Increasingly higher dosages will result in higher toxicity, resembling vitamin A toxicity. Adverse effects include: Type of disorders Very common (≥ 1/10) Common (≥ 1/100, and mediastinal * Epistaxis * Nasal dryness * Nasopharyngitis * Bronchospasm (particularly in people with asthma) * Hoarseness Gastrointestinal * Colitis * Ileitis * Dry throat * Gastrointestinal haemorrhage * Haemorrhagic diarrhoea * Inflammatory bowel disease * Nausea * Pancreatitis Hepatobiliary * Increased transaminase * Hepatitis Skin and subcutaneous tissues * Cheilitis * Dermatitis * Dry skin * Localised exfoliation * Pruritus * Rash erythematous * Skin fragility (with a risk of frictional trauma) * Alopecia- hair shedding from telogen effluvium * Acne fulminans * Aggravated acne (acne flare) * Erythema (facial) * Exanthema * Hair disorders * Hirsutism * Nail dystrophy * Paronychia * Photosensitivity reaction * Pili torti * Pyogenic granuloma * Skin hyperpigmentation * Increased sweating * Erythema multiforme * Stevens-Johnson Syndrome * Toxic epidermal necrolysis. Musculo-skeletal and connective tissue * Arthralgia * Myalgia * Back pain * Arthritis * Calcinosis (calcification of ligaments and tendons) * Premature epiphyseal fusion * Exostosis * Hyperostosis * Osteopenia * Tendonitis * Rhabdomyolysis Kidney and urinary * Glomerulonephritis * Dark or cola-coloured urine Reproductive system and breast disorders * Sexual dysfunction, including erectile dysfunction and decreased libido General * Increased formation of granulation tissue * Malaise Investigation * Increased triglycerides * Decreased HDL * Increased blood cholesterol * Increased blood glucose * Haematuria * Proteinuria * Increased creatine phosphokinase Possible permanent effects<unk>  may stop long bone growth in young people who are still growing. Premature epiphyseal closure can occur in people with acne receiving recommended doses of Accutane. Generally, though, premature epiphyseal closure seems to be primarily related to: * high doses of<unk>  beyond the recommended dose of 1 mg/kg/day * long-duration beyond the usual course of what is required for an acne patient for treatment (usually 5–7 months) * early onset of treatment (young teenage age 12–14 or younger)<unk>  is known to cause meibomian gland dysfunction which causes persistent keratoconjunctivitis sicca (dry eye). Problems with the meibomian and salivary glands are likely due to the non-selective apoptosis of the cells of the exocrine glands. Decreased night vision has been reported to persist in some people after discontinuation of<unk>  therapy. Sexual<unk>  is also associated with sexual side effects, namely erectile dysfunction and reduced libido. In October 2017, the UK MHRA issued a Drug Safety Update to physicians in response to reports of these problems. 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". The review also stated that "the product information should be updated to include ‘sexual dysfunction including erectile dysfunction and decreased libido’ as an undesirable effect with an unknown frequency". There have also been reports of spermatogenesis disorders, such as oligospermia. 27 cases of sexual dysfunction report either negative dechallenge or positive dechallenge. Skin The most common side effects are mucocutaneous: dry lips, skin and nose. 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). Absence of dryness of the lips is considered an indication of non-compliance with treatment (not taking the drug as advised), as it occurs in almost all people who take it. Regular use of lip balm and moisturizer is recommended throughout a course of treatment to reduce these problems. The dose may need to be decreased to reduce the severity of these side effects. The skin becomes more fragile—especially to frictional forces—and may not heal as quickly as normal. Wound healing is delayed. For this reason, elective surgery, waxing of hair, tattooing, tattoo removal, piercings, dermabrasion, exfoliation, etc., are not recommended. Treatment of acne scars is generally deferred until 12 months after completion of a course of<unk> . Acne usually flares up 2–3 weeks into the treatment and is usually mild and tolerable. Occasionally this flare-up is severe, necessitating oral antibiotics such as doxycycline. A short course of oral prednisolone may be required. Some dermatologists favour a few weeks of pre-treatment with oral antibiotics before commencing<unk>  to reduce the chance of a severe flare. A "stepped" course may also be used to reduce the chance of this initial flare, by which the initial dose is low (e.g. 0.5 mg/kg) and subsequently increased throughout the course.<unk>  use can rarely lead to a more severe form of acne, acne fulminans. Teratogenicity<unk>  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.<unk>  is classified as FDA Pregnancy Category X and ADEC Category X, and use is contraindicated in pregnancy. In the EU,<unk>  (oral) is contraindicated in pregnancy and must not be taken by women able to have children unless the conditions of a pregnancy prevention programme are met. The manufacturer recommends pregnancy be ruled out two weeks prior to commencement of<unk> , and women should use two simultaneous forms of effective contraception at least one month prior to commencement, during, and for at least one month following<unk>  therapy. In the U.S., around 2000 women became pregnant while taking the drug between 1982 and 2000, with most pregnancies ending in abortion or miscarriage. About 160 babies with birth defects were born. 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 among 129,544 women of childbearing potential taking<unk>  (0.12%). People taking<unk>  are not permitted to donate blood during and for at least one month after discontinuation of therapy due to its teratogenicity. Psychological effects Rare psychological side effects may include depression, worsening of pre-existing depression, aggressive tendencies, irritable mood and anxiety. Very rare effects include abnormal behaviour, psychosis, suicidal ideation, suicide attempts and suicide. 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. There were 85 reports of suicidal ideation, 56 of suicide and 43 of suicide attempts. The association between<unk>  use and psychopathology has been controversial. Beginning in 1983, isolated case reports emerged suggesting mood change, particularly depression, occurring during or soon after<unk>  use. A number of studies have been conducted since then of the drug's effect on depression, psychosis, suicidal thoughts and other psychological effects. Depression and suicidality<unk>  is the only non-psychiatric drug on the FDA's top 10 list of drugs associated with depression and is also within the top 10 for suicide attempts. A black box warning for suicide, depression and psychosis has been present on<unk> 's packaging in the United States since 2005. In March 2018, European Medicines Agency issued a warning on a possible risk of neuropsychiatric disorders (such as depression, anxiety and mood changes) following the use of oral retinoids, including<unk> , though the limitations of the available data did not allow them to clearly establish whether this risk was due to the use of retinoids. In 2012, a systematic review covering all articles in the literature related to<unk> , depression and suicide, as well as articles related to class effect, dose response, and biologic plausibility found that the literature reviewed was consistent with an association of<unk>  administration and depression and with suicide in a subgroup of vulnerable individuals. Following this systematic review, in a 2014 review a group of Australian dermatologists and psychiatrists collaborated on a set of recommendations for safe prescribing of<unk> . However, whether<unk>  use is causally associated with mental illness remains controversial. Evidence for depression being causally associated with<unk>  use includes 41 reports of positive challenge/dechallenge/rechallenge with<unk> , involving administering<unk> , withdrawing the drug, and then re-administering it. The majority of these cases had no psychiatric history. There is also a temporal relationship between the development of depression and initiation of<unk>  treatment, with most cases developing after 1–2 months of treatment. Further, higher doses of<unk>  increase the risk of developing depression, with 25% of people showing depression on a dose of 3 mg/kg/day as compared with 3–4% at normal doses. Studies have uncovered several biological processes which may credibly explain the affective changes induced by<unk> . Psychosis<unk>  has also been linked to psychosis. Many of the side effects of<unk>  mimic hypervitaminosis A, which has been associated with psychotic symptoms. The dopamine hypothesis of schizophrenia and psychosis suggests that an increase in dopaminergic stimulation or sensitivity in the limbic system causes psychotic symptoms. It has been suggested that dysregulation of retinoid receptors by retinoids such as<unk>  may cause schizophrenia. The evidence for this is threefold: transcriptional activation of the dopamine D2 receptor – in addition to serotonin and glutamate
Isotretinoin
Alitretinoin
Tretinoin
Clobetasol
Clobetasol propionate
Ulobetasol propionate
Ciclesonide
Tazarotene