From WikiHealthIsotretinoin(Redirected from Accutane)
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Isotretinoin is a generic medication used for the treatment of severe acne and most commonly known under the brands Accutane and Roaccutane. It is a retinoid, meaning it is derived from vitamin A and is found naturally in the body, produced by the liver in small quantities. Indicated for:
HistoryPrior to the development of isotretinoin, the mainstay treatment of severe acne was oral antibiotics such as the tetracyclines and erythromycin. While these drugs have proven efficacy, they worked against only one contributing factor of acne, Propionibacterium acnes bacteria. The antibiotics gradually became less effective over time as more resistant strains of the bacterium became prominent. An early, effective treatment of acne was high doses of the fat soluble vitamin A. At these dose levels (sometimes 500,000 IU per day) effects such as reduced production of sebum and dry hair could be noticed. However the vitamin also had many other prominent side effects which inhibited its widespread use. The development of the derivative of retinoic acid, isotretinoin (13-cis-retinoic acid), and its release in 1982 by Hoffmann-La Roche was a great step forward in the treatment of acne. The synthetic compound provided better therapeutic benefit than vitamin A, while also producing fewer side effects. In February 2002 Roche's patents for isotretinoin expired, there are now many other companies selling cheaper generic versions of the drug. Today isotretinoin is usually prescribed after other acne treatments have failed to produce results. The treatment of acne usually begins with topicals, moves onto oral antibiotics (or a combination) and finally isotretinoin therapy. This is because other treatments, while less effective than isotretinoin, produce far fewer side effects. Brand namesIsotretinoin is produced under many brand names by many manufacturers. It is available typically as 5 mg, 10 mg, 20 mg and (in the USA) 40 mg capsules. Some brands of isotretinoin include:
IndicationsIsotretinoin is indicated for treatment for a number of dermatological conditions, most commonly acne. It is generally not used as a first-line treatmen] due to the potential side effects. Antibiotics (such as the tetracyclines) are usually prescribed before isotretinoin. Severe forms of acne (conglobata, fulminans and nodulocystic) as well as acne that scars can be successfully treated with isotretinoin. Acne that has not responded to other treatment will usually respond to isotretinoin. Dysmorphophobic patients may also be prescribed isotretinoin. PharmacodynamicsIsotretinoin noticeably reduces the production of sebum and shrinks the sebaceous glands. It stabilizes keratinization and prevents comedones from forming. The exact mechanism of action is unknown, however it is known that it alters DNA transcription. The dose of isotretinoin a patient receives is dependent on their weight and the severity of the condition. Generally it is prescribed from between 0.5 mg/kg/day to 2 mg/kg/day, for example a 70 kg (155 pounds) person would take from between 35 mg to 140 mg per day dependent on the severity of their condition. Some studies have associated remission of the condition with the total dose taken. It is generally advisable to take a dose of greater than 125 mg/kg over the entire treatment period to see maximum benefit. AbsorptionIsotretinoin, when administered orally, is best absorbed when taken after a high fat meal, as it has a high level of lipophilicity. In a crossover study, it was found that the peak plasma concentration more than doubled when taken after a high fat meal versus a fasted condition. DistributionIsotretinoin is primarily (99.9%) bound to plasma proteins, mostly albumin. MetabolismAt least three metabolites have been detected in human plasma after oral administration of isotretinoin. These are 4-oxo-isotretinoin, retinoic acid and 4-oxo-retinoic acid. Isotretinoin also oxidises, irreversibly, to 4-oxo-isotretinoin. EliminationThe metabolites of isotretinoin are excreted through both urine and feces. The mean elimination half life for isotretinoin is 21 hours, with a standard deviation from this mean of 8.2 hours. Drug interactionsVitamin A, in supplement form, should be strictly avoided while undertaking therapy with isotretinoin. It increases the risk of side effects associated with use. Tetracycline antibiotics, also prescribed for acne, should also be avoided. A significant increase in the risk of pseudotumor cerebri is associated with concurrent use of these drugs. According to some studies, vitamin E reduces the toxicity of high-dose retinoids without reducing drug efficacy. However, this is still unclear. Side effectsThe most feared complication of isotretinoin is its teratogenicity, i.e., the ability to cause birth defects. Isotretinoin has many side effects, listed in the table on the right. The more severe side effects are listed here in more detail. The following side effects can persist, even after discontinuing therapy:
It should also be mentioned that isotretinoin users are not allowed to give blood for at least a month after discontinuing isotretinoin use. Treatment of Side EffectsAcne fulminans- Linked pustules that result in severe scarring (predominantly keloid scarring.) Treatment carried out by a dermatologist would involve first removal of isotretinoin pills completely and any oral steroids (gradually remove), which are often prescribed when initial symptoms start. Medication generally is of a combination of clindamycin and dapsone combined with isotrexin gel (isotretinoin in a topical form.) Any pyrogenic granulomas (granulated pretruding weeping tissue) that does not heal may be cauterised with silver nitrate so the skin may grow correctly again. Once the wound has fully healed so no weeping (months) any keloid scars are injected with steroids to flatten the scar and reduce inflammation. Further scarring may be treated by non-ablative laser called N-lite to promote collagen formation and healing. Accutane and Birth DefectsIsotretinoin is a teratogen - it is highly likely that it will cause birth defects if taken during pregnancy. Isotretinoin is prescribed under a policy that mandates that female patients be placed on two separate, effective forms of birth control [1]. Male patients can still impregnate women while taking the drug but are educated on the ill efftects of the drug on the human fetus so as not to share their medication with any women who are not under medical supervision. DepressionSeveral studies [2][3][4] have emerged suggesting a possible link between isotretinoin and depression. However, there is the possibility that the severe acne is also linked to the depression. Moreover, improvement of a patient's acne by successful treatment with isotretinoin can actually reduce symptoms of anxiety and depression. Statistical evidence shows that the suicide rate among Accutane users is actually lower than average. For additional information on this topic, visit:
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