Knowledge Type: Clinical Articles

Psoriasis is a systemic disease with increased risks of comorbidities, poor mental health and poor quality of life. There may be a genetic link, but the condition can be well managed.

The aim of treatment is to control the symptoms and prevent exacerbations. Treatment depends on the severity of the disease. The Psoriasis Area Severity Index (PASI) score (0-72) grades the symptoms based on plaque appearance and area coverage. Dermatology Life Quality Index (DLQI) indicates the effect of skin diseases, such as psoriasis, on quality of life. Higher PASI and DLQI scores indicate more severe disease and a greater impact on quality of life.

Non-pharmacological management measures that pharmacists can recommend are:

• Stress reduction;
• General health improvement, i.e. avoid smoking, decrease alcohol consumption and reduce weight (diet and exercise);
• Exposure to sunlight;
• Phototherapy – solar or UV radiation. Used in severe psoriasis; and
• Skin hydration by using emollients to keep the psoriatic skin soft and moist, hence reducing itch and tenderness.

These measures can be used alone in mild psoriasis or in conjunction with pharmacotherapy in moderate to severe cases.

Mild psoriasis may be treated with topical agents. Systemic treatment and phototherapy may be required in moderate to severe psoriasis.

Choice of topical treatment depends on location, characteristics of the lesions and patient preference.

Topical Corticosteroids are most widely used due to their known efficacy, ease of use and rapid onset of action. Occlusive dressings can be applied over small areas for a short period to increase the effectiveness of the topical steroid. One FTU (fingertip unit) is enough to cover an area twice the size of an adult hand. Use for the shortest possible time. Systemic absorption can occur, and, hence steroid strength needs to be monitored. Abrupt withdrawal of potent topical corticosteroids can cause rebound flare-up. Dose tapering is recommended prior to withdrawal.

Coal tar cream, gel, ointment, or foam can be applied 1-4 times a day.

Coal tar shampoo is used once a week. Massage into scalp, leave for several minutes and rinse.

Patient compliance may be a problem with coal tar products due to its odour, staining and sensitising properties. Coal tar can have a synergistic action with topical corticosteroids or phototherapy. Salicylic acid is often used in combination with coal tar as it acts as a keratolytic to soften and reduce psoriatic scale.

Salicylic acid cream or ointment can be applied 2-3 times a day.

Salicylic acid lotion is massaged into the scalp and then rinsed after 15 minutes. This is often used twice a day.

Salicylic acid shampoo can be applied twice a week to wet hair and rinsed after 3-5 minutes.

Calcipotriol 0.005% is available as a combination with betamethasone dipropionate 0.05% (Daivobet^®). There is a theoretical risk of hypercalcaemia if used over large areas for long periods due to its action on vitamin D. A maximum of 100g of product per week is recommended. It is recommended that salicylic acid treatment be applied at a different time of the day to calcipotriol. Calcipotriol is unstable when used with salicylic acid.

Dithranol ointment or paste 0.05-2% is only available as an extemporaneous product. Start with a low strength for 5-10 minutes daily. Increase strength and application time (up to 30 minutes for short-contact treatment) according to the response.

Dithranol products are often combined with salicylic acid to improve stability. Combining it with coal tar helps reduce the irritant effect of dithranol.

Dithranol products are not used on sensitive areas like the face due to its irritant property, and it is applied directly to the lesion using gloves.

A calcineurin inhibitor (e.g. pimecrolimus) is effective for application to sensitive areas. It is less effective than topical corticosteroids.

Retinoids (tazarotene) are rarely used. Irritation is common.

The National Health and Medical Research Council (NHMRC) recently published the ‘2021 Cervical Cancer Elimination Progress Report’. This is the first of what is intended to be a regular series of reports regarding the elimination of cervical cancer as a public health concern in Australia. The World Health Organization (WHO) defines cervical cancer elimination as an incidence of four per 100,000 women or lower. Elimination has not yet been achieved by any country. However, Australia is predicted to be the first country to achieve this goal, possibly as early as 2028.

Cervical cancer is a preventable cancer, with nearly all cases attributed to human papillomavirus (HPV) infection. This makes primary prevention with HPV vaccination so important. There are more than 100 types of HPV, around 40 of which are responsible for infections of the genital tract. Just two HPV types, type 16 and 18, are responsible for around 70% of cervical cancers. The remaining 30% of cases are due to other high-risk HPV types. These HPV types can also cause some vaginal, vulval, penile, and anal cancers. Low-risk genital HPV types such as 6 and 11 can cause genital warts.

The majority of HPV infections are asymptomatic and resolve spontaneously within 12 to 24 months. However, HPV infections that persist can cause abnormalities that may progress to cancer. It may take 20 years or more for cervical cancer to develop from HPV. Therefore, HPV vaccination programs do not have an immediate impact on the incidence of cervical cancer. Cervical screening remains an important component of the elimination strategy.

Australia was the first country with a national HPV vaccination program. The school-based program was rolled out to girls in 2007, with boys added in 2013. In 2018, the quadrivalent vaccine was replaced by the nonavalent vaccine, which protects against an additional five HPV types. The virus types covered in the nonavalent vaccine account for around 90% of cervical cancers, 95% of all HPV-related cancers in men, and 90% of genital warts in men and women.

The vaccine does not affect existing infection with a virus type contained in the vaccine. Therefore, the vaccine is most effective when administered before the recipient becomes sexually active. The Australian Immunisation Handbook recommends a dosing schedule of two doses, given six to twelve months apart for adolescents aged 9-14 years. A three-dose schedule is recommended for people 15 years of age and older and anyone with an immunocompromising condition. When a three-dose schedule is used, there should be an interval of two months between the first and second dose and four months between the second and third dose.

The HPV vaccine is generally well tolerated. A large-scale analysis of surveillance data reported to the Therapeutic Goods Administration (TGA) between 2007 and 2017 affirmed the safety profile of the quadrivalent HPV vaccine. The range of adverse events reported is similar in males and females and includes headaches, fever, nausea, dizziness, and fatigue. Rates of anaphylaxis are low and comparable to other vaccines. Syncope has been identified in post-marketing surveillance to be a common adverse effect following HPV vaccination in adolescents. This is a benign reaction to the process of vaccination rather than the vaccine itself. Procedures should be in place following vaccination to minimise the risks associated with syncope-related falls.

The ‘2021 Cervical Cancer Elimination Progress Report’ provides an audit of HPV vaccination coverage as part of Australia’s overall progress towards the elimination of cervical cancer as a public health problem. Some of the key findings of the report include:

• Completion of HPV vaccination by age 15 occurred in 78.2% of adolescents in 2019 (79.6% of females and 76.8% of males);
• The rate of HPV vaccination is close to what is predicted to be required for the eventual elimination of vaccine-preventable HPV types (80%). However, the rate for vaccination of girls is currently below the 90% target set by the WHO; and
• The incidence of cervical cancer in Australia is 6.3 new cases per 100,000 (from 2011 to 2015);
• Indigenous women suffer cervical cancer at twice the rate of non-Indigenous women and have a three-fold higher mortality rate.

While the overall incidence of cervical is low in Australia, there are considerable inequalities for Indigenous Australians. This inequality may be related to lower uptake of the vaccine and poorer access to treatment. Uptake of routine screening may also be a contributing factor, although screening data based on Indigenous status is not included in the report due to a lack of data. The next report in the series is expected to provide meaningful data on this indicator.

Addressing these inequalities is one of the main recommendations noted in the report. Other recommendations include improvements to data collection and the development of a methodology to monitor cervical cancer treatment rates. The NHMRC Centre of Research Excellence in Cervical Cancer Control is optimistic that the issues identified in the report can be addressed to ensure that  Australia advances towards eliminating cervical cancer as a public health problem for all women.

The Australian Government launched its National Strategic Action Plan for Pain Management this week. It is estimated that one in five Australians experience chronic pain, with the rate increasing to one in three adults over 65 years of age.

Chronic pain has a significant impact on a person’s ability to function at home and work, as well as social and emotional impacts. However, it is currently estimated that up to 80% of people living with chronic pain do not receive adequate therapy. This may be related to regional differences in the availability of pain clinics and physiotherapists, with most of these services concentrated in major capital cities. The Australian Commission on Safety and Quality in Healthcare theorise that these differences may be a factor in the considerable regional variation observed in the use of opioids. There is also a lack of general awareness of pain and optimal pain management strategies among both consumers and healthcare professionals. This is also thought to contribute to sub-optimal outcomes.

The Action Plan aims to address these barriers in order to improve access to care. The following eight goals form the basis of the plan:

1. People living with pain are recognised as a national and public health priority;
2. Consumers, their carers and the wider community are more empowered, knowledgeable and supported to understand and manage pain;
3. Health practitioners are well-informed and skilled on best practice evidence-based care and are supported to deliver this care;
4. People living with pain have timely access to consumer-centred best-practice pain management, including self-management, early intervention strategies and interdisciplinary care and support;
5. Outcomes in pain management are improved and evaluated on an ongoing basis to ensure consumer-centred pain services are provided that are best practice and keep pace with innovation;
6. Knowledge of pain flourishes and is communicated to health practitioners and consumers through a national research strategy;
7. Chronic pain is minimised through prevention and early intervention strategies; and
8. People living with pain are supported to participate in work and community.

Achieving the objectives of the plan requires strong partnerships between government, healthcare professionals, primary health networks, and consumers. There are many actions that healthcare professionals can take to support these goals, including:

• Educating patients and their carers about chronic pain with the support of reliable resources;
  • PainBytes (for adolescents, parents and teachers)
  • Brainman videos (available in many languages)
  • PainHEALTH
  • Agency for Clinical Innovation (ACI) Pain Management Network
  • NPS MedicineWise.
• Referral to other healthcare professionals to address specific needs;
  • Physiotherapist for patients with deconditioning
  • Psychologist for patients experiencing pain that is associated with negative mood and behaviours
  • Multidisciplinary pain services for the management of complex cases
  • Online pain management programs (e.g. This Way Up, MindSpot) may be appropriate for some patients who are unable to access traditional pain management services
• Use of strategies to prevent the transition of acute pain to chronic pain, e.g. therapeutic exercise, adequate acute pain management with regular review;
• Educating patients and their carers about their medications, e.g. through the use of approved consumer medicine information documents; and
• Encouraging healthy habits such as improved diet, limited alcohol intake, and smoking cessation.

This new Action Plan will build upon the 2010 National Pain Strategy, which has already affected major change in the way pain is understood and managed in Australia. The National Pain Strategy has contributed to the establishment of new pain clinics in regional areas, dedicated paediatric pain clinics, specialist paediatric telehealth services, and a range of educational materials for healthcare professionals and people living with pain. It is hoped that this progress will continue to improve the quality of life for people affected by chronic pain.

The complete Action Plan is available for download from the Department of Health.

This month marks the first Thyroid Awareness Month in Australia. This campaign is supported by the Australian Thyroid Foundation and aims to raise awareness of thyroid health. Symptoms of thyroid disorders are often varied and non-specific, and it is thought that many cases go undiagnosed. Some of the more common features of thyroid disorders are shown in Table 1.

Table 1. Features of thyroid disorders

Hypothyroidism	Hyperthyroidism
Fatigue	Tremor
Weight gain	Weight loss
Cold intolerance	Heat intolerance
Constipation	Muscle weakness
Dry skin	Palpitations

The two main hormones produced by the thyroid gland are triiodothyronine (T3) and thyroxine (T4). These hormones play an important role in regulating the basal metabolic rate. They also contribute to brain maturation and overall growth in children. The levels of T3 and T4 are tightly maintained via feedback from the pituitary gland in the form of thyroid stimulating hormone (TSH).

Thyroid disorders can be classified as primary, secondary, or tertiary. Primary thyroid disorders are those that are caused by a problem within the thyroid gland itself. The negative feedback response to T4 and T3 remain intact in primary disease. Therefore, primary hypothyroidism is associated with elevated TSH and primary hyperthyroidism is associated with suppression of TSH.

In contrast, secondary and tertiary disorders arise in structures outside of the thyroid. Secondary disease is caused by problems in the anterior pituitary gland, which affects the release of TSH. Tertiary disease is caused by a problem in the hypothalamus. This affects the release of thyroid releasing hormone, which then affects the production of TSH. Primary and secondary thyroid disorders are collectively known as central thyroid disorders. In central thyroid disorders, the feedback responses are impaired. For example, serum levels of T3 and T4 will be low in secondary hypothyroidism, but TSH levels may be normal or low.

The Therapeutic Guidelines publish a guide for interpretation of thyroid laboratory results.

Medications affecting thyroid hormones

Many medications can affect thyroid function, thyroid function tests, and therapies to treat thyroid disorders.

Iodine is one of the main building blocks of T3 and T4 and is found in many foods in the form of inorganic iodide. The Australian recommended daily intake (RDI) is 150mcg for adults, with an upper level of intake of 1,100mcg per day. Iodine excess can have a significant impact on thyroid function and can exacerbate both hypothyroidism and hyperthyroidism.

Excess iodine exposure may occur due to the administration of iodinated contrast media or iodine-containing medicines, such as amiodarone. Each molecule of amiodarone contains two iodine atoms which equates to around 75mg of iodine per 200mg tablet. Deiodination that occurs during metabolism releases approximately 6mg of iodine per 200mg tablet, which is significantly higher than the RDI.

Topical iodinated antiseptics (i.e. povidone-iodine) have been associated with thyroid dysfunction. This may be particularly relevant in neonates and when topical preparations are used long-term. Some complementary medicines also contain iodine. Cases of thyroid dysfunction have been reported with products containing kelp (sometimes labelled as Fucus vesiculosus).

Other medications that can affect thyroid hormones are shown in Table 2.

Table 2. Medications that can affect thyroid hormones

Medications	Effect
Lithium, interferon alfa, interleukin-2, tyrosine kinase inhibitors (e.g. sunitinib, sorafenib), immune checkpoint inhibitors (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab)	Hypothyroidism
Interferon alfa, interleukin-2, alemtuzumab	Thyrotoxicosis
Colestyramine, sucralfate, ferrous sulfate, aluminium hydroxide, sevelamer, calcium carbonate, soy preparations	Reduced absorption of levothyroxine when administered together
Phenytoin, barbiturates, carbamazepine, rifampicin	Induces metabolism of levothyroxine
Biotin (vitamin B7), dopamine, glucocorticoids	May alter diagnostic test results

 

Critical illness is likely to exacerbate the above medication-induced effects on thyroid function. The endocrine response during critical illness is complex and may also impact thyroid hormone levels on its own. The result is typically reduced levels of T3 and increased levels of the inactive form, reverse T3 (rT3). Therefore, thyroid test results should be interpreted with caution during critical illness. In the absence of clinical features of thyroid dysfunction, it is not recommended to start therapy for a thyroid disorder in such a patient.

Thyroid disorders affecting medications

Thyroid dysfunction can also alter the effects of some medications, including:

• Digoxin – patients with hypothyroidism may be more sensitive to the effects of digoxin, and patients with hyperthyroidism may be less sensitive. Digoxin doses may need to be modified;
• Diabetes medications – blood glucose should be regularly monitored and reviewed in patients with diabetes when therapy for hypothyroidism is initiated. As thyroid function is corrected, the patient’s requirement for insulin or oral hypoglycaemic agent may increase. This effect is typically delayed as levothyroxine has a slow onset of action, with peak therapeutic effect taking up to four weeks; and
• Warfarin – the INR may require more frequent monitoring when therapy for thyroid disorders is started or changed. The warfarin dose may need to be reduced when therapy for hypothyroidism is initiated and increased when therapy for hyperthyroidism is started.

Summary

It is estimated that over one million Australians have an undiagnosed thyroid disorder. Raising awareness of some of the more common signs and symptoms may improve diagnosis by encouraging people to speak to their doctor.

Many medications can affect thyroid function, with regular testing recommended for some patients. Correcting thyroid function can also affect medicines the patient may already be taking. Careful monitoring and dose adjustments of concomitant medicines may be required when thyroid therapy is initiated, the dose changed, or when thyroid therapy is ceased.

The Therapeutic Goods Administration (TGA) has approved seven influenza vaccines for use this year, all of which are quadrivalent.

Annual influenza vaccination is recommended for all people aged six months and older to prevent influenza infection and its complications. Influenza vaccines are available for free on the National Immunisation Program (NIP) for all children aged six months to five years and all adults aged 65 years and older. It is also funded for other specific populations with an increased risk of influenza complications (e.g. pregnant women, Aboriginal and Torres Strait Islander people, and people with certain medical conditions). Details on NIP eligibility can be obtained from the Department of Health.

The Australian Influenza Vaccine Committee (AIVC) made the following recommendations regarding the composition of influenza vaccines for the 2021 Southern Hemisphere season.

Egg-based quadrivalent influenza vaccines:

• A/Victoria/2570/2019 (H1N1)pdm09-like virus;
• A/Hong Kong/2671/2019 (H3N2)-like virus;
• B/Washington/02/2019-like (B/Victoria lineage) virus; and
• B/Phuket/3073/2013-like (B/Yamagata lineage) virus.

Cell-based quadrivalent influenza vaccines:

• A/Wisconsin/588/2019 (H1N1)pdm09-like virus;
• A/Hong Kong/45/2019 (H3N2)-like virus;
• B/Washington/02/2019 (B/Victoria lineage)-like virus; and
• B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.

Cell-based vaccines

This is the first year that a cell-based influenza vaccine (Flucelvax®) has been made available in Australia. The cell-based manufacturing process uses mammalian cell cultures to grow the influenza virus instead of embryonated chicken eggs. The resulting vaccine is completely free of ovalbumin (egg protein) compared to traditional influenza vaccines, which may contain traces of ovalbumin. This may be reassuring for patients with an egg allergy, although the Australasian Society of Clinical Immunology and Allergy (ASCIA) advise that these patients can safely receive traditional influenza vaccines. The amount of ovalbumin contained in egg-based influenza vaccines has reduced over the years, with each dose currently containing less than 1µg. The ASCIA estimate that 130µg of egg protein (taken orally) is required to trigger a reaction in egg-allergic individuals.

There are a number of other potential advantages to growing the virus in mammalian cell cultures. Firstly, growing viruses in eggs requires very large numbers of embryonated eggs from pathogen-free flocks. Secondly, not all virus strains grow well in eggs. The H3N2 strain, in particular, may change when grown in eggs. This phenomenon, known as egg-adaptation, can occur when the virus is grown in eggs as the virus adapts to avian receptors in the egg. It is thought that this could contribute to reduced vaccine match and reduced vaccine efficacy. Therefore, growing the virus in mammalian cell cultures could potentially lead to improved vaccine efficacy.

This vaccine is not funded on the NIP.

Adjuvanted vaccines

Fluad® Quad is an adjuvanted vaccine that is available on the NIP for people 65 years of age and older. This vaccine contains the standard antigen dose but is formulated with an adjuvant to enhance the immune response. Fluad® Quad is preferred for older Australians as older people typically produce a weaker immune response to standard influenza vaccines. The increased response observed with Fluad® Quad is particularly pronounced for the A/H3N2 strain, which is more common and severe in older populations.

The Immunisation Handbook recommends that Fluad® Quad should not be co-administered with Shingrix®. Shingrix® is an adjuvanted zoster vaccine that is expected to be available in Australia from mid-2021.

Administration

Influenza vaccination should ideally occur before the start of the influenza season. In Australia, the peak influenza period is typically June to September. However, some experts suggest that the 2021 influenza season may start later due to fewer international travellers arriving.

Optimal protection against influenza is achieved in the three to four months after vaccination, although protection is generally expected to last throughout the year. The Australian Technical Advisory Group on Immunisation (ATAGI) advise that vaccination can continue to be offered as long as influenza viruses are circulating and a valid vaccine is available.

The recommended dose for all of the influenza vaccines registered in Australia is 0.5mL. A second dose is recommended for children younger than nine years of age who have not previously had an influenza vaccine and for people of any age who have recently had a haematopoietic stem cell transplant or solid organ transplant. If a second dose is required, it should be administered four weeks after the first dose.

A summary of vaccines registered for use in Australia this year is shown in Table 1.

Table 1. Influenza vaccines registered in Australia for 2021

Influenza vaccine	Vaccine type	Indicated age group
Vaxigrip® Tetra	Egg-based	6 months and over
Fluquadri®	Egg-based	6 months and over
Fluarix® Tetra	Egg-based	6 months and over
Fluad® Quad	Adjuvanted, egg-based	65 years and over
Afluria® Quad	Egg-based	5 years and over
Influvac® Tetra	Egg-based	3 years and over
Flucelvax® Quad	Cell-based	9 years and over

The relevant product information should be consulted for further information.

Eosinophilic oesophagitis is a chronic immune-mediated disease of the oesophagus. It is characterised by progressive oesophageal dysfunction due to tissue inflammation and fibrosis. The condition is more common in males and is typically seen in patients with a history of atopy.  Eosinophilic oesophagitis is estimated to affect around one in 1,000 people, although the prevalence appears to be rising in Australia.

The clinical features of this condition may include dysphagia, food impaction, and reflux-like symptoms. However, in children and infants, the presentation may involve food refusal, vomiting, weight loss, abdominal pain, or chest pain. The symptoms of eosinophilic oesophagitis can be difficult to distinguish from gastroesophageal reflux disease (GORD). While endoscopy may reveal characteristic changes, oesophageal biopsies showing an increased number of eosinophils throughout the oesophagus is required for diagnosis.

Eosinophilic oesophagitis is thought to be related to allergens in the diet or the environment. Dietary triggers may include dairy foods, egg, soy, wheat, nuts, and seafood. It can be difficult to identify specific trigger foods as the reactions are often delayed. Environmental triggers may include pollens, animals, dust mites, and moulds. Symptoms related to environmental triggers may occur seasonally, with treatment only required at certain times of the year. If this condition is not treated properly, oesophageal narrowing and strictures can occur as a result of chronic inflammation.

The first-line pharmacological treatment for eosinophilic oesophagitis is a proton pump inhibitor. Standard doses are used for four to eight weeks and, if a response is observed, therapy can continue using a maintenance regime as appropriate for GORD. A swallowed topical-acting corticosteroid can be added if symptoms persist.

The options for topical-acting corticosteroids are quite limited. Fluticasone metered-dose inhalers may be used for this purpose. Comprehensive patient counselling is required as the administration instructions differ significantly from those detailed in the consumer medicine information leaflet. In order to deliver the medication to the oesophagus, the patient should be advised to spray the dose into their mouth without inhaling and then swallow. Patients should also avoid eating and drinking in the 30 minutes after administration and, contrary to the usual instructions for corticosteroid inhalers, the patient should not rinse their mouth afterwards. It should also be noted that the dry powder formulation of fluticasone (i.e. the Accuhaler®) is not appropriate for this indication as these devices are breath-activated, so they cannot be used without inhaling.

Another topical corticosteroid recommended by the Therapeutic Guidelines is a budesonide slurry. A viscous mixture is achieved by combining the contents of one budesonide inhalation ampoule (1mg/2mL) with three to five grams of sucralose powder (e.g. the sugar substitute, Splenda®). The resulting mixture may then be swallowed after meals, usually twice daily.

Both of these topical-acting corticosteroids are used to treat eosinophilic oesophagitis on an ‘off-label’ basis. This may present some challenges as the administration instructions for eosinophilic oesophagitis are very different from the usual advice provided to manage respiratory conditions. The newly registered product, Jorveza®, overcomes these issues.

Jorveza® is the first product to be registered for the treatment of eosinophilic oesophagitis. It is presented as an orally disintegrating tablet containing 1mg of budesonide. Budesonide is delivered directly to the site of inflammation when the tablet is allowed to slowly dissolve on the tongue, with the patient gradually swallowing the dissolved material. Jorveza® tablets should not be taken with food or liquid, and patients should wait at least 30 minutes after a dose before eating, drinking, or performing oral hygiene.

The effectiveness and tolerability of budesonide orally disintegrating tablets were studied in a double-blind clinical trial. Adult patients with active eosinophilic oesophagitis were randomly assigned to receive budesonide 1mg twice daily or placebo for six weeks. The primary endpoint was the proportion of patients achieving both clinical and histologic remission at the end of treatment. This was reached in 57.6% of the budesonide group and 0% of the placebo group. Following a further six weeks of open-label induction, the rate of clinical and histologic remission was 84.7%. This suggests that prolonged treatment may be valuable to increase rates of remission.

The rate of just histologic remission was 93.2% in the budesonide group at six weeks (compared to 0% in the placebo group). This is much higher than the rates observed in previous trials for other budesonide formulations using higher doses. For example, a recent trial for a budesonide oral suspension showed only a 39% histologic response rate when dosed at 2mg twice daily. The study authors speculate that the formulations may be responsible for this difference. The effervescent qualities of the orally disintegrating tablets stimulate saliva production for around two or three minutes. During this time, small volumes of budesonide-containing saliva are continuously swallowed, which may result in superior oesophageal contact time.

Overall, budesonide orally disintegrating tablets were well-tolerated in this study. No patients in the budesonide group experienced serious adverse events or withdrew from the study due to treatment-emergent adverse effects. Suspected local fungal infection was more common in the budesonide group compared to the placebo group (23.7% versus 0%). However, symptomatic histologically-confirmed fungal infection occurred in only 5.1% of patients in the budesonide group. Like other systemically active glucocorticoids, budesonide may be associated with impairment of the hypothalamic-pituitary-adrenal (HPA) axis and reduced production of endogenous cortisol. In this trial, decreased plasma cortisol levels were detected in 5.1% of the budesonide arm (0% of the placebo group). Premature discontinuation of the therapy was not required, and levels normalised after the end of the study in each case.

Eosinophilic oesophagitis is a relatively newly identified condition, and understanding of its pathogenesis is currently limited. However, it is important that the condition is identified and treated appropriately to prevent permanent oesophageal damage.

Interstitial cystitis (IC) or bladder pain syndrome (BPS) is a chronic bladder health issue. In the healthy bladder, a natural barrier protects the bladder lining from irritating and toxic substances found in the urine. That barrier is called the glycosaminoglycan (GAG) layer. If this barrier is damaged, urine comes in direct contact with the tissues of the bladder lining and, over time, can cause damage to this tissue as well as allowing bacteria to adhere. Chronic inflammation also affects the integrity of the GAG layer. Replenishing the defective GAG layer with naturally occurring mucopolysaccharides such as hyaluronic acid and chondroitin sulphate can repair this damaged layer.

iAluRil is available as a 50ml prefilled syringe containing hyaluronic acid (1.6% – 800mg/50ml, sodium chondroitin sulphate(2% – 1g/50ml), and calcium chloride (0.87% – 440mg/50ml). It is not listed on the Pharmaceutical Benefits Scheme (PBS).

Indications:

• Interstitial cystitis/painful bladder syndrome;
• Chemical cystitis – damage to the bladder lining caused by chemotherapy;
• Radiotherapy-induced cystitis – damage to the bladder lining caused by radiation to the pelvis; and
• Recurrent urinary tract infections.

Dosage and Administration:

For bladder pain syndrome, the recommended protocol is one prefilled syringe intravesically once a week for the first month, then once every two weeks for a month, followed by once a month until remission.

One prefilled syringe is administered intravesically into the empty bladder (using a catheter). Once iAluRil is instilled into the bladder, it is held for at least half an hour to give time to bond or as long as it is practical or possible. Once it can be held no more, normal urinating can empty the bladder.

No side effects are reported other than irritation that is due to the procedure, not the product itself.

Pertuzumab is a recombinant humanised monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER-2) preventing its binding with other members of the HER family. This inhibits intracellular signalling, arresting cell growth and inducing apoptosis. Additionally, pertuzumab mediates an immune response that lyses tumour cells. Pertuzumab differs to trastuzumab, as it binds to a different extracellular region of the HER-2 antigen.

Pertuzumab has proven to show additional benefit to metastatic HER-2 positive breast cancer patients who progressed on trastuzumab. These favourable results prompted pertuzumab to be researched in the HER-2 positive neoadjuvant setting; NeoSphere clinical trial. The NeoSphere trial demonstrated that early or locally advanced HER-2 positive breast cancer patients who received pertuzumab in addition to trastuzumab plus chemotherapy (docetaxel), in the neoadjuvant setting achieved a higher proportion of pathological complete response (pCR). Given this trial data, it is important to note that pCR still requires verification as to if it can be used as a reliable primary endpoint and early indicator of benefit in neoadjuvant studies for HER-2 targeted agents.

The NeoSphere trial consisted of four treatment groups; A (trastuzumab plus docetaxel), B (pertuzumab, trastuzumab plus docetaxel), C (pertuzumab and trastuzumab) and D (pertuzumab plus docetaxel). Group B had a significantly improved pCR rate of 45.8% compared with group A (29%), D (24%) and C (16.8%). At five year follow up, Group B had the highest progression and disease-free survival, and patients who achieved total pCR in the study had longer progression-free survival than those who did not. In terms of safety and tolerability, the number of serious adverse events was similar across groups A, B and D and lowest in C.

The TRYPHAENA trial aimed to evaluate the cardiac safety of the combination of pertuzumab, trastuzumab and chemotherapy in the neoadjuvant setting for patients with early HER-2 positive breast cancer. The study concluded that the combination of pertuzumab, trastuzumab and chemotherapy resulted in low rates of left ventricular systolic dysfunction.

Published clinical trial data on the efficacy and safety of pertuzumab in the neoadjuvant setting for HER-2 positive locally advanced or early breast cancer patients has lead to worldwide prescribing of pertuzumab to extend to this scope of practice. In Australia, currently the PBAC has not approved PBS funding for pertuzumab for neoadjuvant treatment in patients with HER-2 positive locally advanced or early breast cancer. However, ROCHE has established the HerStart co-pay program, which assists patients with funding neoadjuvant pertuzumab therapy.

On the 21^st of April 2020, landmark policy changes occurred to medication review programs, allowing for Hospital-initiated medication reviews to be federally funded. These changes were in response to the ‘Interim Report: Neglect’ released by the Royal Commission into Aged Care Quality and Safety. Since this date, the government has expanded the funding of medication review programs (HMR and RMMR’s) to allow certain hospital-based doctors to refer patients directly to a community based accredited pharmacist for a comprehensive medication review.  These doctors now include; specialist physicians, palliative care physicians, specialist pain physicians, specialist psychiatrists and general practitioners.  This pathway of funding for a comprehensive medication management review is known as a “Hospital-initiated medication review” or HIMR.

Many studies have proven that discontinuity of care can occur when a patient transitions from the hospital to the community. Discontinuity of care can be due to poor communication between patients and primary healthcare professionals, particularly in relation to medication changes, contributing to medication misadventure in the post-discharge period. The Final Report: Implementing and evaluating a parallel post-discharge HMR Model, investigated the application of a HIMR system in Australia.  The Report concluded that the average time taken to conduct a HIMR (6.54±4.73 days) was less than a HMR (11.11±7.44), meaning direct referral to an accredited pharmacist is more time-efficient than through a general practitioner (previous program model). The introduction of federally funded HIMR aims to expand access to medicine management services, improve patient care and reduce medication misadventure in the immediate post-discharge period.

At the time the Federal government introduced changes to the HMR and RMMR program rules, no clear guidelines on how hospital sites should implement these changes existed. In response, SHPA created a framework (Hospital-initiated medication reviews: Hospital Pharmacy Practice Update) which provides general guidance on how ‘at risk’ patients could be identified and referred from hospital settings for a medicines review. The framework outlines the process for; screening and referral of patients, home visits, HMR reports, medication management plans and follow up.

If you wish to review the framework written by SHPA Transitions of Care and Primary Care Leadership Committee please go to: shpa.org.au.

The Therapeutic Goods Administration (TGA) is adding boxed warnings to the product information and consumer medicine information of all products containing pregabalin or gabapentin. These warnings advise that pregabalin and gabapentin pose a risk of abuse and dependence, and pregabalin may be associated with misuse.

Pregabalin and gabapentin are known as gabapentinoids. These agents were originally developed for the treatment of epilepsy but have increasingly been used in the treatment of neuropathic pain. In the 2019-2020 financial year, over 3.2 million pregabalin prescriptions were supplied on the Pharmaceutical Benefits Scheme (PBS). This is a significant increase from the almost 1.4 million prescriptions dispensed in the 12 months after pregabalin was first listed on the PBS in March 2013.

Misuse and abuse of gabapentinoids appear to be increasing in line with their increased overall use. Misuse and abuse include the self-administration of higher than prescribed doses, combining with other central nervous system (CNS) depressants, and diversion. Euphoria is listed as a common side effect of pregabalin, which may explain why this agent is liable to misuse. This effect appears to be dose-dependent, with higher doses also associated with relaxation, uninhibited behaviour, improved sociability, dissociation, and hallucinations. Euphoria was not reported during pre-marketing trials for gabapentin. However, evidence now suggests that gabapentin can produce euphoria similar to pregabalin. These effects tend to be less potent with gabapentin and have a more delayed onset. Tolerance is reported to quickly develop to the euphoric effects of gabapentinoids. This can lead to recreational users increasing the dosage, often far beyond the recommended daily maximum dose.

The Therapeutic Guidelines advise that pregabalin and gabapentin cause minimal toxicity on their own, with sedation the most common effect in single-drug poisonings. However, morbidity and mortality are significantly higher when combined with other medications. Serious breathing difficulties can occur in people taking gabapentin or pregabalin who have any of the following respiratory risk factors:

• Use of other CNS depressants, such as opioids and benzodiazepines;
• Conditions that reduce lung function, such as chronic obstructive pulmonary disease (COPD); and
• Advanced age.

Gabapentinoids have also been associated with withdrawal symptoms when abruptly discontinued. Symptoms may include insomnia, headache, nausea, anxiety, hyperhidrosis, and diarrhoea. Withdrawal symptoms have been reported following discontinuation of both long-term and short-term treatment, and may be severe in people taking high doses. It is recommended that these agents be discontinued gradually over at least one week.

The TGA advice for healthcare professionals includes:

• Check for a history of substance use disorder before prescribing a gabapentinoid;
• Regularly monitor patients during treatment, particularly those with current or past use of opioids or benzodiazepines;
• If a gabapentinoid must be prescribed with another CNS depressant, the patient should be carefully monitored for signs of CNS depression; and
• When combined with another CNS depressant, the dosage and duration of therapy should be limited to the minimum required for therapeutic effect.

Gabapentinoids have become integral to the management of neuropathic pain. The appropriate use of these agents has the potential to improve pain and reduce the need for other analgesics such as opioids. However, if a gabapentinoid is not appropriate for a patient, alternatives such as a tricyclic antidepressant or a serotonin and noradrenaline reuptake inhibitor may be considered.