Sotret (isotretinoin)

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Isotretinoin is administered orally with meals to maximize GI absorption. Isotretinoin should be administered in 2 divided doses. The manufacturers state that safety of once-daily dosing of isotretinoin has not been established and is not recommended.

To decrease the risk of esophageal irritation, isotretinoin capsules should be swallowed whole with a full glass of liquid. Patients should be instructed not to suck or chew the capsules.

No dosing information is available for this tab.

No dosing information is available for this tab.

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There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

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There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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Isotretinoin is a known human teratogen, and can cause severe, life-threatening birth defects or fetal death if taken during pregnancy. Since the risks clearly outweigh any possible benefits in female patients who are or may become pregnant or who intend to become pregnant during treatment, female patients of childbearing potential should not receive isotretinoin until pregnancy is excluded and other conditions of use have been met. (See Teratogenicity Contraindications and Precautions under Cautions: Precautions and Contraindications.) There is an extremely high risk that severe birth defects will result if pregnancy occurs while receiving isotretinoin in any amount even for short periods of time. There are no accurate means of determining whether an exposed fetus has been affected following isotretinoin exposure. Therefore, patients who become pregnant, miss their expected menstrual period, stop using birth control, or have sexual intercourse without the use of 2 separate contraceptive measures should immediately discontinue isotretinoin and notify their clinician. Such patients should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Clinicians must immediately report any suspected fetal exposure during or up to 1 month following therapy to the US Food and Drug Administration (FDA) Medwatch Program at 1-800-FDA-1088 and also to the iPLEDGE pregnancy registry at 1-866-495-0654 or through the program's website (http://www.ipledgeprogram.com). The iPLEDGE Program Pregnancy Registry collects data on pregnancies that occur in female patients who become pregnant while taking isotretinoin or within 1 month after the last dose. Data from this registry are used to evaluate further ways to reduce fetal exposure to isotretinoin; the information gathered in the registry will be used for statistical purposes only and will be held in the strictest confidence.

Since becoming commercially available in the US in 1982, isotretinoin has been labeled as being contraindicated during pregnancy, with warnings that use in women of childbearing potential be initiated only after advising them of the teratogenic risks, excluding the possibility of pregnancy, and ensuring the use of an effective means of contraception during isotretinoin therapy. Despite the stated contraindication and warnings and subsequent strengthening of precautionary information in the drug's labeling, the FDA, the US Centers for Disease Control and Prevention (CDC), and the manufacturer of Accutane(R) continued to receive reports of infants with congenital abnormalities born to women who had received isotretinoin during pregnancy. FDA states that there is some evidence that overprescribing (e.g., for patients without severe, recalcitrant nodular acne) for women of childbearing potential is partly responsible for such continued reports. However, because isotretinoin has been proven to be uniquely effective for use in severe, recalcitrant nodular acne, with therapeutic benefits for this condition that exceed those of other currently available drugs, FDA, at the recommendation of its Dermatologic Drugs Advisory Group, decided that the drug can remain available for use in the US once the manufacturer of Accutane(R) adopted the recommendations made by this Group and the FDA Fertility and Maternal Health Drugs Advisory Committee for a pregnancy prevention program that included changes in the professional labeling, patient labeling, and packaging; initiation of strengthened education of the patient that includes written informed consent and supervised viewing of an educational videocassette at the time of prescribing; expansion of patient referrals to obstetrician-gynecologists for pregnancy testing; and ensurance by the manufacturer that all unused isotretinoin be returned by the patient. Unfortunately, suboptimal participation (40% or less of women who received isotretinoin) and substantial noncompliance with critical elements of the manufacturer-supported pregnancy prevention program (e.g., 25% did not receive a pregnancy test prior to treatment and 33% initiated therapy prior to receiving their pregnancy test results) has been reported to the FDA. Of the 1995 documented cases of isotretinoin-exposed pregnancies reported by the manufacturer of Accutane(R), 958 pregnancies were identified after the previous pregnancy prevention program was in place. According to a 1999 report to the FDA by this manufacturer, approximately 11% of the pregnant women identified by a patient survey conducted by the Slone Epidemiology Unit of Boston University School of Public Health were pregnant at initiation of isotretinoin therapy and another 14% became pregnant during the first 3 weeks of treatment. Because of such limitations in the previous pregnancy prevention program, the manufacturer of Accutane(R), working with the FDA, developed a restricted distribution system, the System to Manage Accutane Related Teratogenicity (SMART), as an additional component of a risk management program to prevent fetal exposure to isotretinoin. As nonproprietary (generic) isotretinoin preparations became commercially available, additional restricted distribution programs were developed by other manufacturers. The SMART program included mandatory contraceptive measures for women, as well as mandatory pregnancy testing to confirm that a woman is not pregnant before isotretinoin therapy is initiated and does not become pregnant during or immediately after therapy with the drug.

Existing restricted distribution programs designed to reduce the risk of fetal exposure to isotretinoin, including the SMART program, were assessed in 2004 by FDA, and the results of this assessment were presented at a joint meeting of the Drug Safety and Risk Management and Dermatologic and Ophthalmic Drugs Advisory Committees. Those committees strongly recommended the need for improvements in the isotretinoin risk management program to strengthen processes to ensure pregnancy testing and counseling of patients prior to and during therapy to reduce the risk of fetal exposure in the US. The resulting FDA-approved iPLEDGE risk management program is a single, mandatory, computer-based, closed system of registered wholesalers, prescribers, pharmacies, and patients for all commercially available isotretinoin preparations. The iPLEDGE program links access to isotretinoin by female patients of childbearing potential with negative results of pregnancy testing to lower the risk of possible fetal exposure to the drug during pregnancy.

Although isotretinoin has been found in the semen of male patients taking the drug, the amount delivered to a female partner has been found to be about 1 million times lower than an oral dose of 40 mg. While the no-effect limit for isotretinoin-induced embryopathy is unknown, 20 years of postmarketing reports include 4 with isolated defects compatible with features of retinoid-exposed fetuses. However, 2 of these reports were incomplete, and 2 had other possible explanations for the defects observed. Nevertheless, clinicians should report any pregnancy in the partner of a male patient receiving the drug to the iPLEDGE program. (See Dosage and Administration: Restricted Distribution Program.)

It is not known whether isotretinoin is distributed into milk. Because of the potential for serious adverse reactions to isotretinoin in nursing infants, isotretinoin should not be administered to women who are breast-feeding.

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