Accutane, the active substance of which is isotretinoin, is a monoaromatic retinoid, derivative of vitamin A, cisretinoic acid. The drug is out on the market since 1982. It's made by Swiss pharmaceutical company Hoffman-La-Roche. According to reports, in the first two months of its sales doctors prescribed it in sixty thousand cases.
Since then, vast experience of Accutane usage for treatment of acne has been gained. It has been proved to be highly effective in patients with severe forms of the disease. Rash resolution is observed after 4 months of treatment in 85% of patients. Moreover, the number of pustules decreases most rapidly — by 50% already in the first 2–4 weeks of treatment. The number of other inflammatory elements like papules and nodes decreases somewhat later, and, finally, the number of comedones decreases.
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The basis of the drug’s high efficiency is its effect on the main points in the pathogenesis of acne, which are overproduction of sebum, impaired horn formation, inflammation and colonization of Propionibacterium acnes. The main target for the drug are sebocytes. In vivo studies found that when taking isotretinoin in a dose of 0.5-1.0 mg/kg for 6 weeks, there is a decrease in sebum production by almost 90%. Subsequent in vitro studies have demonstrated that this is due to the suppression of proliferation and differentiation of basal sebocytes, their apoptosis, and inhibition of sebum production. The mechanisms of regulation of keratinocyte proliferation processes remain the subject of study, however, the overwhelming effect of the drug on keratinization processes and comedogenesis is obvious.
The anti-inflammatory effects of isotretinoin are associated with the regulation of an antigen-nonspecific immune response to P. acnes, including the suppression of the overexpression of Toll-like receptors-2 (TLR-2) and increased production of pro-inflammatory cytokines by monocytes, as well as the normalization of antimicrobial peptides expression . Although the mechanisms of these effects remain unclear, it is important that they last at least 6 months after treatment and ensure the duration of the clinical effect of the drug.
The optimal daily and cumulative dose of isotretinoin is still under discussion. The individual daily dose of the drug is determined depending on the patient’s body weight, severity of acne, the presence of other chronic diseases and ongoing treatment, as well as the development of side effects. The recommended initial dose of isotretinoin is 0.5 mg/kg and is prescribed for up to 4 weeks. With good tolerability of the drug, it is increased to 1.0 mg/kg. The cumulative dose of the drug is at least 110-120 mg/kg and is achieved in about 5 months of treatment in this mode.
Accutane side effects
Despite its high efficacy, the use of Accutane may be limited by a wide range of possible side effects. The data on the likelihood of developing depression, inflammatory bowel diseases and some other complications (including rare ones like pseudotumor cerebri) remain contradictory. The connection between some of them and the effects of isotretinoin remains a subject of discussion. In this article, we focused on the teratogenic and other effects of the drug which are completely proven.
Up to 20–35% of children whose mothers took Accutane during pregnancy have birth defects - craniofacial, cardiovascular, neurological, thymic lesions, and 60% of children have neurocognitive disorders in the absence of organic brain lesions. Embryopathies are often the cause of premature birth, spontaneous abortion, and fetal death. Due to the high risk of embryopathy while taking Accutane in Europe, the Pregnancy Prevention Program has been approved, the purpose of which is to educate patients and specialists, as well as to control treatment.
An increase in the level of triglycerides and cholesterol in blood serum during treatment with Accutane is observed quite often - in 44 and 31% of patients, respectively, transaminases is somewhat less common (up to 11%). This side effect is transient, reversible and, as a rule, is not an indication for stopping treatment.
Accutane is known as a pretty controversial drug with some serious side effects but nonetheless it has changed lives of many people suffering from severe cystic acne for the better. Almost 40 years of the drug’s usage have convincingly proven its high clinical efficacy in treating patients with severe forms of acne. It is fundamentally different from other acne medications. Accutane works.
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