Neurology Central

Is there a role for pharmacogenetics in the dosing of fentanyl?

Fentanyl is one of the most frequently used opioids for the treatment of severe chronic and acute cancer-related pain. It is the opioid of first choice in patients with renal impairment [1] and seems to be related with a lower incidence of severe constipation than other opioids [2]. Furthermore, it is available in various patient-friendly products for different clinical situations. The fentanyl patches result in continuous delivery of fentanyl during 72 h and are therefore ideal for the treatment of chronic severe pain. The formulations for buccal, sublingual or nasal delivery of fentanyl are, on the contrary, ideal for the management of acute exacerbations of pain, whereas the fentanyl solutions for intravenous or subcutaneous administration are ideal for tailored pain control in the clinic, for example, in the postoperative setting. Despite these, at first sight, practical fentanyl products, adequate pain relief without serious adverse effects is only reached in 75–90% of the patients [3,4]. Furthermore, large interindividual differences are found in the daily dosages needed to achieve pain control even in opioid-naive patients [3,4]. Some of this variation in response can be explained by pharmacokinetic variation, which also vary largely between individuals [5,6]. Only a relatively small part of this variation can be explained by known covariates like age, comedication, impaired liver function, BMI and heating of fentanyl patches (extensively reviewed by Kuip et al. [7]). Pharmacodynamic variation caused by genotypes in receptor signaling or pain modulators, thereby effecting pain sensitivity and opioid-induced effects, may also play an important factor that is not completely unraveled [8]. These different mechanisms suggest that baseline pharmacogenetic screening before initiation of treatment may serve as a helpful diagnostic tool to predict the individual response to fentanyl. 
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