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Home , Parecoxib

New Medicines Committee Briefing

May 2015

Dynastat® (Parecoxib sodium) 40 mg powder for solution for injection

Dynastat® to be reviewed for use within: Primary Care Secondary Care 

Summary:

 Parecoxib is a of a selective -2 (COX-2) inhibitor1.

 Dyloject® () is currently on the formulary but has been discontinued since March

2010.

 Intravenous parecoxib has been proposed for inclusion in the Joint Formulary as a

replacement of Voltarol® (diclofenac) injection.

 Cochrane review stated that a single dose of parecoxib 20 mg or 40 mg provided effective

analgesia for 50 to 60% of those treated compared to about 15% with placebo, and was well

tolerated2.

 A meta-analysis stated that the good postoperative analgesia and minimal interference with

platelet function may make parecoxib an alternative to the non-selective NSAID diclofenac in

providing pre-emptive analgesia in patients undergoing general surgery3.

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Application:

Neurology: Consultant submitting application: Dr Simon Mills (Consultant Anaesthetist) Clinical Director supporting application: Dr Stephen Merron (Medical Director) Dr Mills states that there is currently no COX-2 NSAID available for use in the operating theatre. He proposed that parecoxib be made available as a single dose for patients undergoing spinal surgery, to be given by the consultant anaesthetist. Dr Mills explained that NSAIDS do not depress respiration nor impair gastrointestinal motility as hence making it clinically useful for treating pain after day surgery, as well as its sparing effect after more major surgery. COX- 1 NSAIDs such as affects platelet function making them unsuitable for perioperative use in spinal surgery where the consequence of a haematoma can be devastating. For patients having less invasive spinal surgery, such as uncomplicated lumber discectomy, the improved analgesia with parecoxib should improve the proportion of patients done as a day case. He noted that for patients having more extensive inpatient surgery, the sparing benefits of parecoxib should reduce the known complications of opioid use such as respiratory depression and reduced gastrointestinal motility thereby improving postoperative recovery and potentially reduce length of stay. Improved analgesia and reduced opioid use will reduce postoperative discomfort and nausea and vomiting and should reduce length of stay. Routine use of parecoxib should increase the proportion of same day discharges and therefore improve bed availability in orthopaedics which currently is a massive problem for the trust, causing loss of revenue through cancellation of elective and emergency surgery. Dr Merron supported the application stating that the anaesthetic department are very keen to develop daycase spinal surgery to reduce on inpatient beds and that parecoxib will be one means of helping to achieve this.

Background:

Acute pain occurs as a result of tissue damage, commonly accidentally due to an injury or as a result of surgery. Acute postoperative pain is a manifestation of inflammation due to tissue injury. The management of postoperative pain and inflammation is a critical component of patient care. The most common route for administration of postoperative analgesia is by mouth, but some patients are unable to swallow, feel nauseated, or vomit in the immediate postoperative period, and in these patients intravenous or intramuscular administration may be preferred. NSAIDs are one of the most commonly prescribed medications worldwide, and their efficacy for treating acute pain has been well demonstrated. They reversibly inhibit cyclooxygenase ( endoperoxide synthase), the mediating production of and A2. Prostaglandins mediate a variety of physiological functions

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such as maintenance of the gastric mucosal barrier, regulation of renal blood flow, and regulation of endothelial tone. They also play an important role in inflammatory and nociceptive processes. Cyclooxygenase (COX) activity has been found to be associated with at least two distinct isoenzymes: COX-1 and COX-2. COX- 1 was hypothesized to be involved in the maintenance of physiologic functions such as gastric protection and haemostasis; COX-2 was thought to be involved in pathophysiologic processes such as inflammation, pain and fever. These hypotheses led to the development of the selective COX-2 inhibitors, such as , and . These agents have analgesic efficacy comparable with conventional NSAIDs. In addition, they have no antiplatelet activity at therapeutic doses, and therefore may be associated with reduced gastrointestinal adverse effects compared with conventional NSAIDs such as ibuprofen. Concerns about cardiovascular safety in long term use have led to the withdrawal of rofecoxib, and in some countries . Parecoxib was the first COX-2 to be administered parenterally. It is a prodrug that is rapidly hydrolysed in vivo to its active form, valdecoxib. Clinical trials have indicated that parecoxib is effective in treating postoperative pain resulting from oral surgery, orthopaedic surgery and abdominal hysterectomy pain. Intravenous diclofenac has been included within the North Staffordshire Joint Formulary for prevention and treatment of acute postoperative pain where rapid onset is required. The UHNM with the agreement of the anaesthetists switched over brands of intravenous diclofenac from Voltarol® to Dyloject® in response to NPSA risk assessment of injectable. Voltarol® was assessed as moderate risk product as it requires fresh preparation for each patient and can be irritant during intravenous administration. It is administered by continuous or intermittent infusion. Dyloject® on the contrary was a low risk product as it is a bolus injection. Unfortunately, Dyloject® has been discontinued and theatres have gone back to using Voltarol®. Currently the UHNM surgical guidelines recommend ibuprofen SR 1600 mg oral daily as premedication. Post-operative options include ibuprofen 400 mg oral 8-hrly, or 800 mg SR 12-hrly or 250 mg oral 6-hrly, or 500 mg 12-hrly or diclofenac 50 mg per rectum 8-hrly – maximum dose 150 mg in 24 hr (not prescribe on discharge) and ibuprofen 400 mg 8-hrly or naproxen 250 mg oral 6-hrly, or 500 mg 12-hrly as drugs to take home. The guideline states that intramuscular diclofenac should be avoided as it is painful and can lead to a sterile abscess. There is no alternative for patients with asthma known to be sensitive to and NSAIDs or if oral or rectal not available or suitable.

Therapeutic class and mode of actionError! Bookmark not defined.:

Parecoxib is a prodrug of valdecoxib a selective COX-2 inhibitor. Cyclooxygenase is responsible for generation of prostaglandins. Two isoforms, COX-1 and COX-2, have been identified. COX-2 is the isoform of the enzyme that has been shown to be induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of mediators of pain,

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inflammation, and fever. COX-2 is also involved in ovulation, implantation and closure of the ductus arteriosus, regulation of renal function, and central nervous system functions (fever induction, pain perception and cognitive function). It may also play a role in ulcer healing. COX-2 has been identified in tissue around gastric ulcers in man but its relevance to ulcer healing has not been established. The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and COX-2 selective inhibitors may be of clinical significance in patients at risk of thrombo-embolic reactions. COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) without affecting platelet thromboxane.

Indication:

Parecoxib is indicated for short-term treatment of postoperative pain in adults.

Contraindication:  Hypersensitivity to the active substance  Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme or patients with known hypersensitivity to sulphonamide.  Active peptic ulceration or gastrointestinal (GI) bleeding.  Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid or NSAIDs including COX-2 inhibitors  The third trimester of pregnancy and breast-feeding  Severe hepatic impairment (serum albumin <25 g/l or Child-Pugh score ≥ 10)  Inflammatory bowel disease  Congestive heart failure (NYHA II-IV)  Treatment of post-operative pain following coronary artery bypass graft (CABG) surgery  Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease Adverse effects Very common (≥ 1/10); common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000) Common: Pharyngitis, alveolar osteitis (dry socket), anemia postoperative, hypokalemia, agitation, insomnia, hypoaesthesia, dizziness, respiratory insufficiency, abdominal pain, vomiting, constipation, dyspepsia, flatulence etc. 4

Uncommon: Abnormal sternal serous wound drainage, wound infection, thrombocytopaenia, hyperglycaemia, anorexia, cerebrovascular disorder, myocardial infarction, bradycardia, hypertension (aggravated), orthostatic hypotension etc. Very rare: Anaphylactoid reaction, pancreatitis, oesophagitis, oedema mouth (perioral swelling) etc. Drug interactions Use with Oral Anticoagulants - The concomitant use of NSAIDs with oral anticoagulants increases the risk of bleeding. Oral anticoagulants include warfarin/coumarin-type and novel oral anticoagulants (e.g. apixaban, dabigatran, and rivaroxaban). These should be monitored, particularly during the first few days after initiating Dynastat therapy. Therefore, patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with parecoxib is initiated or the dose of parecoxib is changed. Inhibition of prostaglandins by NSAIDs, including COX-2 inhibitors, may diminish the effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin II antagonists, beta-blockers and diuretics. This interaction should be given consideration in patients receiving parecoxib concomitantly with ACE-inhibitors, angiotensin II antagonists, beta-blockers and diuretics. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors or Angiotensin-II antagonists, may result in further deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Co-administration of NSAIDs and cyclosporin or tacrolimus has been suggested to increase the nephrotoxic effect of cyclosporin and tacrolimus because of NSAID effects on renal prostaglandins. Renal function should be monitored when parecoxib and any of these medicinal products are co- administered. Caution and warning: Cardiovascular - COX-2 inhibitors have been associated with increased risk of cardiovascular and thrombotic adverse events when taken long term. The exact magnitude of the risk associated with a single dose has not been determined, nor has the exact duration of therapy associated with increased risk. Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, and smoking) should only be treated with parecoxib after careful consideration. Acetylsalicyclic acid and other NSAIDs - COX-2 inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effects. Therefore, antiplatelet therapies should not be discontinued. Caution should be exercised when co-administering Dynastat with warfarin and other oral anticoagulants. The concomitant use of parecoxib with other non- acetylsalicylic acid NSAIDs should be avoided. Dynastat may mask fever and other signs of inflammation. Caution should be exercised with respect to monitoring the incision for signs of infection in surgical patients receiving Dynastat.

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Gastrointestinal - Upper GI complications [perforations, ulcers or bleedings (PUBs)], some of them resulting in fatal outcome, have occurred in patients treated with parecoxib. Caution is advised in the treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs; the elderly, patients using any other NSAID or acetylsalicylic acid concomitantly, glucocorticoids, selective serotonin reuptake inhibitors or patients with a prior history of gastrointestinal disease, such as ulceration and GI bleeding. There is further increase in the risk of GI adverse effects (gastrointestinal ulceration or other gastrointestinal complications), when parecoxib is taken concomitantly with acetylsalicylic acid (even at low doses). Skin reactions - Serious skin reactions, including erythema multiforme, exfoliative dermatitis and Stevens-Johnson syndrome (some of them fatal) have been reported through post-marketing surveillance in patients receiving parecoxib. Additionally, fatal reports of toxic epidermal necrolysis have been reported through post-marketing surveillance in patients receiving valdecoxib (the active metabolite of parecoxib) and cannot be ruled out for parecoxib. Patients appear to be at highest risk for these reactions early in the course of therapy; the onset of the reaction occurring in the majority of cases within the first month of treatment. Parecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Serious skin reactions are known to occur with NSAIDs including COX-2 selective inhibitors as well as other medicinal products. However, the reported rate of serious skin events appears to be greater for valdecoxib (the active metabolite of parecoxib) as compared to other COX-2 selective inhibitors. Patients with a history of sulphonamide may be at greater risk of skin reactions. Hypersensitivity - Hypersensitivity reactions (anaphylaxis and angioedema) have been reported in post-marketing experience with valdecoxib and parecoxib. Some of these reactions have occurred in patients with a history of allergic-type reactions to sulphonamides. Parecoxib should be discontinued at the first sign of hypersensitivity. Cases of severe hypotension shortly following parecoxib administration have been reported in post-marketing experience with parecoxib. Some of these cases have occurred without other signs of anaphylaxis. The physician should be prepared to treat severe hypotension. Fluid retention, oedema, renal - fluid retention and oedema have been observed in some patients taking parecoxib. Therefore, parecoxib should be used with caution in patients with compromised cardiac function, pre-existing oedema, or other conditions predisposing to, or worsened by, fluid retention including those taking diuretic treatment or otherwise at risk of hypovolaemia. If there is clinical evidence of deterioration in the condition of these patients, appropriate measures including discontinuation of parecoxib should be taken. Acute renal failure has been reported through post-marketing surveillance in patients receiving parecoxib. Since prostaglandin synthesis inhibition may result in deterioration of renal function and fluid retention, caution should be observed when administering Dynastat in patients with impaired renal function or hypertension, or in patients with compromised cardiac or hepatic function or other conditions predisposing to fluid retention.

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Caution should be used when initiating treatment with Dynastat in patients with dehydration. In this case, it is advisable to rehydrate patients first and then start therapy with Dynastat. Hypertension - As with all NSAIDs, parecoxib can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cardiovascular events. Parecoxib should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of therapy with parecoxib and throughout the course of therapy. If blood pressure rises significantly, alternative treatment should be considered. Hepatic dysfunction - Dynastat should be used with caution in patients with moderate hepatic dysfunction (Child-Pugh score 7-9).

Dosage and administration2:

Posology The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), followed every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day. As the cardiovascular risk of COX-2 specific inhibitors may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. There is limited clinical experience with Dynastat treatment beyond three days. Concomitant use with opioid Opioid analgesics can be used concurrently with parecoxib, dosing as described in the paragraph above. In all clinical assessments parecoxib was administered at a fixed time interval whereas the opioids were administered on as needed basis. Older people No dose adjustment is generally necessary in elderly patients (≥ 65 years). However, for elderly patients weighing less than 50 kg, treatment should be initiated with half the usual recommended dose of Dynastat and reduce the maximum daily dose to 40 mg. Hepatic impairment There is no clinical experience in patients with severe hepatic impairment (Child-Pugh score ≥10), therefore its use is contraindicated in these patients. No dosage adjustment is generally necessary in patients with mild hepatic impairment (Child-Pugh score 5-6). Dynastat should be introduced with caution and at half the usual recommended dose in patients with moderate hepatic impairment (Child-Pugh score 7-9) and the maximum daily dose should be reduced to 40 mg. Renal impairment In patients with severe renal impairment (creatinine clearance < 30 ml/min) or patients who may be predisposed to fluid retention parecoxib should be initiated at the lowest recommended dose 7

(20 mg) and the patient's kidney function should be closely monitored. On the basis of , no dose adjustment is necessary in patients with mild to moderate renal impairment (creatinine clearance of 30-80 ml/min). Paediatric population The safety and efficacy of parecoxib in children under 18 years old have not been established. No data are available. Therefore, parecoxib is not recommended in these patients. Method of administration The IV bolus injection may be given rapidly and directly into a vein or into an existing IV line. The IM injection should be given slowly and deeply into the muscle. Precipitation may occur when Dynastat is combined in solution with other medicinal products and therefore Dynastat must not be mixed with any other medicinal product, either during reconstitution or injection. In those patients where the same IV line is to be used to inject another medicinal product, the line must be adequately flushed prior to and after Dynastat injection with a solution of known compatibility. After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into IV lines delivering the following: • sodium chloride 0.9% solution for injection/infusion; • glucose 5% solution for infusion; • sodium chloride 0.45% and glucose 5% solution for injection/infusion; or • Ringer-Lactate solution for injection. Injection into an IV line delivering glucose 5% in Ringer-Lactate solution for injection, or other IV fluids not listed above is not recommended as this may cause precipitation from solution. Overdose: In case of overdose, patients should be managed by symptomatic and supportive care. Valdecoxib is not removed by haemodialysis. Diuresis or alkalisation of urine may not be useful due to high protein binding of valdecoxib.

NICE Guidance published No

Scottish Medicines Consortium (SMC)4 Yes

SMC in 2003 did not recommend parecoxib for use within NHS Scotland and stated that there is no evidence that parental COX2 selective NSAID, parecoxib is associated with a reduction in clinically significant post-operative haemorrhagic or gastro-intestinal complications compared with non-selective

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NSAIDs. SMC stated that parecoxib is substantially more expensive than non-selective NSAIDs and should therefore not replace these drugs.

Efficacy:

Cochrane Yes Intravenous or intramuscular parecoxib for acute postoperative pain in adults2

Lloyds R, Derry S. et alError! Bookmark not defined. assessed the efficacy and adverse effects of single dose parecoxib in studies of acute postoperative pain. The primary outcome was the proportion of participants achieving at least 50% pain relief over 6 hours while the secondary outcomes included number of participants requiring rescue medication, number of participants reporting adverse events and withdrawals for reasons other than lack of efficacy. The selective criteria for studies included were randomised, double-blind, placebo-controlled clinical trials of parecoxib compared with placebo for relief of moderate to severe postoperative pain in adults with at least 10 patients randomly allocated to each treatment group. Six studies provided data at this dose in which 320 patients were treated with parecoxib 20 mg and 271 with placebo Two review authors independently assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive the proportion of participants with parecoxib and placebo experiencing at least 50% pain relief over 6 hours, using validated equations. The number-needed-to-treat- to-benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were also collected. Seven studies (1446 participants) were included with 320 participants treated with a single dose of parecoxib 20mg and 278 with parecoxib 40mg. There was no significant difference between 20mg and 40mg doses, or between intravenous and intramuscular administration for 50% pain relief over 6 hours: NNTs compared with placebo were 3.1 (2.4 to 4.5), 2.4 (2.1 to 2.8), and 1.8 (1.5 to 2.3) for 10, 20, and 40 mg parecoxib respectively. Fewer participants required rescue medication over 24 hours with parecoxib than placebo: parecoxib 40 mg was significantly better than parecoxib 20 mg (NNTs to prevent use of rescue medication 7.5 (5.3 to 12.8) and 3.3 (2.6 to 4.5) respectively; P < 0.0007). Median time to use of rescue medication was 3.1 hours, 6.9 hours and 10.6 hours with parecoxib 10 mg, 20 mg and 40 mg respectively, and 1.5 hours with placebo. Adverse events were generally mild to moderate, rarely led to withdrawal, and did not differ in frequency between groups. No serious adverse events were reported with parecoxib or placebo. The authors concluded that a single dose of parecoxib 20 mg or 40 mg provided effective analgesia for 50 to 60% of those treated compared to about 15% with placebo, and was well tolerated. Duration of analgesia was longer, and significantly fewer participants required rescue medication over 24 hours with the higher dose.

Efficacy of Parecoxib on postoperative pain after lumber spine surgery5:

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Jirarattanaphochai K, Thienthong S et al.5 conducted a bicenter, double-blinded, randomized, placebo- controlled, parallel trial to assess the efficacy and safety of parecoxib on postoperative pain management after posterior lumbar spine surgery. 120 patients undergoing posterior lumbar discectomy, spinal decompression, or spinal fusion were stratified based on the surgical procedure to 3 groups (discectomy – 40 patients, spinal decompression – 40 patients, and spinal fusion – 40 patients) and randomly allocated to receive multidoses (i.e. 40mg of parecoxib 30mins before surgery and then 40mg every 12 hrs for 48 hours post-surgery) of parecoxib 40 mg/dose or placebo (injections of saline at the same time intervals). Participants were eligible if they were 18 to 65 years of age schedules to undergo posterior lumber discectomy, decompressive laminectomy or spinal fusion. Efficacy was assessed by total used from patient-controlled analgesic pump, pain intensity, pain relief, and the patient’s subjective rating of the medication. Parecoxib 40 mg reduced the total amount of morphine required over 48 hours by 39% relative morphine reduction compared with placebo (P<0.0001). Pain at rest was reduced by 30% (P< 0.0001). 90% of patients given parecoxib experienced at least 50% maximum total pain relief compared with 58% treated with placebo. The NNT for 1 patient to have at least half pain relief was 3.1 (2.0–4.6). Patients’ subjective rating of the medication was described as “excellent, good, and fair” by 48%, 43%, and 8% in the parecoxib group, respectively, compared with 21%, 50%, and 28% of placebo patients (P< 0.004). Overall adverse effects of patients receiving parecoxib and morphine were comparable to those receiving morphine alone. The authors concluded that the study demonstrated that perioperative administration of parecoxib with patient controlled analgesic morphine after lumber spine surgery resulted in significantly improved postoperative analgesic management as defined by reduction in opioid requirement, lower pain scores, and higher patients’ subjective rating of the medication.

Efficacy and safety of parecoxib sodium for acute postoperative pain: A meta-analysis3 This meta-analysis was performed to evaluate the efficacy and safety of parecoxib sodium for acute postoperative pain. Databases were searched from January 1999 to January 2013 to comprehensively collect RCTs of parecoxib sodium for acute postoperative pain. The methodological quality of the included RCTs was assessed and the data were extracted by two independent reviewers. Efficacies and safety (respiratory depression, pruritus, fever, headache, and nausea and vomiting) were pooled using meta‑ analysis while calculating the relative risk (RR) and 95% CI in a fixed-effects model. The inclusive criteria included RCT study, intervention (treatment group - PCA combined with parexocib IV at 40mg then 20/40mg BD (<3 days) and control group - same volume of saline), patients with no statistically significant differences in baselines characteristics etc. Seven RCTs involving 1,939 patients met the inclusion criteria. The quality of the RCTs was assessed using Jadad grade (i.e. maximum grade, A; minimum grade, C; grade >B, good quality) and according to Cochrane handbook 5.01. Data was analysed calculating RR and 95% CI in a random-effects model or in a fixed effects model. Of the 7 studies included, 1207 patients were on the treatment arm with 732 patients on the control group.

The results of the meta‑analysis revealed that the rate of ‘effective’ treatment as described by the patients' global evaluation of study medication (PGESM) was higher in the PCA combined with parecoxib sodium group 24, 48, and 72 hrs after the initial intravenous dose of 40 mg parecoxib compared with that in the control group [PCA alone; RR=1.41, 95% CI (1.13-1.75); RR=1.25, 95% CI (1.15-1.35); and RR=1.30, 95% CI (1.21‑1.40), respectively]. The rate of ‘ineffective’ treatment in the PCA combined with parecoxib sodium group was lower compared with that of the control group [RR=0.43, 95% CI (0.26-0.72); RR=0.44, 95% CI 10

(0.34‑0.57); and RR=0.33, 95% CI (0.23-0.48), respectively]. Combination of PCA with parecoxib sodium reduced the incidence of postoperative fever [RR=0.34, 95% CI (0.22-0.53)], as well as nausea and vomiting [RR=0.69, 95% CI (0.57-0.83)]; however, it did not significantly reduce respiratory depression [RR=0.84, 95% CI (0.38-1.83)], pruritus [RR=0.91, 95% CI (0.54-1.52)] or headache [RR=0.77, 95% CI (0.47-1.28)]. The authors concluded that the combination of PCA with parecoxib sodium successively injected for <3 days significantly increases the scores of PGESM and reduces the incidence of adverse effects and postoperative complications.

Comparison of the effects of parecoxib and diclofenac in preemptive analgesia: A prospective, randomized, assessor-blind, single-dose, parallel-group study in patients undergoing elective general surgery.6 Bajaj P et al in a prospective, randomized, assessor-blind, single-dose, parallel-group, comparative trial compared the efficacy and tolerability parecoxib sodium and diclofenac sodium as pre-emptive analgesics in patients undergoing elective general surgery. Patients aged 18 to 65 years undergoing elective general surgery were enrolled and a single IM injection of parecoxib 40 mg or diclofenac 75 mg was administered 30 to 45 minutes before the induction of anaesthesia. Surgery was performed as per standard protocol. The primary measures of efficacy were pain intensity score (measured on a visual analog scale [VAS]), pain relief score, duration of analgesia, and platelet aggregation response to adenosine diphosphate. Tolerability assessment included monitoring of treatment-emergent adverse events (AEs), physical examination, laboratory analysis, electrocardiography, and chest radiography. Eighty patients (56 men, 24 women; mean [SD] age, 45.96 [12.83] years) were enrolled in the study (40 patients per treatment group) and all patients completed the trial. No pain was reported by any patient in the parecoxib group up to 12 hours while in the diclofenac group, no pain was reported up to 6 hours. At 12 hours, the mean (SD) VAS score was 2.33 (1.39) (moderate pain) in the diclofenac group and 0 (no pain) in the parecoxib group (P < 0.05). At 12 hours, total pain relief was reported by all 40 patients (100.0%) in the parecoxib group but by none (0.0%) in the diclofenac group, and 2 patients in the diclofenac group (5.0%) reported good pain relief (between-group difference for total good pain relief, P < 0.05). Mean (SD) duration of analgesia was significantly longer in the parecoxib group than in the diclofenac group (19.48 [5.61] hours vs 8.32 [4.11 ] hours; P < 0.05). Platelet aggregation was significantly inhibited in the diclofenac group (change from baseline, 64.0%) but not in the parecoxib group (change from baseline, 12.0%) (P < 0.05). Both regimens were well tolerated, and no AEs were reported. The authors concluded that patients treated with parecoxib experienced no pain at 12 hours, and the treatment was well tolerated. The results of this study suggest that good postoperative analgesia and minimal interference with platelet function may make parecoxib an alternative to the non-selective NSAID diclofenac in providing pre-emptive analgesia in patients undergoing general surgery.

Cost analysis and expenditure:

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Total Cost of Qty of Cost incl VAT to Cost incl VAT to Cost incl VAT to Diclofenac Diclofenac administer dose administer dose administer DIVISION DIRECTORATE SPECIALITY injections injections with SodBicarb with SodBicarb equivalent dose of dispensed incl dispensed 4.2% (£) 8.4% (£) parecoxib (£) VAT (£) EMERGENCY MEDICINE ACUTE MEDICINE 1 £0.89 £7.53 £7.95 £6.29 MEDICINE GASTROENTEROLOGY 4 £3.57 £30.10 £31.79 £25.16 SPECIALIST MEDICINE INFECTIOUS DISEASES 21 £18.72 £158.03 £166.90 £132.10 NEUROSCIENCES NEUROLOGY 10 £8.92 £75.25 £79.48 £62.90 NEUROSURGERY 4 £3.57 £30.10 £31.79 £25.16 SPECIALISED TRAUMA TRAUMA & 1 £0.89 £7.53 £7.95 £6.29 ORTHOPAEDICS SURGERY GENERAL SURGERY GENERAL SURGERY 26 £23.18 £195.66 £206.64 £163.55 UHNM Total April 14- March 15 67 £59.74 £504.19 £532.49 £421.46

References

1 Dynastat 40mg Powder for Solution for Injection, Summary of Product Characteristics . Pfizer limited. Last updated 20/01/2015 accessed via https://www.medicines.org.uk/emc/medicine/8771 29/04/15 2 Lloyd R, Derry S, Moore RA, McQuay HJ. Intravenous or intramuscular parecoxib for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD004771. DOI: 10.1002/14651858.CD004771.pub4. 3 Wei W, Zhao T and Li Y. Efficacy and safety of parecoxib sodium for acute postoperative pain: A meta-analysis . EXPERIMENTAL AND THERAPEUTIC MEDICINE 2013; 6: 525-531 4 Scottish Medicines consortium (SMC). Parecoxib (Dynastat®) Available via: https://www.scottishmedicines.org.uk/files/Parecoxib_Dynastat__injection.pdf [accessed 05/05/15] 5 Jirarattanaphochai K, Thienthong S, Sriraj Wimonrat, Jung S, Pulnitiporn A, Lertsinudom S and Foocharoen T. Effect of Parecoxib on Postoperative Pain After Lumber Spine SurgerySPINE 2008; 33: 132-139. 6 Bajaj P1, Ballary CC, Dongre NA, Baliga VP, Desai AA. Comparison of the effects of parecoxib and diclofenac in preemptive analgesia: A prospective, randomized, assessor-blind, single-dose, parallel-group study in patients undergoing elective general surgery. Curr Ther Res Clin Exp. 2004; 65(5):383-97. doi: 10.1016/j.curtheres.2004.10.004.

Produced by Sr Chidi Njoku Primary Care and Secondary Care Interface Pharmacist University Hospital of North Staffordshire Telephone: 01782 674541

e-mail: [email protected] Produced for use within the NHS. Not to be reproduced for commercial purposes.

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