Roaccutane (R)

Isotretinoin (a derivative of vitamin A) is available on hospital-only prescription because of its potential toxicity and teratogenicity. It is used in the treatment of acne, reducing sebum production and surface propionibacterium acnes.

Since it may be obvious early on which patients are going to be referred, it may be worth starting the patient on antibiotics at the time of referral.

Prescribing information (1):

• 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

Isotretinoin is contraindicated in:

• hypervitaminosis A
• uncontrolled hyperlipidaemia
• during pregnancy or lactation (1,2,3)

Before commencement on Isotretinoin therapy:

• baseline investigations are required (FBC, fasting lipid profile, liver function tests)
• if the patient is female then it is important that a negative pregnancy test is confirmed before therapy is commenced. Also female patients must use effective contraception for at least four weeks before treatment, during the treatment period and for at least four weeks following its cessation (1)
• history of previous and current psychiatric health should be obtained (1)

Effective contraception is required when a woman of child bearing age is using isotretinoin (1,2,3)

The British National Formulary addresses the issue of contraception and isotretinoin use (4):

• MHRA/CHM advice: Oral retinoid medicines: revised and simplified pregnancy prevention educational materials for healthcare professionals and women (June 2019)
  • new prescriber checklists, patient reminder cards, and pharmacy checklists are available to support the Pregnancy Prevention Programme in women and girls of childbearing potential taking oral acitretin, alitretinoin, or isotretinoin. Healthcare professionals are reminded that the use of oral retinoids is contra-indicated in pregnancy due to a high risk of serious congenital malformations, and any use in females must be within the conditions of the Pregnancy Prevention Programme (see Conception and contraception and Prescribing and dispensing information)
  • neuropsychiatric reactions have been reported in patients taking oral retinoids. Healthcare professionals are advised to monitor patients for signs of depression or suicidal ideation and refer for appropriate treatment, if necessary; particular care is needed in those with a history of depression. Patients should be advised to speak to their doctor if they experience any changes in mood or behaviour, and encouraged to ask family and friends to look out for any change in mood
• the MHRA advises that women and girls of childbearing potential being treated with the oral retinoids acitretin, alitretinoin, or isotretinoin must be supported on a Pregnancy Prevention Programme with regular follow-up and pregnancy testing
• in females of childbearing potential, exclude pregnancy a few days before treatment, every month during treatment (unless there are compelling reasons to indicate that there is no risk of pregnancy), and 4 weeks after stopping treatment
  • females must practise effective contraception for at least 1 month before starting treatment, during treatment, and for at least 1 month after stopping treatment
  • should be advised to use at least 1 method of contraception, but ideally they should use 2 methods of contraception
  • oral progestogen-only contraceptives are not considered effective
  • barrier methods should not be used alone, but can be used in conjunction with other contraceptive methods
  • females should be advised to discontinue treatment and to seek prompt medical attention if they become pregnant during treatment or within 1 month of stopping treatment

A single course of oral isotretinoin can induce remission of acne patients and is most effective acne treatment available (2). In general patients require isotretinoin treatment for four to eight months

NICE suggest with respect to oral isotretinoin treatment (5):

Consider oral isotretinoin for people older than 12 years who have a severe form of acne that is resistant to adequate courses of standard therapy with systemic antibiotics and topical therapy (table below). For example:

• nodulo-cystic acne
• acne conglobata
• acne fulminans
• acne at risk of permanent scarring

When considering oral isotretinoin for acne take into account the person's psychological wellbeing, and refer them to mental health services before starting treatment if appropriate

If a person with acne is likely to benefit from oral isotretinoin treatment:

• follow the MHRA guidance on important risks and precautions for isotretinoin. This includes:
  • prescribing only by a consultant dermatologist-led team
  • assessing and monitoring mental health
  • assessing and monitoring sexual function

If the person has the potential to become pregnant:

• explain that isotretinoin can cause serious harm to a developing baby if taken during pregnancy
• inform them that they will need to follow the MHRA pregnancy prevention programme

Prescribe oral isotretinoin for acne treatment at a standard daily dose of 0.5 to 1 mg/kg.

Consider a reduced daily dose of isotretinoin (less than 0.5 mg/kg) for people at increased risk of, or experiencing, adverse effects

When giving isotretinoin as a course of treatment for acne:

• continue until a total cumulative dose of 120 to 150 mg/kg is reached, but
• if there has been an adequate response and no new acne lesions for 4 to 8 weeks, consider discontinuing treatment sooner

If a person is taking oral isotretinoin for acne:

• review their psychological wellbeing during treatment, and monitor them regularly for symptoms or signs of developing or worsening mental health problems or sexual dysfunction
• tell them to seek medical advice if they feel their mental health or sexual function is affected or is worsening, and to stop their treatment and seek urgent medical advice if these problems are severe

Use of oral corticosteroids in addition to oral isotretinoin

• if an acne flare (acute significant worsening of acne) occurs after starting oral isotretinoin, consider adding a course of oral prednisolone
• when a person with acne fulminans is started on oral isotretinoin, consider adding a course of oral prednisolone to prevent an acne flare

Treatment choices for mild to moderate and moderate to severe acne vulgaris:

Notes:

• Roche have produced guidance with respect to isotretinoin (6):
  • Initiation of isotretinoin treatment in patients under 18 years of age now requires agreement by two independent prescribers that there is no other appropriate effective treatment before it is prescribed.
  • All patients must be counselled about the benefits and risks of treatment before isotretinoin is prescribed, including possible side effects relating to mental health and sexual function.
  • Patients should also be monitored for these and other side effects during isotretinoin treatment.
  • New risk minimisation materials have been developed to incorporate these new safety measures and support healthcare professionals and patients, as well as highlight the updates to the product information.
  • The Acknowledgement of Risk Form is available for prescribers and should be completed with all patients. Patients should be provided with a copy of this as well as the Patient Reminder Card. A Pharmacist Checklist should be used by pharmacists as a reminder when dispensing isotretinoin.
  • Applicability of the updated Pregnancy Prevention Programme must be assessed for all patients. Isotretinoin is contraindicated in women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met.

Reference:

• MHRA. Isotretinoin for severe acne: uses and effects (Accessed 28/5/23)
• Prescriber 2006; 14 (22):44-55.
• Haider A, Shaw J.C. Treatment of Acne Vulgaris. JAMA. 2004;292:726-735
• British National Formulary. Isotretinoin (Accessed May 25th 2023)
• NICE (May 2023). Acne vulgaris: management
• Roche Products Limited (November 9th 2023). Oral isotretinoin: New safety measures following review into sexual and psychiatric adverse reactions