Oral retinoids: pregnancy prevention—reminder of measures to minimise teratogenic risk
The risk of foetal malformation with oral retinoids is extremely high, even when used at a low dose or for a short time during pregnancy. All oral retinoids have an associated Pregnancy Prevention Programme (PPP), which is supported by educational material for prescribers, pharmacists, and patients. Women of child-bearing potential should have pregnancy excluded before starting treatment. While taking these medicines, one—or preferably two—different forms of contraception must be consistently used
For isotretinoin, the information and guidance in this article should be considered in conjunction with the 2023 Report of the Isotretinoin Implementation Advisory Expert Working Group. Updated educational materials for isotretinoin were also produced in 2023, and these are available in the October 2023 Drug Safety Update.
Article date: June 2013
Oral retinoids are used for severe skin conditions that are resistant to other therapies.
- Isotretinoin (brand leader Roaccutane) is used to treat severe acne
- Alitretinoin (Toctino) is indicated for adults with severe chronic hand eczema
- Acitretin (Neotigason) is used for: severe, extensive, resistant psoriasis; palmo-plantar pustular psoriasis; congenital ichthyosis; and Darier’s disease (keratosis follicularis)
Oral retinoids can only be prescribed within a team led by a consultant dermatologist. However, it is important that all involved are aware of the various measures to help avoid unnecessary exposure to these potent teratogens during pregnancy. Every oral retinoid has a dedicated and specific Pregnancy Prevention Programme (PPP).
Key PPP features:
- All women should be made aware of the teratogenic risks before starting treatment
- Pregnancy must be excluded before treatment with oral retinoids
- Pregnancy test results (with a minimum sensitivity of 25 mIU/mL) must be documented 3 days or less before the prescription is issued
- Women of childbearing potential should be on at least one, or preferably two, complementary forms of effective contraception (eg, barrier and hormonal)
- Contraception should start 1 month before treatment, and should continue throughout oral retinoid treatment and after until the retinoids have left the patient’s system—ie:
- At least 1 month after stopping treatment with isotretinoin or alitretinoin
- At least 2 years after stopping treatment with acitretin
- Females should undergo a pregnancy assessment every 4 weeks at follow-up appointments
- Specialist advice from a physician specialised in teratology must be sought immediately if a pregnancy occurs
- Prescription of oral retinoids should be limited to 30 days’ treatment
- The prescription must be dispensed within 7 days of issue
- Available data suggest that maternal exposure from the semen of patients receiving an oral retinoid is not associated with teratogenic effects
Acitretin
The measures are the same for all three products, with one exception: acitretin has a substantially longer half-life and duration of effect than either isotretinoin or alitretinoin, and therefore the PPP measures must also be undertaken for considerably longer.
The choice of contraception is particularly important for acitretin because it must be used throughout the treatment period and for at least 2 years after the patient has completed her course. These patients must also have regular follow-up appointments with their dermatology prescriber every 3 months during the 2-year period after treatment with acitretin has stopped to ensure patients are continuing to use contraception effectively.
We would like to remind healthcare professionals that measures for the prevention of pregnancy are imperative, with particular attention required for the longer supervision of patients who receive acitretin.
Further information
BNF - Rosacea and Acne (updated November 2017)
Article citation: Drug Safety Update vol 6, issue 11 June 2013: H1.