Bromfenac in acute postoperative pain

Clinical bottom line:
A single oral dose of bromfenac is effective in the relief of postoperative pain. A dose of 25 mg had an NNT of 2.2 (1.9 to 2.6) for at least 50% pain relief over 4 to 6 hours compared with placebo in pain of moderate to severe intensity. This is as effective as 10 mg intramuscular morphine.

There do not appear to be serious adverse effects associated with single oral doses. Although formally approved by the FDA, chronic use of bromfenac has been shown to cause severe hepatic reactions, including jaundice, potentially fatal fulminant hepatitis and liver failure, with some cases requiring transplantation. Since early 1998, therefore, the drug has not been recommended for use above 10 days.

Bromfenac sodium [2-amino-3-(4-bromobenzoyl) benzeneacetic acid sodium salt sesquihydrate; tradename Duract] is a potent nonsteroidal nonnarcotic analgesic agent with anti-inflammatory, antipyretic and prostaglandin synthetase-inhibiting properties. It is structurally related to diclofenac and ketoprofen, and is currently marketed in the US for short-term pain relief. It is not available in the UK.

Systematic review

AD Oldman et al. Unpublished review being prepared for Cochrane Library

Date review completed: March 1998
Number of trials included: 6 (14 bromfenac vs. placebo comparisons)
Number of patients: 1,073 (542 active / 531 control).
Control group: placebo
Main outcomes: Main outcomes: pain relief at 4-6 hours (TOTPAR), Number-needed-to-treat (NNT) (with 95% confidence intervals), relative benefit and relative risk (with 95% confidence intervals).

Inclusion criteria were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which included bromfenac and placebo.

Mean TOTPAR values for each trial were converted to %maxTOTPAR and, and then the proportion of patients achieving at least 50%maxTOTPAR were calculated. This information was used to calculate NNT and relative benefit. Adverse effects frequency data were used to calculate numbers-needed-to-harm and relative risk.

Findings

Bromfenac was significantly superior to placebo at all doses (5 mg, 10 mg, 25 mg, 50 mg and 100 mg). A dose of 25 mg had an NNT of 2.2 (1.9 to 2.6).

Figure: At least 50% pain relief with bromfenac 25 mg compared with placebo

Table: NNTs for different doses of bromfenac compared with placebo

Dose (mg)	No. of Comparisons	Bromfenac at least 50% pain relief/total	Placebo at least 50% pain relief/total	Relative benefit (95% CI)	NNT (95% CI)
5	2	14/69	4 of 69	3.5 (1.2 to 10)	7.1 (3.9 to 28)
10	3	45/116	4/107	9.5 (3.7 to 24)	2.9 (2.3 to 4.0)
25	5	95/187	9/183	10 (5.3 to 20)	2.2 (1.9 to 2.6)
50	3	65/123	15/124	4.3 (2.6 to 7.0)	2.4 (2.0 to 3.3)
100	1	29/47	11 of 48	2.7 (1.5 to 4.7)	2.6 (1.8 to 4.9)

Adverse effects

A meta-analysis was carried out for bromfenac 25 mg vs. placebo. All single dose adverse effects analysed together generated a relative risk of 1.3 (0.8 to 1.9), with no significant difference between bromfenac and placebo.