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 stopping isotretinoin.
Isotretinoin known to cause severe foetal
First NZ report of isotretinoin associated embryopathy
High incidence of severe malformations seen in US study
Implement precautions to avoid pregnancy in women using isotretinoin
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
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.
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.
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
Competing interests (author): none declared.
Correspondence to Dr Marius Rademaker, Dermatology Department, Waikato Hospital, Private Bag 3200, Hamilton. E-mail: Rademakm@waikatodhb.govt.nz