The 2014 guidance on isotretinoin has been withdrawn. From October 2023, healthcare professionals to consult the October 2023 Drug Safety Update and Report of the Isotretinoin Implementation Advisory Expert Working Group when referring patients and when prescribing or dispensing isotretinoin. Patients should consult the isotretinoin Patient Information Leaflet or the isotretinoin Patient Guide.
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. Isotretinoin can only 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
- 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 Europe which currently use many different titles to describe healthcare providers. However in the UK, this definition refers to consultant dermatologists.
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.
2. Prescribing isotretinoin
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.
3. Isotretinoin treatment
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:
- skin changes
- hair loss
- stomach ache
Isotretinoin should be used with caution in people with:
- a history of depression
- dry-eye syndrome
- impaired kidney function
- people who are allergic to peanuts, soya, or the sugar sorbitol as some brands of isotretinoin may contain these ingredients
4. Effects on the skin
Some side effects of isotretinoin on the skin are very common, arising in 1 or more of every 10 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)
- 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.
5. Psychiatric side effects
Acne is known to be associated with an increased risk of psychiatric disorders and there have been reports of psychiatric disorders associated with isotretinoin treatment for acne.
Depression, aggravation of existing depression, aggressive tendencies, anxiety, and changes in mood have been reported rarely in patients taking isotretinoin (ie occurring in 1 or more of every 10,000 patients, but in fewer than 1 in every 1,000 patients).
Abnormal behaviour, psychotic disorder, suicidal ideation, suicide attempt and suicide have been reported very rarely (ie in 1 in every 10,000 patients or fewer).
Before starting treatment patients should inform their doctor if they have, or have ever had, depression or any other psychiatric disorder. 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. However, stopping isotretinoin may not be enough to alleviate symptoms and further psychiatric or psychological evaluation may be necessary.
Some patients may want to continue treatment and can be offered support and close monitoring while treatment is ongoing. Side effects are generally reversible after stopping treatment; however, some may persist after treatment stops.
Due to ongoing concerns, a review of psychiatric reactions was carried out in 2014. The review considered all available evidence from published literature and individual case reports. See the review of isotretinoin and psychiatric adverse reactions.
Due to conflicting study results and the limitations in the data it was not possible to identify a clear biological mechanism by which isotretinoin would cause psychiatric disorders.
Acne itself is associated with psychiatric disorders and the age that many patients take isotretinoin is also the age that some psychiatric disorders are commonly diagnosed.
Although inconclusive, the evidence was considered sufficient to support the current warnings in the product information.
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.
6.1 Pregnancy prevention programme for isotretinoin
A revised pregnancy prevention programme for isotretinoin was implemented in 2005. The programme consists of 3 parts: information, treatment and prescribing.
Brochures providing information for prescribers, pharmacists and patients have been developed. The text for these brochures was developed with input from organisations that hold a marketing authorisation for isotretinoin, the Committee on the Safety of Medicines Expert Working Group on Isotretinoin, the British Association of Dermatologists and the Family Planning Association.
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 1 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)
- giving the patient a pregnancy test 5 weeks after stopping treatment
The doctor must also discuss with all female patients the potential harmful risks that isotretinoin can cause to an unborn baby, the importance of using at least 1 method of effective contraception and preferably 2, 1 of which is a barrier method such as a male condom.
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 7 days.
7. Further information
The British Association of Dermatologists has advice on the safe introduction and continued use of isotretinoin in acne