Revised: 12 June 2013
Avoiding Teratogenicity with Isotretinoin
Website: August 2002
Prescriber Update 2002;23(3):35-36
Marius Rademaker, Hon Associate Professor and Specialist Dermatologist, Waikato Hospital, Hamilton
The teratogenicity of isotretinoin is well documented. The first New Zealand case of embryopathy was
recently reported to CARM. This is a timely reminder that effective contraception is recommended for all
women of childbearing age for whom isotretinoin is a treatment option. It is also important to exclude
pregnancy prior to starting isotretinoin, and for women to continue contraception for one month after
Isotretinoin known to cause severe foetal malformations
Isotretinoin (Oratane™, Roaccutane™) is classified as Category X under the Australian categorisation of
risk of medicine use in pregnancy, meaning the medicine has such a high risk of causing permanent damage to
the foetus that it should not be used in pregnancy or where there is a possibility of pregnancy.1
In humans, isotretinoin can cause central nervous system malformations, absence or deformity of ears, cleft
palate, cardiac and great vessel defects, and eye abnormalities.2,3
These abnormalities occur at various dosages within the usual therapeutic range and have occurred in women
who were treated for less than one week in the first trimester of pregnancy. This suggests that a single
dose of isotretinoin may be teratogenic.4
First NZ report of isotretinoin associated embryopathy
The Centre for Adverse Reactions Monitoring (CARM) has recently received its first report of embryopathy
in association with a patient taking isotretinoin in New Zealand. The woman had been taking isotretinoin 40
mg/day for three months when she became pregnant. It is unknown whether she was using contraception. When
the woman stopped isotretinoin, she was six weeks pregnant. Antenatal ultrasound showed no abnormalities but
the child was born with typical retinoid embyropathy including heart, ear and oesophageal malformations. The
World Health Organisation database has 691 reports of foetal disorders associated with isotretinoin,
including 35 of multiple malformations.
High incidence of severe malformations seen in US study
In a large study4 of 433 spontaneous reports of women exposed to isotretinoin
during pregnancy in the United States, 130 patients (or a third of 396 reports in whom timing of conception
was known) were already pregnant when they started isotretinoin. An additional 65 patients became pregnant
in the first three weeks of isotretinoin use. Pregnancy outcomes were known in 409 pregnancies. Among these,
54% ended in elective abortion and 7% in spontaneous or missed abortion. Of 151 births, 48% were normal, 47%
had congenital malformations, and 5% had abnormalities other than malformations.
Implement precautions to avoid pregnancy in women using isotretinoin
Isotretinoin is known to be highly teratogenic, therefore it is important to prevent pregnancy occurring
during (and immediately after) isotretinoin use. It is essential that all female patients be counselled
about the very significant risk of teratogenicity. The following approach is recommended when prescribing
isotretinoin to all women of childbearing potential.5 These precautions
are also advised for women who do not usually use contraception because of a history of infertility.2,3
- Take a current sexual history. No assumptions should be made on the basis of age, race or religious
beliefs, although clinicians should be sensitive to such issues. It may be necessary to conduct some of
this enquiry with the patient alone, in the absence of parents and partners.
- A menstrual history should be taken: patients with irregular menses present a difficult management
- Before starting isotretinoin treatment, all female patients of childbearing potential should have a
pregnancy test, preferably but not essentially performed on blood since it is more accurate at an
earlier stage of pregnancy.
- An appropriately trained clinician (not necessarily the dermatologist) should advise the woman about
effective contraception. The physician prescribing the isotretinoin needs to ensure that the woman
understands the importance of using contraception during treatment and is agreeable to doing so.
Emergency contraception is an option, should it be required, but this must not be the regular method of
- One month before starting isotretinoin commence the woman on contraception, ideally hormonal such as
either a combined oral contraceptive pill, or an injectable or implantable hormonal contraceptive.
Intra-uterine devices are also an option. The progesterone-only pill may be less reliable in women
- Dermatologists should ensure that all female patients who are at risk of pregnancy fully
understand the risks of pregnancy, are not currently pregnant and have been using appropriate
contraception for one month before starting treatment, and that the responsibilities of the patient and
physician have been discussed. This includes advising the patient that they are responsible for
consulting their GP, Family Planning clinic or dermatologist, if they have knowingly had unprotected
intercourse (or when contraceptive failure is suspected) so that the possibility of using emergency
contraception can be considered.
- Isotretinoin treatment should ideally begin with the patient's next menstrual cycle.
- Regular pregnancy tests should be undertaken during treatment with isotretinoin.
- Contraception should be continued for one month after stopping isotretinoin.
Competing interests (author): none declared.
Correspondence to Dr Marius Rademaker, Dermatology Department, Waikato Hospital, Private Bag 3200,
Hamilton. E-mail: Rademakm@waikatodhb.govt.nz
- Australian Drug Evaluation Committee. Prescribing Medicines in Pregnancy 4th
Edn. 1999: Therapeutic Goods Administration, Australia, p.45.
- Douglas Pharmaceuticals Ltd. Oratane data sheet 24 May 2001.
- Roche Products (New Zealand) Ltd. Roaccutane data sheet 24 May 2001.
- Dai WS, LaBraico JM, Stern RS. Epidemiology of isotretinoin exposure during
pregnancy. J Am Acad Dermatol 1992;26(4):599-606.
- Personal communication from Dr Nick Simpson, Consultant Dermatologist, Newcastle
Upon Tyne, United Kingdom. Presented at the New Zealand Dermatological Society workshop on Isotretinoin,
Auckland, March 2002. Based on the Draft Guidelines on the 'Safe introduction and continued use of
isotretinoin' by the British Association of Dermatologists 2002.