Cannabinoids: access and symptom management in cancer

Cannabinoids: access and symptom management in cancer

Appetite stimulation Anecdotal reports suggest marijuana stimulates appetite AIDS/HIV dronabinol 2.5 mg bd v placebo (n=88) increase in appetite 38% v 8% (p=0.015) weight gain 2kg 22% v 10.5% (p=0.11) dronabinol maintained weight v placebo lost 0.4kg (p=0.14) Current best practice Antiretroviral therapy treatment of underlying disease Beal JE etal, J Pain Sympt Manage 1995

Appetite stimulation in cancer megestrol 800mg daily v dronabinol 2.5 mg bd v both (n=469) appetite improvement 75% v 49% (p=0.0001) 10% weight gain 11% v 2% (p=0.02) no added benefit of combination QoL improvement with megestrol and combination tolerability Jatoi A, J Clin Oncol 2002

Cancer-related pain nabiximols (2.7 mg THC & 2.5 mg CBD) v THC v placebo (n=177) multi-centre, double-blind, randomized, placebocontrolled, parallel group using strong opioids for at least one week (av. background dose: 271 mg MEQ) Johnson et al. J Pain Sympt Manage 2010

Results Statistical significant decrease in pain score: Johnson et al. J Pain Sympt Manage 2010

Results Statistical significant decrease in pain score: Clinical significance? Johnson et al. J Pain Sympt Manage 2010

Results No significant change in: background opioid dose breakthrough opioid dose number of doses total daily dose Adverse effects reported 106 (60%) patients mostly mild or moderate severity common effects: somnolence, dizziness and nausea Johnson et al. J Pain Sympt Manage 2010

Cancer-related pain nabiximols (THC and CBD) v placebo (n=360) multi-centred, randomised, double-blind, placebocontrolled Results: primary end-point 30% reduction doses of opioid pain scores NOT significant NOT significantly changed NOT significantly reduced 27% withdrew before completion of study doses >11 sprays/day were not efficacious or well tolerated Portenoy et al. J Pain 2012

Drug interactions additive sedative effect highly protein bound metabolism via CYP450 isoenzymes THC 2C9 and 3A4 CBD 2C19 and 3A4 cannabis smoking induction CYP1A2 additive tachycardic effects prostaglandin processes Grotenhernmen, Clin Pharmacokinet 2003; Stout, Drug Metab Rev 2014; Bridgeman, Pharm & Ther 2017

Access to cannabis based products for medicinal purposes in WA

Considerations prior to prescribing Based on patient and symptom to be managed determine: product e.g. THC, CBD or combination (various proportions available) formulation e.g. oil, oil-filled capsule, oromucosal solution, solution for vaporisation initial dose, titration schedule and maximum dose

Contraindications under 25 years personal or family history of psychosis substance abuse disorder current or past cannabis misuse disorder pregnancy or breast-feeding Cautions cardiovascular or respiratory disease anxiety or mood disorders taking high dose opioids or benzodiazepines Health Canada 2013

Regulatory pathways Operate concurrently Federal and State Therapeutic Goods Administration (TGA) Regulate: supply (licensing, quality, safety and efficacy) import & export manufacturing advertising WA Department of Health (DoH) Regulate: prescribing dispensing administering transporting storage

1. Is the product licensed in Australia? (And if so, is licensed product available in Australia?) Currently, answer is NO Apply for authority to prescribe via TGA Special Access Scheme (SAS) Category B if approved product can be obtained from imported product available in Australia Category A prescriber will need to import (this will require an importation permit from Office of Drug Control) www.tga.gov.au/form/special-access-scheme www.odc.gov.au/licence-and-permit-application-forms

2. Which Schedule classification is the product? Cannabis based products are classified as Schedule 8 (controlled drugs) e.g. dronabinol, nabiximol, tetrahydrocannabinol (THC) prescribing requires approval by WA Department of Health (DoH) Cannabis based products that contain 2% THC are classified as Schedule 4 (prescription only) e.g. cannabidiol (CBD) can be prescribed and dispensed as regular prescription medicine (do not require WA DoH approval)

2.1. Schedule 8 products for patients with Multiple Sclerosis Notification pathway: Neurologists and Rehabilitation Specialists can apply to WA DoH to be an Approved Prescriber When approved, may prescribe cannabis based products (TGA licensed for MS treatment) without seeking individual authorisation Provide a Notification of Treatment Form to the DoH http://ww2.health.wa.gov.au/articles/a_e/cannabis-based-products

2.2. Schedule 8 products for other patients Authorisation pathway: Specialists can apply to prescribe for individual patient for indication within their speciality field (eg. post-chemo nausea & vomiting by Oncologists & Haematologists) Application must be accompanied by: treatment reason clinical, substance abuse/misuse and psychiatric history management and monitoring plan patient consent form http://ww2.health.wa.gov.au/articles/a_e/cannabis-based-products

Summary 1. Cannabis based products in pharmaceutical forms are legal to prescribe and dispense in WA 2. Products that are not registered therapeutic goods require approval of the Therapeutic Goods Administration 3. Schedule 8 products require approval from the WA Department of Health

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