Isotretinoin, also known as 13-cis-retinoic acid, is a retinoid capsule derived from vitamin A. It was first approved as a treatment for severe acne by the US Food and Drug Administration (FDA) in 1982. However, given its proven safety and efficacy it is now widely used for mild and moderate acne also.
In New Zealand, the brand available is Oratane®. However, there are numerous other brands available overseas. New Zealand regulations prevent us from listing brands available overseas.
Isotretinoin (Oratane®) works in many different ways and is the only treatment that treats all mechanisms of acne. The most significant effect is by shrinking sebaceous glands and reducing sebum (grease) production. This in turn the number of Cutibacterium acnes bacteria (C. acnes, also known as Propionibacterium). However, recent studies suggest it may also have a direct effect on C. acnes and by encouraging a higher proportion of healthy C. acnes subtypes.
The medication also appears to have a direct anti-inflammatory effect.1Layton A. The use of isotretinoin in acne. Dermatoendocrinol 2009; 1: 162-9. doi: 10.4161/derm.1.3.9364. Abnormal keratinocytes (skin cells) are a feature of acne. Isotretinoin helps to encourage normal keratinocyte (skin cell) development and therefore reduces the development of comedones.
How Effective is Isotretinoin?
Simply put, it is by far the most effective treatment for acne – nothing else comes close. It is also the only treatment to offer the possibility of a long-term cure for acne.
Nearly all patients will see significant improvement with their acne.2Tolino E, Skroza N, Proietti I et al. Efficacy and safety of systemic isotretinoin treatment for moderate to severe acne (insights from the real-life clinical setting). Dermatol Ther 2020; 33: e14392. doi: 10.1111/dth.14392. Although, in the first few weeks, the acne may purge before it begins to improve.
Approximately 70% of people can achieve a long-term cure from acne with a single course of treatment. The success rate increases with further courses.
Isotretinoin (Oratane®) is available as a capsule in amounts of 5 mg, 10 mg, 20 mg, and 40 mg. To increase absorption, it should be taken with food. The usual (modern) dose for isotretinoin is 10 to 20 mg per day.
Historically, very high doses of isotretinoin were used – up to 2 mg/kg body weight daily (approx. 120 mg).3Ward A, Brogden RN, Heel RC et al. Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders. Drugs 1984; 28: 6-37. doi: 10.2165/00003495-198428010-00002. However, many people suffered from significant side effects at such a high dose. The traditional high dosing and resulting side effects have put many people off this medication and have probably contributed to the numerous conspiracy theories about isotretinoin.
At Anue, we typically uses doses of about 10 to 20 mg daily (0.1 to 0.3 mg/kg) for the average person.4Rademaker M. Isotretinoin: dose, duration and relapse. What does 30 years of usage tell us? Australas J Dermatol 2013; 54: 157-62. doi: 10.1111/j.1440-0960.2012.00947.x. This lower dose is normally very well tolerated while still being very effective at clearing acne. Some studies even suggest that lower doses result in fewer scars. Unfortunately, other countries have been slow to transition to more modern dosing regimens, which means of course their websites will still discuss much higher doses.
What happens if I miss a dose?
Do not double-up the dose. Instead, continue taking your usual dose the next day. Accidentally skipping the occasional dose, won’t impact your long-term outcome.
Dermatologists have traditionally cited a cumulative dose (total dose of medication taken) of 120 to 150 mg/kg as the adequate duration required to clear acne. However, this number was based on studies performed in the 1980s and 1990s which lacked scientific rigour.5Jones DH, Cunliffe WJ. Remission rates in acne patients treated with various doses of 13-cis-retinoic acid (isotretinoin). Br J Dermatol 1984; 111: 123-5. doi: 10.1111/j.1365-2133.1984.tb04030.x.,6Rademaker M. Making sense of the effects of the cumulative dose of isotretinoin in acne vulgaris. Int J Dermatol 2016; 55: 518-23. doi: 10.1111/ijd.12942.
Weight-based dosing, is now considered obsolete. A more accurate assessment can be made based on a patient’s response to their treatment. For the majority of individuals, the duration of treatment will be 12-18 months.
Pregnant women and active blood donors should not take isotretinoin (see side effects below).
While most will not need blood-test monitoring, patients with liver or kidney problems and those with high lipid (fat) levels should be monitored.
You must inform your dermatologist if you are on a tetracycline antibiotic such as doxycycline, minocycline etc, due to possible interactions with isotretinoin. Vitamin A supplements should be avoided while taking isotretinoin.
Isotretinoin can cause some skin sensitivity, so the use of ‘active’ or irritating cosmetics should be minimised. Please take extra care when shaving and waxing while taking isotretinoin.
Acne is often considered a teenage problem, and this is understandable because the prevalence of acne among teenagers can be as high as 95%.7Heng AHS, Chew FT. Systematic review of the epidemiology of acne vulgaris. Sci Rep 2020; 10: 5754. doi: 10.1038/s41598-020-62715-3.
Adult acne is defined as acne above the age of 25. There are two types of adult acne: persistent and late-onset. Persistent acne is a continuation of acne from the teenage years into adulthood. Whereas, late-onset acne affects those who develop acne for the first time after the age of 25.8Skroza N, Tolino E, Mambrin A et al. Adult Acne Versus Adolescent Acne: A Retrospective Study of 1,167 Patients. J Clin Aesthet Dermatol 2018; 11: 21-5. PMCID: PMC5788264 Both subtypes more frequently affect women and are often associated with inflammation, changes in pigmentation, and scarring.
While adult acne tends to be more stubborn than teenage acne, isotretinoin is still very effective. It is very commonly used for adult acne. However, your dermatologist may request additional testing when appropriate.
Please see our Definitive Guide to Acne for more information about adult acne.
Isotretinoin itself is free from animal products, making it suitable for both vegetarians and vegans. However, it’s important to note that the Oratane® capsule is made from gelatine, which may have bovine (beef) or pork (pork) origins.
There is no vegan-friendly alternative available in New Zealand or Australia. Compounding pharmacies may be able to transfer the medication into a vegan-friendly capsule for a moderate fee. An option for vegan patients is to consume the medication without the capsule. However, this needs to be done with care as isotretinoin is inactivated on exposure to light.
Oratane® and Roaccutane® capsules are of bovine origin and are Halal-certified. 9Personal Correspondence: Douglas pharmaceuticals and Roche pharmaceuticals, Dec 2023 and June 2021
The most common side effects are dry skin (xerosis) and dry lips/mouth (xerostomia). Nose bleeds can occur if the inside of the nose becomes dry. Sun sensitivity is also common, so the appropriate use of sunscreen is important.
Isotretinoin is teratogenic, which means that it can cause birth defects – but only when a woman takes isotretinoin while pregnant. Reliable contraception must be used while women take isotretinoin and for a one full menstrual cycle washout period. Pregnant women cannot receive blood donations from individuals taking this medication.
The medication does not affect male fertility or sperm count, and fathering a child while taking it is not known to cause birth defects.
Other side effects may involve increased triglycerides (a type of fatty acid) in the blood and mild liver inflammation. The risk of this happening is low (see below).
Many patients generally tolerate it very well. Your dermatologist may have initiated treatment for several thousand patients with this medication.
Historically, patients were required to undergo blood test monitoring – as frequently as monthly. However, the newer low-dose regimens are unlikely to cause significant adverse effects and therefore many dermatologists do request blood tests anymore. This approach is supported by several studies demonstrating that blood test monitoring is unnecessary for the majority of patients.10Affleck A, Jackson D, Williams HC et al. Is routine laboratory testing in healthy young patients taking isotretinoin necessary: a critically appraised topic. Br J Dermatol 2022; 187: 857-65. doi: 10.1111/bjd.21840.
Blood test monitoring may still be requested for those at risk of liver disease risk or elevated lipids (fats).
In short, there is no good evidence that isotretinoin causes psychiatric or sexual side effects.
Unfortunately, isotretinoin (Oratane®) has attracted numerous conspiracy studies over the decades of its use. Unfortunately, the pervasive nature of these conspiracies have started to influence government agencies. A recent publication by the Commission on Human Medicines (CHM) Isotretinoin Expert Working Group in the United Kingdom has proposed the possibility of psychiatric and sexual side effects. In its review, the CHM discounted numerous high-quality studies while relying on low-quality studies and reports. Many dermatologists believe that the CHM was clearly politically biased and, as a result, was very quickly criticised in the academic literature by several well-respected dermatologists.11Tan E, Kennedy H, Rademaker M. Burden of proof—Critical flaws in the recommendations from the commission on human medicines Isotretinoin expert working group. Australasian Journal of Dermatology 2023; n/a. doi: https://doi.org/10.1111/ajd.14169.,12Tan E, Kennedy H, Rademaker M. When science and evidence is not enough – challenging the recommendations from the Commission on Human Medicines Isotretinoin Expert Working Group. British Journal of Dermatology 2023. doi: 10.1093/bjd/ljad363.
In contrast, there is an overwhelming number of studies that suggests that it has a protective effect against mental illness. Many of these studies have reported lower rates of mental illness by around 20% in those who have taken isotretinoin compared to the general population. 13Vallerand IA, Lewinson RT, Farris MS et al. Efficacy and adverse events of oral isotretinoin for acne: a systematic review. Br J Dermatol 2018; 178: 76-85. doi: 10.1111/bjd.15668
Furthermore, there is no good evidence that it causes sexual dysfunction.
The Australasian College of Dermatologists has published a helpful position statement. Acne experts from Australia and New Zealand collaborated to write this document. It is available on the ACD website.
The Consumer Medicine Information leaflet for Oratane® is available on Medsafe’s website.
All About Acne also has a page about isotretinoin (Oratane®) on their website.