The CPIC guideline for opioid therapy and CYP2D6, OPRM1 and COMT was recently published in Clinical Pharmacology and Therapeutics and has now been annotated on PharmGKB. This guideline is an update to the CPIC guideline for codeine and CYP2D6, but now includes information on two other genes, OPRM1 and COMT, and a number of other opioids.
The guideline gives specific dosing recommendations for CYP2D6 and three drugs; codeine, tramadol and hydrocodone. Codeine and tramadol are not recommended for CYP2D6 ultrarapid metabolizers due to an increased risk of toxicity, nor for CYP2D6 poor metabolizers, where there is a risk of insufficient analgesia. The authors also recommend that CYP2D6 intermediate and poor metabolizers be monitored for analgesic response following the initiation of hydrocodone therapy. If patients with either of these metabolizer phenotypes fail to have an analgesic response to hydrocodone, a non-codeine or non-tramadol opioid can be considered.
Studies looking at the effects of variants in OPRM1 and COMT on opioid response were also assessed as part of this guideline update. OPRM1 encodes the mu opioid receptor, which binds to many opioids, while COMT codes for the enzyme Catechol-O-methyltransferase. COMT methlyates catecholamines and is thought to regulate pain perception. Due to the low quantity and/or quality of available evidence, the authors specifically issued no recommendations for opioid dosing based on OPRM1 or COMT variants. This is an important feature of the guideline, as testing for variants in these two genes in relation to opioid response is included in some pharmacogenomic tests.
In order to fully capture the size and complexity of this guideline, it is covered by multiple guideline annotations on PharmGKB, including extended dosing guidelines with genotype pickers for codeine, tramadol and hydrocodone. All guideline annotations can be accessed via the PharmGKB Clinical Guideline Annotations page. The full guideline manuscript, supplement and relevant implementation resources are also freely available on the CPIC website.