Isotretinoin's exact mechanism of action is unknown. However it is known that, like other retinoids, the drug alters DNA transcription.
Adverse effects
Adverse drug reactions associated with isotretinoin therapy include:
* Common: Mild acne flare, dryness of skin, lips and mucous membranes, infection of the cuticles, cheilitis, itch, rosacea, skin fragility, skin peeling, rash, flushing, nose bleeds, dry eyes, diffuse alopecia areata, eye irritation, conjunctivitis, reduced tolerance to contact lenses, hyperlipidaemia, raised liver enzymes, permanent thin skin, headaches, permanent hair thinning (This could start or continue after treatment), myalgia and/or arthralgia, back pain.
* Infrequent: severe acne flare, raised blood glucose level, increased erythrocyte sedimentation rate, fatigue.
* Rare: impaired night vision; cataracts; optic neuritis; menstrual disturbances; inflammatory bowel disease; pancreatitis; hepatitis; corneal opacities; papilloedema; idiopathic intracranial hypertension; skeletal hyperostosis; extraosseous calcification; psychosis; and it is believed that severe depression can occur, although there is no conclusive evidence for this.
The following adverse effects have been reported to persist, even after discontinuing therapy: alopecia (hair loss), arthralgias, decreased night vision, inflammatory bowel disease, degenerative disc disease, keloids, bone disease. High dosages of isotretinoin have been reported to cause rosacea (a disease of severe facial skin redness and irritation).
Erectile dysfunction in the form of difficulty in maintaining erection was reported in several patients in a clinical study. Although the definitive cause remains unknown, the impotence may have been caused by the psychiatric side effects of isotretinoin as it was seen to occur alongside with symptoms of depression.
While vitamin E supplements have been advocated by some to reduce the toxicity of high-dose retinoids without reducing drug efficacy, test results have proven this to be false (though no indication of what form of vitamin E was used).
Patients with degenerative conditions, such as muscular dystrophy, should not take isotretinoin as it may exacerbate and/or accelerate the underlying condition. This may be due to a suspected effect similar to accelerated aging on the skin and tissues of the body, including muscle fibers.
Patients receiving isotretinoin therapy are not permitted to donate blood during and for at least one month after discontinuation of isotretinoin therapy due to its teratogenicity.
Patients that get a tattoo while on this medication might get scarring on the tattoed area, and also rejection of the ink.
Teratogenicity (Birth Defects)
Isotretinoin is a teratogen and is
highly likely to cause birth defects if taken during pregnancy. A few of the more common birth defects that this drug can cause are hearing and
visual impairment, missing earlobes, facial dysmorphism, and mental retardation. Isotretinoin is classified as FDA Pregnancy Category X and ADEC Category X, and use is contraindicated in pregnancy.
The
manufacturer recommends that pregnancy be excluded in female patients two weeks prior to commencement of isotretinoin, and that they should use effective contraception (sometimes two simultaneous forms are recommended) at least one month prior to commencement, during, and for at least one month following isotretinoin therapy.
In the U.S. more than 2,000 women have become pregnant while taking the drug between 1982 and 2003, with most pregnancies ending in abortion or miscarriage. About 160 babies with birth defects were born.
Depression
Several studies have suggested a possible link between isotretinoin and clinical depression.
The argument that isotretinoin caused depression and suicide has won a few lawsuits, and is partially responsible for the strict control of the drug, especially in the United States. Various case reports of depression, suicidal ideation, suicide attempt, and suicide in patients treated with isotretinoin have been reported to the U.S. FDA Adverse Events Reporting System, with 431 cases reported between 1982 and May 2001 – of these, 37 patients had committed suicide. This suicide rate is in line with national rates and does not exceed the national average. However,
Congressman Bart Stupak stated that the total suicides caused by Accutane may be as high as 50,000 due to the underreporting of the suicides and since it is used for neuroblastoma, a form of brain cancer. High risk neuroblastoma is treated with biological-based therapy 13-cis-retinoic acid (isotretinoin or Accutane). While analyses have suggested an association between isotretinoin therapy and depression, no causal relationship has been established and further studies are required.
Studies have shown that patients with acne, the population group eligible to receive isotretinoin therapy, have an increased risk of clinical depression compared with the general population. Chee Hong describes Isotretinoin-related depression as "an idiosyncratic side-effect", claiming, often anxiety can bring on acne and depression, creating more anxiety. Correspondingly, treatment of severe acne with isotretinoin has been shown to reduce anxiety and depression, for tests have shown acne to be a main depressant in most tested patients' lives.
One study utilising positron emission tomography (PET) showed functional brain imaging changes in patients treated with isotretinoin, however the clinical relevance of this finding is unclear.
U.S. Representative Bart Stupak (D-MI) is known for his distrust of Accutane. He believes unadvertised psychological side effects from the drug drove his teenage son, Bartholomew Thomas "B.J" Stupak Jr., to commit suicide in 2000.
Crohn's Disease and Ulcerative Colitis
Several scientific studies have posited that isotretinoin is a possible cause of Crohn's Disease and Ulcerative colitis in some individuals.
Three cases in the United States have gone to trial thus far, with all three
resulting in multi-million dollar judgments against the makers of isotretinoin; there are an additional 425 cases pending.
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