Isotretinoin

Isotretinoin (Accutane) alters keratinization in the acroinfundibulum of sebaceous glands and shrinks them, thereby reducing sebum excretion and comedo-genesis. These features underlie its usefulness in acne vulgaris, since sebum secretion is a hallmark of acne-prone skin. Furthermore, the drug has antiinflammatory activity.

Isotretinoin is rapidly absorbed orally, with peak blood concentrations 3 hours after ingestion. It is not stored in tissue, and the elimination half-life is 10 to 20 hours, either after a single dose or during chronic therapy.

Isotretinoin is most useful for the treatment of severe recalcitrant nodular acne vulgaris. It may also be helpful in other disorders of keratinization, but it is not useful for psoriasis. High doses of isotretinoin (2mg/kg/day) are effective as cancer chemoprevention agents to reduce the frequency of cutaneous malignancies in patients at increased risk, such as those with xeroderma pigmentosum, an inherited disorder in which DNA repair is deficient, or in immunosuppressed patients.

The most serious toxicity of isotretinoin is teratogenicity. Pregnant women should never receive the drug, and women should not conceive for at least 1 month after its discontinuation. Other toxicities:

• Skin complaints, particularly xerosis, conjunctivitis, and cheilitis.

• Hypertriglyceridemia in about a quarter of patients.

• Elevation of liver function test findings, which is usually reversible.

Headache, which rarely may be attributable to pseudotumor cerebri.

• Arthralgias, including skeletal changes such as hyperostoses, tendinous calcifications, premature epiphysial closure, and pathological fractures.

• Depression and suicidal ideation may occur, but no mechanism of action for these events has been established.

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