Who Should Not Take Isotretinoin

Isotretinoin is the most effective remedy for severe acne, but the list of its restrictions is longer than that of most dermatological drugs. The editors have organized the absolute and relative contraindications, dangerous combinations with other substances and the life situations in which particular caution is needed.

Absolute contraindications

Isotretinoin is an effective but demanding drug. The European prescribing information (SmPC) for oral forms defines a list of conditions in which its use is impermissible. The editors present them in an organized form.

For women of reproductive age, prescription is possible only on condition that a pregnancy prevention program is followed. If the patient cannot or does not wish to comply with its requirements, this is effectively a contraindication as well.

In the case of allergy, it is worth reading the composition of the specific drug carefully: excipients differ between manufacturers, and it is they that sometimes cause reactions.

Any of these restrictions is grounds not to start treatment or to postpone it until the cause is eliminated.

Pregnancy and contraception: the main restriction

The teratogenicity of isotretinoin was described as early as 1985 in the classic work by Lammer and colleagues inNEJM. The malformations affect the face, ears, heart, thymus and central nervous system, and the risk of spontaneous abortion also rises sharply. There is no safe dose during pregnancy.

Pregnancy prevention programs (iPLEDGE in the US, the European program updated by the EMA in 2018) require:

• a negative pregnancy test before starting treatment;
• effective contraception for a month before starting, throughout the course and for a month after it ends;
• monthly pregnancy tests during treatment;
• a pregnancy test after completing therapy.

Patients are strictly forbidden to give their capsules to other people and to donate blood during treatment and for a month afterwards - because the blood could be transfused to a pregnant woman.

For men there are no such strict restrictions: the available data do not indicate a clinically significant risk to the fetus via semen. However, the rule on blood donation applies to men as well.

Relative contraindications: when particular caution is needed

Besides the absolute restrictions, there are a number of conditions in which isotretinoin can be used only after a careful assessment of the benefit-risk ratio and with enhanced monitoring.

First of all, this is a history of depression and other mental disorders. The prescribing information contains a warning about possible neuropsychiatric reactions, although a causal link has not been definitively proven. The doctor assesses mental state before treatment, and the patient and family are advised to pay attention to mood changes.

The second group is metabolic risks: diabetes mellitus, obesity, hereditary disorders of lipid metabolism, alcohol abuse. In such patients hypertriglyceridemia occurs more often.

The third is bone and muscle diseases, as well as adolescents who are actively growing: with high doses and prolonged use of retinoids, changes in bone tissue have been described. People with inflammatory bowel diseases can also be included here: current guidelines do not consider them an absolute contraindication but recommend caution.

Dangerous combinations

Some contraindications are related not to diseases but to the concurrent use of other substances. The best-known combination is isotretinoin and tetracyclines (doxycycline, minocycline), which are widely used for acne. Both groups can raise intracranial pressure, so they are not combined.

The second is vitamin A supplements, including some multivitamins and cod liver oil. Isotretinoin is itself a derivative of vitamin A, so additional intake increases the risk of hypervitaminosis.

The third is alcohol and other hepatotoxic substances. The editors include here oral anabolic steroids, which athletes sometimes combine with isotretinoin for "steroid" acne. Both groups affect the liver and lipids, and the combination amplifies the risks.

Finally, one should be cautious with photosensitizing procedures, aggressive peels, waxing and laser interventions during the course and for some time afterwards: the skin becomes thinner and more vulnerable.

Sport, blood donation and other life situations

Sport is not a contraindication to isotretinoin, but it requires adaptation. The drug can cause muscle and joint pain and an increase in creatine kinase, especially after intense exertion. People who train should discuss the level of exertion for the duration of the course with a doctor.

Dryness of the mucous membranes, particularly the eyes, makes wearing contact lenses uncomfortable, and the reduction in night vision mentioned in the prescribing information is important for those who drive at night.

As for donation: during treatment and for a month afterwards, blood cannot be donated, regardless of sex.

Taking isotretinoin on one's own without a prescription is the riskiest scenario. Such a person does not undergo screening for contraindications, does not receive pregnancy tests or lipid monitoring, that is, loses all the mechanisms that make the drug acceptably safe.

Editorial conclusions

The absolute contraindications to isotretinoin are pregnancy, breastfeeding, liver failure, very high lipids, hypervitaminosis A, tetracycline use and allergy to components.

The relative restrictions concern mental disorders, metabolic disturbances and some chronic diseases - here an individual approach is needed.

Dangerous combinations with vitamin A, tetracyclines, alcohol and hepatotoxic drugs should be known to every patient.

We also recommend reading our materials on tests during isotretinoin treatment, on its effect on the liver and kidneys, and on athletic performance.

References

1. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med. 1985;313(14):837–841.
2. European Medicines Agency. Isotretinoin: Article 31 referral — measures to minimise risk of pregnancy and neuropsychiatric disorders. EMA; 2018.
3. U.S. Food and Drug Administration. Isotretinoin capsules: prescribing information and iPLEDGE REMS. Silver Spring (MD): FDA.
4. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945–973.
5. Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1–1006.e30.
6. Layton A. The use of isotretinoin in acne. Dermatoendocrinol. 2009;1(3):162–169.