Absorica Drug Information

Embryo-Fetal Toxicity ABSORICA/ABSORICA LD is contraindicated in pregnancy. Based on human data, ABSORICA/ABSORICA LD can cause fetal harm when administered to a pregnant patient. There is an extremely high risk that life-threatening birth defects will result if pregnancy occurs while taking any amount of ABSORICA/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. Major congenital malformations, spontaneous abortions, and premature births have been documented following exposure to isotretinoin during pregnancy.

If a pregnancy occurs during ABSORICA/ABSORICA LD treatment, immediately discontinue ABSORICA/ABSORICA LD and refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Immediately report any suspected fetal exposure during or 1 month after ABSORICA/ABSORICA LD treatment to the FDA via the MedWatch telephone number 1-800-FDA-1088, and also to the iPLEDGE pregnancy registry at 1-866-495-0654 or via the internet (www.ipledgeprogram.com). Patients must be informed not to donate blood during ABSORICA/ABSORICA LD treatment and for 1 month following discontinuation because the blood might be given to a pregnant patient whose fetus must not be exposed to isotretinoin.

ABSORICA/ABSORICA LD is available only through a restricted program under a REMS. 5.2 iPLEDGE REMS ABSORICA/ABSORICA LD are available only through a restricted program under a REMS called the iPLEDGE REMS because of the risk of embryo-fetal toxicity. Notable requirements of the iPLEDGE REMS include the following: Prescribers must be certified in the REMS and comply with the REMS requirements, including the following: Assess the reproductive status of all patients prior to initiating treatment and during treatment. Counsel patients who cannot get pregnant on the risk and REMS requirements prior to initiating treatment.

Counsel patients who can get pregnant on the risk and REMS requirements prior to and during treatment. Counsel patients who can get pregnant on pregnancy prevention requirements prior to and during treatment, or refer patients who can get pregnant to an expert for such counseling. Comply with the pregnancy testing requirements.

Assess the pregnancy status for patients who can get pregnant by reviewing pregnancy tests and documenting a negative result prior to each prescription. Report all pregnancies to the REMS. Patients who can get pregnant must be enrolled in the REMS and must comply with the REMS requirements, including the following Comply with the pregnancy testing and pregnancy prevention requirements.

Demonstrate comprehension of the risk and REMS requirements before each prescription is dispensed. Obtain the prescription within the 7-day prescription window (i.e., within 7 days of the pregnancy test collection). Patients who cannot get pregnant must be enrolled in the REMS and must comply with the REMS requirements, including to not share isotretinoin and not donate blood.

Pharmacies that dispense ABSORICA/ABSORICA LD must be certified in the REMS and must comply with the REMS requirements, including the following: Obtain authorization to dispense and only dispense to patients who are authorized to receive ABSORICA/ABSORICA LD. Dispense a maximum of a 30-day supply with a Medication Guide. Do not dispense refills.

Wholesalers and distributors must be registered in the REMS and must only distribute to certified pharmacies. Further information, including a list of qualified pharmacies and distributors, is available at www.ipledgeprogram.com or 1-866-495-0654.

ABSORICA and ABSORICA LD are Not Substitutable Given that the bioavailability and the recommended dosage of ABSORICA and ABSORICA LD are different, ABSORICA and ABSORICA LD are not substitutableon a mg per mg basis. For example, ABSORICA and ABSORICA LD have a 20 mg strength; however, these strengths have different bioavailability and are not substitutable.

Psychiatric Disorders ABSORICA/ABSORICA LD may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. Be alert to the warning signs of psychiatric disorders to help ensure patients receive the help they need (Prescribers should read the REMS educational material on recognizing psychiatric disorders ). Prior to initiation of ABSORICA/ABSORICA LD treatment, ask patients and family members about any history of psychiatric disorder, and at each visit during treatment assess patients for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation is necessary.

If a patient develops depression, mood disturbance, psychosis, or aggression, instruct patients (or caregivers) to immediately stop ABSORICA/ABSORICA LD and promptly contact their health care provider. Discontinuation of ABSORICA/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. Avoid concomitant use of ABSORICA/ABSORICA LD with tetracyclines. Early signs and symptoms of intracranial hypertension include papilledema, headache, nausea and vomiting, and visual disturbances.

Screen patients with these symptoms for papilledema and, if present, immediately discontinue ABSORICA/ABSORICA LD and refer the patient to a neurologist for further diagnosis and care.

Serious Skin Reactions There have been postmarketing reports of erythema multiforme and severe skin reactions 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/ABSORICA LD should be discontinued if they occur.

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, discontinue ABSORICA/ABSORICA LD and seek medical attention.

Lipid Abnormalities Elevations of serum triglycerides above 800 mg/dL have been reported with isotretinoin use. In clinical trials, marked elevations of serum triglycerides, decreases in high-density lipoproteins (HDL), and increases in cholesterol levels were reported in 25%, 15%, and 7% of patients treated with isotretinoin capsules, respectively. 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. Fasting lipid tests should be performed before ABSORICA/ABSORICA LD treatment and then at intervals until the lipid response to ABSORICA/ABSORICA LD is known, which usually occurs within 4 weeks.

Careful consideration should be given to risk/benefit of ABSORICA/ABSORICA LD in patients who are at higher risk of hypertriglyceridemia (e.g., patients with diabetes, obesity, increased alcohol intake, lipid metabolism disorder or familial history of lipid metabolism disorder). If ABSORICA/ABSORICA LD treatment is instituted in such patients, more frequent checks of serum values for lipids are recommended. ABSORICA/ABSORICA LD should be stopped if hypertriglyceridemia cannot be controlled.

Hearing Impairment

Impaired hearing has been reported in patients taking isotretinoin; in some cases, the hearing impairment has been reported to persist after treatment has been discontinued. Mechanism(s) and causality for this reaction have not been established. Patients who experience tinnitus or hearing impairment should discontinue ABSORICA/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/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/ABSORICA LD immediately.

Musculoskeletal Abnormalities Bone Mineral Density Changes, Osteoporosis, and Fractures Isotretinoin may have a negative effect on bone mineral density (BMD) in some patients. In a clinical trial of ABSORICA and another isotretinoin capsule product, 27/306 (9%) of pediatric subjects 12 years of age and older had BMD declines, defined as ≥ 4% lumbar spine or total hip, or ≥ 5% femoral neck, during the 20-week treatment period. Repeat scans conducted within 2 to 3 months after the post-treatment scan showed no recovery of BMD.

Therefore, healthcare providers should use caution when prescribing ABSORICA/ABSORICA LD to patients with a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism or patients diagnosed with anorexia nervosa. There have been spontaneous reports of osteoporosis, osteopenia, fractures and/or delayed healing of fractures in patients while on treatment with isotretinoin or following cessation of treatment with isotretinoin. Patients in early and late adolescence who participate in sports with repetitive impact may be at an increased risk of spondylolisthesis with and without pars fractures, and hip growth plate injuries have been reported.

Musculoskeletal Abnormalities Approximately 16% of subjects treated with isotretinoin capsules in a clinical trial developed musculoskeletal symptoms (including arthralgia) during treatment. In general, these symptoms were mild to moderate, but occasionally required discontinuation of isotretinoin. In a trial of pediatric subjects treated with isotretinoin capsules, approximately 29% (104/358) developed back pain.

Back pain was severe in 14% (14/104) of the cases and occurred at a higher frequency in female subjects than male subjects. Arthralgias were experienced in 22% (79/358) of pediatric subjects. Arthralgias were severe in 8% (6/79) of subjects.

Evaluate the musculoskeletal system of patients who present with these symptoms during or after a course of ABSORICA/ABSORICA LD. Consider discontinuing ABSORICA/ABSORICA LD if any significant abnormality is found. 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 treatment with isotretinoin have more of an effect than a single course of treatment on the musculoskeletal system. It is important to administer ABSORICA/ABSORICA LD at the recommended dose for no longer than the recommended duration. Hyperostosis A high prevalence of skeletal hyperostosis was noted in clinical trials for disorders of keratinization with a mean dose of 2.24 mg/kg/day of isotretinoin capsules (approximately 1.1 times the maximum recommended daily dosage).

Additionally, skeletal hyperostosis was noted in 6 of 8 patients in a prospective trial of disorders of keratinization. Minimal skeletal hyperostosis and calcification of ligaments and tendons have also been observed by x-ray in prospective trials of nodular acne patients treated with a single course of treatment at recommended doses. The skeletal effects of multiple isotretinoin treatment courses for acne are unknown.

In a clinical trial of 217 pediatric subjects 12 years of age and older with severe recalcitrant nodular acne, hyperostosis was not observed after 16 to 20 weeks of treatment with approximately 1 mg/kg/day of isotretinoin capsules given in two divided doses. Hyperostosis may require a longer time frame to appear. The clinical course and significance remain unknown.

Premature Epiphyseal Closure There are spontaneous literature reports of premature epiphyseal closure in acne patients receiving recommended doses of isotretinoin capsules. The effect of multiple courses of isotretinoin on epiphyseal closure is unknown. In a 20-week clinical trial that included 289 pediatric subjects 12 years of age and older on ABSORICA or another isotretinoin capsule product who had hand radiographs taken to assess bone age, a total of 9 (3%) subjects had bone age changes that were clinically significant and for which a drug-related effect cannot be excluded.

Ocular Abnormalities

Carefully monitor for visual problems. If visual difficulties occur, discontinue ABSORICA/ABSORICA LD treatment and obtain an ophthalmological examination. Corneal Opacities Corneal opacities have occurred in patients receiving isotretinoin capsules and more frequently when higher drug dosages were used in patients with disorders of keratinization.

The corneal opacities that have been observed in clinical trial subjects treated with isotretinoin capsules have either completely resolved or were resolving at follow-up 6 to 7 weeks after discontinuation of isotretinoin. Decreased Night Vision Decreased night vision has been reported during isotretinoin use and in some instances the event has persisted after treatment was discontinued. Because the onset in some patients was sudden, advise patients of this potential problem and warn patients to be cautious when driving or operating any vehicle at night.

Dry Eyes Dry eyes has been reported in patients during isotretinoin use. Patients who wear contact lenses may have trouble wearing them while on ABSORICA/ABSORICA LD treatment and afterwards.

Hypersensitivity Reactions

Anaphylactic reactions and other allergic reactions have been reported with isotretinoin use. Cutaneous allergic reactions and serious cases of allergic vasculitis, often with purpura (bruises and red patches) of the extremities and extracutaneous involvement (including renal) have been reported. Severe allergic reaction necessitates discontinuation of therapy and appropriate medical management.

Allergic Reactions Due to the Inactive Ingredient (FD&C Yellow No. 5) in the 25 mg ABSORICA Capsule The 25 mg ABSORICA capsule contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of tartrazine sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. The mg, and 40 mg ABSORICA capsules do not contain FD&C Yellow No. 5 and all of the ABSORICA LD capsules do not contain FD&C Yellow No. 5.

Thus, in patients with allergic reactions to tartrazine, avoid using the 25 mg ABSORICA capsules.

Laboratory Abnormalities and Laboratory Monitoring for Adverse Reactions Laboratory Monitoring Pregnancy Testing: Obtain a screening and confirmatory pregnancy test prior to treatment initiation. Repeat a pregnancy test prior to each prescription, at the end of the entire course of ABSORICA/ABSORICA LD treatment, and 1 month after the discontinuation of ABSORICA/ABSORICA LD ]. Lipid Tests: Obtain pretreatment and follow-up fasting lipid tests under fasting conditions.

Wait 36 hours after consumption of alcohol before testing is performed. It is recommended that these tests be performed periodically until the lipid response to ABSORICA/ABSORICA LD is known. The incidence of hypertriglyceridemia is 25% in patients treated with isotretinoin capsules.

Liver Function Tests: As elevations of liver enzymes have been observed during clinical trials, and hepatitis has been reported in patients on isotretinoin capsules, perform pretreatment and follow-up liver function tests periodically until the response to ABSORICA/ABSORICA LD is known ]. Additional Laboratory Abnormalities Glucose: With isotretinoin use, some patients have experienced problems in the control of their blood sugar. In addition, new cases of diabetes have been diagnosed during isotretinoin use.

CPK: Some patients undergoing vigorous physical activity while taking isotretinoin have experienced elevated CPK levels; however, the clinical significance is unknown. There have been rare postmarketing reports of rhabdomyolysis with isotretinoin use, some associated with strenuous physical activity. In a clinical trial of 924 subjects, marked elevations in CPK (≥350 U/L) were observed in approximately 24% of subjects treated with isotretinoin capsules.

In another clinical trial of 217 pediatric subjects 12 years of age and older elevations in CPK were observed in 12% of subjects, including those undergoing strenuous physical activity in association with reported musculoskeletal adverse events such as back pain, arthralgia, limb injury, or muscle sprain. In these subjects, approximately half of the CPK elevations returned to normal within 2 weeks and half returned to normal within 4 weeks. No cases of rhabdomyolysis were reported in this clinical trial.