3. Less serious adverse effects from RCTs. Oral isotretinoin versus itself (different formulations or combined with topical) or other active therapies.
| Adverse effects (AE) outcomes (clinical and laboratory) | Study | Oral isotretinoin versus itself (different formulations or combined with topical) or other active therapies | Estimate of effect: risk ratio, 95% CI | |
|
Intervention Number of participants who experienced the AE/Number of analysed participants |
Control Number of participants who experienced the AE/Number of analysed participants |
|||
| 1.Overall incidence ‐ measured at 1st month | Gollnick 2001 | Oral isotretinoin 0.5 to 0.8 mg/kg/day for 6 months 16/35 |
Oral minocycline (50 mg twice daily) plus topical azelaic acid cream (twice daily) for 6 months* 12/50 |
1.90 (1.03 to 3.51)a |
| 2. Overall incidence ‐ during the 20‐week therapy | Tan 2014 | Oral isotretinoin (0.5 mg/kg/day for the first 4 weeks with escalation to 1 mg/kg/day for subsequent 16 weeks) plus vehicle gel 116/133 |
Oral doxycycline 200 mg plus adapalene 0.1% /benzoyl peroxide 2.5% gel (both once daily) 70/133 |
1.66 (1.39 to 1.97)a |
| 3. Overall incidence ‐ during the 8‐week therapy | Faghihi 2014 |
Oral isotretinoin, 20 mg once a day plus vehicle neutral gel applied on the face twice daily, both for 8 weeks 3/29 |
Oral isotretinoin, 20 mg once a day plus 5% dapsone gel applied on the face twice daily, both for 8 weeks 18/29 |
0.17 (0.06 to 0.51)a |
| 4. Overall incidence ‐ during 20‐week therapy | Webster 2014 |
Standard oral isotretinoin, 0.5 mg/kg/day first 8 weeks, followed by 1 mg/kg/day until week 20 385/460 |
Isotretinoin‐Lidose, 1 mg/kg/day for 20 weeks 403/464 |
0.96 (0.91 to 1.02) |
| 5. Overall incidence ‐ during 20‐week therapy | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 293/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 296/300 |
1.01 (0.99 to 1.03 |
| 6. Overall incidence ‐ during 16‐week therapy | Rademaker 2013b | Oral isotretinoin 5 mg once daily 28/29 |
Placebo 26/30 |
4.31 (0.45 to 41.09) |
| 7. Severe/persistent skin symptoms | Gollnick 2001 | Oral isotretinoin 0.5 to 0.8 mg/kg/day for 6 months 7/35 |
Oral minocycline (50 mg twice daily) plus topical azelaic acid cream (twice daily) for 6 months 3/50 |
3.33 (0.93 to 12.01) |
| 8. Systemic side effects | Gollnick 2001 | Oral isotretinoin 0.5 to 0.8 mg/kg/day for 6 months 6/35 |
Oral minocycline (50 mg twice daily) plus topical azelaic acid cream (twice daily) for 6 months 6/50 |
1.43 (0.50 to 4.07) |
| 9. Melasma‐like pigmentation | Dhir 2008 | Oral isotretinoin 20 mg twice a day for 24 weeks 5/25 |
Oral isotretinoin 20 mg twice a day along with topical clindamycin (1%) during the daytime and adapalene (0.1%) at bedtime for 24 weeks 3/25 |
1.66 (0.44 to 6.24) |
| 10. Flare‐up (during the first eight weeks of treatment) | Dhir 2008 |
Oral isotretinoin 20 mg twice a day for 24 weeks 3/25 |
Oral isotretinoin 20 mg twice a day along with topical clindamycin (1%) during the daytime and adapalene (0.1%) at bedtime for 24 weeks 6/25 |
0.50 (0.14 to 1.78) |
| 11. Dry lips | Tan 2014 | Oral isotretinoin (0.5 mg/kg/day for the first 4 weeks with escalation to 1 mg/kg/day for subsequent 16 weeks) plus vehicle gel 66/133 |
Oral doxycycline 200 mg plus adapalene 0.1%/benzoyl peroxide 2.5% gel (both once daily) 9/133 |
7.33 (3.81 to 14.10)a |
| Rademaker 2013b | Oral isotretinoin 5 mg once daily 18/29 |
Placebo 3/30 |
14.73 (3.60 to 60.26) | |
| 12. Cheilitis | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 28/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 28/28 |
1.00 (0.93 to 1.07) |
| Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 274/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 271/300 |
1.01 (0.96 to 1.06) | |
| Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 12/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
25.00 (1.65 to 379.57)a | |
| Tan 2014 | Oral isotretinoin (0.5 mg/kg/day for the first 4 weeks with escalation to 1 mg/kg/day for subsequent 16 weeks) plus vehicle gel 32/133 |
Oral doxycycline 200 mg plus adapalene 0.1%/benzoyl peroxide 2.5% gel (both once daily) 2/133 |
16.00 (3.91 to 65.42)a | |
| 13. Cheilitis or dry lips | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 15/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 13/15 |
4.43 (1.75, 11.23)a |
| 14. Xerosis (dry skin) | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 28/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 21/28 |
1.33 (1.06 to 1.65)a |
| Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 15/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 2/15 |
6.20 (1.98 to 19.43)a | |
| Strauss 2001 |
Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 152/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 159/300 |
0.96 (0.82 to 1.12) | |
| Rademaker 2013b | Oral isotretinoin 5 mg once daily 6/29 |
Placebo 4/30 |
1.70 (0.42 to 6.77) | |
| Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 12/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
25.00 (1.65 to 379.57)a | |
| Tan 2014 | Oral isotretinoin (0.5 mg/kg/day for the first 4 weeks with escalation to 1 mg/kg/day for subsequent 16 weeks) plus vehicle gel 43/133 |
Oral doxycycline 200 mg plus adapalene 0.1%/benzoyl peroxide 2.5% gel (both once daily) 22/133 |
1.95 (1.24 to 3.08)a | |
| 15. Pruritus | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 28/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 16/28 |
1.73 (1.25 to 2.38)a |
| Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
3.00 (0.13 to 68.26) | |
| Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 1/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
3.00 (0.13 to 67.06) | |
| 16. Rhinitis sicca | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 21/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 16/28 |
1.31 (0.89 to 1.93) |
| 17. Nasal dryness (dry nose) | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 96/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 91/300 |
1.05 (0.83 to 1.34) |
| Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 10/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 1/15 |
10.00 (1.46 to 68.69)a | |
| 18. Epistaxis | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 14/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 9/28 |
1.56 (0.81 to 2.99) |
| Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 10/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
21.00 (1.34, 328.86)a | |
| Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 122/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 103/300 |
1.18 (0.96 to 1.46) | |
| Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 8/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
17.00 (1.09 to 265.02)a | |
| 19. Nasopharyngitis | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 23/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 17/300 |
1.35 (0.74 to 2.48) |
| 20. Sore mouth | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 12/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 5/28 |
2.40 (0.97 to 5.92) |
| 21. Dry mouth | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 3/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 1/15 |
3.00 (0.35 to 25.68) |
| Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 4/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
9.00 (0.54 to 150.81) | |
| 22. Facial dermatitis | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 18/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 8/28 |
2.25 (1.18 to 4.30)a |
| 23. Dermatitis | Goldstein 1982 |
Oral isotretinoin 1 mg/kg/day for 8 weeks 10/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 11/28 |
0.91 (0.46 to 1.79) |
| Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 46/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 25/300 |
1.84 (1.16 to 2.91)a | |
| 24. Skin fragility | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 11/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 11/28 |
1.00 (0.5 to 1.92) |
| 25. Localised exfoliation | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 126/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 113/300 |
1.12 (0.92 to 1.36) |
| 26. Erythema | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 3/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
7.00 (0.39 to 124.83) |
| Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 4/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
9.00 (0.54 to 150.81) | |
| 27. Erythematous eruption | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 108/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 86/300 |
1.26 (0.99 to 1.59) |
| 28. Desquamation | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 7/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
15.00 (0.93 to 241.20) |
| Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 7/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
15.00 (0.95 to 236.42) | |
| 29. Fingertip peeling | Goldstein 1982 |
Oral isotretinoin 1 mg/kg/day for 8 weeks 10/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 18/28 |
0.56 (0.31 to 0.98) |
| 30. Tender finger tips | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
3.00 (0.13 to 68.26) |
| 31. Desquamation of palms and soles | Goldstein 1982 |
Oral isotretinoin 1 mg/kg/day for 8 weeks 5/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 16/28 |
0.31 (0.13 to 0.74)a |
| 32. Eczema | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
3.00 (0.13, 68.26) |
| 33. Fissuring | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
3.00 (0.13 to 68.26) |
| 34. Crusting of lesions | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
3.00 (0.13 to 68.26) |
| 35. Morbiliform eruption | Lester 1985 |
Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 0/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 1/15 |
0.33 (0.01 to 7.58) |
| 36. Herpes simplex | Lester 1985 |
Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 0/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 1/15 |
0.33 (0.01 to 7.58) |
| 37. Flushing | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 1/15 |
1.00 (0.07 to 14.55) |
| 38. Pyogenic granuloma‐like lesions | Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 1/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
3.00 (0.13 to 67.06) |
| 39. Light intolerance | Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 1/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
3.00 (0.13 to 67.06) |
| 40. Phototoxicity | Pigatto 1986 |
Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 0/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 1/12 |
0.33 (0.01 to 7.45) |
| 41. Alopecia | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 3/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
7.00 (0.39 to 124.83) |
| Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 3/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
7.00 (0.40 to 122.44) | |
| Goldstein 1982 |
Oral isotretinoin 1 mg/kg/day for 8 weeks 9/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 15/28 |
0.60 (0.32 to 1.14) | |
| 42. Dry hair | Lester 1985 |
Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 2/15 |
0.50 (0.05 to 4.94) |
| 43. Dry eyes or xerophthalmia | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 2/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
5.00 (0.26 to 96.13) |
| Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 2/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
5.00 (0.27 to 94.34) | |
| Rademaker 2013b | Oral isotretinoin 5 mg once daily 5/29 |
Placebo 2/30 |
2.92 (0.52 to 16.42) | |
| Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 90/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 80/300 |
1.13 (0.87 to 1.45) | |
| 44. Eye irritation | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 16/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 6/28 |
2.67 (1.22 to 5.81)a |
| Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 84/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 71/300 |
1.18 (0.90 to 1.55) | |
| 45. Eye pain | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 6/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 1/28 |
6.00 (0.77 to 46.66) |
| 46. Mild conjunctival injection (assessed only at 8 weeks) | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 7/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 7/28 |
1.00 (0.40 to 2.48) |
| 47. Conjunctivitis | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
3.00 (0.13 to 68.26) |
| 48. Photophobia | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
3.00 (0.13 to 68.26) |
| 49. Pterygium, right eye | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
3.00 (0.13 to 68.26) |
| 50. Small posterior subcapsular cataract opacities | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 2/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
5.00 (0.26 to 96.13) |
| 51. Headache | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 8/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 4/28 |
2.00 (0.68 to 5.89) |
| Rademaker 2013b |
Oral isotretinoin 5 mg once daily 7/29 |
Placebo 14/30 |
0.36 (0.12 to 1.11) | |
| Strauss 2001 |
Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 40/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 48/300 |
0.83 (0.57 to 1.23) | |
| 52. Lethargy | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 13/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 4/28 |
3.25 (1.21 to 8.75)a |
| 53. Fatigue | Rademaker 2013b | Oral isotretinoin 5 mg once daily 3/29 |
Placebo 3/30 |
1.04 (0.19 to 5.62) |
| 54. Tiredness | Lester 1985 |
Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 0/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 2/15 |
0.20 (0.01 to 3.85) |
| 55. Joint pain | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 6/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 3/28 |
2.00 (0.55 to 7.22) |
| 56. Back pain | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 16/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 11/300 |
1.45 (0.69 to 3.08) |
| 57. Musculoskeletal symptoms | Rademaker 2013b | Oral isotretinoin 5 mg once daily 6/29 |
Placebo 2/30 |
3.65 (0.67 to 19.85) |
| 58. Increased thirst | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 9/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 7/28 |
1.29 (0.56 to 2.97) |
| Lester 1985 |
Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 0/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 2/15 |
0.20 (0.01 to 3.85) | |
| 59. Increased appetite | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 6/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 1/28 |
6.00 (0.77 to 46.66 ) |
| 60. Anorexia | Pigatto 1986 |
Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 2/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 3/12 |
0.67 (0.13 to 3.30) |
| 61. Abdominal pain | Goldstein 1982 |
Oral isotretinoin 1 mg/kg/day for 8 weeks 3/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 4/28 |
0.75 (0.18 to 3.05) |
| 62. Nausea | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 1/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 1/28 |
1.00 (0.07 to 15.21) |
| Pigatto 1986 |
Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 0/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 7/12 |
0.07 (0.00 to 1.05) | |
| Tan 2014 |
Oral isotretinoin (0.5 mg/kg/day for the first 4 weeks with escalation to 1 mg/kg/day for subsequent 16 weeks) plus vehicle gel 3/133 |
Oral doxycycline 200 mg plus adapalene 0.1%/benzoyl peroxide 2.5% gel (both once daily) 9/133 |
0.33 (0.09 to 1.20) | |
| 63. Vomiting | Pigatto 1986 |
Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 0/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 3/12 |
0.14 (0.01 to 2.50) |
| Tan 2014 |
Oral isotretinoin (0.5 mg/kg/day for the first 4 weeks with escalation to 1 mg/kg/day for subsequent 16 weeks) plus vehicle gel 1/133 |
Oral doxycycline 200 mg plus adapalene 0.1%/benzoyl peroxide 2.5% gel (both once daily) 10/133 |
0.10 (0.01 to 0.77)a | |
| 64. Diarrhea | Pigatto 1986 |
Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 0/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 2/12 |
0.14 (0.01 to 2.50) |
| 65. Infections | Rademaker 2013b |
Oral isotretinoin 5 mg once daily 11/29 |
Placebo 15/30 |
0.61 (0.22 to 1.72) |
| 66. Indigestion | Lester 1985 |
Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 0/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 1/15 |
0.33 (0.01 to 7.58) |
| 67. Decreased sweating | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 1/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
3.00 (0.13 to 68.26) |
| 68. Insomnia | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 8/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 8/28 |
1.00 (0.44 to 2.29) |
| 69. Mild psychiatric disorders | Strauss 2001 |
Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 1/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 11/300 |
0.09 (0.01 to 0.70)a |
| 70. Depressive episode (moving from BDI‐IIb scores ≤ 13 at baseline to > 13 during treatment) | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 7/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 6/300 |
1.17 (0.40 to 3.43) |
| 71. Bone loss | Webster 2014 |
Standard oral isotretinoin, 0.5 mg/kg/day first 8 weeks, followed by 1 mg/kg/day until week 20 0/231 |
Isotretinoin‐Lidose, 1 mg/kg/day for 20 weeks 1/245 |
0.35 (0.01 to 8.63) |
| 72. Bone age change | Webster 2014 |
Standard oral isotretinoin, 0.5 mg/kg/day first 8 weeks, followed by 1 mg/kg/day until week 20 4/192 |
Isotretinoin‐Lidose, 1 mg/kg/day for 20 weeks 5/204 |
0.85 (0.23 to 3.12) |
| 73. Elevated serum triglycerides (> 140 mg/dL) | Goldstein 1982 |
Oral isotretinoin 1 mg/kg/day for 8 weeks 2/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 3/28 |
0.67 (0.12 to 3.69) |
| 74. Raised triglyceride levels | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 4/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
9.00 (0.53 to 153.79) |
| 75. Elevated serum triglycerides (during first 10 weeks of therapy) | Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 4/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
9.00 (0.54 to 150.81) |
| 76. Marked abnormality in serum triglycerides level (> 250 mg/dL and increase from baseline ≥ 100%) | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 75/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 48/300 |
1.56 (1.13, 2.16)a |
| 77. Marked abnormality in serum cholesterol level (> 320 mg/dL and increase from baseline ≥ 50%) | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 1/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 0/300 |
3.00 (0.12 to 73.35) |
| 78. Persistent elevated serum alkaline phosphatase (during therapy and follow‐up phase) | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 3/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 3/15 |
1.00 (0.24 to 4.18) |
| 79. Raised alkaline phosphatase | Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 4/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
9.00 (0.54 to 150.81) |
| 80. Marked abnormality in alkaline phosphatase level (> 190 U/L and increase from baseline ≥ 50%) | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 0/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 0/300 |
Not estimable |
| 81. Persistent raised SGOTc (AST)d and SGPTe (ALT)f levels (during therapy) | Lester 1985 |
Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 0/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 1/15 |
0.33 (0.01 to 7.58) |
| 82. Raised ASTd or ALTf | Pigatto 1986 |
Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 0/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 5/12 |
0.09 (0.01 to 1.48) |
| 83. Marked abnormality in ALTf (SGPT)e level (> 60 U/L and increase from baseline ≥ 50%) |
Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 8/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 7/300 |
1.14 (0.42 to 3.11) |
| 84. Marked abnormality in ASTd (SGOT)c level (> 50 U/L and increase from baseline ≥ 50%) | Strauss 2001 |
Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 5/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 9/300 |
0.56 (0.19 to 1.64) |
| 85. Persistent elevated serum protein (during therapy and follow‐up phase) | Lester 1985 | Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 3/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 0/15 |
7.00 (0.39 to 124.83) |
| 86. Raised serum protein | Pigatto 1986 | Oral isotretinoin 1 mg/kg/day for 10 weeks followed by 0.5 mg/kg/day for 10 weeks 1/12 |
Minocycline 100 mg/day for 10 weeks and then reduced to 50 mg/day for 10 weeks 0/12 |
3.00 (0.13 to 67.06) |
| 87. Marked abnormality in GGTg level (> 120 U/L and increase from baseline ≥ 50%) | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 7/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 4/300 |
1.75 (0.52 to 5.92) |
| 88. Marked abnormality in LDHh level (> 500 U/L and increase from baseline ≥ 50%) | Strauss 2001 | Standard oral isotretinoin 0.85 to 1.18 mg/kg/day for 20 weeks 1/300 |
Micronised oral isotretinoin 0.32 to 0.4 mg/kg/day for 20 weeks 0/300 |
3.00 (0.12 to 73.35) |
| 89. Transient abnormalities in semen evaluations | Goldstein 1982 | Oral isotretinoin 1 mg/kg/day for 8 weeks 0/28 |
Oral etretinate 1 mg/kg/day for 8 weeks 0/28 |
Not estimable |
| Lester 1985 |
Oral isotretinoin 1.0 to 2.0 mg/kg/day for 16 weeks 0/15 |
Oral tetracycline 0.5 to 1 g/day for 16 weeks 3/15 |
0.14 (0.01 to 2.55) | |
aResults that showed a statistically significant difference between interventions
bBDI‐II (Beck Depression Inventory‐II)
cSGOT (serum glutamic oxaloacetic transaminase)
dAST (aspartate aminotransferase)
eSGPT (serum glutamic pyruvic transaminase)
fALT (alanine aminotransferase)
gGGT (gamma‐glutamyl transpeptidase)
hLDH (lactate dehydrogenase)
*The intervention groups which had lower less serious adverse event rates in each comparison are in bold.