Fentanyl tolerance

Fentanyl transdermal system should only be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to fentanyl transdermal system 25 mcg/h. 

Do not administer fentanyl transdermal system to children younger than 2 years of age. Administer to children only if they are opioid tolerant and 2 years of age or older. 

Only use in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to fentanyl transdermal system 25 meg/h. Patients who are considered opioid tolerant are those who have been taking, for a week or longer, morphine 60 mg/day or more, oral oxycodone 30 mg/day or more, oral hydromorphone 8 mg/day or more, or an equianalgesic dose of another opioid. 

Pediatric patients initiating therapy on a fentanyl transdermal system 25 mcg/h should be opioid-tolerant and receiving oral morphine equivalents 60 mg/day or more. 

The patient who uses fentanyl repeatedly may develop a tolerance to the drug s analgesic effect. 

In addition to the development of tolerance, persistent administration of opioid analgesics has been observed to increase the sensation of pain leading to a state of hyperalgesia. This phenomenon has been observed with several opioid analgesics, including morphine, fentanyl, and remifentanil. Spinal dynorphin and activation of the bradykinin receptor have emerged as important candidates for the mediation of opioid-induced hyperalgesia. 

Eilers HM et al The reversal of fentanyl-induced tolerance by administration of "small-dose" ketamine. Anesth Analg 2001 93 213. [PMID 11429368]... 

In line with the trend towards prolonged application intervals, 3M and Purdue have started developing a fentanyl patch that is effective for 7 days. It will be interesting to see how well long-term application and occlusion at a particular site will be tolerated in comparison with the relatively good dermal tolerance of three days treatment. 

The major physiological effects of fentanyl are euphoria, drowsiness, respiratory depression, decreased gastrointestinal mobility, nausea, and muscular rigidity. People build up a tolerance to fentanyl the more they use it, causing them to need more to obtain the same effects they once received from a smaller dose. The high of fentanyl can last 10-72 hours, depending on the ingestion method, the fentanyl derivative used, and the amount taken. 

As with any narcotic, fentanyl is addictive. Because it interacts with the mu receptor, which has an effect on addiction, it is highly addictive. Fentanyl users also build a tolerance to the drug s effects, thus needing more of the drug to reach the same euphoric experiences. Building up a tolerance to the drug can be harmful to the user. As the user continues to consume more and more of the drug to achieve the same effects, an overdose becomes likely. 

Consistent with the preclinical pharmacological profile of DPI-3290, recent early clinical studies with this compound have indicated strong analgesic activity in man. These actions are dose dependent and rapid in onset, with less apparent adverse changes in saturated 02 or emesis when compared with equivalent analgesic doses of morphine or fentanyl. Patients appeared to tolerate doses of DPI-3290 well in these early studies with no dose-limiting adverse events. 

Sedation in critical care units is used to reduce patient anxiety and improve tolerance to tracheal tubes and mechanical ventilation. Whenever possible, patients are sedated only to a level that allows them to open their eyes to verbal command oversedation is harmful. Commonly used drugs include propofol and midazolam, and opioids such as fentanyl, alfentanil, or morphine. 

Transdermal fentanyl for chronic non-cancer pain control has been studied in two open trials (60,61). In a multicenter, open, randomized study of 256 patients with a history of chronic non-cancer pain, 65% preferred transdermal fentanyl, whereas 28% preferred modified-release oral morphine. Subjective pain control and quality of hfe were significantly better in the patients who used transdermal fentanyl. Despite a preference for transdermal fentanyl, more patients withdrew because of adverse effects in the first fentanyl period (16%) than in the first morphine period (9%). The difference could have been related to patients previous experience of morphine, with enhanced tolerance of its adverse effects. 

Only few transdermal products (e.g., steroidal hormone, caffeine, theophylline, fentanyl, scopolamine, nicotine, methylphenidate) have been tested or marketed for use in the pediatric population. The development of transdermal products in pediatric doses could be very beneficial for children who are unable to tolerate oral medications. The need for several sizes of patches to cover different doses needed by different subsets of the pediatric population and to avoid accidents with cutting adult patches can be a limitation. The younger, the better permeation. Hence a compromise between topical versus transdermal efficacy and safety should be sought. 

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