Jane S. Ricciuti, RPh, MS


December 27, 2002

In This Article

Dermatologic Agents


Manufacturer: Roche

Drug Approval Classification: Supplemental New Drug Application (Approval Date: 11/1/02)

Clinical Summary: Product labeling for Accutane has been strengthened to clarify those circumstances in which pregnancy tests and Accutane Qualification Stickers are applicable.

Information specific to pediatric patients has been added based on the results of recent studies conducted in this patient population. A statement has been added regarding the long-term use of Accutane advising that Accutane be given at the recommended doses for no longer than the recommended duration. Prescribers were advised to exercise caution when systemic corticosteroids or phenytoin are used with Accutane.

Adverse Effects: Accutane labeling has added information derived from postmarketing safety reports that have indicated the possibility of aggressive and/or violent behaviors. No mechanism of action has been established for these events.

In Accutane's "Warnings" section, the following wording was included:

WARNINGS: Psychiatric Disorders: Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. Discontinuation of Accutane therapy may be insufficient; further evaluation may be necessary. No mechanism of action has been established for these events (see ADVERSE REACTIONS: Psychiatric). Prescribers should read the brochure, Recognizing Psychiatric Disorders in Adolescents and Young Adults: A Guide for Prescribers of Accutane (isotretinoin).

Pharmacokinetics: The results of an isotretinoin multiple-dose pharmacokinetics study in 38 pediatric patients (12-15 years) and 19 adult patients (> 18 years) were added to Accutane's labeling. In both age groups, 4-oxo-isotretinoin was the major metabolite; tretinoin and 4-oxo-tretinoin were also observed. There were no statistically significant differences in the pharmacokinetics of isotretinoin between pediatric and adult patients.

In pediatric patients (12-15 years), the mean +/- SD elimination half-lives (t1/2) of isotretinoin and 4-oxo-isotretinoin were 15.7 +/- 5.1 hours and 23.1 +/- 5.7 hours, respectively. The accumulation ratios of isotretinoin ranged from 0.46 to 3.65 for pediatric patients.

An isotretinoin drug interactions study with phenytoin indicated no alteration in the pharmacokinetics of phenytoin. Caution was advised for the use of phenytoin or systemic corticosteroids with isotretinoin. Phenytoin is known to cause osteomalacia, and systemic corticosteroids are known to cause osteoporosis. No formal clinical studies have been conducted to assess whether there is an interactive effect on bone loss.


Accutane (isotretinoin) labeling

Medscape DrugInfo

Accutane (isotretinoin)


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