Published: August 2002


Avoiding Teratogenicity with Isotretinoin

Information on this subject has been updated. Read the most recent information.

Prescriber Update 23(3): 35-36
August 2002

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 stopping isotretinoin.

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

  1. 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.
  2. A menstrual history should be taken: patients with irregular menses present a difficult management problem.
  3. 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.
  4. 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 contraception.
  5. 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 taking isotretinoin.
  6. 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.
  7. Isotretinoin treatment should ideally begin with the patient's next menstrual cycle.
  8. Regular pregnancy tests should be undertaken during treatment with isotretinoin.
  9. 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:

  1. Australian Drug Evaluation Committee. Prescribing Medicines in Pregnancy 4th Edn. 1999: Therapeutic Goods Administration, Australia, p.45.
  2. Douglas Pharmaceuticals Ltd. Oratane data sheet 24 May 2001.
  3. Roche Products (New Zealand) Ltd. Roaccutane data sheet 24 May 2001.
  4. Dai WS, LaBraico JM, Stern RS. Epidemiology of isotretinoin exposure during pregnancy. J Am Acad Dermatol 1992;26(4):599-606.
  5. 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.


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