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 its use, ABSORICA and ABSORICA LD are reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics.

ABSORICA is not substitutable with ABSORICA LD.

If a second course of ABSORICA/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.

ABSORICA/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/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/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/ABSORICA LD are available only through restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the iPLEDGE REMS.

ABSORICA/ABSORICA LD must only be prescribed to female patients who are known not to be pregnant as confirmed by a negative CLIA-certified laboratory conducted pregnancy test. Females of reproductive potential must have had two negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial ABSORICA prescription.The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for ABSORICA/ABSORICA LD The second pregnancy test (a confirmation test) must be done in a CLIA-certified laboratory. The interval between the two tests must be at least 19 days.

The recommended dosage is:

• ABSORICA is 0.5 to 1 mg/kg/day given in two divided doses with or without meals for 15 to 20 weeks
• ABSORICA LD is 0.4 to 0.8 mg/kg/day given in two divided doses with or without meals for 15 to 20 weeks
• Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dosage adjustments up to 2 mg/kg/day for ABSORICA (1.6 mg/kg/day for ABSORICA LD) in divided doses, as tolerated

To decrease the risk of esophageal irritation, instruct patients to swallow the capsules with a full glass of liquid. During treatment, the dosage may be adjusted according to response of the disease and/or adverse reactions, some of which may be dose-related.

The safety and effectiveness of once daily dosing with ABSORICA/ABSORICA LD has not been established and is not recommended.

A normal course of treatment is 15 to 20 weeks. If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, may discontinue ABSORICA/ABSORICA LD. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, may initiate a second course of ABSORICA/ABSORICA LD in patients who have completed skeletal growth. The use of another course of ABSORICA/ABSORICA LD therapy is not recommended before a two-month waiting period because the patient’s acne may continue to improve after a 15 to 20-week course of therapy. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth.

Long-term use of ABSORICA/ABSORICA LD even in low doses, has not been studied, and is not recommended. It is important that ABSORICA/ABSORICA LD be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of ABSORICA/ABSORICA LD  on bone loss is unknown.

ABSORICA/ABSORICA LD is 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).

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 therapy 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.

Perform liver function tests prior to use of ABSORICA/ABSORICA LD. Since elevations of liver enzymes have been observed during clinical trials, and hepatitis has been reported in patients on isotretinoin, pretreatment and follow-up liver function tests should be performed at weekly or biweekly intervals until the response to ABSORICA/ABSORICA LD has been established.

Patients must be informed not to donate blood during isotretinoin therapy and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to isotretinoin.

ABSORICA/ABSORICA LD may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. Healthcare providers should be alert to the warning signs of psychiatric disorders to help ensure patients receive the help they need. Prior to initiation of ABSORICA/ABSORICA LD therapy, patients and family members should be asked about any history of psychiatric disorder, and at each visit during therapy patients should be assessed for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation is necessary.

Patients should immediately stop ABSORICA/ABSORICA LD and the patient (or caregiver) should promptly contact their prescriber if the patient develops depression, mood disturbance, psychosis, or aggression. Discontinuation of ABSORICA/ABSORICA LD may be insufficient; further evaluation may be necessary such as a referral to a mental healthcare professional.

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.

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.

Elevations of serum triglycerides in excess of 800 mg/dL have been reported in patients treated with isotretinoin. Marked elevations of serum triglycerides were reported in approximately 25% of patients receiving isotretinoin in clinical trials. In addition, approximately 15% developed a decrease in high-density lipoproteins and about 7% showed an increase in cholesterol levels. In clinical trials, the effects of triglycerides, HDL and cholesterol were reversible upon cessation of isotretinoin therapy. Some patients have been able to reverse triglyceride elevation by reduction in weight, restriction of dietary fat and alcohol, and reduction in the dose while continuing isotretinoin.

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/ABSORICA LD use. Early signs and symptoms of intracranial hypertension include papilledema, headache, nausea and vomiting, and visual disturbances. Patients with these symptoms should be screened for papilledema and, if present, they should be told to discontinue ABSORICA/ABSORICA LD immediately and be referred to a neurologist for further diagnosis and care.

Impaired hearing has been reported in patients taking isotretinoin; in some cases, the hearing 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/ABSORICA LD treatment and be referred for specialized care for further evaluation.

Clinical hepatitis considered to be possibly or probably related to isotretinoin therapy has been reported. Additionally, mild to moderate elevations of liver enzymes have been observed in approximately 15% of individuals treated during clinical trials with isotretinoin, 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.

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.

Isotretinoin may have a negative effect on bone mineral density (BMD) in some patients. Therefore, physicians should use caution when prescribing ABSORICA/ABSORICA LD to patients with a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism. This would include patients diagnosed with anorexia nervosa and those who are on chronic drug therapy that causes drug-induced osteoporosis/osteomalacia and/or affects vitamin D metabolism, such as systemic corticosteroids and any anticonvulsant.

There have been spontaneous reports of osteoporosis, osteopenia, bone fractures and/or delayed healing of bone fractures in patients while on therapy with isotretinoin or following cessation of therapy with isotretinoin. While causality to isotretinoin has not been established, an effect cannot be ruled out. Patients may be at an increased risk when participating in sports with repetitive impact where the risks of spondylolisthesis with and without pars fractures and hip growth plate injuries in early and late adolescence are known.

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. Long-term effects have not been studied. It is important that ABSORICA/ABSORICA LD be given at the recommended doses for no longer than the recommended duration.

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. 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 therapy at recommended doses. The skeletal effects of multiple isotretinoin treatment courses for acne are unknown.

There are spontaneous literature reports of premature epiphyseal closure in acne patients receiving recommended doses of isotretinoin. The effect of multiple courses of isotretinoin on epiphyseal closure is unknown.

Visual problems should be carefully monitored. If visual difficulties occur, discontinue ABSORICA/ABSORICA LD treatment and obtain an ophthalmological examination.

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 patients 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 has been reported during isotretinoin therapy and in some instances the event has persisted after therapy was discontinued. Because the onset in some patients was sudden, patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night.

Dry eye has been reported in subjects during isotretinoin therapy. Patients who wear contact lenses may have trouble wearing them while on ABSORICA/ABSORICA LD treatment and afterwards.

Anaphylactic reactions and other allergic reactions have been reported in isotretinoin-treated patients. 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.

Some patients receiving isotretinoin have experienced problems in the control of their blood sugar. In addition, new cases of diabetes have been diagnosed during isotretinoin therapy, although no causal relationship has been established.

Some patients undergoing vigorous physical activity while on isotretinoin therapy have experienced elevated CPK levels; however, the clinical significance is unknown. There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity.

Approximately 16% of patients treated with isotretinoin in a clinical trial developed musculoskeletal symptoms (including arthralgia) during treatment. In general, these symptoms were mild to moderate, but occasionally required discontinuation of the drug.

Micro-dosed progesterone preparations (“minipills” that do not contain an estrogen) are an inadequate method of contraception during ABSORICA therapy.

ABSORICA/ABSORICA LD is closely related to vitamin A. Therefore, the use of both vitamin A and ABSORICA/ABSORICA LD at the same time may lead to vitamin A side effects. Patients should be advised against taking vitamin supplements containing Vitamin A to avoid additive toxic effects.

Concomitant treatment with ABSORICA/ABSORICA LD and tetracyclines should be avoided because isotretinoin use has been associated with a number of cases of pseudotumor cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines.

Phenytoin is known to cause osteomalacia. No formal clinical trials have been conducted to assess if there is an interactive effect on bone loss between phenytoin and isotretinoin. Therefore, caution should be exercised when using these drugs together.

Isotretinoin use is associated with depression in some patients. Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John’s Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John’s Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John’s Wort.

Systemic corticosteroids are known to cause osteoporosis. No formal clinical trials have been conducted to assess if there is an interactive effect on bone loss between systemic corticosteroids and isotretinoin. Therefore, caution should be exercised when using these drugs together.

ABSORICA/ABSORICA LD is contraindicated in female patients who are or may become pregnant. ABSORICA/ABSORICA LD is contraindicated during pregnancy because isotretinoin can cause fetal harm when administered to a pregnant woman. There is an increased risk of major congenital malformations, spontaneous abortions, and premature births following isotretinoin exposure during pregnancy in humans. If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to a fetus.

Major congenital malformations, spontaneous abortions, and premature births have been documented following pregnancy exposure to isotretinoin. Females of Reproductive Potential must comply with the pregnancy testing and contraception requirements described in the iPLEDGE program. There are no accurate means of determining whether an exposed fetus has been affected.

It is not known whether this drug is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from ABSORICA/ ABSORICA LD, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

GoToSource

• Use in patients under the age of 12. GoToSource

• Rosacea, psoriasis, pityriasis rubra pilaris, condyloma acuminatum, granuloma annulare, darier’s disease, systemic cutaneous lupus erythematosus, non-melanoma skin cancer and hidradenitis suppurativa. GoToSource

• Seborrhea, seborrheic dermatitis, non-melanoma skin cancer chemoprevention for at-risk patients and advanced photoaging with multiple actinic keratoses. GoToSource

• Folliculitis. GoToSource

• Plane warts. GoToSource

• Mild acne. GoToSource

Drug-induced aseptic meningitis (inflammation of membrane covering the brain and spinal cord). GoToSource

Bilateral transient myopia (nearsightedness) and angle closure with IOP elevation. GoToSource

Rhabdomyolysis (breakdown of skeletal muscle). GoToSource

Pyoderma gangrenosum (inflammatory skin disorder). GoToSource

Stevens-Johnson syndrome (severe drug reaction), cheilitis (lip inflammation), acne flare, photophobia (light sensitivity) and elevated liver enzymes. GoToSource

Pityriasis rosea-like eruption (skin rash). GoToSource

Tubulointerstitial nephritis (kidney disorder). GoToSource

Paronychia (inflammation of fingers or toes in one or more of three nail folds) and granulation tissue formation. GoToSource

Sweet’s syndrome (inflammatory skin condition). GoToSource

Pseudotumor cerebri (increased pressure around the brain) and herpes encephalitis. GoToSource

Birth defects. GoToSource

Depression. GoToSource

Onychocryptosis (ingrown toenail) and asymptomatic external urethritis. GoToSource

Hearing loss and tinnitus. GoToSource

Ulcerative colitis (inflammatory bowel disease). GoToSource

Skeletal hyperostosis (bony hardening of ligaments). GoToSource

Myalgia (muscle pain), arthralgia (joint pain) and arthritis. GoToSource

Premature epiphyseal closure. GoToSource

Pancreatitis (inflammation of the pancreas). GoToSource

Lipid abnormalities and thrombocytopenia (low number of platelets in blood). GoToSource

Suicidal ideation and behavior and alopecia (hair loss). GoToSource

Diabetes. GoToSource

Conjunctivitis, hordeolum (eyelid disorder), chalazion (eyelid cyst), blepharitis (eyelid inflammation), eye pain and dry eye. GoToSource

Lawsuits filed for birth defects, suicide, inflammatory bowel disease, crohn’s disease, ulcerative colitis and stevens-johnson syndrome.