Fentanyl, safety

Some articles, for example, include an identical table of effective and lethal doses of high potency Fentanyl derivatives. The estimated safety margins are as high as 30,000. I could find no source for these data. I sent out several inquiries but thus far have received no definitive answers. I also discussed the questions with Harry Salem, who continues to study the toxicology of opioids at Edgewood. He is hopeful that the concomitant use of drugs tailored to suppress the effect of potent opioids on respiration may produce much safer agents. 

Fentanyl is commonly used to relieve pain from intubation of premature infants, although the safety of the... 

Selected orally active compounds (Graudums et al. (Grunenthal GmbH), 1997 Sundermann et al. (Grunenthal GmbH), 2000) exhibited a wide range of p-opioid affinity (Ki 0.1 to 0.0001 pM) but affinities to the PAA and/or BTZ site were always quite constant (Ki 1 to 0.1 pM). Compounds with very pronounced p-affinities are at least 10 times more potent than morphine in vivo, have an excellent safety index and a relatively mild effect on respiration in comparison to other very strong opioids, e.g. fentanyl. 

ChellyJE, Grass J, Houseman TW, et al. The safety and efficacy of a fentanyl patient-controlled transder-mal system for acute postoperative analgesia a multicenter, placebo-controlled trial. Anesth Analg. 2004 98 427-433. 

Clark AJ, Ahmedzai SH, Allan LG, et al. Efficacy and safety of transdermal fentanyl and sustained-release oral morphine in patients with cancer and chronic non-cancer pain. CurrMed Res Opin. 2004 20 1419-1428. 

Lately, the nasal route is receiving attention for the management of postoperative pain. Mucosal administration requires only a 1.1-1.5 times higher dose of fentanyl than the intravenous dose. ° For this new application field, called PCINA (patient-controlled-intranasal-analgesia), the pharmaceutical industry demands safety precautions of the delivery device, which can be fulfilled through implementation of intelligent microelectronic features. 

Mystakidou K, Befon S, Kouskouni E, Gerolymatos K, Georgaki S, Tsilika E, Vlahos L. From codeine to transdermal fentanyl for cancer pain control a safety and efficacy clinical trial. Anticancer Res 2001 21(3C) 2225-30. 

Mollhoff T, Herregods L, Moerman A, Blake D, MacAdams C, Demeyere R, Kirno K, Dybvik T, Shaikh S Remifentanil Study Group. Comparative efficacy and safety of remifentanil and fentanyl in fast track coronary artery bypass graft surgery a randomized, double-blind study. Br J Anaesth 2001 87(5) 718-26. 

Sufentanyl (R-30,730)(18) was the most potent compound in a novel series of 4-substituted fentanyl derivatives. Sufentanil, which is 4500 times more potent than morphine, has a rapid onset but relatively short duration of action and its margin of safety is reported to be unusually high (LD5Q/ED50>25000).146... 

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. 

Fentanyl is a synthetic opioid related to the phenylpiperidines. The actions of fentanyl and congeners are similar to those of other p-receptor agonists. Fentanyl is a popular anesthetic because of its relatively short time to peak analgesic effect, rapid termination of effect after small bolus doses, and cardiovascular safety (see Chapter 13). 

It exhibits a profile of pharmacological action very much identical to morphine, and differs exceptionally on two accounts, namely flrst-it does not cause emesis secondly, it does not release histamine. Its safety measure in frequency cases has not yet been fully understood. It is observed to cross the placental barrier therefore, its usage during labour may ultimately give rise to respiratory depression in the newly bom infant. However, Fentanyl s transient action after the parenteral administration is caused solely on account of redistribution, rather than to "metabolism" or "excretion". Hence, longer usage of this drug may cause in accumulation and toxicities. 

In a double-blind, placebo-controlled study in 72 patients undergoing laparoscopic cholecystectomy, oral etoricoxib 120 mg given 1.5 hours before surgery reduced the need for postoperative patient controlled analgesia (PCA) with fentanyl, but opioid-related adverse effects were not reduced. Furthermore, the safety of short-term perioperative use of coxibs has been questioned, as some studies have reported more adverse effects (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) with parecoxib or valdecoxib compared with placebo. ... 

White CM, Dunn A, Tsikouris J, Waberski W, Felton K, Freeman-Bosco L, Giri S, Kluger J. An assessment of the safety of short-term amiodarone therapy in cardiac surgical patients with fentanyl-isoflurane anesthesia. AnesthAnalg (1999) 89, 585-9. 

Hoya Y, Okamoto T, Yanaga K. Evaluation of analgesic effect and safety of fentanyl transdermal patch for cancer pain as the first line. Support Care Cancer 2010 18 761-76. 

Relative they are contraindicated in the management of acute or post-operative pain. They are not indicated for use in opioid non-tolerant patients. The safety and efficacy of fentanyl buccal tablets and fentanyl oralet have not been establidied in pediatric patients below the age of 16 years. They ould be used cautiously in patients with a history ofbradyarrhthymias, or with evidence of increased intracranial pressure or impaired consciousness, or with history of chronic obstructive pulmonary disease, or preexisting medical conditions predisposing them to respiratory depression. 

The results support clinical efficacy already at the lowest dose of 100 pg and a trend of dose-response relationship. The safety of Fentanyl TAIFUN was similar to that of placebo, with the exception of an increase in mild to moderate somnolence. The TAIFUN metered inhaler is depicted in Figure 111.4. 

Fentanyl inhalation does not cause any chnically significant adverse events and is comparable to intravenous fentanyl in terms of safety, tolerance, and... 

Viscusi ER, Siccardi M, Damaraju CV, Hewitt DJ, Kershaw R The safety and efficacy of fentanyl iontophoretictransdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management an analysis of pooled data from three randomized, active-controlled clinical trials. Anesth A al 2007 105(5) 1428-1436. 

Van der Linde HI, Deuren BV, Somers Y, Teisman A, Gallacher DJ (2011) The fentanyl/ etomidate-anesthetized beagle (FEAB) model in safety pharmacology assessment. Curr FYotoc Pharmacol 10 Unitl0.13... 

The efficacy and safety of a fentanyl ionto-phoretic transdermal system have been explored in a meta-analysis of six trials [72 ]. In comparisons of the fentanyl transdermal system and morphine in patient-controlled analgesia, fewer of those who received fentanyl withdrew because of adverse effects, fewer had nausea and pruritus, and none had respiratory depression however, more had headaches. 

Fenoterol, safety in severe asthma, 23.182 Fentanyl, buccal and transdermal administration, 20.77 Fertility drugs... 

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