The safety profile of parecoxib for the treatment of postoperative pain: a pooled analysis of 28 randomized, double-blind, placebo-controlled clinical trials and a review of over 10 years of postauthorization data

Figures & data

Table 1 Patient demographics

Characteristic	Parecoxib (N=5,402)	Placebo (N=3,885)
Sex, n (%)
Male	2,087 (38.6)	1,851 (47.6)
Female	3,315 (61.4)	2,034 (52.4)
Race, n (%)
White	4,241 (78.5)	3,150 (81.1)
Black	349 (6.5)	202 (5.2)
Hispanic	264 (4.9)	95 (2.4)
Asian	186 (3.4)	168 (4.3)
Other	136 (2.5)	120 (3.1)
N/A	226 (4.2)	150 (3.9)
Age
Mean (SD)	46.7 (18.2)	51.8 (16.1)
Range	18–96	18–90

Abbreviation: N/A, not available.

Table 2 Summary of exposure to parecoxib in the 28 randomized placebo-controlled trials

Duration of exposure	Number of patients (N=5,402)
Cumulative up to 3 days	4,763
Cumulative up to 7 days	5,402
Dose administereda, mg
1	102
2	101
5	102
10	101
20	903
40	2,987
50	51
60	364
80	640
100	51
Number of administrations
1	2,282
2	450
3	295
4	407
5	224
6	1,292
7	247
8	78
9	6
10	121

Notes:

a Includes any mode of administration (intramuscular, intravenous).

Table 3 Occurrence of important safety risks during the 28 randomized placebo-controlled trials

Risk	Parecoxib (% of patients)	Placebo (% of patients)	RR (95% CI)
GI-related eventa
Hemorrhage	0.1	0.2	0.96 (0.33, 2.76)
Perforation	0.0	<0.1	–
Ulceration	0.1	<0.1	2.52 (0.52, 12.11)
Renal failure and impairmentb	1.0	0.9	1.14 (0.75, 1.75)
Cardiovascular thrombotic eventc
Arterial	0.3	0.2	1.44 (0.65, 3.20)
Venous	0.2	0.1	1.44 (0.49, 4.21)
Mixed or unspecified	0.2	0.2	1.44 (0.54, 3.83)
Hypersensitivity reaction
Anaphylactic (all types)d	8.7	8.6	1.01 (0.88, 1.15)
Hypotensione	2.6	2.1	1.25 (0.96, 1.64)
Angioedema (all types)f	2.5	2.8	0.88 (0.68, 1.23)
Severe cutaneous reactiong	0	0	–
Masking signs of inflammation
Skin and soft tissue infectionsh	0	<0.1	–
Incision site infectioni	<0.1	0	–

Notes:

a Based on the MedDRA version 17.1 SMQs of GI hemorrhage, GI perforation, and GI ulceration.

b Based on the MedDRA version 17.1 HLT of renal failure and impairment.

c Based on the MedDRA version 17.1 SMQs of embolic and thrombotic events arterial, embolic and thrombotic events venous, and embolic and thrombotic events vessel type unspecified and mixed arterial and venous.

d Based on the MedDRA version 17.1 SMQ of anaphylactic reaction.

e Based on the MedDRA version 17.1 PT of hypotension.

f Based on the MedDRA version 17.1 SMQ of angioedema.

g Based on the MedDRA version 17.1 SMQ of severe cutaneous adverse reactions.

h Based on the MedDRA version 17.1 HLT of skin structures and soft tissue infections.

i Based on the MedDRA version 17.1 PT of incision site infection.

Abbreviations: GI, gastrointestinal; HLT, high-level term; MedDRA, Medical Dictionary for Regulatory Activities; PT, preferred term; RR, relative risk; SMQs, standard MedDRA queries.

Table 4 Occurrence of important safety risks among parecoxib-treated subjects (derived from postmarketing data based on 69,567,300 standard units of parecoxib)a

Risk	Total (n)	Serious (n)	Outcome
GI-related eventb	35	35	Recovered=12
			Recovering=3
			Not recovered=4
			Unknown=12
			Fatal=4
Renal failure and impairmentc	77	68	Recovered=32
			Recovering=9
			Recovering with sequela=1
			Not recovered=8
			Unknown=21
			Fatal=6
Embolic and thrombotic eventd	66	64	Recovered=20
			Recovering=4
			Recovering with sequela=2
			Not recovered=2
			Unknown=18
			Fatal=20
Hypersensitivity reactione	190	98	Recovered=125
			Recovering=15
			Recovering with sequela=1
			Not recovered=8
			Unknown=34
			Fatal=7
Hypotension-related eventsf	32	25	Recovered=20
			Recovering=3
			Unknown=6
			Fatal=3
Severe cutaneous reactiong	17	17	Recovered=9
			Recovering=1
			Not recovered=2
			Unknown=3
			Fatal=2
Masking signs of inflammationh	18	18	Recovered=7
			Recovering=1
			Not recovered=3
			Unknown=3
			Fatal=4

Notes:

a Includes medically confirmed cases of each event through March 31, 2014.

b Based on the MedDRA version 16.1 SMQs of GI hemorrhage, GI perforation, and GI ulceration.

c Based on the MedDRA version 16.1 HLT of renal failure and impairment.

d Based on the MedDRA version 16.1 SMQs of embolic and thrombotic events arterial, embolic and thrombotic events venous, and embolic and thrombotic events vessel type unspecified and mixed arterial and venous.

e Based on the MedDRA version 16.1 SMQ of hypersensitivity.

f Based on the MedDRA version 16.1 PT of hypotension.

g Based on the MedDRA version 16.1 SMQ of severe cutaneous adverse reactions.

h Based on the MedDRA version 16.1 serious AEs with a PT whose primary allocation is to the system organ class category of infections and infestations.

Abbreviations: AEs, adverse events; GI, gastrointestinal; HLT, high-level term; MedDRA, Medical Dictionary for Regulatory Activities; PT, preferred term; SMQs, standard MedDRA queries.

Table 5 Risk difference (parecoxib vs placebo) of important safety risks during the 28 randomized placebo-controlled trials, adjusted for study

Risk	Parecoxib (weighted % of patients)	Placebo (weighted % of patients)	Weighted risk difference (95% CI)	P-value
GI-related eventa
Hemorrhage	0.16	0.14	0.02 (−1.14, 0.19)	0.78
Perforation	0.00	0.07	−0.07 (−0.15, 0.02)	0.13
Ulceration	0.17	0.05	0.12 (−0.02, 0.26)	0.09
Renal failure and impairmentb,*	1.27	0.63	0.64 (0.23, 1.04)	<0.01
Embolic and thrombotic eventc
Arterial	0.37	0.20	0.18 (−0.05, 0.40)	0.13
Venous	0.19	0.14	0.05 (−0.12, 0.23)	0.55
Mixed or unspecified	0.21	0.16	0.06 (−0.13, 0.24)	0.55
Hypersensitivity reaction
Anaphylactic (all types)d	9.04	8.86	0.18 (−1.03, 1.39)	0.77
Hypotensione,**	2.88	2.06	0.82 (0.17, 1.47)	0.01
Angioedema (all types)f	2.67	2.53	0.14 (−0.53, 0.81)	0.68
Severe cutaneous reactiong	0	0	–	–
Masking signs of inflammation
Skin and soft tissue infectionsh	0.00	0.10	−0.10 (−0.20, 0.00)	0.06
Incision site infectioni	0.02	0.00	0.02 (−0.02, 0.07)	0.29

Notes:

a Based on the MedDRA version 17.1 SMQs of GI hemorrhage, GI perforation, and GI ulceration.

b Based on the MedDRA version 17.1 HLT of renal failure and impairment.

c Based on the MedDRA version 17.1 SMQs of embolic and thrombotic events arterial, embolic and thrombotic events venous, and embolic and thrombotic events vessel type unspecified and mixed arterial and venous.

d Based on the MedDRA version 17.1 SMQ of anaphylactic reaction.

e Based on the MedDRA version 17.1 PT of hypotension.

f Based on the MedDRA version 17.1 SMQ of angioedema.

g Based on the MedDRA version 17.1 SMQ of severe cutaneous adverse reactions.

h Based on the MedDRA version 17.1 HLT of skin structures and soft tissue infections.

i Based on the MedDRA version 17.1 PT of incision site infection.

* A majority of the events in the renal failure impairment group were classified as oliguria.

** A majority of cases of hypotension were classified as mild or moderate in severity.

Abbreviations: GI, gastrointestinal; HLT, high-level term; MedDRA, Medical Dictionary for Regulatory Activities; PT, preferred term; SMQs, standard MedDRA queries.