[9] It is known to cause birth defects due to in-utero exposure because of the molecule's close resemblance to retinoic acid, a natural vitamin A derivative that controls normal embryonic development.

Isotretinoin may represent an efficacious and safe alternative systemic form of therapy for recalcitrant condylomata acuminata (RCA) of the cervix.

[24] In the United States, since March 2006, the dispensing of isotretinoin is run through the iPLEDGE program, under the direction of the Food and Drug Administration.

Because severe cystic acne has the potential to cause permanent scarring over a short period, restrictions on its more immediate availability have proved contentious.

[49] This was in response to an EU review, published in August 2017, which states that a plausible physiological explanation of these side effects "may be a reduction in plasma testosterone".

Other common mucocutaneous side effects are inflammation and chapping of the lips (cheilitis), redness of the skin (erythema), rashes, peeling, eczema (dermatitis), itching (pruritus) and nose bleeds (epistaxis).

Isotretinoin is a teratogen highly likely to cause birth defects if taken by women during pregnancy or even a short time before conception.

A few of the more common birth defects this drug can cause are hearing and visual impairment, missing or malformed earlobes, facial dysmorphism, and abnormalities in brain function.

After the FDA put the more strict iPLEDGE program in place for the companies marketing the drug in the US, in 2011, 155 pregnancies occurred (0.12%) among 129,544 women of childbearing potential taking isotretinoin.

[55] People taking isotretinoin are not permitted to donate blood during and for at least one month after discontinuation of therapy due to its teratogenicity.

[15][57][58][59] In a total of 5577 adverse reactions reported to the UK's MHRA up to 31 March 2017, the plurality (1207, or 22%) concerned psychiatric effects.

[65] In 2012, a systematic review covering all articles in the literature related to isotretinoin, depression, and suicide, as well as articles related to class effect, dose-response, and biological plausibility found that the literature reviewed was consistent with an association of isotretinoin administration and depression and with suicide in a subgroup of vulnerable individuals.

[57] Studies have uncovered several biological processes which may credibly explain the affective changes induced by isotretinoin.

[57] The dopamine hypothesis of schizophrenia and psychosis suggests that an increase in dopaminergic stimulation or sensitivity in the limbic system causes psychotic symptoms.

[68][69] The evidence for this is threefold: transcriptional activation of the dopamine D2 receptor – in addition to serotonin and glutamate receptors – is regulated by retinoic acid;[68] schizophrenia and the retinoid cascade have been linked to the same gene loci;[68] and retinoid dysfunction causes congenital anomalies identical to those observed in people with schizophrenia.

Risk factors for skeletal effects include older age, greater dosage, and longer course of treatment.

More rare ocular side effects include blurred vision, decreased night vision (which may be permanent), colour blindness, development of corneal opacities, inflammation of the cornea (keratitis), swelling of the optic disk (papilloedema, associated with IIH), photophobia and other visual disturbances.

[90] A possible biological basis for the case reports of depression involves decreased metabolism in the orbitofrontal cortex (OFC) of the frontal lobe.

[57] Studies in mice and rats have found that retinoids, including isotretinoin, bind to dopaminergic receptors in the central nervous system.

Isotretinoin is also thought to affect the serotonergic system – it increases expression of 5-HT1A receptors in the pre-synaptic neuron, which inhibit serotonin secretion.

[57] Other brain regions regulated by retinoic acid and potentially disrupted by isotretinoin include the frontal cortex and the striatum.

[96] Accutane also negatively interacts with tetracycline, another class of acne drug, and with micro-dosed ('mini-pill') progesterone preparations, norethisterone/ethinylestradiol ('OrthoNovum 7/7/7'), St. John's Wort, phenytoin, and systemic corticosteroids.

[94] The compound 13-cis retinoic acid was first studied in the 1960s at Roche Laboratories in Switzerland by Werner Bollag as a treatment for skin cancer.

[97] In 1979, an article was published reporting the drug's effectiveness as a treatment of cystic and conglobate acne on fourteen patients, thirteen of which experienced complete clearing of their disease.

[97] Scientists involved in the clinical trials published articles warning of birth defects at the same time the drug was launched in the US, but isotretinoin was taken up quickly and widely, both among dermatologists and general practitioners.

In 1983 the FDA's advisory committee was convened and recommended stronger measures, which the FDA took and were at that time unprecedented: warning blood banks not to accept blood from people taking the drug and adding a warning to the label advising women to start taking contraceptives a month before starting the drug.

On 29 June 2009, Roche Pharmaceuticals, the original creator and distributor of isotretinoin, officially discontinued both the manufacture and distribution of their Accutane brand in the United States due to what the company described as business reasons related to low market share (below 5%), coupled with the high cost of defending personal injury lawsuits brought by some people who took the drug.

[102] Among others, actor James Marshall sued Roche over allegedly Accutane-related disease that resulted in the removal of his colon.

[104] Several trials over inflammatory bowel disease claims have been held in the United States, with many of them resulting in multimillion-dollar judgments against the makers of isotretinoin.

[105] As of 2017, isotretinoin was marketed under many brand names worldwide: A-Cnotren, Absorica, Accuran, Accutane, Accutin, Acne Free, Acnecutan, Acnegen, Acnemin, Acneone, Acneral, Acnestar, Acnetane, Acnetin A, Acnetrait, Acnetrex, Acnogen, Acnotin, Acnotren, Acretin, Actaven, Acugen, Acutret, Acutrex, Ai Si Jie, Aisoskin, Aknal, Aknefug Iso, Aknenormin, Aknesil, Aknetrent, Amnesteem, Atlacne, Atretin, Axotret, Casius, Ciscutan, Claravis, Contracné, Curacne, Curacné, Curakne, Curatane, Cuticilin, Decutan, Dercutane, Effederm, Epuris, Eudyna, Farmacne, Flexresan, Flitrion, I-Ret, Inerta, Inflader, Inotrin, Isac, Isdiben, Isoacne, Isobest, Isocural, Isoderm, Isoface, IsoGalen, Isogeril, Isolve, Isoprotil, Isoriac, Isosupra, Isosupra Lidose, Isotane, Isotina, Isotinon, Isotren, Isotret, Isotretinoin, Isotretinoina, Isotretinoína, Isotretinoine, Isotretinoïne, Isotrétinoïne, Isotretinoinum, Isotrex, Isotrin, Isotroin, Izotek, Izotziaja, Lisacne, Locatret, Mayesta, Medinac, Myorisan, Neotrex, Netlook, Nimegen, Noitron, Noroseptan, Novacne, Oralne, Oraret, Oratane, Piplex, Policano, Procuta, Reducar, Retacnyl, Retin A, Roaccutan, Roaccutane, Roacnetan, Roacta, Roacutan, Rocne, Rocta, Sotret, Stiefotrex, Tai Er Si, Teweisi, Tretin, Tretinac, Tretinex, Tretiva, Tufacne, Zenatane, Zerocutan, Zonatian ME, and Zoretanin.