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Study flow diagram.
Figuras y tablas -
Figure 1

Study flow diagram.

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Comparison 1 Ibuprofen versus paracetamol, Outcome 1 Proportion of patients with > 50% max pain relief (TOTPAR) over 6 hours.
Figuras y tablas -
Analysis 1.1

Comparison 1 Ibuprofen versus paracetamol, Outcome 1 Proportion of patients with > 50% max pain relief (TOTPAR) over 6 hours.

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Comparison 1 Ibuprofen versus paracetamol, Outcome 2 Proportion of patients with > 50% max pain relief (TOTPAR) over 2 hours.
Figuras y tablas -
Analysis 1.2

Comparison 1 Ibuprofen versus paracetamol, Outcome 2 Proportion of patients with > 50% max pain relief (TOTPAR) over 2 hours.

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Comparison 1 Ibuprofen versus paracetamol, Outcome 3 Number of patients using rescue medication at 6 hours.
Figuras y tablas -
Analysis 1.3

Comparison 1 Ibuprofen versus paracetamol, Outcome 3 Number of patients using rescue medication at 6 hours.

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Comparison 1 Ibuprofen versus paracetamol, Outcome 4 Number of patients using rescue medication at 8 hours.
Figuras y tablas -
Analysis 1.4

Comparison 1 Ibuprofen versus paracetamol, Outcome 4 Number of patients using rescue medication at 8 hours.

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Comparison 2 Combined (ibuprofen and paracetamol) versus single drugs, Outcome 1 Proportion of patients with > 50% max pain relief (TOTPAR) over 6 hours.
Figuras y tablas -
Analysis 2.1

Comparison 2 Combined (ibuprofen and paracetamol) versus single drugs, Outcome 1 Proportion of patients with > 50% max pain relief (TOTPAR) over 6 hours.

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Comparison 2 Combined (ibuprofen and paracetamol) versus single drugs, Outcome 2 Proportion of patients with > 50% max pain relief (TOTPAR) over 2 hours.
Figuras y tablas -
Analysis 2.2

Comparison 2 Combined (ibuprofen and paracetamol) versus single drugs, Outcome 2 Proportion of patients with > 50% max pain relief (TOTPAR) over 2 hours.

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Comparison 2 Combined (ibuprofen and paracetamol) versus single drugs, Outcome 3 Number of patients using rescue medication at 8 hours.
Figuras y tablas -
Analysis 2.3

Comparison 2 Combined (ibuprofen and paracetamol) versus single drugs, Outcome 3 Number of patients using rescue medication at 8 hours.

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Summary of findings for the main comparison. Ibuprofen versus paracetamol for pain relief following the surgical removal of lower wisdom teeth

Ibuprofen versus paracetamol for pain relief following the surgical removal of lower wisdom teeth

Patient or population: Patients with pain after surgical removal of lower wisdom teeth
Intervention: Ibuprofen

Control: Paracetamol

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed1 risk

Corresponding risk

Control

Ibuprofen

Proportion of patients with > 50% maximum pain relief (TOTPAR) over 6 hours ‐ Ibuprofen 400 mg versus paracetamol 1000 mg
Categorical scale
Follow‐up: 6 hours

Study population

RR 1.47
(1.28 to 1.69)

646
(5 studies)

⊕⊕⊕⊕
high

When all doses considered RR = 1.45 (95% CI 1.31 to 1.61) (6 studies, 926 participants; high quality evidence)

56 per 100

83 per 100
(72 to 95)

Proportion of patients with > 50% maximum pain relief (TOTPAR) over 2 hours ‐ Ibuprofen 400 mg versus paracetamol 1000 mg
Categorical scale
Follow‐up: 2 hours

Study population

RR 1.30
(1.09 to 1.55)

645
(5 studies)

⊕⊕⊕⊕
high

When all doses considered RR = 1.29 (95% CI 1.13 to 1.46) (6 studies, 926 participants; high quality evidence)

62 per 100

81 per 100
(68 to 97)

Number of patients not using rescue medication at 6 hours (non‐event)
‐ Ibuprofen 400 mg versus paracetamol 1000 mg

Follow‐up: 6 hours

Study population

RR 1.50
(1.25 to 1.79)

542
(4 studies)

⊕⊕⊕⊕
high

When all doses considered RR = 1.44 (95% CI 1.13 to 1.64) (5 studies, 823 participants; high quality evidence)

50 per 100

75 per 100
(63 to 90)

Adverse events

The majority of adverse events were minor in nature and usually included nausea, vomiting, headaches and dizziness.

Side effect profiles have not been included in a meta‐analysis as multiple adverse events were recorded in single patients. However, the differences in the observed adverse events for ibuprofen and paracetamol were small

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 This is the median control group risk based on paracetamol being the control group.

Figuras y tablas -
Summary of findings for the main comparison. Ibuprofen versus paracetamol for pain relief following the surgical removal of lower wisdom teeth
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Summary of findings 2. Combined (ibuprofen and paracetamol) versus single drugs for pain relief after surgical removal of lower wisdom teeth

Combined (ibuprofen and paracetamol) versus single drugs for pain relief after surgical removal of lower wisdom teeth

Patient or population: Patients with pain after surgical removal of lower wisdom teeth
Intervention: Combined (ibuprofen and paracetamol) versus single drugs

Control: Single drugs

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed1 risk

Corresponding risk

Control

Combined (ibuprofen and paracetamol)

Proportion of patients with > 50% maximum pain relief (TOTPAR) over 6 hours ‐ Paracetamol 1000 mg/ibuprofen 400 mg versus paracetamol 1000 mg or ibuprofen 400 mg
Categorical scale
Follow‐up: 6 hours

Study population

RR 1.77
(1.32 to 2.39)

170
(1 study)

⊕⊕⊕⊝
moderate2

38 per 100

67 per 100
(50 to 91)

Proportion of patients with > 50% maximum pain relief (TOTPAR) over 2 hours ‐ Paracetamol 1000 mg/ibuprofen 400 mg versus paracetamol 1000 mg or ibuprofen 400 mg
Categorical scale
Follow‐up: 2 hours

Study population

RR 1.29
(0.91 to 1.85)

170
(1 study)

⊕⊕⊕⊝
moderate2

37 per 100

48 per 100
(34 to 68)

Number of patients not using rescue medication at 8 hours ‐ Paracetamol 1000 mg/ibuprofen 400 mg versus paracetamol 1000 mg or ibuprofen 400 mg
Follow‐up: 8 hours

Study population

RR 1.60
(1.36 to 1.88)

467
(2 studies)

⊕⊕⊕⊕
high

50 per 100

80 per 100
(68 to 94)

Adverse events

The majority of adverse events were minor in nature and usually included nausea, vomiting, headaches and dizziness. Side effect profiles have not been included in a meta‐analysis as multiple adverse events were recorded in single patients. However, the differences in the observed adverse events for ibuprofen and paracetamol were small

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 This is the median control group risk based on paracetamol/ibuprofen as single drugs being the control group.

2 Quality of evidence downgraded due to single study and serious imprecision.

Figuras y tablas -
Summary of findings 2. Combined (ibuprofen and paracetamol) versus single drugs for pain relief after surgical removal of lower wisdom teeth
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Table 1. Doses used in included studies

 

Daniels 2009

Forbes 1990

Hersch 2000*

Mehlisch 1995

Mehlisch 2010

Mehlisch 2010a

Olson 2001*

Paracetamol 500 mg

 

 

 

 

 

 

√  

 

Paracetamol 600 mg

 

 

√  

 

 

 

 

 

Paracetamol 1000 mg

 

√  

 

√  

√  

√  

 √  

 √  

Ibuprofen 200 mg

 

 

 

√  

 

 

√  

 

Ibuprofen 400 mg

 

√   

√  

√     

√  

 √  

√  

 √  

Ibuprofen 512 mg

 

√   

 

 

 

 

 

 

Paracetamol 250 mg/ibuprofen 100 mg

 

 

 

 

 

 

√  

 

Paracetamol 500 mg/ibuprofen 200 mg

 

 

 

 

 

√    

√   

 

Paracetamol 1000 mg/ibuprofen 400 mg

 

 

 

 

 

√  

√   

 

*Liquigel formula.
Figuras y tablas -
Table 1. Doses used in included studies
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Table 2. Use of rescue medication

Study

Use of rescue medication (RM)

Mean time to RM

Use of RM (%)

Use of RM (n)

Total

Observation period

Daniels 2009

6 hours

Paracetamol 1000

44

35

80

Ibuprofen 400

23

18

80

Ibuprofen 512

33

26

80

Forbes 1990

6 hours

Paracetamol 600

3.89 hours

81

29

36

Ibuprofen 400

4.63 hours

63

20

32

Hersch 2000

6 hours

Paracetamol 1000

51

32

63

Ibuprofen 200

31

19

61

Ibuprofen 400

22

13

59

Mehlisch 1995

6 hours

Paracetamol 1000

60

60

101

Ibuprofen 400

26

25

98

Mehlisch 2010

8 hours

Paracetamol 1000

261 minutes

71

24

34

Ibuprofen 400

296 minutes

68

47

69

Paracetamol 1000/ibuprofen 400

376 minutes

31

21

67

Paracetamol 500/ibuprofen 200

329 minutes

61

20

33

Mehlisch 2010a

8 hours in phase 1

Paracetamol 500

74

56

76

Paracetamol 1000

69

51

74

Ibuprofen 200

39

29

75

Ibuprofen 400

28

21

74

Paracetamol 250/ibuprofen 100

38

27

71

Paracetamol 1000/ibuprofen 400

28

42

149

Paracetamol 500/ibuprofen 200

22

31

143

Olson 2001

6 hours

Paracetamol 1000

38

25

66

Ibuprofen 400

21

14

67
Figuras y tablas -
Table 2. Use of rescue medication
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Table 3. Adverse events

Study

Adverse events (AE)

Total AE (n)

Total AE %

Serious/Severe AE

Serious/Severe AE %

Daniels 2009

Paracetamol 1000

25 (81)

31

3

12

Ibuprofen 400

19 (80)

24

1

3

Ibuprofen 512

24 (80)

30

2

6

Forbes 1990

Paracetamol 600

5 (41)

12

Not specified

Not specified

Ibuprofen 400

8 (43)

19

Not specified

Not specified

Hersch 2000

Paracetamol 1000

12 (63)

19

0

0

Ibuprofen 200

7 (61)

11

0

0

Ibuprofen 400

4 (59)

7

0

0

Mehlisch 1995

Paracetamol 1000

17 (101)

17

0

0

Ibuprofen 400

12 (98)

12

0

0

Mehlisch 2010

Paracetamol 1000

24 (34)

71

11

46

Ibuprofen 400

39 (69)

57

14

36

Paracetamol 1000/ibuprofen 400

38 (67)

57

11

29

Paracetamol 500/ibuprofen 200

14 (33)

42

6

43

Mehlisch 2010a

Paracetamol 500

38 (76)

50

7

18

Paracetamol 1000

30 (74)

40

5

17

Ibuprofen 200

31 (75)

41

7

23

Ibuprofen 400

33 (74)

45

5

15

Paracetamol 250/ibuprofen 100

22 (71)

31

8

36

Paracetamol 1000/ibuprofen 400

44 (149)

30

15

34

Paracetamol 500/ibuprofen 200

51 (143)

36

7

14

Olson 2001

Paracetamol 1000

10 (66)

15

1

10

Ibuprofen 400

7 (67)

11

2

29
Figuras y tablas -
Table 3. Adverse events
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Comparison 1. Ibuprofen versus paracetamol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Proportion of patients with > 50% max pain relief (TOTPAR) over 6 hours Show forest plot

6

926

Risk Ratio (M‐H, Random, 95% CI)

1.45 [1.31, 1.61]

1.1 Ibuprofen 200 mg versus paracetamol 1000 mg

1

92

Risk Ratio (M‐H, Random, 95% CI)

1.29 [0.90, 1.84]

1.2 Ibuprofen 400 mg versus paracetamol 1000 mg

5

646

Risk Ratio (M‐H, Random, 95% CI)

1.47 [1.28, 1.69]

1.3 Ibuprofen 400 mg versus paracetamol 600 mg

1

68

Risk Ratio (M‐H, Random, 95% CI)

2.41 [1.13, 5.16]

1.4 Ibuprofen 512 mg versus paracetamol 1000 mg

1

120

Risk Ratio (M‐H, Random, 95% CI)

1.43 [1.15, 1.78]

2 Proportion of patients with > 50% max pain relief (TOTPAR) over 2 hours Show forest plot

6

926

Risk Ratio (M‐H, Random, 95% CI)

1.29 [1.13, 1.46]

2.1 Ibuprofen 512 mg versus paracetamol 1000 mg

1

120

Risk Ratio (M‐H, Random, 95% CI)

1.28 [0.98, 1.67]

2.2 Ibuprofen 400 mg versus paracetamol 1000 mg

5

645

Risk Ratio (M‐H, Random, 95% CI)

1.30 [1.09, 1.55]

2.3 Ibuprofen 200 mg versus paracetamol 1000 mg

1

93

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.85, 1.41]

2.4 Ibuprofen 400 mg versus paracetamol 600 mg

1

68

Risk Ratio (M‐H, Random, 95% CI)

1.74 [0.96, 3.14]

3 Number of patients using rescue medication at 6 hours Show forest plot

5

823

Risk Ratio (M‐H, Random, 95% CI)

1.44 [1.26, 1.64]

3.1 Ibuprofen 200 mg versus paracetamol 1000 mg

1

93

Risk Ratio (M‐H, Random, 95% CI)

1.38 [0.94, 2.02]

3.2 Ibuprofen 400 mg versus paracetamol 1000 mg

4

542

Risk Ratio (M‐H, Random, 95% CI)

1.50 [1.25, 1.79]

3.3 Ibuprofen 512 mg versus paracetamol 1000 mg

1

120

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.86, 1.60]

3.4 Ibuprofen 400 mg versus paracetamol 600 mg

1

68

Risk Ratio (M‐H, Random, 95% CI)

1.93 [0.87, 4.30]

4 Number of patients using rescue medication at 8 hours Show forest plot

2

402

Risk Ratio (M‐H, Fixed, 95% CI)

2.02 [1.57, 2.60]

4.1 Ibuprofen 200 mg versus paracetamol 500 mg

1

75

Risk Ratio (M‐H, Fixed, 95% CI)

2.36 [1.31, 4.25]

4.2 Ibuprofen 400 mg versus paracetamol 500 mg

1

75

Risk Ratio (M‐H, Fixed, 95% CI)

2.77 [1.57, 4.89]

4.3 Ibuprofen 200 mg versus paracetamol 1000 mg

1

75

Risk Ratio (M‐H, Fixed, 95% CI)

1.87 [1.10, 3.17]

4.4 Ibuprofen 400 mg versus paracetamol 1000 mg

2

177

Risk Ratio (M‐H, Fixed, 95% CI)

1.66 [1.11, 2.48]
Figuras y tablas -
Comparison 1. Ibuprofen versus paracetamol
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Comparison 2. Combined (ibuprofen and paracetamol) versus single drugs

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Proportion of patients with > 50% max pain relief (TOTPAR) over 6 hours Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1 Paracetamol 1000 mg/ibuprofen 400 mg versus paracetamol 1000 mg or ibuprofen 400 mg

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Proportion of patients with > 50% max pain relief (TOTPAR) over 2 hours Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 Paracetamol 1000 mg/ibuprofen 400 mg versus paracetamol 1000 mg or ibuprofen 400 mg

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Number of patients using rescue medication at 8 hours Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Paracetamol 1000 mg/ibuprofen 400 mg versus paracetamol 1000 mg or ibuprofen 400 mg

2

467

Risk Ratio (M‐H, Fixed, 95% CI)

1.60 [1.36, 1.88]
Figuras y tablas -
Comparison 2. Combined (ibuprofen and paracetamol) versus single drugs
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