Dynastat is the first COX-2 inhibitor for injection on the market. It is indicated for the short-term treatment of postoperative pain.
The efficacy of 20 mg and 40 mg parecoxib is comparable to the efficacy of 30 mg ketorolac (Toradol). A smaller study (patient population: 92) of healthy subjects demonstrated a reduction in the number of adverse gastrointestinal (GI) effects when patients were treated with parecoxib instead of ketorolac.
Parecoxib 40 mg is roughly four times more expensive than ketorolac 30 mg.
In the light of the studies conducted and a cost comparison, the Institute does not generally recommend Dynastat for the treatment of postoperative pain. Whether Dynastat triggers fewer adverse drug reactions in risk groups has not yet been studied, but it may be appropriate to treat these patients with parecoxib.
Dynastat (parecoxib) was marketed on Monday, 13 May 2002 The approved indication is for the short-term treatment of postoperative pain. The Institute does not recommend use for more than two days, since clinical experience beyond this period of time is limited. The preparation is formulated for parenteral administration either intravenously or intramuscularly.
There are two non-specific NSAID products on the market today for the parenteral treatment of postoperative pain: Toradol, which contains ketorolac, and Xefo, which contains lornoxicam. Dynastat has been compared with ketorolac only.
Dynastat contains the water-soluble prodrug parecoxib, which is quickly converted in the liver (half-life: about 20 minutes) to the pharmacologically active substance valdecoxib, which is a specific COX-2 inhibitor.
Valdecoxib is primarily metabolised in the liver and has an elimination half-life of about 8 hours. Its metabolites are of no clinical importance when parecoxib is administered in therapeutic doses.
Dynastat is marketed in the strength 40 mg parecoxib as a powder for solution for injection and as a powder and solvent for solution for injection.
The recommended dose is 40 mg, followed by 20 or 40 mg every 6 or 12 hours as required. The daily dose must not exceed 80 mg. The solution for injection contains 20 mg/ml. The Institute recommends half that dose for elderly patients over 65 and weighing less than 50 kg and for patients with moderate hepatic impairment. The Institute recommends against using parecoxib as a postoperative treatment for patients having undergone coronary artery bypass surgery.
A total of 12 studies have been conducted to evaluate the postoperative analgesic efficacy of parecoxib. In all these studies, parecoxib was compared with placebo and in some of the studies also with either intravenous ketorolac, intravenous morphine, peroral valdecoxib or peroral tramadol. The study populations were patients who had undergone dental, gynaecological, orthopaedic or coronary artery bypass surgery. The results showed that the postoperative analgesic effect of parecoxib 20 and 40 mg is comparable to that of ketorolac 30 mg administered in a single dose. The analgesic effect of parecoxib and ketorolac sets in at about the same time, depending on the type of surgery the study subjects underwent.
The analgesic efficacy of parecoxib administered intravenously is comparable with that of parecoxib administered intramuscularly.
Adverse drug reactions
The adverse GI effects after use of parecoxib in healthy elderly people has been evaluated in two studies. In one study, GI effects after seven days of parecoxib treatment were compared with those after treatment with naproxen, ketorolac and placebo. This study was discontinued because of the adverse GI effects of the ketorolac and naproxen therapy.
In the second study, the adverse GI effects after seven days of treatment with 40 mg parecoxib twice daily were compared with the adverse effects of five days of treatment with 15 mg ketorolac four times daily and seven days with placebo. This study showed that parecoxib did not cause gastroscopically observed gastroduodenal ulcers in healthy elderly subjects, as opposed to treatment with ketorolac, with which ulceration was seen in up to 23% (seven) of the subjects. There were also fewer erosions with parecoxib than with ketorolac. Symptoms of adverse GI effects such as abdominal pain and dyspepsia were observed in the subjects given ketorolac and parecoxib as well as the placebo subjects, so the clinical relevance of the results is uncertain. No studies have been conducted on patients predisposed to ulcers and erosions. Consequently, it is not known whether there is a reduced risk of adverse GI effects in this group of patients. Also, the studies were of a longer duration than normal postoperative iv/im pain therapy would be. It is not known whether gastroscopic examination results after only two days of treatment with parecoxib or ketorolac would be different.
Effects on platelet function were the subject of two studies: one on healthy younger subjects (18-55 years old) and the other on healthy older subjects (65-75 years old). The studies had a duration of five days each. Parecoxib 40 mg twice daily was administered in both studies, and ketorolac 15 mg four times daily to the older group (a reduced dose due to their age) and ketorolac 30 mg four times daily to the younger group. Results showed that platelet function was significantly reduced in the patients treated with ketorolac compared with the patients who received parecoxib. Results were as anticipated for COX-2 inhibitors.
In another study, this one with patients after coronary artery bypass surgery, 1.3% of the roughly 150 patients given parecoxib developed apoplexy, versus none of the approximately 150 patients who received placebo. The cause was unknown, but the Institute advises against using parecoxib to treat patients after bypass surgery.
Valdecoxib is metabolised in the liver mainly by CYP enzymes. No clinical studies have been conducted that support dose adjustment through the co-administration of medical products that are CYP substrates or that have an effect on CYP enzymes in the liver.
Cost at 13 May 2002
||Form of administration
||Contents of package
||Price (pharmacy retail price in DKK)
||Cost per initial dose (DKK)|
|40 mg per vial
||powder for solution for injection
|40 mg per vial
||powder and solvent for solution for injection
||5 vials + solvent
||solution for injection
||5 vials @ 1 ml
||substance for injection
||1 vial @ 2 ml
It is apparent from the prices listed above that Dynastat is roughly four times as expensive as Toradol, about twice as expensive as Xefo 8 mg and slightly less expensive than Xefo 16 mg.
Last modified: May 13th 2002