47. Isotretinoin - the drug formerly known as Accutane

Doctor Jacob here, and today we're talking about isotretinoin, the drug formally known as Accutane.

Isotretinoin is the generic name of the drug that used to be called Accutane. I say used to be called, because Accutane is no longer sold. The medication has gone generic and its original manufacturer stopped producing it. Isotretinoin is sold by its new manufacturers under many other names, such as Claravis, Amnesteem, Zenatane, Myorisan and Sotret. A newer version of the medication called Absorica was released in the year 2013. It's more expensive and may enhance the absorption of isotretinoin when taken without good. However, you should know that all patients can obtain the same results by taking any of the commercially available forms of isotretinoin.

This drug is indicated for the treatment of severe acne, and it's been in use since 1979, but a dermatologist may also prescribe isotretinoin for patients with moderate acne resistant to other treatments, acne that leaves scars, acne causing significant psychological distress, severe forms of hormonal acne and other conditions, such as severe rosacea, dissecting cellulitis of the scalp or hidradenitis suppurativa - these conditions are not acne.

Isotretinoin treats all forms of acne, including clogged pores, which are the blackheads and whiteheads, inflammatory pimples or zits, as well as deeper seated nodules or cysts. When used properly and under the supervision of a dermatologist experienced in its use, isotretinoin is safe and highly effective for all forms of acne. It's the only treatment that can actually cure acne. In fact, two out of three patients are cured after one course, which typically lasts 6 to 8 months. Of the remaining one third of patients, about half will have mild acne that can be easily controlled with topical treatments, and the other half have more severe acne and eventually elect a second 6 to 8 month course of isotretinoin.

Now let's talk a little bit about how isotretinoin works. Isotretinoin works by shrinking up your oil glands deep within the pores. Not only does it shrink them, but it actually induces them to die through a process we call programmed cell death, or apoptosis in the medical terminology. This results in a permanent improvement in the acne, as dead cells in the oil glands are cleared away and generally do not return. There is one exception, and that is with adult onset female hormonal acne. Generally there is an improvement, but sometimes after a few years the oil glands under hormonal stimulation, the ones that remain can grow again.

In addition to killing off oil glands through programmed cell death, isotretinoin also works in other ways. This drugs makes the cells move faster through the layers of the skin. In the skin's epidermis, cells of the skin continually regenerate. Regeneration starts at the bottom layer of the epidermis, which is called the basal layer. Cells divide in the basal layer to regenerate all the other layers of the epidermis, and the outermost layer is continually shed. By increasing the rate at which the cells move from the basal layer and differentiate to the outermost layer of skin, isotretinoin actually thins out the layers of skin. This is important for how it works, as the pores also have layers of skin along their alignment. By thinning out the layers of the skin, not only at the surface but inside the pores, isotretinoin essentially makes it easier for any oil produced deep within the pores to exit the pores onto the skin's surface.

Skin cells typically stick to each other with a good amount of stickiness, and by hastening the transit rate of cells through the epidermis, the cells at the outermost layer have less time to mature and make their cellular glue which holds them together. Thus, isotretinoin makes the cells being shed at the outermost layer less sticky. Sticky cells are not easily shed, and when mixed with sebum clog up the pores. Because isotretinoin decreases the stickiness of the shedding skin cells and also because isotretinoin decreases the output of oil from the oil glands, acne-inducing sludged deep within the pores doesn't form, resulting in clear skin.

And finally, isotretinoin decreases the number of bacteria on the skin indirectly within the pores, by taking away their food source, sebum. Sebum is oil made within the pores and bacteria are clever creatures that have evolved to live in the pores and use sebum as food. Because oil glands are shrunken and destroyed by isotretinoin, they make a lot less sebum and as a result there is less food for the bacteria to feed on. Typically, during the formation of an acne pimple, inflammatory by-products released by bacteria during their metabolism as they feed on sebum, cause inflammation deep within the pores. So less food for bacteria means fewer number of bacteria, which means less inflammation in the pores. This helps keep the skin clear.

So now that we know how isotretinoin works, let's talk about how one course of treatment is dosed. A course usually lasts 6 to 8 months, and every patient who undergoes treatment has a goal dose calculated based upon his or her body weight. The end point of one course of treatment is to ingest a total amount of medication equal to your goal dose. Typically, dosing is started at a lower dose the first month, and every month thereafter is subsequently raised, assuming there are no significant side effects. Dosing can be once a day or twice a day, typically with food and preferably with a fatty meal - that's just a meal that contains some form of fats, like butter. The fatty food enhances its absorption. The exception to this is the drug Absorica, which is a form of isotretinoin specifically formulated to be absorbed without food.

The total treatment goal is typically reached over 6 to 8 months, so every pill a patient takes is like taking a step forward towards the goal finish line. Most other acne medications are typically discontinued during isotretinoin therapy. Isotretinoin causes temporary skin dryness, and certain topical medications, for example retinoids and benzoyl peroxide can worsen this dryness, therefore medications like retinol, Retin-A, tretinoin, adapalene, Differin, Epiduo, Tazorac, Fabior, tazarotene, Ziana or Veltin are not used in combination with isotretinoin.

Also, oral antibiotics from the tetracycline family, including doxycyline and minocycline are typically not used in combination with isotretinoin. The combination of oral antibiotics of this tetracycline family with isotretinoin raises the risk for developing a certain complication called pseudotumor cerebri, in which there is increased pressure within the brain.

Certain anti-acne medicines may be continued during isotretinoin therapy. Birth control pills or other forms of hormonal contraception can be used, as can spironolactone. Your dermatologist would advise you on which medications to continue and which to discontinue. I typically recommend to continue sulfur-based cleansers or soaps. Additionally, clindamycin lotion can be of benefit and may be continued.

When getting started, acne may initially worsen with isotretinoin therapy, especially in patients with more severe acne. The initial worsening typically resolves with further treatment, so what needs to happen is to start at a very low dose and slowly increase your dose, month by month. A good dermatologist will do this, because by starting at a low dose, this typically minimizes the initial flare-up in your acne.

In very, very severe cases, systemic cortico-steroids are sometimes given before of concurrently with isotretinoin therapy for the first few weeks. These steroids can help mitigate the flare-up caused by isotretinoin. In more severe cases, if isotretinoin is started at a higher dose instead of gradually raising the dose starting at a low dose, this flare-up can result in scarring. That's why I always start patients, especially more severe ones, at a tiny dose and increase month by month, slowly.

Let's talk a little bit about what happens after a course of isotretinoin has been completed. Almost everyone's skin is clear when finishing a course of isotretinoin, however not all patients are cured, meaning that in one out of three patients acne may come back, but typically in a more mild form. After treatment, acne may take several months or even years to come back, and the acne is more likely to be responsive to topical therapies. Response rates after a second course of isotretinoin are similar to those after the first course of treatment. This means that for patients who need to undergo a second course, about two thirds of them are cured after their second 6 to 8 month course of isotretinoin. Of the remaining one third, half have mild acne that can easily be controlled with topicals, whereas half of those end up going on a third course of isotretinoin.

The majority of patients experience long-term improvement in acne severity after just one course of isotretinoin. Continued improvement actually occurs for several months even after finishing therapy. Thus, additional courses of isotretinoin shouldn't be considered for at least four or five months after finishing a course. Most relapses do occur within the first two years after stopping therapy.

The highest relapse rate occurs in patients with chest and back acne, or in those patients who didn't receive a complete course of therapy equal to their goal dose. Goal doses are typically calculated in the range of 120-150 mg per kilogram of the patient's body weight.

That's all for today. Next time we'll talk about the safety of isotretinoin, including possible side effects and how to keep safe while on this drug.

I'm Doctor Jacob, we'll see you then.