Figure 1. Photo showing the chemical structure of Isotretinoin1
Isotretinoin, most popularly known by its brand name Accutane, is a prescription medication approved for severe acne. However, many dermatologists may prescribe isotretinoin for less severe cases of acne due to the scarring and/or psychosocial distress acne may cause. To this date, it remains the most effective treatment for severe acne.
Why is it so effective? In short, Isotretinoin is a vitamin A derivative that targets practically all the major factors that lead to the development of acne. One of the major factors that seems to be most crucial in the formation of acne is the increased and abnormal growth of both the sebaceous glands and hair follicles. Sebaceous glands, which produce an oily substance called sebum, are found in the skin and commonly in association with hair follicles (forming the pilosebaceous unit). While sebum is important for skin barrier and function, overproduction of sebum and clogging of this unit has proven to be a major cause in the development of acne.3
The exact way by which the drug works has not been completely decoded, although research has shown that isotretinoin has both direct and indirect anti-inflammatory properties and most importantly, decreases growth and maturation of the cells that become part of the sebaceous glands. Isotretinoin also decreases overall sebum production, and leads to proper development of the keratin that forms the hair follicle. Isotretinoin, although not an antibiotic, has been shown to decrease total numbers of P acnes, which is a specific species of bacteria associated with acne formation. As a result, this drug typically leads to clearing of acne in several months and in some, permanent resolution of acne.
Accutane is dosed such that each patient receives 120-150 mg/kg spread out over the entire treatment period, which may be between 15-20 weeks (this is extremely patient dependent, and may be longer or shorter than anticipated).2 The initial dose started is typically 0.5 mg/kg daily divided into two doses, although some dermatologists may initiate treatment at a dose of 1 mg/kg daily. It is important to take Accutane with food, as this will increase its absorption. After one month of treatment, the dosage may be adjusted depending on patient tolerance. It should be noted that it often takes 1-2 months before any improvement is seen, and in some cases there will be temporary worsening of acne prior to improvement.
There is no doubt that Isotretinoin is a powerful medication, and with that power comes some potentially serious side effects, which is why the dose is titrated slowly over months. The most concerning side effect is the potential for serious birth effects. Therefore, any female patient wanting to be prescribed Isotretinoin must have two negative pregnancy tests (30 days apart) prior to initiation of treatment and must use two forms of continuous contraception one month prior to and after treatment. Additionally, both the prescriber and patient must enroll in the online registry system, iPLEDGE, which is a government-required program dedicated to preventing fetal exposure to isotretinoin.2 Other common side effects include chapped lips, dry and/or itchy skin, dryness of the nose, eye and eyelid irritation, joint and muscle pains, worsening of acne, and temporary hair thinning.2
Isotretinoin may also cause elevated blood fat and cholesterol levels, which is why dermatologists order monthly lab work and testing. Monthly testing typically includes complete blood count, liver function tests, creatine kinase, blood fat and cholesterol levels, and beta- hcg to test for pregnancy.2 Rare side effects that should warrant contacting your physician include photosensitivity, gastrointestinal symptoms, changes in night vision, severe headache, skin rash, and changes in mood. This drug is absolutely contraindicated in patients that are pregnant, lactating, or in patients with severe kidney or liver disease.2
1. Isotretinoin. Wikipedia. https://en.wikipedia.org/wiki/Isotretinoin. Published February 2, 2020. Accessed March 22, 2020.
2. Rigopoulos D, Larios G, Katsambas AD. The role of isotretinoin in acne therapy: why not as first-line therapy? facts and controversies. Clin Dermatol. 2010;28(1):24–30. doi:10.1016/j.clindermatol.2009.03.005
3. Schneider MR, Paus R. Sebocytes, multifaceted epithelial cells: Lipid production and holocrine secretion. The International Journal of Biochemistry & Cell Biology. 2009;42(2):181-185. doi:10.1016/j.biocel.2009.11.017