Isotretinoion is indicated for the treatment of severe acne, and it has been in use since 1979. Your dermatologist may also prescribe oral isotretinoin for patients with moderate acne resistant to other treatments, acne that leaves scars, acne that causes psychological distress, severe hormonal acne, severe rosacea, and other disorders related to acne such as dissecting cellulitis of the scalp or hidradenitis suppuritiva. Isotretinoin treats all forms of acne, including clogged pores (blackheads or whiteheads), inflammatory pimples, and deeper nodules or cysts.
When used properly and under the supervision of your dermatologist, isotretinoin is safe and highly effective for all forms of acne. Isotretinoin is the only treatment that can actually cure acne. In fact, two-thirds of patients are cured after a 6 to 8 month course of isotretinoin. Of the remaining third, half will have mild acne that can easily be controlled with topical treatments, and the other half will have more severe acne and may need a second 6 to 8 month course of isotretinoin.
How Isotretinoin Works
Isotretinoin works by shrinking your oil glands (called sebaceous glands) deep within your pores. Not only does it shrink them, but it actually induces programed cell death of oil glands, called apoptosis. This results in a permanent improvement in acne, as dead cells in the oil glands are cleared away and do not return.
Isotretinoin also makes the cells move faster through the layers of the skin. In the skin’s epidermis (the outermost layer of skin), cells of the skin continually regenerate. Regeneration starts at the bottom layer of the epidermis, called the basal layer. Cells divide in the basal layer to regenerate all the other layers of the skin, and the outermost layer of the skin is continuously shed. By increasing the rates at which the cells move from the basal layer and differentiate to the outermost layer of skin and shed, isotretinoin actually thins out the skin layers. This is important for its mechanism of action, as pores also have skin layers along their lining. By thinning out the layers of skin inside the pores, isotretinoin essentially makes it easier for any sebum produced deep within the pores to exit to the surface.
Skin cells typically stick to each other with a good amount of tack. By hastening the transit rate of cells through the epidermis, the cells of the outermost layer have less time to mature and make the cellular glue that holds cells 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 because isotretinoin decreases output of sebum from the pores’ sebaceous glands, acne-inducing sludge deep within the pores does not form.
Lastly, isotretinoin decreases the number of bacteria on the skin indirectly by taking away their food source: sebum. Bacteria are clever creatures that have evolved to live in the pores and use sebum as food. Because the oil glands are shrunken and destroyed, 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 byproducts released by bacteria during their metabolism as they feed on sebum cause inflammation deep within the pores. Less food for the bacteria means fewer numbers of bacteria, which means less inflammation in the pores. This helps acne clear.
The endpoint of one course of treatment is to ingest a total amount of medication equal to your goal dose, which is calculated based on your body mass. Typically, dosing is initiated at a low dose for the first month of therapy, and is subsequently raised. Dosing can be once or twice daily, typically with food, preferably with a fatty meal. Taking the medication with fatty food enhances its absorption. The total treatment goal is typically reached over approximately six to eight months.
Most other acne medications are typically discontinued during isotretinoin therapy. Isotretinoin causes temporary skin dryness, and certain topical medications worsen this dryness. Therefore, retinoid topical medications such as retinol, tretinoin, Retin-A, Atralin, adapalene, Differin, EpiDuo, tazarotene, Fabior, Tazorac, Ziana, and Veltin are not used in combination with isotretinoin. Oral antibiotics of the tetracycline family, including doxycycline and minocycline, are also typically not used in combination with isotretinoin; the combination of oral antibiotics of the tetracycline family with isotretinoin raises the risk of developing a complication called pseudotumor cerebri, which is described later below.
Certain anti-acne medications may be continued during isotretinoin therapy. Birth control pills or other forms of hormonal contraception can be used with isotretinoin. Spironolactone also may be used in combination with isotretinoin. Your dermatologist can advise you on which medications to continue during therapy with isotretinoin.
Acne may initially worsen with isotretinoin therapy, especially in patients with more severe acne. This initial worsening typically resolves with further treatment with isotretinoin. If your acne is severe, a good doctor will start you with a very low dose and will slowly increase your dose. In very severe cases, systemic cortisone type medications are sometimes given before isotretinoin therapy or concurrently for the first two to four weeks of treatment in an attempt to prevent severe flares.
Oral isotretinoin is the only acne medication that can permanently alter the natural course of acne. Almost everyone’s skin is clear after a single course of isotretinoin. However, not all patients are cured, meaning that in certain patients the acne may come back, but typically in a more mild form. After isotretinoin treatment, acne is more likely to be responsive to topical therapies. Response rates after a second course of isotretinoin are similar to those following the initial course of treatment. This means that for patients who need to undergo a second course of isotretinoin therapy, about two-thrids of them are cured after their second 6 to 8 month course of isotretinoin. Of the remaining third, half will have mild acne that can easily be controlled with topical treatments, and the other half will have more serious acne and may need a third 6 to 8 month course of isotretinoin.
The majority of patients experience long-term improvement in acne severity after one course of isotretinoin. Continued improvement may occur for several months after finishing therapy; thus, an additional course of isotretinoin shouldn’t be considered for at least four or five months after the end of the course of isotretinoin.
Most relapses occur within the first 2 years after stopping therapy; the highest relapse rates occur in patients with chest & back acne, or in those patients who didn’t receive a full course of therapy equal to their goal dose.
Isotretinoin causes birth defects in women who become pregnant while taking this medication; it causes both spontaneous abortions and severe life-threatening birth defects. Birth defects include skull and face malformations, heart problems, problems with an immune organ called the thymus, and brain malformations. Children born to a mother taking isotretinoin who appear physically normal at birth may have a higher rate of mental retardation and lower IQs. Fetal abnormalities have not been attributed to the use of isotretinoin in men; therefore, men can safely father children while taking this medication. Once women have stopped therapy for at least one month, they may safely conceive with no additional risk of birth defects above the average risk level.
Despite stringent rules in the United States intended to prevent pregnancy with isotretinoin, some women taking isotretinoin still become pregnant. In 2006, the US FDA established a computer-based risk management program with the goal of eliminating fetal exposure to isotretinoin (iPLEDGE). Prescribers, pharmacies dispensing isotretinoin, and all patients receiving isotretinoin are required to comply with the registry requirements. A detailed overview of the iPLEDGE program is linked.
Side Effects on the Skin and Mucous Membranes
Isotretinoin works for acne by shrinking oil glands and increase the rate of transit of cells through the epidermis (peeling the skin).
100% of patients taking isotretinoin experience dry lips. An ointment such as Aquaphor applied every few hours as well as right before sleep typically makes this very tolerable. Lip dryness increases with increasing doses of isotretinoin. Many people breathe through their mouths while sleeping, and a humidifier placed near the bed can be helpful in preventing additional lip dryness.
If the chore of applying ointment such as Aquaphor to the lips is sufficiently neglected, cracking at the corners of the lips will occur. Frequently, these cracked lip corners become secondarily infected by a bacteria called Staph aureus. The symptoms are irritation and pain. At that point, your dermatologist will need to prescribe an antibacterial ointment such as mupirocin ointment to be applied 4 to 6 times per day to the corners of the lips, especially before sleep. After one week of this treatment, the condition will clear. To prevent this condition, diligent and frequent application of ointment such as Aquaphor several times a day is necessary.
Sometimes, dry skin can result as well, particularly on the face. A mild lotion such as Cetaphil lotion or Aveeno lotion is typically sufficient should dry skin occur. A mild facial cleanser should be used. Avoid harsh or medicated soaps and scrubs while taking isotretinoin. Particularly, avoid benzoyl peroxide, salicylic acid, and glycolic acid based cleansers.
Occasionally, the skin on the hands, forearms, or arms may become dry to the point that an itchy rash called eczema occurs. If this happens, let your dermatologist know, as prescription cortisone-type creams can help. Moisturizing with a thicker moisturizing cream such as Eucerin cream, CeraVe cream, or VaniCream after exiting the shower or bath is helpful as well.
The eyes may become dry as well during therapy with isotretinoin. This is more noticeable if the patient already has pre-existing dry eyes. Lubricating eye drops (artificial tears) are helpful if this occurs.
The inner lining of the nasal cavity may become dry during isotretinoin therapy. If the dryness progresses, nose bleeds can occur due to cracks in the nasal lining. However, nose bleeds due to nasal dryness are easily prevented. Firstly, a small amount of an ointment such as Aquaphor is applied to the 5th finger (pinky) and inserted into each nostril. The ointment is then spread with the finger over the nasal lining. This is done upon waking and before sleeping for each nostril. Secondly, a humidifier placed near your bed will help.
The skin may sunburn more easily during isotretinoin therapy, especially for fair skinned individuals or those persons living in sunny climates. Sunscreen should be used regularly and should be re-applied every two hours of continuous sun exposure. Sun protective clothing such as a hat is also useful.
Skin does not heal as quickly and is more fragile while taking isotretinoin, because it thins out the skin. This effect goes away after therapy is completed. Therefore, waxing for hair removal is best avoided during isotretinoin therapy. Avoidance of elective surgery, dermabrasion, chemical peels, and laser treatments is also wise for at least 3 months after stopping isotretinoin.
Rarely, a benign (non-cancerous) but annoying skin tumor called pyogenic granuloma (also called lobular capillary hemangioma) can occur. It is rare, but isotretinoin slightly increases the risk of developing this skin growth while taking the drug. It is removed by a dermatologist by excising it and putting stitches, or by scraping it away and burning the roots of the tumor. The skin is numbed with a local anesthetic shot prior to these procedures. There would be a scar present after the removal of the tumor. It can come anywhere on the body, but often is seen on the fingers or the lips.
Occasionally, patients experience rectal bleeding when constipated while taking isotretinoin. This is usually fixable by taking fiber supplements and stool softener pills such as docusate.
The Myth of Inflammatory Bowel Disease & Isotretinoin
Inflammatory bowel disease, also called IBD, is a serious disorder of the gastrointestinal system that can be treated but has no known cure. Crohn’s disease and ulcerative colitis are two types of inflammatory bowel disease. Symptoms include abdominal pain, loose stools, blood in the stools, and weight loss. The disorder usually occurs in young adults aged 12 to 35. Coincidentally, this is the same population that often gets acne. Observational studies have found conflicting results on the relationship between isotretinoin therapy and inflammatory bowel disease (IBD). More studies are necessary to determine whether isotretinoin therapy is a risk factor for IBD, but I am not convinced at all from the data available. Many patients taking isotretinoin have previously taken tetracycline type oral antibiotics for a long time; studies have suggested that long term use of these antibiotics is a risk factor for the development of IBD.
Depression and Suicide
Concerns have been raised about a possible association of isotretinoin with depression and suicide. Studies have concluded that data on suicidal behavior and depression during treatment with isotretinoin are inadequate to establish a causal relationship. Some doctors have proposed that psychological distress over severe acne, rather than isotretinoin, could be a contributing factor to suicide or depression in patients treated with the drug. More studies are needed to determine if there is a cause-and-effect relationship between isotretinoin and depression or suicide. Based upon my clinic experience, high daily doses of isotretinoin can increase the chance of developing depressed mood, which is ameliorated by decreasing the daily dose. However, the risk of developing depressed mood, even while taking high daily doses of isotretinoin, is low. The vast majority of patients are elated with the acne’s improvement.
Patients should keep in mind that although isotretinoin will improve their acne, other aspects of their lives typically will not change much. Stated another way, the only aspect of life that isotretinoin improves is acne. For teenagers, this means that isotretinoin will not necessarily help you to get the boyfriend or girlfriend you want, or the summer job of your dreams. It only fixes acne. Also, isotretinoin does not fix acne scarring. Scarring can be treated, but that’s a separate discussion.
Patients with active depression, bipolar disorder, or other psychiatric disorders should specifically discuss the state of their condition with their dermatologist. Typically, a psychologist, psychiatrist, or primary care physician will be involved in monitoring the condition of patients with active mental health conditions during treatment with isotretinoin. If you feel severe depression or suicidal thoughts during treatment with isotretinoin, discontinue the medication and contact your dermatologist immediately.
Other Side Effects
Muscle aches may occur in patients taking oral isotretinoin, particularly those who engage in vigorous physical activity during the first few months of therapy. Reducing the vigor will cure this issue.
Liver damage may occur infrequently, but is more common if alcohol is used. Your dermatologist will monitor your bloodwork for liver damage periodically while you are taking isotretinoin. Alcohol use should be limited to 1 drink daily for patients over age 21. Having more than one drink daily is not permitted while taking this medication. If your dermatologist discovers laboratory evidence of liver damage, he or she may temporarily or permanently discontinue your isotretinoin therapy.
High triglycerides (a type of fat in the blood) occurs in up to 45 percent of patients on isotretinoin therapy, and elevations of cholesterol are seen in approximately 30 percent. These elevations are transient in about 80 percent of patients and are rarely severe enough to require termination of therapy. Your dermatologist will monitor lipids with a blood test periodically while you take this medicine. Patients who develop high triglycerides while taking isotretinoin are at increased risk for developing metabolic syndrome, which includes obesity and type 2 diabetes.
Isotretinoin may rarely cause high fluid pressure within the brain (pseudotumor cerebri). Obese females are most at risk. Hormonal contraception also increases the risk of developing pseudotumor cerebri, as do tetracycline type antibiotics. The symptom is severe and persistent headache. Some people say the worst pain is right behind the eyes. There may be short periods of vision loss; this can happen in one or both eyes. It usually lasts a few seconds and might happen once in a while or several times a day. In rare cases, people with this condition lose their vision forever. If you experience severe headache or vision changes while taking isotretinoin, contact your dermatologist right away and seek emergency care quickly.
Nail abnormalities can occur, often at high doses. They typically improve with time and often resolve completely.
A bone problem called diffuse skeletal hyperostosis and/or calcifications in ligaments and tendons may rarely occur, especially among patients being treated with high doses for longer than usual periods.
Overall, isotretinoin is a wonderfully effective medicine for the treatment of severe, cystic acne. Although serious side effects can occur, most patients experience only dry lips and dry skin. Let your doctor know if you are experiencing severe headaches, depression, or suicidal thoughts, as these can be signs of serious issues which need immediate attention.
Mild Acne - Moderate Acne - Severe (Cystic) Acne - Hormonal Acne - Acne During Pregnancy - Acne & Breastfeeding - Retinol - Anti-acne Cleanser - Anti-acne Toner - Benzoyl Peroxide - Zinc Monomethionine & Fish Oil - Pimple Spot Treatment - Blemish Treatment - Scar Treatment - Sunscreen - Moisturizer - Avoiding Exacerbators - Comedogenic Ingredient List - Azelaic Acid - Birth Control Pills - Clindamycin - Doxycycline - Isotretinoin - iPledge - Spironolactone - Minocycline - Bactrim (SMX/TMP)