Isotretinoin
Nodulocystic acne, if left untreated, may cause physical and emotional scarring. This form of acne is unlikely to respond to topical therapy. Initially, patients should be prescribed an oral antibiotic. If the acne fails to respond after six months of conventional therapy, treatment with isotretinoin should be considered.6
Isotretinoin is an oral retinoid preparation that decreases the size and secretion of the sebaceous glands, normalizes follicular keratinization, inhibits P. acnes growth and exerts an anti-inflammatory effect.15 Isotretinoin is labeled for use in patients with nodulocystic acne and can markedly improve this condition in most persons. There is a growing international consensus that, although the primary indication for isotretinoin is nodulocystic acne, patients who have an inadequate response to appropriate conventional therapy for less severe acne may also benefit from this drug.16 Patients who have scarring inflammatory acne and those with acne that causes severe psychologic distress may also be candidates.6,16 However, isotretinoin is FDA*labeled only for treatment of severe recalcitrant nodular acne.17
The typical dosage of isotretinoin is 0.5 to 1 mg per kg daily in two divided doses, with a standard cumulative maximum of 120 to 150 mg per kg per treatment course.6,15,16,18,19 Because the intensity of the side effects of isotretinoin is dose-related, the lower dosage may be chosen. However, dosages of 0.5 mg per kg daily or less are more frequently associated with treatment failure.16,20 Initiation of isotretinoin therapy may cause a marked flare-up of the patient's acne. It is, therefore, common practice to introduce the medication slowly, beginning at 0.1 to 0.5 mg per kg daily, and increasing to the desired dosage of 1 mg per kg daily by the end of the first month of treatment.6,15 The average duration of therapy is five months, at which time most patients will have reached the desired goal of 120 to 150 mg per kg. However, a longer course of therapy is necessary in patients taking lower initial or daily dosages.
Adjuvant therapy with other agents may be considered during isotretinoin treatment. Topical antibiotics may be beneficial, but use of topical keratolytics and drying agents should be discontinued because concomitant use may lead to extensive dryness. Occasionally, oral erythromycin or prednisone is used at the beginning of isotretinoin therapy to control the initial acne flare-up. None of the tetracyclines should be used for this purpose because the combination of a tetracycline and isotretinoin increases the likelihood of pseudotumor cerebri development.20
Pustules generally clear more rapidly than papules or nodules. Lesions on the face, upper arms and legs tend to respond more quickly than those on the trunk. After reaching the goal dosage of 120 to 150 mg per kg, isotretinoin therapy should be discontinued even if the acne is not completely clear because improvement continues for one to two months following cessation of treatment.
In a study of patients who were observed for 10 years, a single course of isotretinoin therapy completely cleared acne in more than 60 percent.16 If relapse occurred, it usually developed within the first three years after isotretinoin therapy; 78 percent of relapses were reported to occur within the first 18 months.16 Of the 39 percent of patients who experienced a relapse, 16 percent required re-initiation of oral antibiotics, and 23 percent required additional isotretinoin therapy.16 In those who relapse, repeated full courses of isotretinoin may be required. Of the 23 percent of patients who required repeated courses in one study, 17 percent had two courses, 5 percent had three courses and 1 percent had four to five courses, with predictably successful results and without additional adverse reactions.21
The side effect profile of isotretinoin is extensive, and physicians prescribing this medication should be well-versed in its potentially dangerous consequences. Patients should be evaluated every four weeks for adverse effects and to ensure compliance with therapy.18 A reduction in dosage or cessation of therapy usually causes fairly rapid resolution of clinical and laboratory side effects.
Mucocutaneous reactions are the most common adverse effects.19 Drying of the mucosal surfaces occurs in nearly all users, with cheilitis being the most common finding. Frequent application of moisturizing agents is necessary. Many patients who wear contact lenses are forced to switch to eyeglasses during the course of therapy because of conjunctival dryness. Reddening of the skin and increased photosensitivity vary among different populations.19
More serious adverse effects are rare, and most involve the musculoskeletal system.19 Arthralgias and muscle stiffness occur more frequently in those who participate in vigorous exercise. Long-term retinoid therapy may be complicated by skeletal changes, including osteoporosis and osteophyte formation. However, no studies have reported notable bony changes associated with short-term isotretinoin therapy for the treatment of acne. Mild to moderate headaches are fairly common; if the headache is severe or associated with visual changes, the patient should be evaluated for the presence of pseudotumor cerebri, a rare consequence of therapy. Patients may complain of fatigue or mild mood alterations and, rarely, isotretinoin may precipitate a depression. There have been reports of patients committing suicide while taking isotretinoin, and patients at risk should be monitored carefully.22
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