Fentanyl transmucosal system

If disturbances of gastrointestinal function prevent the use of oral sustained-release morphine, the fentanyl transdermal system (fentanyl patch) can be used over long periods. Furthermore, buccal transmucosal fentanyl can be used for short episodes of breakthrough pain (see Alternative Routes of Administration). Administration of strong opioids by nasal insufflation has been shown to be efficacious, and nasal preparations are now available in some countries. Approval of such formulations in the USA is growing. In addition, stimulant drugs such as the amphetamines have been shown to enhance the analgesic actions of the opioids and thus may be very useful adjuncts in the patient with chronic pain. 

Dosages and routes of administration For acute (postoperative) pain and for anesthesia, fentanyl is given by the intravenous route. For pre-medication in anesthesia and for break-through pain the compound can also been given as an oral-transmucosal formulation (Ashburn and Streisand, 1994). A transdermal patch has been developed for chronic pain treatment (Jeal and Benfield, 1997 O Siordin, 1998). The intravenous doses for premedication are 50-100 pg, oral-transmucosal systems contain 200-400 pg and patch formulations have a delivery rate of 25-100 pg/h. 

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

Figure 15 Transmucosal fentanyl drug delivery system Actiq .

Iontophoresis techniques (i.e., the use of electric current to facilitate transdermal delivery) have also been advocated as a way to enhance transdermal opioid delivery to the systemic circulation.11 By varying the amount of electric current, iontophoresis may ultimately allow the patient to control the rate of transdermal administration of the opioid.10,76,78 Finally, certain opioids such as fentanyl can be administered systemically via lozenges or a lollipop that dissolves in the mouth (transmucosal delivery), or via nasal spray (intranasal administration).21,54 It will be interesting to see if these newer methods of administration will gain widespread acceptance in the future. 

Oral transmucosal fentanyl citrate has two advantages it is more acceptable as a flavored lozenge than an oral elixir or tablet would be, especially in children, and 25% goes directly into the systemic circulation without first-pass metabolism (SEDA-20, 77). Its main adverse effect is dose-dependent nausea and/or vomiting, which occurs in 25-50% of patients. In a double-blind, placebo-controlled comparison of oral transmucosal fentanyl citrate (10 pg/kg) and oral oxycodone (0.2 mg/kg) in outpatient wound care procedures in 22 children, there were similar outcomes and no adverse effects in either group (40). 

Metabolic pathways fentanyl buccal tablets have an absolute bioavailability of 65% following oral administration, compared to an absolute bioavailability of 50% following oral administration of fentanyl oralet. The difference is mainly due to the fact that 50% of the total dose administered of fentanyl buccal tablet is absorbed transmucosally vs. 25% of fentanyl oralet. The remaining half of the total dose of fentanyl buccal tablets and 75% of the total dose of fentanyl oralet is swallowed and undergoes more prolonged absorption from the gastrointestinal tract. About 1/3 of this amount (25% of the total dose) escapes hepatic and intestinal first-pass elimination and becomes systemically available. Therefore, a unit... 

R. Nave, H. Schmitt, L. Popper, Faster absorption and higher systemic bioavailability of intranasal fentanyl spray compared to oral transmucosal fentanyl citrate in healthy subjects. Drug Delivery 20 (2013), p. 216-223. 

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