Adverse drug reactions associated with isotretinoin therapy include:
*Common: Extreme severe 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, temporary/permanent hair thinning (this could start or continue after treatment), myalgia and/or arthralgia, back pain.
*Infrequent: mild acne flare, raised blood glucose level, decreased libido/erectile dysfunction, 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; depression
*There are reports of spontaneous premature epiphyseal closure (reduced growth in height) in acne patients receiving recommended doses of Accutane. This is also mentioned, at least in some countries, in the leaflet for Accutane. The effect of multiple courses of Accutane on epiphyseal closure is unknown.
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).
During of a prospective study in Mexico that evaluated the efficacy and safety of isotretinoin in acne, six male patients reported clinical symptoms of depression along with difficulties in maintaining adequate penile erection, suggesting a potential link between isotretinoin and risk of erectile dysfunction.
Research suggests that vitamin E supplementation in the form of alpha-tocopherol reduces the toxicity of isotretinoin treatment in subjects with cancer and myelodysplastic syndrome.. In contrast, a randomized study in 82 subjects taking isotretinoin (1mg/kg/day) for acne vulgaris found no difference in the incidence or severity of side-effects in the group taking an additional 800 IU/day of vitamin E in the form of d-l-alphatocopherol.
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.Its most common side-effects are mucocutaneous and ocular in nature (i.e., cheilitis, ocular sicca, and decreased dark adaptation). It can also cause xerosis. Patients should be made aware of these side-effects before taking isotretinoin and also that utilization of moisturizers and eye drops can help to mitigate such side-effects. Sometimes, however, the dose of isotretinoin needs to be decreased to reduce the induction of side-effects. .
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 or malformed 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 two simultaneous forms of effective contraception 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. As a consequence, the iPLEDGE program was introduced by the U.S. Food and Drug Administration on 12 August 2005 in an attempt to ensure that female patients receiving isotretinoin do not become pregnant. As of 1 March 2006, only prescribers registered and activated in iPLEDGE are able to prescribe isotretinoin, and only patients registered and qualified in iPLEDGE will be able to have isotretinoin dispensed. The iPLEDGE program also applies to males, even though there has been no evidence of isotretinoin excretion through seminal fluids.
Depression
Since the 1980s, scientific research has suggested a relationship between isotretinoin administration and the onset of psychological symptoms including depression, suicidal ideation, and psychosis. However, there have also been studies arguing that there is no evidence of such a link. In a study in 2006, it was demonstrated for the first time that isotretinoin administration enhances depression-related behaviors in mice. The mechanism by which this occurs was not elucidated, although altered neuronal gene regulation and changes in hippocampal neurogenesis were thought to be involved.Several recent studies have shown a link between isotretinoin and clinical depression. Psychiatrist Dr. Doug Bremner found decreased frontal lobe function on brain imaging in patients treated with Accutane (isotretinoin). Bremner's study, which utilized positron emission tomography (PET), found that patients treated with isotretinion experienced an average twenty-one percent decrease in frontal-lobe brain activity. However, there were no changes in the depressive state of the patients that could be measured with the Hamilton depression scale. Bremner's findings have prompted members of the scientific community to call for more studies regarding isotretinion's links to depression and suicidal behavior.
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.
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.
U.S. Representative Bart Stupak (D-MI) believes unadvertised psychological side-effects from the drug drove his teenage son Bartholomew Thomas 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.Adapted from the Wikipedia article Isotretinoin, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki
