Take Home Message: Oral Isotretinoin against Acne (at a lower dose = 0.05-0.1 mg/kg/day or 5mg/d) should be used to allow sebum suppression (disappearance of oily skin) for a sufficient amount of time – that is for 8 to 12 months. (See abstract below)(Study from New Zealand)
-Oral isotretinoin cumulative dosage is being challenged.
–A total dose of 120mg/Kg can be very long to attain. Ideally it was supposed to be for a relatively high dosage (Not by “US school” standards) so that ideally* the treatment would be used for around a year: 25mg in a 65Kg individual for example (*not scientific though)
-For example a 60Kg adult female on 5mg per day will need almost 4 years (1440days) to attain the total cumulative dose !
-Conversely a 60Kg individual on 80mg a day will need only 3 months (“US-school” dosages typically range between 60 and 100mg per day)
–There is a trend to use lower doses (0.3-0,5 mg/Kg) especially in Europe which contrasts with the US. This is to reduce side effects, such as skin irritation and peeling; and chapping of the lips – however this does not enable long-lasting sebum suppression (4-8 weeks)
-When patients ask the duration of treatment, and that a long duration is answered, many specialists propose to stop and see after a few months. Other physicians will increase the dose….conclusion: the total dose of isotretinoin is challenged and this study suggests that sebum suppression (skin not oily) is the answer
-Some isotretinoin guidelines recommend cumulative doses of 120-140 mg/kg. This arose from a mathematical calculation of the daily dose (1 mg/kg/day), taken for a fixed 16-weeks. This time period was a compromise in an attempt to minimise the teratogenetic exposure to women; it was not based on any particular science.
–Much lower dosages of isotretinoin (eg. 0.05 mg/kg/day) are equally effective, both in speed of response and total clearance of acne. However patients treated with very-low daily dosages for only 16-weeks, may relapse earlier. Unfortunately this has been incorrectly interpreted as being a reflection of cumulative dose.
-We now appreciate that higher dose isotretinoin (0.5-1.0 mg/kg/day) has a prolonged effect on sebum suppression, through apoptosis of both sebaceous gland cells and, more importantly, their stem cells; this persists for 4-8 months after discontinuation of isotretinoin. However, this effect on stem cells is not seen with very-low dose isotretinoin (0.05-0.1 mg/kg/day), so the sebum suppression only lasts for another 4-8 weeks after stopping.
We reviewed 1453 acne patients treated with isotretinoin for the first time: 326 (22.4%) relapsed requiring a 2nd course. Relapsers were more likely to be women (61% v 47%, p<0.001), have received a larger daily dose (0.71 mg/kg/day v 0.58 mg/kg/day, p<0.001) and/or a greater cumulative dose (126 mg/kg v 101 mg/kg, p<0.001).
Neither daily nor cumulative dose influences relapse of acne. The length of sebum suppression is more important, and needs to be continued for 8-12 months to maximize long term remission.
Reference: Regional Congress of Dermatology (RCD) 2016 – Singapore. RCD16-0030 Acne & Rosacea THINK LENGTH OF SEBUM SUPPRESSION, NOT CUMULATIVE DOSE, WHEN USING ISOTRETINOIN FOR ACNE M. RADEMAKER1 1Univerity of Auckland, Waikato Clinical Campus- Waikato Hospital, Hamilton, New Zealand