Sammi: Welcome to this evening’s Understanding Cannabis Medicines (part 3): Support Services for GPs webinar. My name is Samantha and I am your host for this evening. Before we get started, I would just like to make an Acknowledgement of Country. We recognise the traditional custodians of the land and sea on which we live and work and we pay our respects to Elders past and present.
So moving along I would just like to introduce our presenters and our facilitator for this evening. So, we are joined by our facilitator, Dr Harry Nespolon this evening who I am sure all of you are familiar with. Harry is the current President of the RACGP and the Director of the Northern Sydney Local Health District and Principal of two general practices in Sydney. Harry is also a Fellow of the RACGP and has been a quality assurance examiner for the OSCE component of the Fellowship Exam for 10 years.
Now to our presenters. Dr Catherine Lucas is a dual accredited Clinical Pharmacologist and Nuclear Physician and Pharmacist. She holds positions with both the University of Newcastle and Hunter New England Local Health District as a Staff Specialist, Clinical Academic and as a Medical Educator of a State-wide expert consultative clinical pharmacology service on the use of cannabis medicines.
And our second presenter for this evening is Myfanwy Graham, who is a Senior Specialist Medicines Information Pharmacist based at the New South Wales Cannabis Medicines Advisory Service and instrumental in its inception and development. Additionally, Myfanwy holds an academic appointment at the University of Newcastle and has also had multiple peer reviewed publications. So thank you to our facilitator and presenters for joining us this evening.
Alrighty, so I will hand over to our facilitator Harry now to take us through the learning outcomes for this evening, and we will then jump over to Catherine and Myfanwy to begin the presentation.
Harry: Welcome everyone. I hope that you are all having a good night. The learning outcomes are, that by the end of the online event you should be able to identify the role of the New South Wales Cannabis Medicine Advisory Service and the context in which the Service may assist prescribers, list sources of appropriate information about cannabis medicines including product formulation, dosing regimens and potential interaction with other medicines, source scientific evidence and clinical guidance for a range of health conditions in patients and discuss the adverse events, monitoring and reporting pathways. I hope that you do enjoy tonight’s presentation and I will hand you over to our presenters for the night.
Myfanwy: Good evening everyone, it is fantastic to see so many webinar participants joining us online. My name is Myfanwy and I am a Senior Pharmacist in the New South Wales Cannabis Medicines Advisory Service. I am also joined this evening by the Medical Director of the Service, Dr Catherine Lucas. By the end of the webinar this evening, we hope to have provided further information about the following topics: A quick review about access to cannabis medicines in New South Wales, an overview about the New South Wales Cannabis Medicines Advisory Service, cannabis medicines formulation, dosing and interactions, clinical guidance and support, approach to patient-centred care, measuring therapeutic effects, reporting adverse events, the Australian Centre for Cannabinoid Clinical and Research Excellence, and New South Wales clinical trials.
In looking at this webinar, please refer to the two previous RACGP webinars, Understanding Cannabis Medicines part 1 and part 2, for background on evidence, access and prescribing.
So, Sativex which is nabiximols is the only cannabis medicine on the Australian Register for Therapeutic Goods for the sole indication of moderate to severe specificity in multiple sclerosis. All other cannabis medicines are unregistered and are considered experimental. The unregistered cannabis medicines are compliant with the Therapeutic Goods order number 93 which specifies minimum quality requirements for cannabis medicines. There are no pre-determined conditions for which a cannabis medicine can be prescribed. Authorisation to prescribe a cannabis medicine occurs on a case by case basis. All applications to prescribe must be accompanied by clinical evidence. All registered conventional medicines and non-pharmacological therapies need to have been trialled or deemed inappropriate due to contraindications or lack of response. For example for pain, has the patient been referred to a multidisciplinary pain clinic?
Important considerations for unregistered cannabis medicines include the following: Safety and efficacy data may not be available or it may not have been reviewed by an Australian regulator. Internationally the supply of cannabis medicines is increasing which may impact on ongoing supply. Other than Sativex which is nabiximols, which is registered for mild to moderate spasticity in MS, there is no product information or consumer medicines information which has been reviewed by an Australian regulator. The decision is solely the responsibility of the prescriber as per off label use of registered medicines. It is important to review available evidence and evaluate the risk versus the benefits persistent with the approach taken with off label prescribing of any drug.
Documented informed consent would be imperative whereby the patient would be informed of the nature of the treatment and potential harms, and where the product is an unregistered medicine, that is has not been assessed for efficacy or safety by the TGA.
The pathways for unregistered medicines include clinical trials and we have included a link to The Australian and New Zealand Clinical Trials Registry which has a search function to locate the clinical trials investigating the use of cannabis medicines. Some useful search terms other than cannabis include cannabinoids, tetrahydrocannabinol, cannabidiol, nabiximols, dronabinol and nabilone when searching the registry. The special access scheme which includes category A or category B and it is important to note that under category A, only imported cannabis medicines can be prescribed. And there is no true advantage to using category A for cannabis medicines.
Authorised prescriber pathway involves ethics committee endorsement of a particular treatment plan. Authorised prescribers can prescribe a specific cannabis medicine for individual patients with a particular indication in their immediate care without further TGA approval. However, they do need to report the number of patients treated to the TGA on a six monthly basis.
And the New South Wales Cannabis Medicines Advisory Service was established in January 2018 and is the first of its kind advisory service for cannabis medicine to my knowledge, in the world. The service is available to New South Wales practitioners only and is not nation-wide. The service offers free clinical support and advice for medical practitioners considering prescribing a cannabis medicine. So we provide information about cannabis medicines, their formulations, dosing, potential drug interaction, and advice tailored to patients’ specific clinical context, current scientific evidence to support applications, guidance tools for monitoring, potential therapeutic and adverse effects and information on open clinical trials using cannabis medicines.
We have included some statistics from our service, so over 590 enquiries have been received to date and the top three enquiry groups include GPs, around 30%, other specialists at 24%, pharmacists at 20% and the top three most common enquiries were medical practitioners with a patient in mind requesting patient-specific clinical guidance and evidence reviews. We also addressed enquiries about the approvals process and application support and many enquiries related to product selection including what doses are available and administration routes. The average response time is 24-48 hours for end of life and 3-5 business days for non-palliative enquiries, providing all required information has been provided. And many enquiries are clinically complex patient specific enquiries with multiple comorbidities and medications.
So it is important to clearly delineate the difference between cannabis medicines which are also known as medicinal cannabis and street or black market cannabis. Cannabis medicines are standardised medical grade cannabis plant derived, semi-synthetic or synthetically produced cannabinoid products developed for medicinal use. Cannabis medicines conform with the therapeutic goods order number 93 standard for medicinal cannabis also known as TGO 93, which specifies minimum quality requirements for cannabis medicines. Street cannabis is also known as black market cannabis. It is accessed from unregulated sources and is illicit. The composition of the street cannabis product is unknown and it may contain harmful substances. So historically there have been reports of bacterial contamination. There have been several reports of opportunistic infection with fungi in immune-compromised patients with the finding that cannabis was contaminated by fungus spores. Pesticide use for cultivation of cannabis crops is well-established and human consumption of pesticides may confer substantial sequelae including malignancy, developmental issues, reproductive, neurological and endocrine disorders. And there are three pathways by which street cannabis may be contaminated with heavy metal substances including soils, during processing and post-processing adulteration whereby metals may be added to the preparation to increase weight and thereby appreciate its street value.
So moving on to cannabis medicine formulation, there are a variety of cannabis medicine dosage forms and there are a number of considerations in selecting a dosage form. Many cannabis medicines are in oil form, and other dosage forms include capsules and tinctures. It is important to consider the content of the carrier oil and potential allergy or previous hypersensitivity, for example some of the cannabis medicines are in a sesame oil and if a person has sesame allergies. And tetrahydrocannabinol and cannabidiol are both highly lipophilic and have poor oral viability, estimated to be as low as 6%. Oral THC formulations exhibit variable absorption and undergo extensive hepatic versus past metabolism resulting in lower peak plasma THC concentration relative to inhalation. And a longer delay to reach peak concentration. Following oral administration CBD a similar plasma concentration time profile to the oral THC has been observed. And based on this profile, oral formulations may be useful for patients requiring symptomatic relief over a longer period.
Oral mucosa preparations undergo rapid absorption via the oral mucosa and hence is useful for symptoms requiring rapid relieve. So producing plasma drug concentrations higher relative to oral, but reduced relative to inhaled THC. However part of the dose may be swallowed and orally absorbed. Flos or granulate refers to the whole dried female flower, which is administered by vaporisation and there are no devices on the Australian Register of Therapeutic Goods and there are potential restrictions on where the product can consumed as well. So, cannabinoids administered by inhalation exhibit similar pharmacokinetics to those administered intravenously. After inhalation, peak plasma concentration for first THC and CBD are attained rapidly within 3-10 minutes and maximum concentrations are higher relative to oral ingestion. The pharmacokinetics are vaporised and smoked cannabinoids are comparable.
Transdermal administration of cannabinoids avoids the first pass metabolism, but their extremely hydrophobic nature limits diffusion across the aqueous layer of the skin. Studies with human studies skin have determined the permeability of CBD to be ten-fold higher than of delta-9 THC and delta-8 THC, less potent but more stable relative to delta-9 THC and consistent with CBD as being relatively lipophilic. I should note that throughout the slides this evening when we refer to tetrahydrocannabinol, we are referring to delta-9 tetrahydrocannabinol.
We will move on to TGO 93 compliant formulations. So we frequently get asked about what cannabis medicines are available and there are a variety of cannabis medicines available with different strengths, pharmacokinetics and dosing regimens. This slide outlines the strength of various formulations which are available, however please note there are a variety of products available with different strengths, including cannabidiol predominant products including liquid formulations with strengths ranging from 1.2 mg per ml to 150 mg per ml. CBD capsules containing 50 mg per capsule, and CBD topical balm 5%. There are also combined Tetra Hydra Cannabinol and Cannabidiol 1:1 liquid formulations with strengths ranging from 8.33 mg per ml of both THC and CBD up to 25 mg per ml of both THC and CBD. There are also combined THC and CBD capsules as well. When referring to THC throughout this presentation, it is important to note that it is in relation to Delta 9 Tetra Hydra Cannabinol. THC predominant liquid formulations range in strength from 10 mg per ml to 25 mg per ml. There are also granulate flos products, which are THC predominant ranging from 13.5% to 22% and a combined THC and CBD product and also CBD predominant products as well.
So moving on to general principles of dosing, the dose and frequency of administration is individualised for the patient and indications. And the following general principles should apply in relation to dosing. The starting load in terms of dose and frequency and go slow, titrating according to effect whilst monitoring for side effects and due to dose titration in an initial trial period of three months. First titration of an initial trial period of three months is suggested to determine patient response.
The following table on the next slide, is derived from the Sativex product information. And this is a dose titration guidance and practitioners may titrate more slowly depending on patient response. The patient is commenced on one spray in the evening and on day three this is increased to two sprays in the evening. On day five, this is increased to one spray in the morning and two sprays at night and is incrementally increased as per the dosage guidance table up to a maximum of 12 sprays per day until they achieve optimum symptom relief.
So continuing with dosing, New South Wales CMAS also performs literature reviews to determine whether there is indication-specific dose guidance data. So for many indications there is limited evidence but there is data about dosing. The following dosage guidance is derived from the TGA guidance for the use of medicinal cannabis for the prevention and management of nausea and vomiting in Australia. For example, for dronabinol, this would equate to 2.5 mg up to 20 mg between one and four times a day.
And we will discuss now the costs of cannabis medicines. So although cannabis medicines are not covered by the Pharmaceutical Benefits Scheme, they are comparable in cost to street cannabis. So for palliative indications, the approximate cost is $21 to $70 per week for cannabis medicines which equates to around $3 to $10 a day and a recent Australian survey has indicated that there is a mean spending of $68.60 per week on street cannabis which equates to around $9.80 a day.
Another important consideration is that THC is generally not appropriate for known or suspected personal or family history of a significant psychiatric illness, as current evidence supports the association between THC and an increased risk of psychosis and schizophrenia. Also unstable cardiovascular disease due to sympathomimetic effects including tachycardia and has been associated with myocardial infarction and stroke. In addition, pregnancy due to reports of pre-term labour and low birth weight, and cannabinoids can also pass into breast milk. Other considerations include significant renal herpetic illness due to increased bioavailability of THC and the prolongation of half-life, potential for dependence of withdrawals, age less than 25 years, specifically with THC due to the potential neurocognitive effects. Epilepsy and seizures as THC may be pro-convulsive. Conversely research is ongoing in relation to the use of CBD for the treatment of epilepsy. In older patients, pharmacokinetic parameters may be altered such as renal and hepatic impairment and relative increase in body fat. Consequently this can result in an increased bioavailability of THC and prolongation of half-life. Hypersensitivity to cannabinoids or excipients such as sesame carrier oil needs to be considered and an important consideration is also driving and operating heavy machinery which is an absolute contraindication. And there is a prescribed cannabis medicine and a prescribed fitness to drive fact sheet available.
So we will move on now to drug interactions, for drug-drug interactions, which may be pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions result in a change, so either an increase or a decrease in blood levels of either one or both drugs, whilst pharmacodynamic interactions relate to the observed effect. Pharmacodynamic interactions may be interactions between co-administered drugs which produce the same effect and this effect is augmented. For example the enhanced sedative effect seen when benzodiazepines are administered with alcohol. Co-administration of medicines may also augment the adverse effects of drugs with similar side effects. Some added effects may be desirable such as antiemetic effects or analgesic effects.
So let us look at a couple of examples with cannabis. So we see additive effects when co-administered with other medications. There is clear evidence that THC can enhance sedatives, psychomotor, respiratory and other effects as seen with depressants and alcohol. And when co-administered with anti-cholinergic agents, cocaine or sympathomimetic drugs, cannabinoids which are known to produce tachycardia, have been shown to enhance the tachycardic and hypertensive effects of cannabinoids.
There has been at least one case reported of a patient experiencing symptoms of hypermania when marijuana was co-administered with fluoxetine and there has been at least one case reported of a possible interaction in a patient taking warfarin who regularly smoked tobacco and marijuana. There has also been a recent case reported of an interaction between warfarin and cannabidiol so therefore INR should be monitored when cannabinoids are initiated.
And looking at some of the pharmacokinetic reactions. A major source of drug interaction is via induction or inhibition of CYP enzymes. The enzymes involved in the metabolism of THC are thought to be CYP2C9 and CYP3A4, whilst those thought to be involved in metabolising CBD are CYP2C19 and CYP3A4. So CYP2D6 might possibly also be involved in the metabolism of these two compounds.
So let us look at drug interactions affecting THC and CBD. So co-administered drugs which inhibit or induce enzymes involved in the metabolism of THC and CBD may lead to either an increased blood concentrations in the case of inhibition, or decreased blood concentrations in the case of induction. Co-administration of ketoconazole which is a CYP3A4 inhibitor with THC was observed to increase the plasma THC concentration by 20%. The other commonly used drugs are also 3A4 inhibitors and theoretically these agents such as clarithromycin, itraconazole, might also produce a similar effect to ketoconazole.
Rifampicin is an enzyme inducer, particularly 3A4 and this drug, when co-administered with THC was observed to reduce THC concentrations by 40%. When co-administered with CBD, CBD concentrations were decreased by 20% and there are other commonly used drugs and compounds such as St John’s Wort, phenytoin, carbamazepine which are inducers which may theoretically have a similar effect. And on the previous slide, it was noted that CYP2C9 is involved in the metabolism of THC. Genetic variability in enzymes may also influence the THC concentrations achieved after administration of THC. THC concentrations were observed to be three times higher in poor metabolisers than in people with what is classed as normal metabolism. However, there are no specific studies that have looked at co-administration of cannabis with CYP2C9 inducers or inhibitors. But we can anticipate that there may be an effect. While CYP2C19 has been shown in vitro work to be involved in metabolism of CBD, a study with omeprazole, a CYP2C19 was co-administered with CBD did not show increased CBD levels in the blood.
So in terms of the effect of cannabinoids, THC and CBD on the metabolism of other drugs, in vitro work has suggested that THC may inhibit CYP2C9 and CYP3A4, while CBD is shown to be an inhibitor to various extents for a range of CYP enzymes, including the ones listed on this slide. From an induction perspective, in vitro work suggests minimal induction of CYP by THC and CBD and overall the clinical relevance of recreational or medicinal use of THC and CBD concomitantly with other medications remains poorly described or unknown. So hence the need for caution.
It is also important to note that cannabis medicines are not administered by smoking. However, there are drug interactions related to cannabis smoking. The potential exists for drug interactions to occur when patients smoke cannabis, so smoking tobacco and smoking marijuana induce CYP1A2 enzyme and induction of CYP1A2 has been observed to lead to reduced clozapine and olanzapine levels in smokers compared to non-smokers. An important point to consider is what happens when a smoker who is on a drug which is a CYP1A2 substrate ceases smoking and the enzyme is no longer induced. There may be an increase in plasma drug levels which may result in adverse effects. Therefore patients who smoke cannabis and are being treated with a CYP1A2 substrate drug such as an anti-psychotic agent, should be regularly monitored with regards to their smoking consumption so it may be adjusted if required.
So drugs used for immunosuppression in transplant patients may also potentially be affected by co-administered cannabis. The dose/trough ratio is observed to be decreased in patients exposed to marijuana, suggesting inhibition of CNI metabolism with a magnitude of effect being greater cyclosporin A than tacrolimus. And there has also been a case reported of suspected tacrolimus toxicity in a stem cell transplant patient who was concurrently using oral marijuana. Proposed mechanisms of interaction include inhibition of CYP3A enzymes and possibly an interaction by the efflux pump P-glycoproteins which play a major role in the absorption of tacrolimus.
Of importance is the observation of drug interaction between CBD and clobazam and another anticonvulsant drug, topiramate. With increasing dose of CBD, serum concentrations of topiramate increased whilst concentrations of the active metaboliser desmethylclobazam increased. This increase in active metabolite concentrations may be due to inhibition of CYP2C19 which is primarily responsible for the metabolism of N-desmethylclobazam. This prolongs the elimination half-life of the metabolite resulting in accumulation of the metabolite in the body. There are TGA guidance documents which are available from the TGA website and include topics such as multiple sclerosis, palliative care, epilepsy and paediatric and young patients, nausea and vomiting and chronic non-cancer pain. And the New South Wales Cannabis Medicines Advisory Service provides clinical guidance and support on use of cannabis medicines to treat a range of health conditions and symptoms.
Catherine: I would like to take this opportunity now to discuss the importance of patient-centred care, particularly in the general practice context. The patient’s current treating medical practitioner with whom there is already an established therapeutic relationship is the most appropriate person to prescribe and subsequently monitor the outcomes of cannabis medicine if applicable, in a shared care model following consultation and ideally in consensus with their other treating medical practitioners and patient care team. All members of the patient’s care team should be aware of the trial of therapy with a cannabis medicine. The reason that we deem the current treating medical practitioner to the most appropriate prescriber is that they have a comprehensive understanding of the patient’s medical history including their relevant family history particularly with regard to psychiatric adverse effects and their patient’s lifestyle and encompassing a holistic care model for the patient, and to communicate adequately within the multidisciplinary team based model of care to ensure that all practitioners are aware of the therapy. And, CMAS is here as the first point of contact for general practitioners considering prescribing a cannabis medicine and we strongly encourage medical practitioners to work in partnership with us and their patients regarding their cannabis medicines. And just a reminder that we are a free Government funded service here to help both you and your patients by providing you with the relevant information that you need to support your application with evidence.
Myfanwy: And it is also important to consider the patient’s social circumstances, not just the patient. So we are considering looking at obligations to patients. So patients using cannabis should be warned not to drive or to perform hazardous tasks such as operating heavy machinery, because impairment of mental and physical coordination resulting from the use of cannabis or cannabinoids may decrease their ability to perform such tasks. Another important note is that some cannabis medicines require refrigerated storage and there are differences related to cannabis medicine possession in different countries and it would be important for the patient to contact the Embassy of the country they are considering travelling to prior to travelling.
We will now look at measuring therapeutic effects. So another important consideration is measuring of potential therapeutic effects and adverse effects. It is important to negotiate pre-defined measures of success with patients prior to commencement of therapy in relation to their symptoms. Adverse effects may occur at different dose levels in different patients and careful monitoring needs to be implemented for adverse effects including but not limited to abdominal pain, dizziness, euphoria, nausea, paranoid reaction, drowsiness, abnormal thinking, vomiting, asthenia, balance problems, confusion and so on.
In addition to adverse effects, consider non-responsiveness, patient reported improvements may not be matched by functional gains which is a really important consideration. And consider quantity cognitive testing. So cognition potentially may be sacrificed to alleviate other symptoms and it is important to monitor.
We have included a couple of examples of how therapeutic effects may be measured. One in pain and one in palliative care. So firstly, treatment goals need to be clearly documented and discussed with the patient. Secondly, they need to be related to the symptoms for which the patient is prescribed cannabis medicine and if possible, they should also be measurable. So for example in pain, this may include the use of pain scales and in palliative care, symptom assessment scale.
In relation to adverse effects, it is important to note that adverse effects may become apparent after commencement or after change in dose. Adverse effects may be related to other concurrent medications and doses of these medicines should be adjusted as appropriate. Adverse effects, even those anticipated, must be reported to the TGA, including dependence and withdrawal symptoms. And if clinical review determines that the patient is not deriving benefit or is experiencing toxicity, the cannabis medicine treatment should be discontinued.
For TGO92 compliant cannabis medicine, it is important to report even anticipated adverse effects. The notifier or prescriber needs to report to the TGA within 15 calendar days and also to the supplier and importer. The prescriber has an obligation to notify the TGA as a condition of their special access scheme approval and for life threatening adverse effects, the notifier or prescriber needs to call an ambulance to transfer the patient to an emergency department. For serious but not life threatening adverse effects, the notifier or prescriber needs to contact the New South Wales Poisons Information Centre team for clinical toxicology guidance.
Adverse effect reporting pathways for street cannabis are dependent on how the product is labelled. So, for example if it is labelled and sold as a medicine, it needs to be reported to the New South Wales Chief Pharmacist Unit. If it is labelled as synthetic, it needs to be reported to New South Wales Poisons Information Centre and if it is labelled or sold as food, it needs to be reported to the New South Wales Food Authority.
We would also like to take the opportunity to discuss the Australian Centre for Cannabinoid Clinical and Research Excellence, also known as ACCRE, which is based at the Hunter Medical Research Institute in Newcastle. And ACCRE is involved in the development of the prescribing protocols for cannabis medicines, so both in palliative care and non-palliative care indications. They are involved in the establishment of the New South Wales Cannabinoid Blood Analysis program, involved in standardised data collection about safety and efficacy of cannabis medicines, and are currently developing the New South Wales CARE trial for palliative care patients to be launched in 2019.
With New South Wales clinical trials, the New South Wales Government has committed nine million dollars towards three clinical trials to: evaluate the safety and effectiveness of cannabis medicine, reduce seizures in children with severe treatment-resistant epilepsy in partnership with the Sydney Children’s Hospital Network, improve appetite and appetite related symptoms in adult palliative care patients with advanced cancer, prevent chemotherapy induced nausea and vomiting in adult patients where standard treatments have proven ineffective, and as referenced earlier, the Australian and New Zealand Clinical Trials Registry is a really good resource for locating clinical trials related to cannabis medicine.
A few notes about our service. So the New South Wales Cannabis Medicines Advisory Service as Catherine mentioned is the first point of contact for doctors considering prescribing a cannabis medicine for their patients. The service is available 9 a.m. to 5 p.m. Monday to Friday and we have included our phone number and email contact details here.
Catherine: So we will take the opportunity to refresh the learning outcomes of this evening, which include identifying the role of the New South Wales Cannabis Medicines Advisory Service, and also the context in which we may be able to assist prescribers, to list the sources of appropriate information about cannabis medicines including the product formulation, dosing regimens and health conditions in patients which we are able to assist you with, and to discuss adverse events, monitoring and reporting pathways which we have touched on previously.
Sammi: Thanks for going over that, Catherine. We just lost our audio there for a second. Harry had a question that he wanted to jump in and ask you guys about, okay?
Harry: So I just wondered if we could go back. If we were giving advice to patients who were driving, as I understand it if they ask us if they are tested, they will still come up positive. I was just wondering if you could talk about that a little bit more?
Catherine: Our primary concern in the context of driving is paramount to the testing that the actual patient’s cognitive impairment and subsequent risk to themselves and other road users and pedestrians, so regardless of whether the testing is involving the cannabinoids that they are potentially being prescribed, both tetrahydrocannabinol and cannabidiol, there is a misconception that the latter in terms of having less cognitive adverse effects is safe to drive with, and that is certainly not the case. There are reports of drowsiness and impairment also with CBD, so it is emphatically an absolute contraindication, not just because of the positive testing which can be positive for a very protracted period of time, particularly when patients redistribute from their adipose stores. And because that timeframe is unpredictable and very patient-specific depending on things like body habitus, consumption pattern, there is no safe timeframe to give the patient, so absolute contraindication. Patients must be advised not to drive and you can support that advice with the written fact sheet that is available free online specifically pertaining to it that has been developed by the Ministry of Health.
Harry: And just to underline that, writing a letter will not prevent them from running into problems.
Catherine: Absolutely. There is certainly no exemptions. So the equivalent of any other medication, say if someone is on a high dose opioid, regardless of whether it is legally prescribed, they are not going to be covered with a medical letter. That does not negate the impairment and the risks. That also applies to the clinical trial context. We have had the misconception from some people that the patient is prescribed within a clinical trial context that there is an exemption for driving, but that is, yes, not the case in any circumstances.
Harry: The next issue which I just thought we might also emphasise is that the application process requires approval from both the State and the Commonwealth? Is that…?
Catherine: Sorry Harry, I understand the question was does the application to prescribe a cannabis medicine require State and Commonwealth approval? Is that correct?
Catherine: Correct. So, for the process of applying for cannabis medicines has been streamlined, whereby there is a single submission to the Therapeutic Goods Administration, so the Commonwealth level, and that is for both schedule 4 and schedule 8 cannabis medicines. If the cannabis medicine in a schedule 8 cannabis medicine, then the TGA forwards the application to New South Wales Health where they also look at the application as well. So it really is a single streamlined pathway.
Harry: And also, that when you are filling in these applications with your assistance, it still requires the patient to have come to the end of their therapeutic regime before the cannabinoids will be approved, is that correct?
Catherine: That is most definitely correct. So cannabis medicines are not a first line therapy. All registered standard therapeutic options must have been exhausted prior to the consideration of the use of a cannabis medicine, or they may have been deemed inappropriate due to adverse effects as well.
Harry: And one of the questions was about, and I am not sure if there is any work on this, but whether or not cannabinoids are good in early labour?
Catherine: If you revisit the slide that we had on precautions and contraindications, there was reference to particularly THC preparations but also cannabis medicines would not be appropriate for use in pregnant patients, so the answer in that respect would be no.
Harry: So you do not think it will give them enough pain relief.
Catherine: Well there would be risks to the patient. There would be risks in terms of potential adverse effects for the mother and the child and they cross the placenta, so there are a number of different important considerations in relation to pregnant patients, yes.
Harry: With that, I do not think we have got any other questions, and I think while we were off air here I gather you guys did go through the learning outcomes. I might just leave it open for a few more seconds to see if there are any other burning questions from the audience, because if not we might call it a night.
Sammi: Yes, let’s give it another two minutes and we will give our participants the opportunity to type some questions through now that we have a bit of time and see what comes through.
Harry: I guess one of the other questions might be, do we know how many, I think there is at least one Australian producer that is licensed that is producing cannabinoids. Is that increased recently at all?
Catherine: We are happy to advise individual practitioners on the most appropriate product, whether that be one that is available on shore or that has been sourced internationally, or locally. But the primary consideration is first whether the cannabis medicine is appropriate for the patient and then the particular ratio of THC and CBD, the cannabinoids for that patient’s indication and then at that point we would be discussing with the practitioner the most appropriate product or products and would be able to advise them as to whether they are locally or internationally produced and what is available on shore and the relevant dosing guidance for their indications.
Harry: Thank you.
Sammi: So that brings us to the end of this evening’s presentation. We thank you all for joining us and I just want to say a big thank you to our facilitator Harry and to our two presenters, Catherine and Myfanwy for a fantastic job. And that brings us to the end of the session, so thank you for joining us everybody and good night.