Accutane

Brand NameAccutane
Generic Nameisotretinoin
Marketed byHoffman-La Roche Inc.
NDA/BLA HolderHoffman LaRoche
NDA/BLA NumberNDA 18-662
NDA/BLA Approval Date5/7/1982
StatusApproved
Review ClassificationPriority
REMS Approval Date3/25/2009
Class REMSNo
REMS Source Documenthttp://www.fda.gov/OHRMS/DOCKETS/98fr/E8-6201.pdf
Boxed Warning?Yes
Boxed Warning

Access the iPLEDGE system via the internet (www.ipledgeprogram.com) or telephone (1-866-495-0654) to obtain an authorization and the "do not dispense to patient after" date. isotretinoin must only be dispensed in no more than a 30-day supply.

REFILLS REQUIRE A NEW PRESCRIPTION AND A NEW AUTHORIZATION FROM THE iPLEDGE SYSTEM.

A Medication Guide must be given to the patient each time isotretinoin is dispensed, as required by law.

This Medication Guide is an important part of the risk management program for the patient.

Accutane must not be used by female patients who are or may become pregnant. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking Accutane in any amount, even for short periods of time. Potentially any fetus exposed during pregnancy can be affected. There are no accurate means of determining whether an exposed fetus has been affected.

Birth defects which have been documented following Accutane exposure include abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. Cases of IQ scores less than 85 with or without other abnormalities have been reported. There is an increased risk of spontaneous abortion, and premature births have been reported.

Documented external abnormalities include: skull abnormality; ear abnormalities (including anotia, micropinna, small or absent external auditory canals); eye abnormalities (including microphthalmia); facial dysmorphia; cleft palate. Documented internal abnormalities include: CNS abnormalities (including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular abnormalities; thymus gland abnormality; parathyroid hormone deficiency. In some cases death has occurred with certain of the abnormalities previously noted. If pregnancy does occur during treatment of a female patient who is taking Accutane, Accutane must be discontinued immediately and she should be referred to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling.

Special Prescribing Requirements

Because of Accutane's teratogenicity and to minimize fetal exposure, Accutane is approved for marketing only under a special restricted distribution program approved by the Food and Drug Administration. This program is called iPLEDGE™. Accutane must only be prescribed by prescribers who are registered and activated with the iPLEDGE program. Accutane must only be dispensed by a pharmacy registered and activated with iPLEDGE, and must only be dispensed to patients who are registered and meet all the requirements of iPLEDGE

Indication

Severe Recalcitrant Nodular Acne

Accutane is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. "Severe," by definition,2 means "many" as opposed to "few or several" nodules. Because of significant adverse effects associated with its use, Accutane should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, Accutane is indicated only for those female patients who are not pregnant, because Accutane can cause severe birth defects (see Boxed CONTRAINDICATIONS AND WARNINGS).

A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients.1,3,4 If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off Accutane. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure).

Route of AdministrationOral capsules
Mechanism of ActionIsotretinoin is a retinoid, which when administered in pharmacologic dosages of 0.5 to 1.0 mg/kg/day (see DOSAGE AND ADMINISTRATION), inhibits sebaceous gland function and keratinization. The exact mechanism of action of isotretinoin is unknown.
RisksTeratogenicity
Risks (MedGuide Language)
  • Accutane is used to treat a type of severe acne (nodular acne) that has not been helped by other treatments, including antibiotics.
  • Because Accutane can cause birth defects, Accutane is only for patients who can understand and agree to carry out all of the instructions in the iPLEDGE program.
  • Accutane may cause serious mental health problems.
Approved Labelinghttp://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018662s059lbl.pdf
Medication Guide?Yes
Medication Guidehttp://www.fda.gov/downloads/Drugs/DrugSafety/ucm085812.pdf
Medication Guide Version2007
Communication Plan?Not Available
Communication PlanNot Available
Elements to Assure Safe Use?Yes
Elements to Assure Safe Use

The iPLEDGE program is a computer-based risk management program designed to further the public health goal to eliminate fetal exposure to isotretinoin through a special restricted distribution program approved by the FDA. The program strives to ensure that:

  • No female patient starts isotretinoin therapy if pregnant
  • No female patient on isotretinoin therapy becomes pregnant

This enhanced program is a SINGLE pregnancy risk management program for prescribing and dispensing all isotretinoin products (brand and generic products).

The iPLEDGE program requires registration of all wholesalers distributing isotretinoin, all healthcare professionals prescribing isotretinoin, all pharmacies dispensing isotretinoin, and all male and female patients prescribed isotretinoin. This program is designed to create a verifiable link between the negative pregnancy test and the dispensing of the isotretinoin prescription to the female patient of childbearing potential. The iPLEDGE program requires that all patients meet qualification criteria and monthly program requirements. Before the patient receives his/her isotretinoin prescription each month, the prescriber must counsel the patient and document in the iPLEDGE system that the patient has been counseled about the risks of isotretinoin.

There are also additional qualification criteria and monthly requirements for female patients of childbearing potential.

Implementation System?Not Available
Implementation SystemNot Available
Assessment ProgramNot Available
Assessment Program TimelineNot Available
Branded ProgramiPLEDGE
Program Description

Access the iPLEDGE system via the internet (www.ipledgeprogram.com) or telephone (1-866-495-0654) to obtain an authorization and the "do not dispense to patient after" date. isotretinoin must only be dispensed in no more than a 30-day supply.

REFILLS REQUIRE A NEW PRESCRIPTION AND A NEW AUTHORIZATION FROM THE iPLEDGE SYSTEM.

A Medication Guide must be given to the patient each time isotretinoin is dispensed, as required by law.

This Medication Guide is an important part of the risk management program for the patient.

Link to Branded Programhttps://www.ipledgeprogram.com/
Deemed/ApprovedDeemed
Approval Lettershttp://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/018662s059ltr.pdf

Sources

REMS Document: from FDA Approved REMS
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm

Approval Letters: from FDA Medication Guide Website
(http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.Search_Drug_Name)

Approved Labeling: from FDA Medication Guide Website
(http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.Search_Drug_Name)

Medication Guide: from FDA Medication Guide Website
(http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.Search_Drug_Name)

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