Day Unit Pharmacist during the implementation phase.
73.1 51.4
20%
Figure 3. Pharmacy Service - Communication No. of Respondents
Day Unit Pharmacist
79.0
40%
No. of Respondents
Method
80.0 59.2
Aim To improve the clinical pharmacy service within a metropolitan day oncology hospital in the absence of an on-site pharmacy.
82.1
80%
25
22
Before implementation
20
After implementation
15 8
10 5 0
2 Excellent
8
4 Good
Adequate
Poor
Communication Rating
Training in providing cancer treatment education, documenting a medication management plan (MMP) and discharge medication record (DMR) was provided by the pharmacy educator and clinical lead pharmacist. Through engagement of pharmacy, clinic and nurse management, additional workspace was created for the clinical lead pharmacist and a mobile workstation on wheels implemented for the day unit pharmacist. Key performance indicators (KPIs) were identified with a target MMP and DMR completion rate of 90% of all new parenteral cancer treatments. KPI data was collected using an electronic prescribing system between May and July 2017. Post-implementation, a written questionnaire was conducted with nursing, administrative and medical staff to evaluate the impact of pharmacy service changes. These questions specifically addressed the respondent’s perception of efficiency, communication and service quality.
Results There were 217 new parenteral cancer treatments administered in the day oncology hospital between May and July 2017. The average completion rates for MMPs and DMRs were 83% and 73% respectively. A written questionnaire was provided to 23 nursing, administrative and medical staff. Twenty-two questionnaires were completed (response rate of 95.7%). Acknowledgments
¬¬ Yvette Ellis (Icon Cancer Care Wesley) in assisting with data management ¬¬ Emma Alder (Icon Pharmacy National Manager) in providing resources for the new pharmacy model
91% of respondents reported an improvement in pharmacy service efficiency and communication. 95% of the respondents rated “excellent” in overall quality of pharmacy service since the implementation of the new model.
Discussion Although the KPI results during the study period fell short of the targets, continuous improvement is expected when all pharmacists have been trained and rotated through the Day Unit Pharmacist role. Post implementation, improvement will be assessed by regular monthly monitoring of KPIs. A limitation of the study was the exclusion of patient involvement from the written questionnaire. Due to the short study period and the operational nature of the changes it was decided that patient satisfaction would be measured outside of the study. Furthermore, pharmacist role satisfaction was not measured pre and post-implementation of service changes. The broadened scope of practice and increased patient contact may have resulted in increased role satisfaction and enhanced professional development.
Conclusion The implementation of two clinical pharmacist roles, mobile workspace, introduction of KPIs related to MMP, DMR and patient education provision have all assisted in improving clinical pharmacy service to the day hospital in the absence of an on-site pharmacy.
Expanding the Pharmacy Technician role
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to support clinical teams and improve medication safety
Laura Marshall and Bettina Kirk — Epic Pharmacy, The Wesley Hospital
Background In 2016 a Clinical Support Technician role was established at a large private hospital, primarily focussing on pre-admission medication histories. A need to expand the scope of this role was identified for two reasons: 1. Increasing pharmacist workloads (particularly on weekends) 2. Concerns over unclear identification of High Alert Medications (HAMs) (list as outlined in the hospital’s policy)
Aim The aim was to investigate tasks that a technician can undertake at ward level which can help: ¬ ¬ Prioritise pharmacist time
660 HAM stickers were applied to medication charts, aiding clearer identification of high-risk drugs to the multidisciplinary team.
Summary On average, the technician found that:
1.2
items
were ordered for
every patient seen
Methods
1
Over a three month period an experienced technician spent approximately two hours per day working at ward level. This included visits to Medical and Surgical wards and the Rehabilitation facility.
10 patients seen
¬ ¬ Pro-actively reduce medication ordering by nurses ¬ ¬ Improve High Alert Medication (HAM) identification
Upon arriving at the ward, tasks were agreed with the ward pharmacist; these included: ¬ ¬ Pro-active replenishing of patient medication ¬ ¬ Application of HAM stickers to medication chart orders ¬ ¬ Technician referrals to pharmacists
Results During the three month period 1216 inpatients were seen by the technician and 1563 medications were pro-actively ordered and dispensed on weekdays, with the technician spending approximately 5 minutes with each patient. This resulted in a statistically significant reduction of reactive dispensing on weekends (with a mean difference of 29 scripts per day, P=0.035), from 967 scripts per 1000 bed days in 2016 to 855 scripts per 1000 bed days in 2017; a total reduction of 11.6%. In addition, 119 patients were referred to ward pharmacists for reasons such as: ¬ ¬ Clinical intervention ¬ ¬ Identification of transcription errors resulting in accidental omissions of medications ¬ ¬ Clarification of ambiguous medication orders
referral
was made to the pharmacist for every
1required in 2 patients HAM stickers applying to
their medication chart Conclusion Expanding the scope of the Clinical Pharmacy Technician role made a substantial contribution towards: ¬ ¬ A noticeable reduction in the volume of orders coming into pharmacy on weekends, improving efficiencies in workflow ¬ ¬ Freeing up valuable clinical time for pharmacists and nurses ¬ ¬ Medication concerns being brought to the attention of a pharmacist in a timely manner ¬ ¬ Better identification of HAMs to the multidisciplinary team These outcomes can all further contribute to medication safety and enhancing the pharmacy service.
¬ ¬ A need for a patient history/medication reconciliation to be completed
If you have any queries regarding Circuit content and authors please contact the Epic Pharmacy Practice Unit by email: circuit.editor@epicpharmacy.com.au Every effort has been made to ensure this newsletter is free from error or omission.
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