ABSORICA® (isotretinoin)

ABSORICA® (isotretinoin)

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ABSORICA® (isotretinoin)

Chemically, isotretinoin is 13-cis-retinoic acid and is related to both retinoic acid and retinol (vitamin A). It is a yellow to orange crystalline powder with a molecular weight of 300.44. It is practically insoluble in water, soluble in chloroform and sparingly soluble in alcohol and in isopropyl alcohol.

ABSORICA

ABSORICA (isotretinoin) Capsules contain 10 mg, 20 mg, 25 mg, 30 mg, 35 mg or 40 mg of isotretinoin (a retinoid) in hard gelatin capsules for oral administration. In addition to the active ingredient, isotretinoin, each capsule contains the following inactive ingredients: propyl gallate, sorbitan monooleate, soybean oil and stearoyl polyoxylglycerides. The gelatin capsules contain the following dye systems:

  • 10 mg – iron oxide (yellow) and titanium dioxide;
  • 20 mg – iron oxide (red), and titanium dioxide;
  • 25 mg – FD&C Blue #1, FD&C Yellow #5, FD&C Yellow #6 and titanium dioxide;
  • 30 mg – iron oxide (black, red and yellow) and titanium dioxide;
  • 35 mg – FD&C Blue #2, iron oxide (black, red and yellow) and titanium dioxide;
  • 40 mg – iron oxide (black, red and yellow) and titanium dioxide.

ABSORICA LD

ABSORICA LD (isotretinoin) Capsules contain 8 mg, 16 mg, 20 mg, 24 mg, 28 mg and 32 mg of micronized isotretinoin (a retinoid) in suspension filled in hard gelatin capsules for oral administration. In addition to the active ingredient, isotretinoin, USP each capsule contains the following inactive ingredients: butylated hydroxy anisole, gelatin, hard gelatin capsule shell, polysorbate 80 and soybean oil. The gelatin capsules contain the following dye systems:

  • 8 mg – D&C Yellow #10, FD&C Blue #1, FD&C Red #40 and titanium dioxide
  • 16 mg – FD&C Blue #1, FD&C Red #40, and titanium dioxide
  • 20 mg – FD&C Blue #1, FD&C Red #40, and titanium dioxide
  • 24 mg – D&C Yellow #10, FD&C Yellow #6 and titanium dioxide
  • 28 mg – FD&C Blue #1, FD&C Red #40, and titanium dioxide
  • 32 mg – ferrosoferric oxide, ferric oxide (red and yellow) and titanium dioxide

The imprinting ink of 8 mg, 16 mg, 24 mg and 32 mg capsules contain the following ingredients: potassium hydroxide, propylene glycol, shellac and titanium dioxide.

The imprinting ink of 20 mg and 28 mg capsules contain the following ingredients: ferrosoferric oxide, propylene glycol and shellac glaze.

Indications

ABSORICA and ABSORICA LD 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 its 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/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

Mechanism of Action

ABSORICA/ABSORICA LD is a retinoid, which when administered at the recommended dosage, inhibits sebaceous gland function and keratinization. Clinical improvement in nodular acne patients occurs in association with a reduction in sebum secretion. The decrease in sebum secretion is temporary and is related to the dose and duration of treatment with isotretinoin capsules and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation. The exact mechanism of action of ABSORICA/ABSORICA LD in the treatment of severe recalcitrant nodular acne is unknown.

Dosage and administration

Recommended Dosage ABSORICA is not substitutable with ABSORICA LD. The recommended dosage of:

  • 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.

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. 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.

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

If a dose of ABSORICA/ABSORICA LD is missed, just skip that dose. Do not take two doses of ABSORICA/ ABSORICA LD at the same time.

Duration of Use

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.

Contraindications

  • ABSORICA/ABSORICA LD is contraindicated in pregnancy
  • 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)

Warnings and precautions

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 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.

If a pregnancy occurs during ABSORICA/ABSORICA LD treatment, discontinue ABSORICA/ABSORICA LD immediately and refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling

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 substitutable

Psychiatric Disorders: ABSORICA/ABSORICA LD may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors

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/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/ABSORICA LD should be discontinued if they occur.

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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.

Hearing Impairment: 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.

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

Musculoskeletal Abnormalities: Arthralgias, back pain, decreases in bone mineral density and premature epiphyseal closure

Ocular Abnormalities e.g., corneal opacities, decreased night vision: If visual symptoms occur, discontinue and refer for an ophthalmological exam

Hepatotoxicity: Monitor liver function tests prior to and during therapy

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.

Adverse reactions

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.

Drug interactions

Vitamin A: 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 related adverse reactions. Patients treated with ABSORICA/ABSORICA LD should be advised against taking supplements containing Vitamin A to avoid additive toxic effects.

Tetracyclines: Concomitant treatment with ABSORICA/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

Phenytoin: 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.

Systemic Corticosteroids: 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 with concomitant use of systemic corticosteroids and isotretinoin. Therefore, caution should be exercised when using these drugs together.

Use in specific populations

Pregnancy: ABSORICA/ABSORICA LD are contraindicated during pregnancy because isotretinoin can cause fetal harm when administered to a pregnant patient. There is an increased risk of major congenital malformations, spontaneous abortions, and premature births following isotretinoin exposure during pregnancy in humans. If ABSORICA/ABSORICA LD is used during pregnancy, or if the patient becomes pregnant while taking ABSORICA/ABSORICA LD, the patient should be apprised of the potential hazard to a fetus. If pregnancy occurs during treatment of a patient who is taking ABSORICA/ABSORICA LD, ABSORICA/ABSORICA LD must be discontinued immediately and the patient should be referred to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling.

Lactation: 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/ABSORICA LD, and for at least 8 days after the last dose of ABSORICA/ABSORICA LD.

Pediatric Use: The safety and effectiveness of ABSORICA/ABSORICA LD for the treatment of severe recalcitrant nodular acne have been established in pediatric subjects ages 12 to 17 years. Use of ABSORICA/ABSORICA LD in this age group for this indication is supported by evidence from a clinical trial that compared the use ABSORICA to another isotretinoin capsule product in 397 pediatric subjects (12 to 17 years) and pharmacokinetic data in pediatric subjects

Geriatric Use: Clinical studies of ABSORICA/ABSORICA LD did not include sufficient numbers of geriatric subjects (subjects aged 65 years of age and older) to determine whether they respond differently from younger adults. Although reported clinical experience has not identified differences in responses between geriatric and younger adults, effects of aging may increase some risks associated with ABSORICA/ABSORICA LD therapy.

Overdosage

In humans, isotretinoin overdosage has been associated with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia. These symptoms quickly resolved without apparent residual effects.

Patients who can become pregnant who present with an ABSORICA/ABSORICA LD overdosage should be evaluated for pregnancy. Because an overdosage would be expected to result in higher levels of isotretinoin in semen than found during a normal treatment course, male patients treated with ABSORICA/ABSORICA LD should use a condom, or avoid reproductive sexual activity with a patient who is or might become pregnant, for 1 month after the overdose.

All patients with ABSORICA/ABSORICA LD overdose should not donate blood for at least 1 month.

Storage and Handling of ABSORICA and ABSORICA LD

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature]. Protect from light.

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