Isotretinoin (Roaccutane▼): introduction of new safety measures, including additional oversight of the initiation of treatment for patients under 18 years of age
We have strengthened the safe use of isotretinoin through the introduction of additional oversight of the initiation of isotretinoin in patients under 18 years and through improved assessment and monitoring of mental health and sexual function issues. We ask healthcare professionals to review these new measures and supporting materials and integrate them into their clinical practice when referring patients and when prescribing or dispensing isotretinoin.
Summary of measures
- 2 independent prescribers need to agree the initiation of isotretinoin in patients under 18 years
- New counselling requirements about potential mental health and sexual function side effects
- Assessment of mental health and sexual function before starting treatment and monitoring of mental health and sexual function during treatment
- New roles and responsibilities for healthcare professionals
- New regulatory risk minimisation materials
Following the April 2023 recommendations, the Isotretinoin Implementation Advisory Expert Working Group of the Commission on Human Medicines (CHM) has developed guidance to support the safe implementation of the new regulatory position – consult the Report of the Isotretinoin Implementation Advisory Expert Working Group.
Advice for healthcare professionals:
- all patients must be counselled about the benefits and risks of treatment before isotretinoin is prescribed, including possible mental health and sexual function side effects; we also ask the referrer (usually the GP) to provide information about isotretinoin to the patient and provide counselling (where possible) regarding the benefits and risks of isotretinoin treatment
- isotretinoin is teratogenic; all patients of childbearing potential must be entered into the Pregnancy Prevention Programme
- prescribers should assess patients’ mental health before prescribing isotretinoin including the use of patient-reported outcome measures
- ask patients about any sexual function concerns before prescribing isotretinoin
- give the patient sufficient time to consider, reflect and ask questions before starting isotretinoin treatment
- use the new regulatory risk minimisation materials with all patients: Acknowledgement of Risk Form, Patient Reminder Card, Pharmacist Checklist
- the Lead Prescriber, who initiates isotretinoin treatment, must have expertise in the use of systemic retinoids for the treatment of severe acne and a full understanding of the risks of isotretinoin therapy and monitoring requirements
- initiation of isotretinoin treatment in patients under 18 years of age now requires agreement by 2 independent healthcare professionals that there is no other appropriate effective treatment before it is prescribed. This means that isotretinoin should only be prescribed for severe acne that is resistant to adequate courses of standard therapy
- review patients approximately 1 month after initiation of treatment in a face-to-face (in-person) appointment
- monitor patients for side effects including mental health and sexual function side effects at each follow up appointment including objective mental health patient reported outcome measures
- any healthcare professional involved in the treatment of patients with acne, particularly prescribers of isotretinoin, should review the full details of the new requirements in the Report of The Commission on Human Medicines Isotretinoin Implementation Advisory Expert Working Group
- report suspected adverse drug reactions associated with isotretinoin on a Yellow Card
Advice for healthcare professionals to provide to patients:
- isotretinoin is an effective treatment for acne. It should be used for acne that is severe or at risk of causing permanent scarring when other appropriate treatments have not been effective
- all medicines have side effects. Not every patient experiences side effects, but you should know about them and what to do if they occur. This includes possible mental health and sexual function side effects
- inform your healthcare professional if you have any personal or family history of mental health issues or any sexual function concerns
- isotretinoin if taken during pregnancy can seriously harm an unborn baby. Patients must not become pregnant during treatment with isotretinoin and for 1 month after isotretinoin is stopped
- if you may be able to get pregnant your doctor must enter you into the Pregnancy Prevention Programme before you are treated with isotretinoin
- take time to think about the information provided by your doctor about the benefits and risks of isotretinoin and decide whether it is the right treatment for you
- your doctor will check that you understand the information in the Acknowledgement of Risk Form – you need to agree to all applicable points in the Acknowledgement of Risk Form in order to receive isotretinoin; make sure to keep your copy of the completed form safe
- read the Patient Reminder Card and keep it safe. It contains important safety information that you need to be aware of before and during treatment
- if you are under 18 years of age, 2 healthcare professionals must agree that there is no other appropriate effective treatment option before you start isotretinoin
- patients already being treated with isotretinoin should continue to follow their agreed treatment plan from their prescriber, but seek medical advice if they have any side effects or concerns
- report side effects associated with isotretinoin directly to the MHRA via the Yellow Card scheme
Isotretinoin treatment and new safety measures
Isotretinoin should only be prescribed for severe forms of acne (such as nodular or conglobate acne or acne at risk of permanent scarring) resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy. Isotretinoin capsules are also known by the brand names Roaccutane and Reticutan in the UK.
In April 2023, the Commission on Human Medicines (CHM) published recommendations following their review of mental health and sexual side effects suspected to be associated with isotretinoin. The review considered all the available evidence, including information from patients and their families, and recommended new measures to strengthen the safety of isotretinoin treatment.
The product information for isotretinoin medicines has been updated following the review’s recommendations. This includes the addition of new warnings and precautions on potential mental health and sexual function side effects to the product information and the requirement for 2 healthcare professionals to agree that there is no other appropriate effective treatment in patients under 18 years of age.
Isotretinoin Implementation Advisory Expert Working Group
Following their review, the CHM formed an Isotretinoin Implementation Advisory Expert Working Group, composed of experts and representatives of the healthcare organisations to advise on how best to implement the recommendations in clinical practice. The CHM endorsed the guidance from the Isotretinoin Implementation Advisory Expert Working Group.
New guidance
The Isotretinoin Implementation Advisory Expert Working Group has worked with the MHRA to develop guidance specifying which healthcare professionals have the appropriate expertise to be the:
-
Lead Prescriber, who makes the decision to initiate isotretinoin treatment
-
Second Approved Named Healthcare Professional who agrees that isotretinoin is the most appropriate treatment option for adolescents under 18 years of age
-
Follow-Up Prescriber responsible for continuing and monitoring isotretinoin treatment
The Lead Prescriber must have expertise in the use of systemic retinoids for the treatment of severe acne and a full understanding of the risks of isotretinoin therapy and monitoring requirements.
The Isotretinoin Implementation Advisory Expert Working Group also developed guidance on the assessment and monitoring of mental health and sexual function.
For further details see the Report of the CHM Isotretinoin Implementation Advisory Expert Working Group.
New regulatory risk minimisation materials
New compulsory regulatory risk minimisation materials have been developed for use with all patients consisting of an Acknowledgement of Risk Form, a Patient Reminder Card and a Pharmacist Checklist. These are available electronically and will be sent to relevant healthcare professionals, including dermatology teams and pharmacy services GP practices, by post.
The Acknowledgment of Risk Form must be completed with all patients initiating isotretinoin treatment.
The new Acknowledgment of Risk Form has been developed to:
- continue to record the patient’s acknowledgment of the known risk of harm to unborn babies during pregnancy
- record acknowledgment of other risks including possible mental health and sexual function side effects
- continue to record enrolment onto the revised Pregnancy Prevention Programme if the patient is of childbearing potential
- record the agreement of 2 independent healthcare professionals that there is no other appropriate effective treatment in patients under 18 years of age.
A package of additional supporting documents has also been developed by the British Association of Dermatologists, British Dermatology Nursing Group and other stakeholders to support these changes. These additional documents can be adapted to local needs and systems.
All healthcare professionals involved in the treatment of patients who may require isotretinoin should refer to the Report of the CHM Isotretinoin Implementation Advisory Expert Working Group for further details, including a description of the isotretinoin treatment pathway.
Report any reactions on a Yellow Card
Isotretinoin is a black triangle medicine and all suspected adverse reactions, including any sexual and psychiatric adverse reactions, should be reported via the Yellow Card scheme. Reports can be made of suspected reactions experienced at any time, including historic adverse experiences with medicines.
Please include in the report as much detail as possible, particularly if a side effect continued or started after treatment was stopped. Information about medical history, any concomitant medication, onset timing, treatment dates, and product brand name should also be included.
Report to the Yellow Card scheme electronically using:
- the Yellow Card scheme website
- the Yellow Card app; download from the Apple App Store or Google Play Store
- some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)
Article citation: Drug Safety Update volume 17, issue 3: October 2023: 1.