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. 2015 Jun 15;2015(6):CD007402. doi: 10.1002/14651858.CD007402.pub3
Study ID Treatment Local AEs Systemic AEs Serious AEs Withdrawals
Airaksinen 1993 (1) Ketoprofen gel 2 x 5 g (125 mg) daily, n = 29
(2) Placebo gel, n = 27
(1) 5/29
(2) 4/27
(1) 1/29 (nausea after paracetamol)
(2) 0/27
None AE: none
Other: none reported
Ăkermark 1990 (1) Indomethacin spray 1% (Elmetacin), 3‐5 x 0.5‐1.5 mL daily, n = 23
(2) Indomethacin capsules, 3 x 25 mg daily, n = 23
(3) Placebo spray and capsules, n = 24
(1) 4/22
(2) 0/22
(3) 0/24
No usable data ‐ reported for events not participants None reported AE: (1) 1, (2) 1, (3) 0
Lost to follow‐up: (1) 1, (2) 2, (3) 3
Aoki 1984 (1) Piroxicam gel 5%, 3 or 4 x 1 g daily, n = 84
(2) Indomethacin gel 1%, 3 or 4 x 1 g daily, n = 84
(3) Placebo gel, n = 84
(1) 1/79
(2) 2/70
(3) 2/74
None None reported AE: none
23 excluded for protocol violations: (1) 7, (2) 7, (3) 9
26 withdrew for reasons unrelated to treatment: (1) 5, (2) 13, (3) 8
Auclair 1989 (1) Niflumic acid gel 2.5%, 3 x 5 g daily, n = 117
(2) Placebo gel, n = 110
All AEs
(1) 5/123
(2) 6/116
Most commonly cutaneous eruptions
No usable data None reported AE: (1) 1/123, (2) 0/116
26 excluded from efficacy analysis for not meeting entry criteria and protocol violations
Billigmann 1996 (1) Ibuprofen microgel 5% 3 x 200 mg daily, n = 80
(2) Placebo gel, n = 80
(1) 11/80
(2) 4/80
None reported None reported AE: (1) 2/80 (allergic rash, dermatitis)
No reason given: (1) 3/80, (2) 5/80
 Symptom‐free: (1) 1/80, (2) 1/80
Campbell 1994 (1) Ibuprofen cream 5% (Proflex) 4 x 4" daily, n = 26
(2) Placebo cream, n = 25
No data (1) 1/26 (headache)
(2) 0/25
No data AE: none
Exclusions 49: 3 presented late, 2 missing forms, 1 appeared twice, 43 did not return diaries
Chatterjee 1977 (1) Benzydamine HCl cream 3% 3 x daily, n = 25
(2) Placebo cream, n = 25
None None None AE: none
1 participant lost to follow‐up (group not reported)
Costantino 2011 (1) DHEP‐heparin plaster (Flectorparin) x 1 daily, n = 142
(2) DHEP plaster (Flector) x 1 daily, n = 146
(3) Placebo plaster, n = 142
Possibly or probably drug‐related
 (1) 2/142
 (2) 1/145
 (3) 6/142
 
 All mild and gone by 14 days, except 1 (moderate) in placebo group Not reported
 No systemic GI events None AE: none
Other:
(1) 0/142
 (2) 2/146 (protocol deviation, lost to follow‐up)
 (3) 2/142 (lost to follow‐up)
Coudreuse 2010 (1) DHEP‐heparin plaster (Flectorparin), n = 120
 (2) Placebo, n = 120 (1) 1/117
 (2) 7/116
 
 All AEs mild or moderate, resolved spontaneously (1) 1/117
 (2) 0/116 None AE:
(1) 1/117 (increased oedema)
(2) 0/116
Other:
(1) 6/117 (recovery 3, no reason 3)
(2) 3/116 (recovery 1, no reason 2)
Curioni 1985 (1) Ibuproxam, n = 20
(2) Ketoprofen, n = 20
(3) Etofenamate, n = 20
None None None AE: none
Other: none
Diebshlag 1990 (1) Ketorolac gel 2% 3 x 3 g daily, n = 13
(2) Etofenamate gel 5% 3 x 3 g daily, n = 12
(3) Placebo gel, n = 12
(1) 1/13
(2) 1/12
(3) 0/12
None None AE: none
1 ketorolac participant did not attend 15 day follow‐up due to car accident
Dreiser 1988 (1) Ibuprofen cream 5%, 3 x 4 cm daily, n = 32 (3 x 10 cm for large joints)
(2) Placebo cream, n = 32
No usable data None Not reported AE: none
4 placebo participants lost to follow‐up
Dreiser 1989 (1) Ketoprofen gel 2.5%, 2 x 5 cm daily, n = 30
(2) Placebo gel, n = 30
(1) 0/30
(2) 2/30
None None reported AE: (2) 2/30 (intolerance)
LoE: (1) 1/30, (2) 1/30
Dreiser 1990 (1) Niflumic acid gel 2.5%, 3 x 5 g daily, n = 30
(2) Placebo gel, n = 30
(1) 0/30
(2) 3/30
None None AE: (2) 1/30 (erythema)
Exclusion: 1 from (2) from efficacy analysis for inadequate baseline pain
Dreiser 1994 (1) Flurbiprofen plaster 2 x 40 mg daily, n = 65
(2) Placebo plaster, n = 66
(1) 2/65
(2) 0/66
None None AE: 0
(1) 1/65 excluded from efficacy analysis for protocol violation
 (2) 2/66 (1 LoE, 1 cured)
Fioravanti 1999 (1) DHEP lecithin gel 3 x 5 g (= 65 mg) daily, n = 50
(2) DHEP gel 3 x 5 g (= 65 mg) daily, n = 50
(1) 0/50
(2) 1/50
No data None reported AE: none
Other: none
Fujimaki 1985 (1) Piroxicam gel 0.5% 3 or 4 x 1 g daily, n = 92
(2) Indomethacin gel 1% 3 or 4 x 1 g daily, n = 90
(3) Placebo gel, n = 89
(1) 1/83
(2) 5/82
(3) 2/82
(1) 0/83
(2) 1/82 (nausea and vomiting)
(3) 0/82
None AE: (1) 0, (2) 4, (3) 0
Unknown reasons: (1) 2, (2) 1
Did not return after 1st visit/irregular visits: (1) 6, (2) 6, (3) 7
Gallacchi 1990 (1) Diclofenac hydroxyethylpyrrolidine gel 1%, 4 x 2 g daily, n = 25 (Flector gel)
(2) Diclofenac sodium 1% 4 x 2 g daily, n = 25 (Voltaren Emugel)
No AEs None None AE: none
Other: none
González de Vega 2013 (1) Traumeel gel 3 x 2 g daily, n = 140
(2) Traumeel ointment, n = 143
 (3) Diclofenac gel 1% 3 x 2 g daily, n = 137
No usable data
 
 Infrequent, mild to moderate No usable data None AE: none
Other:
(1) 11/140
 (2) 12/137
Governali 1995 (1) Ketoprofen gel 5% 3 x 2‐3 g daily, n = 15
(2) Ketoprofen cream 1%, 3 x 2‐3 g daily, n = 15
No side effects None None AE: none
Other: none
Gualdi 1987 (1) Flunaxaprofen gel 2 x 3‐5 cm daily, n = 30
(2) Ketoprofen gel 2 x 3‐5 cm daily, n = 30
(1) 1/30
(2) 3/30
No data None reported AE: none
Other: none
Haig 1986 (1) Benzydamine cream 3%, 6 x daily, n = 21
(2) Placebo cream, n = 22
No AEs reported None None reported AE: none reported
Other: no data
Hoffmann 2012 (1) DHEP‐heparin plaster (Flectorparin) x 1 daily, n = 121
 (2) DHEP (Flector) plaster x 1 daily, n = 115
 (3) Placebo plaster, n = 118 Most AEs were minor local reactions (e.g. pruritus and erythema) in area of plaster, of mild to moderate intensity and resolved without interrupting treatment No treatment‐related systemic AEs recorded (2) 1 participant had 3 SAEs, none judged related to study medication AE: none
Exclusions:
(1) 5/121
(2) 10/115
(3) 7/118
Excluded from per protocol analysis due to poor compliance or personal decision
Hofman 2000 (1) Diclofenac sodium gel 1%, 4 x 2 cm daily, n = 69
(2) Lysine clonixinate gel 5%, 4 x 2 cm (22.5 mg) daily, n = 73
(1) 1/58
(2) 1/61
None None AE: none
LoE: (1) 9, (2) 8
Hosie 1993 (1) Felbinac foam 3% 3 x 2 g daily + placebo tablets, 3 x 1 daily, n = 140 (127 analysed for efficacy)
(2) Ibuprofen tablets 3 x 400 mg daily + placebo foam 3 x 2 g daily, n = 147 (134 analysed for efficacy)
(1) 1/127
(2) 3/134
GI events: (1) 14/127, (2) 11/134
For (1) more mild, none definitely drug related, for (2) definitely related to study drug
None AE: none
Exclusions: (1) 13, (2) 13 did not return for 7 day follow‐up
Jenoure 1997 (1) DHEP plaster (Tissugel), 2 x daily, n = 44
(2) Placebo plaster 2 x daily, n = 41
(1) 1/44
(2) 1/41
No data None reported AE: none reported
Other: none reported
Joussellin 2003 (1) DHEP plaster (Flector Tissugel 1%), 1 x daily, n = 68
(2) Placebo plaster 1 x daily, n = 66
(1) 1/68 (pruritus)
 (2) 3/66 (pruritus 2, burning 1)
 
 All AEs mild or moderate (1) 1/68 (allergic reaction)
 (2) 0/66 None reported AE:
(1) 0/66
(2) 1/66
Other:
(1) 3/66
(2) 2/66
Julien 1989 (1) Ketoprofen gel 2.5% 2 x 5 cm (= 50 mg) daily, n = 30
(2) Placebo gel, n = 30
(1) 1/30
(2) 0/30
Not reported None AE: none
Other: none
Klainguti 2010 (1) DHEP‐heparin plaster (Flectorparin) x 1 daily, n = 62
 (2) DHEP plaster (Flector) x 1 daily, n = 61
 (3) Placebo, n = 59 (1) 0/62
(2) 0/61
(3) 1/59
 All AEs mild in nature and resolved spontaneously
(1) 1/65 (facial infection)
(2) 1/61 (abdominal pain)
(3) 0/59
None AE: none
Other:
(1) 3/65
 (2) 1/61
 (3) 3/59
Kockelbergh 1985a (1) Ketoprofen gel 2.5% 2 x 5 cm (= 15 mg) daily, n = 38
(2) Placebo gel, n = 36
(1) 1/38
(2) 1/26
Not reported None AE: none
Other: none
Kuehl 2011 (1) DETP 1.3% plaster 2 x daily, n = 207
 (2) Placebo plaster, n = 211 (1) 16/207
 (2) 12/211 (1) 15/207
 (2) 23/211 None AE:
(1) 4/207
 (2) 9/211
LoE:
(1) 21/207
(2) 25/211
Other:
(1) 58/207
(2) 62/211
Li 2013 (1) DHEP plaster (Flector) 2 x daily, n = 192
 (2) Placebo plaster 2 x daily, n = 192 (1) 4/192
 (2) 3/192 (1) 10/192
 (2) 4/192 None AE:
(1) 2/192
 (2) 0/192
Other:
(1) 5/192
 (2) 1/192
Linde 1985 (1) Benzydamine 3% cream 3 x daily, n = 50
(2) Placebo gel, n = 50
(1) 4/40
(2) 2/41
None None AE: none
(1) 6, (2) 6 excluded from 1st assessment
 (1) 3, (2) 4 excluded from final assessment
Machen 2002 (1) Ibuprofen gel 5% 3 x daily, n = 40
(2) Placebo gel, n = 41
(1) 4/40
(2) 2/41
None None AE: none
(1) 1 LoE, 1 protocol violation
 (2) 4 LoE
Mahler 2003 (1) DHEP + lethicin gel 3 x 5 g daily, n = 52
(2) DHEP gel 3 x 5 g daily, n = 48
(1) 1/52
(2) 0/48
(1) 1/52
(2) 0/48
None AE: none
5 lost to follow‐up
Mazières 2005b (1) Ketoprofen plaster 100 mg, x 1 daily, n = 81
(2) Placebo plaster, n = 82
At 21 days:
(1) 12/81
(2) 6/82
(1) 13/81
(2) 14/82
None AE: (1) 3/81
(1) 7/81 (1 LoE, 6 cured)
(2) 7/82 (5 LoE, 2 cured)
Mazières 2005a (1) Ketoprofen plaster 100 mg, x 1 daily, n = 87
(2) Placebo plaster, n = 85
At 21 days:
(1) 29/87
(2) 27/85
(1) 11/87
(2) 7/85
None AE: (1) 9/87, (2) 6/85
(1) 6/87 (2 LoE, 4 cured)
(2) 5/85 (4 LoE, 1 cured)
McLatchie 1989 (1) Felbinac gel 3% 3 x 3 cm daily, n = 118
(2) Placebo gel, n = 113
(1) 3/118
(2) 2/113
Mild transient local irritation
None reported None AE: none
Other: none
Morris 1991 (1) Felbinac gel 3% 3 x 1 cm daily, n = 41
(2) Placebo gel, n = 43
None None None AE: none
(1) 4 (protocol violations)
(2) 1 (lost to follow‐up)
Exclusions: 11 from efficacy analysis because evaluated by 4 different investigators
NCT01255423 (1) Diclofenac sodium gel 1% x 4 daily, n = 104
 (2) Placebo gel x 4 daily, n = 100 (1) 1/104
(2) 3/102
Total AE
(1) 11/104
(2) 8/102
None None
NCT01272934 (1) Diclofenac sodium gel 1% x 4 daily, n = 104
 (2) Placebo gel x 4 daily, n = 100 (1) 1/102
(2) 0/103
Total AE (excluding SAE)
(1) 6/102
(2) 3/103
(1) 0/102
(2) 1/103 (ruptured ligaments in wrist)
AE: see SAE
NCT01272947 (1) Diclofenac sodium gel 1% x 4 daily, n = 104
 (2) Placebo gel x 4 daily, n = 100 None (1) 2/104
(2) 2/100
None None
Noret 1987 (1) Ketoprofen gel 2.5% 2 x 5 cm (7.5 mg) daily, n = 48
(2) Placebo gel, n = 45
(1) 1/51
(2) 0/47
None reported Not reported AE: (1) 1/51 (skin allergy)
(1) 1 LoE, 1 unrelated to trial
 (2) 1 LoE, 1 unrelated to trial
Parrini 1992 (1) Ketoprofen foam 15% 3 x 2 g (200 mg) daily, n = 83
(2) Placebo foam, n = 86
None None None AE: none
Other: none
Picchio 1981 (1) Ibuprofen gel 10% 3 x daily , n = 20
(2) Ketoprofen gel 1% 3 x daily, n = 20
None None None AE: none
Other: not reported
Predel 2004 (1) Diclofenac sodium plaster, 2 x daily (140 mg/plaster), n = 60
(2) Placebo plaster, n = 60
12 participants experienced 16 mild AEs with no differences between groups None None AE: (1) 1/60
Other: none
Predel 2012 (1) Diclofenac gel (Voltaren Emulgel 2.32%) 2 x 5 cm daily, n = 80
 (2) Diclofenac gel (Voltaren Emulgel 2.32%) 3 x 5 cm daily, n = 80
 (3) Placebo gel, n = 82 (1) 0/80
 (2) 1/80
(3) 1/82
All mild to moderate
(1) 2/80
 (2) 1/80
 (3) 3/82 None AE:
(1) 0/80
 (2) 0/80
 (3) 1/82
Other:
(1) 1/80
 (2) 2/80
 (3) 2/82
(protocol violations, lost to follow‐up)
Predel 2013a (1) Diclofenac 4% spray gel 4 or 5 sprays 3 x daily (96‐120 mg diclofenac sodium), n = 118
 (2) Placebo spray gel, n = 114 (1) 1/118
 (2) 4/114 (1) 5/118
 (2) 4/114
All AEs mild, reversible
None AE:
(1) 1/118
 (2) 1/114
Other:
(1) 3/118
 (2) 43/114
Predel 2013b (1) Diclofenac gel (Voltaren Emulgel) 4 x 2 g daily, n = 36
 (2) Placebo gel 4 x 2 g daily, n = 36 None (1) 0/36
 (2) 1/36 None AE: none
Other: none
Ramesh 1983 (1) Ibuprofen cream 5% 3 or 4 x 5‐10 cm daily, n = 40
(2) Placebo cream, n = 40
(1) 1/40
(2) 1/40
None reported Not reported AE: (1) 1/40, (2) 1/40
Other: none
Rowbotham 2003 (1) DHEP plaster (Flector Tissuegel) 2 x daily, n = 191
(2) Placebo plaster, n = 181
(1) 27/191 (pruritis 14)
(2) 31/181 (pruritis 21)
(1) 21/191
(2) 22/181
None reported ("vast majority mild") AE: none
(1) 3/191, (2) 4/181 (did not finish trial and complete daily diaries)
Russell 1991 (1) Piroxicam gel 0.5% 4 x 5 mg daily, n = 100
(2) Placebo gel, n = 100
(1) 4/102
(2) 10/102
GI or CNS events: (1) 4, (2) 7
Any AE: (1) 7/102, (2) 15/102
None reported AE: (1) 1/102, (2) 8/102
Other: (1) 6 LoE, 1 "other"
(2) 42 LoE
Exclusions: 7 did not comply with study medication schedule, 6 lost to follow‐up, 1 protocol violation
Saillant 1998 (1) DHEP plaster (Flector Tissugel 1%) 1 x daily, n = 70
 (2) Placebo plaster 1 x daily, n = 70 None None None AE: none
Other:
(1) 5/70
(2) 5/70
Sanguinetti 1989 (1) Felbinac gel 3% 3 x daily, n = 42
(2) Placebo gel, n = 40
(1) 3/42
 (2) 1/40 None None reported AE: none
Other: none reported
Sinniger 1981 (1) Fentiazac cream 5% 2 or 3 x daily, n = 10
(2) Placebo cream, n = 10
"No untoward side effects" None None AE: none
Other: none reported
Spacca 2005 (1) DHEP lecithin gel (Effigel), 3 x 5 g, daily, n = 79
(2) Placebo gel, n = 76
"No signs of cutaneous irritation or sensitisation observed" No AEs observed None AE: none
Other: none reported
Sugioka 1984 (1) Piroxicam gel 0.5% 3 or 4 x 1 g daily, n = 183
(2) Indomethacin gel 1% 3 or 4 x 1 g daily, n = 183
(1) 5/178
(2) 26/179
None reported None reported AE: none reported
Exclusions due to protocol violations:
 (1) 8, (2) 18
Withdrawals:
 (1) 11, (2) 12
Thorling 1990 (1) Naproxen gel 10% 2‐6 x daily, n = 60
(2) Placebo gel, n = 60
(1) 1/60
(2) 0/60
None None AE: none
(1) 1 LoE, 1 protocol violation
 (2) 1 participant request
Tonutti 1994 (1) Ketoprofen gel 5%, 3 x 2‐3 g daily, n = 15
(2) Etofenamate gel 5%, 3 x 2‐3 g, n = 15
None No AEs attributable to the medication None AE: None
LoE: (1) 1, (2) 2
Vecchiet 1991 (1) Meclofenamic acid gel 5% 2 x 10 cm daily (2 g), n = 30
(2) Placebo, n = 30
Tolerability excellent or good in nearly all participants No data None AE: none reported
(2) 5 lost to follow‐up
Whitefield 2002 (1) Ibuprofen gel 5% + placebo tablet 3 x daily, n = 50
(2) Ibuprofen 400 mg tablet + placebo gel 3 x daily, n = 50
No data 6 AEs reported, none judged related to study medication None reported AE: none
Recovered: (1) 3, (2) 2
LoE: (2) 1
Lost to follow‐up: (1) 1, (2) 1
AE: adverse event; CNS: central nervous system; DHEP: diclofenac epolamine; GI: gastrointestinal; HCl: hydrochloride; LoE: lack of efficacy; n: number; SAE: serious adverse event.