It is important to document in detail for medico legal protection for ‘unapproved’ medical cannabis products accessed via the Special Access Scheme or Authorised Provider pathways.
The patient is to be assessed from a wholistic perspective identifying their potential risks and required precautions when being prescribed any form of cannabinoid-based medicine.
Consider:
Cannabis medicine products containing THC are generally not appropriate for people with:
“Plasma THC and CBD concentrations may be increased or decreased when co-administered with medications that inhibit or induce enzymes involved in the metabolism of THC and CBD.” ACRE 2021
Medical cannabis or cannabinoid-based medicines can range from one active ingredient to a combination of many cannabinoids and terpenes extracted from the plant or an isolate enriched with terpenes or other compound.
The following are excerpts from the Australian Centre for Cannabinoid Clinical and Research Excellence Prescribing Guidances (https://www.australiancannabinoidresearch.com.au/resources)
‘Enzyme Inhibition or Induction The cytochrome P450 (CYP) enzymes CYP2C9 and CYP3A4 play a significant role in the metabolism of THC26. Pharmacogenetic data also supports CYP2C9 being a significant contributor to THC metabolism27. CBD is primarily metabolised by CYP2C19 and also CYP3A426 . Other CYP enzymes including CYP1A1, CYP1A2, CYP2C9, CYP2D6 and CYP3A5 may also play a role in CBD metabolism28,29’
‘Induction or inhibition of these CYP enzymes may affect the pharmacokinetics of THC and CBD.’
‘It is possible that other drugs which are inhibitors or inducers of the enzymes CYP3A4, CYP2C9 and CYP2C19 may affect the pharmacokinetics of THC and CBD. Care should be taken when prescribing such medications, during dose modifications or when discontinuing these medications in patients taking cannabinoids. For further information on drugs which are CYP inhibitors and inducers please refer to resources such as the Australian Medicines Handbook .’ (https://www.racgp.org.au/racgp-membership/member-offers/australian-medicines-handbook)
‘…caution should be exercised when considering prescribing cannabis products with medications that undergo significant metabolism by CYP2C19, CYP2C9 and CYP1A2 or by UGT enzymes due to the possibility of altered disposition32. Narrow therapeutic index (NTI) drugs which are metabolised by these enzymes should be closely monitored.’
‘Patients should also be informed of the possibility of drug-drug interactions when cannabinoids are co-administered with other medications, particularly with NTI drugs.’
Brown and Winterstein reviewed CBD’s potential for adverse drug events and drug-drug interactions (https://www.mdpi.com/2077-0383/8/7/989) whilst considering the underlying indications for CBD, the medications used for those disorders in the context of ADE/DDI risk, and proposed general recommendations for co-prescribing (i.e., reduced dose) or avoiding certain combinations. The table below outlines DDI between CBD and enzyme substrates, inhibitors, or inducters.
Brown J.D, Winterstein A.G (2019) Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use, J. Clin. Med. Vol. 8, Page 989
Weekly monitoring of the patient during the initiation phase and then ongoing clinical reviews assists in gauging symptom control, identifying any adverse drug outcomes especially for drugs with a narrow therapeutic range or known drug to drug interactions or impact on liver function.
Arnold J.C (2021) A primer on medicinal cannabis safety and potential adverse effects, Australian Journal of General Practice, Vol. 50, Iss. 6, doi: 10.31128/AJGP-02-21-5845 < https://www1.racgp.org.au/ajgp/2021/june/a-primer-on-medicinal-cannabis-safety-and-potentia >
Arnold J.C, Nation T, McGregor I.S. (2020) Prescribing medicinal cannabis. Aust Prescr Vol. 43, p.p 152-9. Doi: er10.18773/austprescr.2020.052 < https://www.nps.org.au/australian-prescriber/articles/prescribing-medicinal-cannabis >
Brown J.D, Winterstein A.G (2019) Potential Adverse Drug Events and Drug–Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use, J. Clin. Med. Vol. 8, Page 989, doi:10.3390/jcm8070989 < https://www.mdpi.com/2077-0383/8/7/989 >
MacCallum C.A, Lo L.A, Boivin M. (2021) “Is medical cannabis safe for my patients?” A practical review of cannabis safety considerations, European Journal of Internal Medicine, Vol. 89 p.p.10-18 < https://pubmed.ncbi.nlm.nih.gov/34083092/ >
Martin J, Graham M, Lucas C, Schneider J, Patel J, Ryan J, Lycett M. (2021) Prescribing Guidance: The prescribing cannabis medicines for management of spasticity, Ver.3, Australian Centre for Cannabinoid Clinical and Research Excellence, < https://www.australiancannabinoidresearch.com.au/media/1120/nsw-prescribing-guidance-spasticity-v3.pdf >
Martin J, Graham M, Lucas C, Schneider J, Patel J, Ryan J, Lycett M. (2021) Prescribing Guidance: The prescribing cannabis medicines for management of chronic non-cancer pain (CCP), Ver.3, Australian Centre for Cannabinoid Clinical and Research Excellence, < https://www.australiancannabinoidresearch.com.au/media/1117/nsw-prescribing-guidance-cncp-v3.pdf >
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