Daily Subcutaneous Parecoxib Injection for Cancer Pain: An Open Label Pilot Study

Kenner, David; Bhagat, Sandeep; Fullerton, Sonia

doi:10.1089/jpm.2014.0249

Cited by 13 publications

(12 citation statements)

References 22 publications

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“…Parecoxib is licensed for the short-term treatment of postoperative pain by intravenous or intramuscular injection 3 and has been given by daily subcutaneous injection for cancer pain. 4 In our study of CSCI use, bone pain was the most frequent documented indication, involving 54/72 (75%) patients. This is in keeping with recorded use of diclofenac and ketorolac CSCI, 5–8 the other parenteral NSAIDS commonly used within palliative care.…”

Section: Discussionmentioning

confidence: 69%

Use of parecoxib by continuous subcutaneous infusion for cancer pain in a hospice population

Armstrong

Wilkinson

McCorry

2017

BMJ Support Palliat Care

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ObjectivesTo characterise the use of the parenteral non-steroidal anti-inflammatory drug parecoxib when given by continuous subcutaneous infusion (CSCI) in a hospice population. Clinical experience suggests parecoxib CSCI may be of benefit in this population, but empirical evidence in relation to its safety and efficacy is lacking.MethodsRetrospective chart review of patients with a cancer diagnosis receiving parecoxib CSCI from 2008 to 2013 at the Marie Curie Hospice, Belfast. Data were collected on treatment regime, tolerability and, in patients receiving at least 7 days treatment, baseline opioid dose and changes in pain scores or opioid rescue medication requirements.ResultsParecoxib CSCI was initiated in 80 patients with a mean administration of 17.9 days (median 11, range 1–94). When used for a period of 7 days, there was a statistically significant reduction in pain scores (p=0.002) and in the number of rescue opioid doses required (p=0.001), but no statistically significant opioid-sparing effect (p=0.222). It was generally well tolerated, although gastrointestinal, renal adverse effects and local site irritation were reported.ConclusionsParecoxib may have a valuable place in the management of cancer pain, especially towards the end of life when oral administration is no longer possible and CSCI administration is relied on. Further studies into the efficacy and tolerability of parecoxib CSCI are merited.

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Section: Discussionmentioning

confidence: 69%

Use of parecoxib by continuous subcutaneous infusion for cancer pain in a hospice population

Armstrong

Wilkinson

McCorry

2017

BMJ Support Palliat Care

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“…It is a kind of inactive ester amide prodrug, which is rapidly converted to valdecoxib ( Figure 1(b) ), a specific compound of COX-2, by enzymatic hydrolysis of the liver [ 7 ]. The elimination of valdecoxib is widely carried out in the liver in many ways, including cytochrome P450 3A4 (CYP3A4) and CYP2C9 isoenzyme metabolism and sulfaglucosylation (about 20%) [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

Guo

et al. 2020

BioMed Research International

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A sensitive and reliable ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of parecoxib and its metabolite valdecoxib in beagles. The effects of dexmedetomidine on the pharmacokinetics of parecoxib and valdecoxib in beagles were studied. The plasma was precipitated by acetonitrile, and the two analytes were separated on an Acquity UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm); the mobile phase was acetonitrile and 0.1% formic acid with gradient mode, and the flow rate was 0.4 mL/min. In the negative ion mode, the two analytes and internal standard (IS) were monitored by multiple reaction monitoring (MRM), and the mass transition pairs were as follows: m/z 369.1→119.1 for parecoxib, m/z 313.0→118.0 for valdecoxib, and m/z 380.0→316.0 for celecoxib (IS). Six beagles were designed as a double cycle self-control experiment. In the first cycle, after intramuscular injection of parecoxib 1.33 mg/kg, 1.0 mL blood samples were collected at different times (group A). In the second cycle, the same six beagles were intravenously injected with 2 μg/kg dexmedetomidine for 7 days after one week of washing period. On day 7, after intravenous injection of 2 μg/kg dexmedetomidine for 0.5 hours, 6 beagle dogs were intramuscularly injected with 1.33 mg/kg parecoxib, and blood samples were collected at different time points (group A). The concentration of parecoxib and valdecoxib was detected by UPLC-MS/MS, and the main pharmacokinetic parameters were calculated by DAS 2.0 software. Under the experimental conditions, the method has a good linear relationship for both analytes. The interday and intraday precision was less than 8.07%; the accuracy values were from -1.20% to 2.76%. Cmax of parecoxib in group A and group B was 2148.59±406.13 ng/mL and 2100.49±356.94 ng/mL, t1/2 was 0.85±0.36 h and 0.85±0.36 h, and AUC0‐t was 2429.96±323.22 ng·h/mL and 2506.38±544.83 ng·h/mL, respectively. Cmax of valdecoxib in group A and group B was 2059.15±281.86 ng/mL and 2837.39±276.78 ng/mL, t1/2 was 2.44±1.55 h and 2.91±1.27 h, and AUC0‐t was 4971.61±696.56 ng·h/mL and 6770.65±453.25 ng·h/mL, respectively. There was no significant change in the pharmacokinetics of parecoxib in groups A and B. Cmax and AUC0−∞ of valdecoxib in group A were 37.79% and 36.19% higher than those in group B, respectively, and t1/2 was increased from 2.44 h to 2.91 h. Vz/F and CLz/F were correspondingly reduced, respectively. The developed UPLC-MS/MS method for simultaneous determination of parecoxib and valdecoxib in beagle plasma was specific, accurate, rapid, and suitable for the pharmacokinetics and drug-drug interactions of parecoxib and valdecoxib. Dexmedetomidine can inhibit the metabolism of valdecoxib in beagles and increase the exposure of valdecoxib, but it does not affect the pharmacokinetics of parecoxib.

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“…However, there is only weak evidence to support its use in the palliative care setting. 1 Parecoxib is the pro-drug of the active metabolite valdecoxib, a potent parenteral selective cyclooxygenase-2 inhibitor. Currently, it is licenced by the Australian Therapeutic Goods Administration in the perioperative setting for opioid-sparing analgesia in non-cardiac patients and by the US Food and Drug Administration as a non-narcotic injectable medicine for the treatment of acute pain.…”

Section: Introductionmentioning

confidence: 99%

Parecoxib as an adjunct therapy for the treatment of refractory non-surgical cancer pain

Thakerar

Dines-Muntaner

Trifunovich

et al. 2020

J Oncol Pharm Pract

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Background Evidence for the use of short-term daily parenteral parecoxib for refractory or uncontrolled non-surgical cancer pain is limited. This study aimed to characterise the real-world off-label use and report on clinical experiences in an Australian cancer cohort. Methods Eligible patients received at least one dose of parecoxib of an intended three-day course between October 2015 and December 2018. Data were collected to characterise the parecoxib treatment cohort (cancer diagnosis, metastases, sites and types of pain and prior analgesia). Parecoxib-related adverse events, pain scores (worst and median), and concurrent opioid use were assessed at 24 h pre (T0) and 24 (T1), 48 (T2), 72 (T3) and 96 h (T4) post first parecoxib dose. Results Sixty-five patients (39 males and 26 females) and 68 courses of parecoxib (three patients treated twice) were included in analyses: metastatic disease (86%), bone pain (54%) and taking ≥3 classes of analgesic medications (69%). Pain types varied (46% non-specific, 22% neuropathic and 32% other). Most (94%) received parecoxib by subcutaneous administration. Following parecoxib, median 24-h pain scores and worst pain scores improved for 59% (40/68) and 50% (34/68) of patients, respectively. In the first 24 h (T0 to T1), median (4 vs. 2, p < 0.01) and worst (6 vs. 5, p < 0.01) pain scores were reduced and sustained to T4 (4 vs. 2.5, p = 0.01). Breakthrough analgesia requirements reduced for 63% (43/68) of patients, while total concurrent opioid use remained constant. Mean/median oral morphine equivalence for T0 vs. T1 was 111 mg/75 mg vs. 162 mg/90 mg, (p > 0.8). Two patients ceased parecoxib due to renal/liver function abnormalities and two experienced mild injection-site reactions. Conclusions In this real-world study, parecoxib was utilised as adjunctive therapy in a select patient cohort to contribute to reduced pain scores with no new safety signals. Prospective randomised studies in larger cohorts would improve understanding of the effects of parecoxib.

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Daily Subcutaneous Parecoxib Injection for Cancer Pain: An Open Label Pilot Study

Abstract: Short-term daily subcutaneous parecoxib injection was effective for malignant bone pain when added to existing analgesic therapy and was well tolerated. Further research is warranted into the short-term use of parecoxib in hospitalized patients with intractable malignant bone pain.

Cited by 13 publications

References 22 publications

Use of parecoxib by continuous subcutaneous infusion for cancer pain in a hospice population

Use of parecoxib by continuous subcutaneous infusion for cancer pain in a hospice population

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

Parecoxib as an adjunct therapy for the treatment of refractory non-surgical cancer pain

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