About the iPLEDGE® Program
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. For more details about the iPLEDGE® Program and to learn how to register, visit their website.
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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 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 patients prescribed isotretinoin. This program is designed to verify the patient's negative pregnancy test in order to approve the dispensing of the isotretinoin prescription to females of reproductive 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® Program that the patient has been counseled about the risks of isotretinoin.
As part of the ongoing risk management for isotretinoin products, it is crucial that females of reproductive potential select and commit to use 2 forms of effective contraception simultaneously for 1 month before, during, and for 1 month after isotretinoin therapy. Females of reproductive potential must have 2 negative urine or blood (serum) pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial isotretinoin prescription. The first pregnancy test is a screening test and can be conducted in the prescriber's office. The second pregnancy test must be done in a CLIA-certified laboratory according to the package insert. Each month of therapy, the patient must have a negative result from a urine or blood (serum) pregnancy test conducted by a CLIA-certified laboratory prior to receiving each prescription.
Each month, the prescriber must enter the female patient's pregnancy results and the 2 forms of contraception she has been using in the iPLEDGE® Program. The iPLEDGE® Program verifies that all criteria have been met by the prescriber, patient, and pharmacy prior to granting the pharmacy authorization to fill and dispense isotretinoin. The pharmacist must obtain authorization from the iPLEDGE® Program via the program's web site or phone system prior to dispensing each isotretinoin prescription for both male and female patients.
ABSORICA and ABSORICA LD can cause severe life-threatening birth defects and is contraindicated in pregnancy. There is an extremely high risk that severe birth defects will result if pregnancy occurs. See additional safety information below.
ABSORICA and ABSORICA LD (isotretinoin) capsules are indicated for the treatment of severe recalcitrant nodular acne in non-pregnant patients 12 years of age and older with multiple inflammatory nodules with a diameter of 5 mm or greater. Because of significant adverse reactions associated with their use, ABSORICA and ABSORICA LD are reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics.
Limitations of Use:
If a second course of ABSORICA or ABSORICA LD therapy is needed, it is not recommended before a two-month waiting period because the patient’s acne may continue to improve following a 15 to 20-week course of therapy
IMPORTANT SAFETY INFORMATION
WARNING: EMBRYO-FETAL TOXICITY – CONTRAINDICATED IN PREGNANCY
ABSORICA and ABSORICA LD can cause severe life-threatening birth defects and is contraindicated in pregnancy. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking any amount of ABSORICA or ABSORICA LD even for short periods of time. Potentially any fetus exposed during pregnancy can be affected. There are no accurate means of determining prenatally whether an exposed fetus has been affected. If pregnancy occurs, discontinue ABSORICA and ABSORICA LD immediately and refer the patient to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling.
Because of the risk of embryo-fetal toxicity, ABSORICA and ABSORICA LD are available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the iPLEDGE® REMS.
Pregnancy: ABSORICA and ABSORICA LD are contraindicated in pregnancy
Hypersensitivity: ABSORICA and ABSORICA LD are contraindicated in patients with hypersensitivity to isotretinoin (or Vitamin A, given the chemical similarity to isotretinoin) or to any of its components (anaphylaxis and other allergic reactions have occurred)
WARNINGS AND PRECAUTIONS
ABSORICA and ABSORICA LD are Not Substitutable: The bioavailability and the recommended dosage of ABSORICA and ABSORICA LD are different. For example, while ABSORICA and ABSORICA LD both have a 20 mg strength, these strengths have different bioavailability and are not substitutable.
Psychiatric Disorders: ABSORICA and ABSORICA LD may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. Prior to and during therapy, assess for these conditions.
Patients should immediately stop ABSORICA and ABSORICA LD and promptly contact their prescriber if they develop depression, mood disturbance, psychosis, or aggression. Discontinuation of ABSORICA and ABSORICA LD may be insufficient; further evaluation may be necessary such as a referral to a mental healthcare professional.
Intracranial Hypertension (Pseudotumor Cerebri): Isotretinoin use has been associated with cases of intracranial hypertension (pseudotumor cerebri), some of which involved concomitant use of tetracyclines. Concomitant treatment with tetracyclines should therefore be avoided with ABSORICA and ABSORICA LD use.
Serious Skin Reactions: There have been postmarketing reports of erythema multiforme and severe skin reactions [e.g., Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)] associated with isotretinoin use. These reactions may be serious and result in death, life-threatening events, hospitalization, or disability. Patients should be monitored closely for severe skin reactions, and ABSORICA and ABSORICA LD should be discontinued if they occur.
Acute Pancreatitis: Acute pancreatitis has been reported with isotretinoin use in patients with either elevated or normal serum triglyceride levels. In rare instances, fatal hemorrhagic pancreatitis has been reported. If symptoms of pancreatitis occur, the patient should discontinue ABSORICA and ABSORICA LD and seek medical attention.
Lipid Abnormalities: Elevations of serum triglycerides above 800 mg/dL have been reported with isotretinoin use. These lipid changes were reversible upon isotretinoin capsule cessation. Some patients have been able to reverse triglyceride elevation by reduction in weight and restriction of dietary fat and alcohol while continuing isotretinoin or through dosage reduction. The cardiovascular consequences of hypertriglyceridemia associated with isotretinoin are unknown.
Hearing Impairment: Impaired hearing has been reported in patients taking isotretinoin; in some cases, the impairment has been reported to persist after therapy has been discontinued. Mechanism(s) and causality for this reaction have not been established. Patients who experience tinnitus or hearing impairment should discontinue ABSORICA or ABSORICA LD treatment and be referred for specialized care for further evaluation.
Hepatotoxicity: Clinical hepatitis has been reported with isotretinoin use. Additionally, mild to moderate elevations of liver enzymes have been observed in approximately 15% of individuals treated during clinical trials with isotretinoin capsules, some of which normalized with dosage reduction or continued administration of the drug. If normalization does not readily occur or if hepatitis is suspected during treatment, ABSORICA and ABSORICA LD should be discontinued.
Inflammatory Bowel Disease: Isotretinoin has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. In some instances, symptoms have been reported to persist after isotretinoin treatment has been stopped. Patients experiencing abdominal pain, rectal bleeding or severe diarrhea should discontinue ABSORICA or ABSORICA LD immediately.
Musculoskeletal Abnormalities: Effects of multiple courses of isotretinoin on the developing musculoskeletal system are unknown. There is some evidence that long-term, high-dose, or multiple courses of therapy with isotretinoin have more of an effect than a single course of therapy on the musculoskeletal system. It is important that ABSORICA and ABSORICA LD be given at the recommended dose for no longer than the recommended duration.
Ocular Abnormalities: Visual problems should be carefully monitored. If visual difficulties occur, the patient should discontinue ABSORICA and ABSORICA LD treatment and obtain an ophthalmological examination.
Most common adverse reactions (incidence ≥ 5%) are: dry lips, dry skin, back pain, dry eye, arthralgia, epistaxis, headache, nasopharyngitis, chapped lips, dermatitis, increased creatine kinase, cheilitis, musculoskeletal discomfort, upper respiratory tract infection, reduced visual acuity.
Vitamin A: ABSORICA and ABSORICA LD are closely related to vitamin A. Therefore, the use of both vitamin A and ABSORICA or ABSORICA LD at the same time may lead to vitamin A related adverse reactions. Patients treated with ABSORICA and ABSORICA LD should be advised against taking supplements containing Vitamin A to avoid additive toxic effects.
Tetracyclines: Concomitant treatment with ABSORICA and ABSORICA LD and tetracyclines should be avoided because isotretinoin use has been associated with a number of cases of intracranial hypertension (pseudotumor cerebri), some of which involved concomitant use of tetracyclines
USE IN SPECIFIC POPULATIONS
There are no data on the presence of isotretinoin in either animal or human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in nursing infants from isotretinoin, advise patients that breastfeeding is not recommended during treatment with ABSORICA and ABSORICA LD, and for at least 8 days after the last dose of ABSORICA or ABSORICA LD.
These are not all of the possible side effects of ABSORICA and ABSORICA LD. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or Sun Pharmaceutical Industries, Inc. at 1-800-818-4555.
Please see full Prescribing Information for Boxed Warning, Contraindications, and other important Warnings and Precautions.
*ABSORICA/ABSORICA LD Clinical Statement
The effectiveness of ABSORICA/ABSORICA LD for the treatment of severe recalcitrant nodular acne in patients 12 years of age and older has been established and is based on a double-blind, randomized, parallel-group trial in subjects with severe recalcitrant nodular acne who received ABSORICA or another isotretinoin capsule product under fed conditions. A total of 925 subjects were randomized 1:1 to receive ABSORICA or another isotretinoin capsule product. Study subjects ranged from 12 to 54 years of age (including 397 pediatric subjects aged 12 to 17 years); 60% were male, 40% were female; and the racial groups included 87% White, 4% Black, 6% Asian, and 3% Other. Enrolled subjects had a weight of 40 to 110 kg and had at least 10 nodular lesions on the face and/or trunk. Subjects were treated with an initial dose of 0.5 mg/kg/day in 2 divided doses for the first 4 weeks, followed by 1 mg/kg/day in 2 divided doses for the following 16 weeks.1 Isotretinoin with the ABSORICA formulation was the active drug in all clinical studies referenced in this piece.
1. ABSORICA/ABSORICA LD [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; October 2019. 2. Madan HK, Venkateshwaran R, Madan S, Kochar R, inventors. Low dose oral pharmaceutical composition of isotretinoin. US patent 9,750,711. September 5, 2017. 3. Madan S, Kumar S, Segal J. Comparative pharmacokinetic profiles of a novel low-dose micronized-isotretinoin 32 mg formulation and lidose-isotretinoin 40 mg in fed and fasted conditions: two open-label, randomized, crossover studies in healthy adult participants. Acta Derm Venereol. 2020;100(1-4):1-7. 4. Del Rosso JQ, Gold LS, Segal J, Zaenglein AL. An open-label, phase IV study evaluating lidose-isotretinoin administered without food in patients with severe recalcitrant nodular acne: low relapse rates observed over the 104-week post-treatment period. J Clin Aesthet Dermatol. 2019;12(11):13-18. 5. Hession MT, Graber EM. Atrophic acne scarring: a review of treatment options. J Clin Aesthet Dermatol. 2015;9(1):50-58. 6. Layton AM, Henderson CA, Cunliffe WJ. A clinical evaluation of acne scarring and its incidence. Clin Exp Dermatol. 1994;19(4):303-308. 7. Layton AM, Knaggs H, Taylor J, Cunliffe WJ. Isotretinoin for acne vulgaris—10 years later: a safe and successful treatment. Br J Dermatol. 1993;129(3):292-296. 8. Fabbrocini G, Cacciapuoti S, Monfrecola G. A qualitative investigation of the impact of acne on health-related quality of life (HRQL): development of a conceptual model. Dermatol Ther. 2018;8(1):85-99. 9. Del Rosso JQ. Face to face with oral isotretinoin: a closer look at the spectrum of therapeutic outcomes and why some patients need repeated courses. J Clin Aesthet Dermatol. 2012;5(11):17-24. 10. Claravis [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; April 2018. 11. Colburn WA, Gibson DM, Wiens RE, Hanigan JJ. Food increases the bioavailability of isotretinoin. J Clin Pharmacol. 1983;23(11-12):534-539. 12. Guidance for industry: Food-effect bioavailability and fed bioequivalence studies. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, December 2002. 13. Deshmukh-Taskar PR, Nicklas TA, O’Neil CE, et al. The relationship of breakfast skipping and type of breakfast consumption with nutrient intake and weight status in children and adolescents: the National Health and Nutrition Examination Survey 1999–2006. J Am Diet Assoc. 2010;110(6):869-878. 14. Deshmukh-Taskar PR, Radcliffe JD, Liu Y, Nicklas TA. Do breakfast skipping and breakfast type affect energy intake, nutrient intake, nutrient adequacy, and diet quality in young adults? NHANES 1999-2002. J Amer Col Nutr. 2010;29(4):407-418. 15. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973. 16. Webster GF, Leyden JJ, Gross JA. Results of a phase III, double-blind, randomized, parallel-group, non-inferiority study evaluating the safety and efficacy of isotretinoin-lidose in patients with severe recalcitrant nodular acne. J Drugs Dermatol. 2014;13(6):665-670. 17. Data on file. Sun Pharmaceutical Industries, Inc.; May 2018. 18. Webster GF, Leyden JJ, Gross JA. Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-lidose) and the innovator isotretinoin formulation: a randomized, 4-treatment, crossover study. J Am Acad Dermatol. 2013;69(5):762-767. 19. Blagden N, deMatas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev. 2007;59(7):617-630. 20. Choudhary S, Gupta L, Rani S, Dave K, Gupta U. Impact of dendrimers on solubility of hydrophobic drug molecules. Front Pharmacol. 2017;8:261. 21. Food and Drug Administration, Department of Health and Human Services. Determination that Accutane (isotretinoin) capsules, 10 milligrams, 20 milligrams, and 40 milligrams, were not withdrawn from sale for reasons of safety or effectiveness. https://www.federalregister.gov/documents/2010/07/07/2010-16439/determination-that-accutane-isotretinoin-capsules-10-milligrams-20-milligrams-and-40-milligrams-were. Accessed 08/24/2020. 22. Dispense as written (DAW). HMSA Provider Resource Center. https://hmsa.com/portal/provider/zav_pel.rx.DIS.400.htm. Accessed August 19, 2020.