Published: 5 March 2020

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Isotretinoin: Why it’s important to prevent pregnancy

Prescriber Update 41(1): 5-7
March 2020

Isotretinoin indicated for treatment of severe acne

Isotretinoin is a synthetic vitamin A derivative (retinoid) indicated for the treatment of patients with severe forms of nodulocystic acne that persist following other treatments¹. Isotretinoin suppresses sebaceous gland activity leading to reduced sebum production, smaller sebaceous glands, less follicular occlusion and less inflammation².

Isotretinoin is teratogenic

Isotretinoin is teratogenic at all therapeutic doses. Fetal malformation may occur with only a short period of exposure to isotretinoin during pregnancy¹ and has been reported after a single dose³.

Isotretinoin embryopathy consists of craniofacial, cardiac, thymic and central nervous system malformations⁴. Isotretinoin adversely affects 25–40 percent of fetuses exposed during embryogenesis (ie, the first 10 weeks following conception)⁵. For pregnancies that end in birth, the rate of malformations associated with isotretinoin exposure in utero has been reported as 11–30 percent, with most estimates at the upper end of this range⁶. Fetal exposure to isotretinoin beyond the critical period of organogenesis can cause developmental delays and other central nervous system effects in approximately 40 percent of cases⁴.

Isotretinoin exposure is still occurring in pregnancy

Despite the well-known teratogenic effects of isotretinoin, pregnancy exposures still occur. A review of the National Collections data indicated that during the period 1 July 2011 to 30 June 2017, 39 live-born infants were potentially exposed to an oral retinoid during pregnancy or within 30 days of the estimated pregnancy start date. In 31 of these cases, isotretinoin was dispensed after the estimated pregnancy start date. This number is likely to be an underestimate as the data does not include pregnancies that ended prior to 20 weeks gestation⁷.

Isotretinoin is contraindicated in pregnancy

Acne commonly occurs in adolescents and young adults. Due to its teratogenic effects, isotretinoin is contraindicated in pregnancy. Extreme care is therefore required when prescribing isotretinoin to treat acne in women of childbearing age – only prescribe if the conditions in Table 1 are met.

Table 1: Conditions that must be met when prescribing isotretinoin to treat acne in a woman of childbearing potential^a,b,c

Severe acne that is resistant to other therapies. Can understand the need for pregnancy prevention and is willing to adhere to the requirements. Has been informed by her doctor of the hazards of becoming pregnant during and 1 month after treatment with isotretinoin, she has been warned of the possibility of contraceptive failure and she confirms that she has understood the warnings. Is willing to use two forms of effective contraception (ie, a barrier method and hormonal contraception) without any interruption for 1 month before starting isotretinoin, during treatment with isotretinoin and for 1 month after stopping isotretinoin. Oral progesterone-only contraceptives are not considered an effective form of contraception during treatment with isotretinoin. Has a negative pregnancy test within 3 days prior to starting treatment with isotretinoin. Repeat pregnancy tests monthly and 5 weeks after stopping treatment. Starts isotretinoin therapy only on day 2 or 3 of the next menstrual period.

1. Douglas Pharmaceuticals Ltd. 2019. Oratane New Zealand Data Sheet 29 October 2019. URL: medsafe.govt.nz/profs/Datasheet/o/oratanecap.pdf (accessed 10 January 2020).
2. New Zealand Formulary. 2020. New Zealand Formulary v91: Isotretinoin (systemic) 1 January 2020. URL: nzf.org.nz/nzf_6452 (accessed 10 January 2020).
3. BPAC NZ. 2017. Prescribing isotretinoin for patients with acne in primary care 20 January 2017. URL: bpac.org.nz/2017/isotretinoin.aspx (accessed 9 January 2020).

Contraceptive measures should be continued for one month after stopping isotretinoin to ensure that the drug and its active metabolite have completely cleared from the body¹.

Additional measures to reduce the risk of pregnancy exposure to isotretinoin

There are decision support tools available to support the appropriate prescribing of isotretinoin. The bestpractice isotretinoin module contains information about appropriate pregnancy prevention measures and contains a printable patient acknowledgement/consent form. Oratane is currently the only funded brand of isotretinoin available in New Zealand. Additional materials are available from Douglas Pharmaceuticals at: oratane.co.nz

Dispense isotretinoin in the manufacturer’s original pack. The pack contains safety information, including information on pregnancy prevention⁸. A copy of the Consumer Medicine Information leaflet should also be given to the patient when isotretinoin is dispensed for the first time (available at medsafe.govt.nz/Medicines/infoSearch.asp).

Exposure to isotretinoin via semen is not believed to cause teratogenic effects. Advise male patients not to share their isotretinoin with anyone¹.

Patients taking isotretinoin should not donate blood during treatment and for at least one month after stopping the medicine^1,2.

References

1. Douglas Pharmaceuticals Ltd. 2019. Oratane New Zealand Data Sheet 29 October 2019. URL: medsafe.govt.nz/profs/Datasheet/o/oratanecap.pdf (accessed 10 January 2020).
2. New Zealand Formulary. 2020. New Zealand Formulary v91: Isotretinoin (systemic) 1 January 2020. URL: nzf.org.nz/nzf_6452 (accessed 10 January 2020).
3. James WD. 2005. Acne. New England Journal of Medicine 352(14): 1463–72. DOI: 10.1056/NEJMcp033487 (accessed 10 January 2020).
4. Crijns I, Straus S, Luteijn M, et al. 2012. Implementation of the harmonized EU isotretinoin Pregnancy Prevention Programme: A questionnaire survey among European regulatory agencies. Drug Safety 35(1): 27–32. DOI: 10.2165/11595570-000000000-00000 (accessed 10 January 2020).
5. BPAC NZ. 2013. Managing acne in primary care March 2013. URL: bpac.org.nz/bpj/2013/march/managing-acne.aspx (accessed 9 January 2020).
6. Moodie P, Jaine R, Arnold J, et al. 2011. Terminations of pregnancy associated with isotretinoin use in New Zealand. New Zealand Medical Journal 124(1339): 59–66. URL: nzma.org.nz/issue-id/vol-124-no-1339-29-july-2011 (accessed 10 January 2020).
7. Medsafe. 2018. Isotretinoin - review of (1) pregnancy prevention measures and (2) obsessive compulsive disorder. Presented at the 173rd Medicines Adverse Reaction Committee meeting, 8 March 2018. URL: medsafe.govt.nz/committees/MARC/reports/174-Isotretinoin-%20review%20of%20(1)%20pregnancy%20prevention%20measures%20and(2)%20obsessive%20compulsive%20disorder_Redacted.pdf (accessed 9 January 2020).
8. Medsafe. 2018. Minutes of the 174th Medicines Adverse Reactions Committee meeting. URL: medsafe.govt.nz/profs/adverse/Minutes174.htm#3.2.4 (accessed 10 January 2020).