Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly observed, particularly among patients with chronic urticaria or asthma. The identification of a safe and reliable alternative is a frequent problem in clinical practice. Our aim was to investigate the clinical tolerability of etoricoxib, a new selective cyclooxygenase-2 inhibitor, in a group of patients with well-established NSAID hypersensitivity.
We assessed 31 adults (21 women and 10 men) who reported one or more adverse reactions to NSAIDs, manifested as cutaneous, respiratory or anaphylactic symptoms. Sixteen of them reported reactions to a single NSAID (single reactors) and 15 to more than one NSAID (multiple reactors); the most frequently involved drug was acetylsalicylic acid. First, each patient underwent allergologic tests (skin and/or oral challenge tests) with culprit NSAIDs and then tolerability tests with increasing doses of etoricoxib up to 120 mg. All challenges were performed under single-blind, placebo-controlled conditions.
NSAID hypersensitivity was diagnosed in all 31 patients: 3 displayed positive results to pyrazolone skin tests and the other 28 to challenges with culprit NSAIDs. None reacted to either placebos or etoricoxib.
Etoricoxib seems to be a safe alternative for patients with well-demonstrated NSAID hypersensitivity.
"Provocation with COX-2 inhibitors was open and not placebo controlled. However, the challenges were only considered positive if the patient developed objective symptoms, in agreement with other studies [21,36]. Since we performed this study, the challenged drug dosages have been revised; the lowest dosage of 0.1 mg has appeared to be unnecessary and has been removed from the protocol. "
[Show abstract][Hide abstract] ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently cause adverse drug reactions. Many studies have shown that drugs which selectively inhibit the cyclooxygenase-2 enzyme (COX-2) are safe alternatives in the majority of patients. However, hypersensitivity reactions to COX-2 inhibitors have been published. Hardly any data are available regarding the safety of alternatives in case of COX-2 inhibitor hypersensitivity. We aimed to investigate the tolerance to COX-2 inhibitors in patients with non-selective NSAID hypersensitivity. Furthermore, in COX-2 hypersensitive patients tolerance of a second COX-2 inhibitor was investigated.
We retrospectively analyzed 91 patients with proven non-selective NSAID hypersensitivity that underwent oral challenges with a COX-2 inhibitor. Patients with intolerance to the first challenged COX-2 inhibitor received a second challenge with a different COX-2 inhibitor.
19 out of 91 (21% ) patients had a positive reaction to the first oral challenge with a COX-2 inhibitor. 14 of them underwent a second challenge with a different COX-2 inhibitor and 12 (86% ) did not react.
A relatively high percentage (21% ) of the non-selective NSAID hypersensitive patients did not tolerate a COX-2 inhibitor and oral challenge is advised prior to prescription of a COX-2 inhibitor. For the majority of patients reacting to a COX-2 inhibitor an alternative can be found.
"Selective COX-2 inhibitors appear to block both peripheral and central hyperalgesia, but have little or no effect on platelet aggregation and asthma. These characteristics make them attractive candidates for perioperative use (Viola et al. 2007; Schwartz et al. 2008). Etoricoxib (a new selective COX-2 inhibitor available in many countries) has been reported to reduce postoperative pain after orthopedic surgery (Toivonen et al. 2007; Turan et al. 2008). "
[Show abstract][Hide abstract] ABSTRACT: The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. A total of 12 adult patients were included who received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery. Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E(2) (PGE(2)) using liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF area under the curve (AUC) [AUCs((O-24h))] for etoricoxib amounted to about 5% of the total AUC in plasma (range: 2-7%). Individual CSF lag times with respect to (50%) peak plasma concentration were </=2 h in all but one case (median: 1 h). PGE(2) production in tissue was significantly blocked by the COX-2 inhibitor starting with the appearance of etoricoxib in tissue and lasting for the whole observation period of 24 h (P < 0.01). In conclusion, etoricoxib reaches the CSF and site of surgery at effective concentrations and reduces PGE(2) production at the presumed site of action.
Archiv für Experimentelle Pathologie und Pharmakologie 02/2010; 381(2):127-36. DOI:10.1007/s00210-009-0482-0 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The concepts of flexible manufacturing are increasingly being applied within the electronics industry, particularly in the assembly of printed circuit boards. This paper discusses a class of problems which blur the traditional distinction between design and operation. Additionally, examples and solution methodologies are given for the class of problems under two distinct operating policies.
Robotics and Automation. Proceedings. 1986 IEEE International Conference on; 05/1986
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