ISOTRETINOIN 4759-48-2 CAS NO.4759-48-2

Isotretinoin, also known as 13-cis-retinoic acid (and colloquially referred to by its former brand name Accutane or Roaccutane), is a medication primarily used to treat severe acne. Rarely, it is also used to prevent certain skin cancers (squamous-cell carcinoma), and in the treatment of other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. It is a retinoid, meaning it is related to vitamin A, and is found in small quantities naturally in the body. Its isomer, tretinoin, is also an acne drug.

Isotretinoin is primarily used as a treatment for severe acne. The most common adverse effects are a transient worsening of acne (lasting 1-4 months), dry lips (cheilitis), dry and fragile skin, and an increased susceptibility to sunburn. Uncommon and rare side effects include muscle aches and pains (myalgias), and headaches. Isotretinoin is known to cause birth defects due to in-utero exposure because of the molecule's close resemblance to retinoic acid, a natural vitamin A derivative which controls normal embryonic development. It is also associated with psychiatric side effects, most commonly depression but also, more rarely, psychosis and unusual behaviours. Other rare side effects include hyperostosis, and premature epiphyseal closure, have been reported to be persistent.

In the United States, a special procedure is required to obtain the pharmaceutical. In most other countries, a consent form is required which explains these risks. Women taking isotretinoin must not get pregnant during and for 1 month after the discontinuation of isotretinoin therapy. Sexual abstinence or effective contraception is mandatory during this period. Barrier methods by themselves (e.g., condoms) are not considered adequate due to the unacceptable failure rates of approximately 3%. Women who become pregnant while taking isotretinoin therapy are generally counselled to have a termination.

Isotretinoin was first marketed as Accutane by Hoffmann-La Roche. It sold well for many years, but in 2009, Roche decided to remove Accutane from the US market after juries had awarded millions of dollars in damages to former Accutane users over inflammatory bowel disease claims. The American College of Gastroenterologists has released a position paper stating that people with inflammatory bowel disease should not be precluded from having their acne treated with isotretinoin. It then became generic and as of 2017 was marketed under many brand names worldwide.

Possible permanent effects[edit]

Isotretinoin may stop long bone growth in young people who are still growing.^[5] Premature epiphyseal closure can occur in people with acne receiving recommended doses^[22] of Accutane.^[23][24][25]

Isotretinoin is known to cause meibomian gland dysfunction which causes persistent keratoconjunctivitis sicca (dry eye).^[26] Problems with the meibomian and salivary glands are likely due to the non-selective apoptosis of the cells of the exocrine glands.^[27] Decreased night vision has been reported to persist in some people after discontinuation of isotretinoin therapy.^[28]

Skin and mucocutaneous tissue[edit]

The most common side effects are mucocutaneous: dry lips, skin and nose. Other common mucocutaneous side effects are inflammation and chapping of the lips (cheilitis), redness of the skin (erythema), rashes, peeling, eczema (dermatitis), itching (pruritus) and nose bleeds (epistaxis).^[29] Absence of dryness of the lips is considered an indication of non-compliance with treatment (not taking the drug as advised), as it occurs in almost all people who take it.^[29]

Regular use of lip balm and moisturizer is recommended throughout a course of treatment to reduce these problems. The dose may need to be decreased to reduce the severity of these side effects.^[30] The skin becomes more fragile—especially to frictional forces—and may not heal as quickly as normal. For this reason waxing of hair, tattooing, tattoo removal, piercings, dermabrasion, exfoliation, etc. are not recommended. Treatment of acne scars is generally deferred until 12 months after completion of a course of isotretinoin.

Acne usually flares up 2–3 weeks into the treatment and is usually mild and tolerable. Occasionally this flare-up is severe, necessitating oral antiobiotics such as erythromycin. A short course of oral prednisolone may be required. Some dermatologists favour a few weeks of pre-treatment with oral antibiotics before commencing isotretinoin to reduce the chance of a severe flare. A "stepped" course may also be used to reduce the chance of this initial flare, by which the initial dose is low (e.g. 0.5 mg/kg) and subsequently increased throughout the course.

Isotretinoin use can rarely lead to a more severe form of acne, acne fulminans.