Isotretinoin side effects, safety, danger, caution , use for acne treatment by Ray Sahelian, M.D. natural health consultant

Isotretinoin is a medicine used since 1982 for the treatment and prevention of severe acne. The inflammation in acne is caused in part by an increased secretion of sebum (oily substance) from glands in the skin (sebaceous glands). The sebum provokes inflammation, and the inflammation resolves (heals) with the formation of a scar (keratinization). The exact mechanism of action of isotretinoin is not known; however, it may reduce acne by reducing the secretion of sebum. If less sebum is secreted it is likely that there will be less inflammation and keratinization. Roche Laboratories Inc., is the maker of isotretinoin.

Gastrointestinal Isotretinoin side effects

People taking the acne drug isotretinoin appear to run an increased risk of developing inflammatory bowel disease. American Journal of Gastroenterology, July 2006. Inflammatory bowel disease, or IBD, includes Crohn's disease and a similar condition called ulcerative colitis.

Patients on the medication are many times more likely than non-users to develop ulcerative colitis within a year. The biological mechanism by which isotretinoin might contribute to IBD is not clear, but some researchers have speculated that the drug may affect immune function in the intestines. Both Crohn's disease and ulcerative colitis are thought to involve abnormal immune system activity. American Journal of Gastroenterology, online March 30, 2010.

Liver and Cardiac Isotretinoin side effects

Isotretinoin seems to raise the risk for potential heart and liver problems more than doctors had expected. The findings came from lab tests on 13,772 patients taking the popular acne drug and underscore the need to closely monitor people taking isotretinoin, which is sold as Accutane and in three generic versions. Abnormal results for cholesterol and liver function were more common than expected in those using isotretinoin. Most dermatologists already knew isotretinoin could increase levels of cholesterol, liver enzymes and blood fats called triglycerides that can raise the risk of heart disease. But the new study found higher than expected percentages of patients developing these abnormal lab results.

Depressive symptoms and suicidal ideation during isotretinoin treatment: a 12-week follow-up study of male Finnish military conscripts.
J Eur Acad Dermatol Venereol. 2009; Rehn LM, Meririnne E, Höök-Nikanne J, Isometsä E, Henriksson M. Helsinki City Health Center, Department of Psychiatry, Helsinki, Finland.
To investigate the putative association between isotretinoin treatment and depressive symptoms or suicidal ideation among Finnish male military conscripts. Consecutive acne patients were enrolled into an uncontrolled, prospective 12-week follow-up study conducted at the Central Military Hospital, Helsinki, Finland. Depression and suicidal ideation were investigated with the Beck Depression Inventory (BDI) at baseline, weeks 4-6, and weeks 10-12. BDI mean score was low at baseline and declined further significantly during the follow-up from 3.0 to 1.8 among patients on isotretinoin. Moreover, the proportion of patients with clinically significant depressive symptoms (BDI > or= 10) declined non-significantly from 7.1 % to 3.2 %. Suicidal ideation was reported by 17 (13.5 %) patients at baseline and 9 (7.1%) patients at the end of the follow-up (NS). During the follow-up, one non-depressed patient attempted suicide while intoxicated by alcohol. On group level, isotretinoin seems not to be typically associated with treatment-emergent depression or suicidal ideation among young men. However, the possibility that individual patients may be susceptible for mood effects of isotretinoin as a rare idiosyncratic reaction can not be excluded.

Isotretinoin Dosage

The recommended dose of isotretinoin is 0.5 mg per kg of body weight daily. The daily dose usually is administered in two divided doses for 14 to 20  weeks. Isotretinoin should be taken with food.

Isotretinoin Drug Interaction

Isotretinoin is closely related to vitamin A. Therefore, the use of both vitamin A and isotretinoin at the same time may lead to vitamin A side effects. Additional drugs that may interact with isotretinoin include alcohol, benzoyl peroxide, salicylic acid, or other drying medicines used for acne; corticosteroids (example: prednisone); medicines for seizures; other drugs that make you more sensitive to the sun such as sulfa drugs; progestin-only birth control hormones (examples: 'Minipills' like Aygestin, Micronor, Nor-QD or injectable / implantable products such as Depo-Provera or Norplant.

Skin aging use orally not effective
Topical retinoids are used to treat photoaging; oral isotretinoin is gold standard for acne; "off label" indications, including photoaging, have been reported with insufficient evidence of efficacy. This is a randomized controlled phase II trial with clinical and histological assessment to evaluate efficacy and safety of oral isotretinoin for photoaging. Study population was comprised of 32 menopausal or sterilized women, aged 40-55, divided in 2 groups: A (21) received 20mg isotretinoin, 3 times per week, nightly moisturizer, and daily sunscreen, for three months; B (11) just moisturizer / sunscreen. Main outcome measures were: overall clinical assessment; profilometry, corneometer and elasticity tests in periocular regions and left forearm; before/after biopsies from left forearm in patients of B and in 10 randomly selected of A. Microscopic blinded evaluation of epidermal thickness, dermal elastosis, new collagen, p53 epidermal expression was performed by quantitative digital image analysis. Clinical evaluation showed slight improvement; profilometry, corneometer and skin elasticity tests presented significant difference in pre/post values, but no differences between A/B. Histological findings and p53 expression were comparable between groups before treatment; microscopic analysis showed no differences between groups for most variables, after treatment. Slight but significant difference between A/B for p53 with major reduction post isotretinoin was observed. There were minor side effects and no significant laboratory test alterations. We concluded that no significant clinical, microscopic changes but p53 epidermal expression reduction were observed. The role of ultra-violet induced p53 mutation in skin carcinogenesis reinforces retinoids chemoprevention. Oral isotretinoin seemed safe but not effective to treat photoaging. Caution should be considered for women prone to pregnancy. Further controlled studies are necessary. Int J Dermatol. 2010 Feb. A randomized and controlled trial about the use of oral isotretinoin for photoaging.Department of Dermatology, UNIFESP-Univesidade Federal de Sao Paulo, Sao Pailo, SP, Brazil.

Isotretinoin and Pregnancy

Isotretinoin is known to cause birth defects when used during pregnancy. It can cause brain and heart defects in infants if a woman takes it during or immediately before pregnancy. Women who take it must have pregnancy tests and use birth control or abstain from sex.