Acne is a common inflammatory disorder of the face, back, and chest that is characterised by the presence of blackheads, pustules, and potentially cysts and scars. About 80% of adolescents will have acne for some period, and it can occur in adults too. Most types of acne are readily treatable, although options for severe acne are limited.
Isotretinoin is an oral treatment for severe types of acne. The licences for oral isotretinoin products state that it can be prescribed by, or under supervision of, physicians with expertise in the use of systemic retinoids for the treatment of severe forms of acne (such as nodular or conglobate acne, or acne that is at risk of permanent scarring) that is resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy, and with a full understanding of the risks of isotretinoin therapy and the monitoring requirements.
The definition 'physicians with expertise in the use of systemic retinoids' was chosen as the most appropriate term to describe the provision of care in all European countries, which currently use many different titles to describe healthcare providers. However in the UK, this definition refers to consultant dermatologists.
Isotretinoin is available only on prescription and should be prescribed only in a consultant-led team. Prescriptions for isotretinoin should be issued under the consultant’s name from a hospital-based pharmacy. This way, specialists with the most experience can advise patients about the important safety issues associated with isotretinoin.
In the UK, the brand leader is made by Roche under the product name of Roaccutane; other generic or non-proprietary isotretinoin products are also available.
No medicine is without risk and isotretinoin is no exception. Since it was licensed in the UK in 1983, the MHRA has kept the safety of isotretinoin under close review. Although isotretinoin is an effective treatment for severe acne, it has important side effects and should not be used by some people, particularly by women who might be pregnant or are considering becoming pregnant. The issue of isotretinoin in pregnancy is discussed in further detail below.
The following information summarises the main advice for use of, and side effects associated with, isotretinoin. This is not a complete list and anyone prescribed isotretinoin should read carefully the patient information leaflet which accompanies the medicine. Anyone with concerns about acne or its treatment should discuss them with their doctor.
Isotretinoin is an anti-inflammatory agent derived from vitamin A that decreases the skin’s production of the oily substance sebum, which is thought to help lessen the number of bacteria that inhabit these areas of the skin. A course of treatment usually lasts between 16 weeks and 24 weeks, and at least 8 weeks should pass before another course is given (during which time a full assessment of the response to treatment should be made by a specialist).
The following people should not receive treatment with isotretinoin:
- Children aged 12 years or younger
- Women who are, or who might be, pregnant (see below)
- Women who are breast-feeding
- People with impaired liver function
- People with high levels of fat in their blood
- People with hypervitaminosis A - the presence of too much vitamin A in the body, symptoms of which include irritability, fatigue, skin changes, hair loss, headache, and stomach ache
- People who are allergic to peanuts, soya, or the sugar sorbitol: isotretinoin contains these ingredients
- Isotretinoin should be used with caution in people with: a history of depression (see below); diabetes; dry-eye syndrome; and impaired kidney function
The following medicines should not be taken alongside isotretinoin treatment:
- Vitamin A (see above)
- Keratolytic agents (e.g. salicylic acid - the active ingredient of some treatments for warts, corns, calluses, patches of dry scaly skin, acne, and fungal nail infections)
- Tetracyclines (antibiotics used for treatment of: infections such as chlamidya and those of the respiratory tract; acne; gum disease; and chronic bronchitis)
Advice for people who have been prescribed isotretinoin:
- Attend all appointments scheduled for you, which should be about once a month. This ensures that the specialist can check the medicine is working safely for you
- An improvement in the appearance of the skin may not be seen for until a few months of treatment. There may also be a slight worsening of acne on starting treatment, which usually subsides in 7-10 days
- Some side effects of isotretinoin are dose-related; some are generally reversible after changing the dose or stopping treatment; and some may persist after treatment has stopped
- Lip balm, moisturiser, and eye ointment may help alleviate any drying of the skin
- Avoid the sun and exposure to ultraviolet light (ie avoid the use of tanning beds); use sunscreen (sun protection factor, SPF, 15) from the start of treatment
- Avoid waxing, surgical dermabrasion, or laser surgery of the skin during treatment and for at least 6 months after stopping. This will help prevent any stripping, scarring, or pigmentation of the skin
- Do not donate blood while you are taking isotretinoin and for at least one month after stopping. This will help prevent transmission of the drug to those who should not receive it
- Do not give your medication to anyone else. Return any unused capsules to the pharmacy
Effects on the skin
Some side effects of isotretinoin on the skin are very common, arising in one or more of every ten patients that take the medicine. These include: chelitis (inflammation and cracking of the lips); dermatitis (inflammation of the skin); dry skin; localised exfoliation (scaling of the skin); pruritus (itching); rash erythematosus (a red rash); and fragile skin.
These effects vary in severity, frequency, and duration between patients. Use of a skin moisturiser cream or ointment, and use of a lip balm, may help relieve dryness of the skin and lips.
Depression, aggravation of existing depression, aggressive tendencies, anxiety, and changes in mood have been reported rarely in patients taking isotretinoin (i.e. occurring in one or more of every 10,000 patients, but in fewer than one in every 1,000 patients); abnormal behaviour, psychotic disorder, suicidal ideation, suicide attempt, and suicide have been reported very rarely (ie, in one in every 10,000 patients or fewer).
Before starting treatment patients should inform their doctor if they have, or have ever had, depression. During treatment, family and friends may be able to help the patient monitor their mood, and the doctor will ask about any changes in mood during follow up appointments. If a patient receiving isotretinoin develops symptoms of depression or mood changes it may be necessary for isotretinoin treatment to stop. Some patients may want to continue treatment and can be offered support while treatment is ongoing. Side effects are generally reversible after stopping treatment; however, some may persist after treatment stops (for further information see Current Problems in Pharmacovigilance May 2006).
Isotretinoin is a teratogen - that is, if taken by pregnant women, it may cause serious harm to the developing baby, even if taken only for a short period. The possibility of pregnancy must be excluded before a woman of child-bearing potential can begin isotretinoin, and measures must be taken to ensure women taking isotretinoin, or who have recently stopped isotretinoin, do not become pregnant.
A revised Pregnancy Prevention Programme for isotretinoin was implemented in 2005. The Programme consists of three parts:
Brochures providing information for doctors, pharmacists, and women have been developed by a group consisting of: the manufacturers of isotretinoin; the Expert Working Group of the Committee on the Safety of Medicines; the British Association of Dermatologists; and the Family Planning Association. The brochures are:
doctor’s guide to prescribing (33Kb)
doctors checklist (42Kb)
pharmacist’s guide to dispensing (40Kb)
patient’s information brochure (29Kb)
contraception brochure (68Kb)
There is also an acknowledgment form for female patients to sign after speaking with the doctor.
A doctor must establish that a woman prescribed isotretinoin is not at risk of becoming or being pregnant by: giving the patient a pregnancy test before starting treatment (ensuring that contraception has been used for one month); assessing the potential for pregnancy during treatment by scheduling monthly follow-up visits to the clinic (this assessment may or may not involve a pregnancy test); as well as giving the patient a pregnancy test five weeks after stopping treatment.
Moreover, the doctor must discuss with all female patients the potential harmful risks that isotretinoin can cause to an unborn baby, the importance of using at least one method of effective contraception, and preferably two, one of which is a barrier method such as a male condom. It is important to talk to the doctor about any medicines or herbal products that you plan to take during isotretinoin treatment because some medicines or herbal products, such as St John’s wort, can interfere with contraceptive methods.
These controls stipulate that for female patients who are prescribed isotretinoin under the Pregnancy Prevention Programme, prescriptions of isotretinoin are limited to 30 days’ supply and the prescription is valid only for seven days.