No

Retinoic Acid Derivative

Treatment of severe recalcitrant cystic and/or conglobate acne unresponsive to conventional therapy

X

Sensitivity to parabens, vitamin A, or other retinoids; patients who are pregnant or intend to become pregnant during treatment

Use with caution in patients with diabetes mellitus, hypertriglyceridemia; not to be used in women of childbearing potential unless woman is capable of complying with effective contraceptive measures; therapy is normally begun on the second or third day of next normal menstrual period; effective contraception must be used for at least 1 month before beginning therapy, during therapy, and for 1 month after discontinuation of therapy. Because of the high likelihood of teratogenic effects (~20%), do not prescribe isotretinoin for women who are or who are likely to become pregnant while using the drug. Isolated reports of depression, psychosis and rarely suicidal thoughts and actions have been reported during isotretinoin usage.

>10%:

Dermatologic: Redness, cheilitis, inflammation of lips, dry skin, pruritus, photosensitivity

Endocrine & metabolic: Increased serum concentration of triglycerides

Gastrointestinal: Xerostomia

Local: Burning

Neuromuscular & skeletal: Bone pain, arthralgia, myalgia

Ocular: Itching eyes

Respiratory: Epistaxis, dry nose

1% to 10%:

Cardiovascular: Facial edema, pallor

Central nervous system: Fatigue, headache, mental depression, hypothermia

Dermatologic: Skin peeling on hands or soles of feet, rash, cellulitis

Endocrine & metabolic: Fluid imbalance, acidosis

Gastrointestinal: Stomach upset

Hepatic: Ascites

Neuromuscular & skeletal: Flank pain

Ocular: Dry eyes, photophobia

Miscellaneous: Lymph disorders

<1%: Mood change, pseudomotor cerebri, alopecia, pruritus, hyperuricemia, xerostomia, anorexia, nausea, vomiting, inflammatory bowel syndrome, bleeding of gums, increase in erythrocyte sedimentation rate, decrease in hemoglobin and hematocrit, hepatitis, conjunctivitis, corneal opacities, optic neuritis, cataracts

Symptoms of overdose include headache, vomiting, flushing, abdominal pain, ataxia; all signs and symptoms have been transient

Decreased effect: Increased clearance of carbamazepine

Increased toxicity: Avoid other vitamin A products; may interfere with medications used to treat hypertriglyceridemia

Store at room temperature and protect from light

Reduces sebaceous gland size and reduces sebum production; regulates cell proliferation and differentiation

Absorption: Oral: Demonstrates biphasic absorption

Distribution: Crosses the placenta; appears in breast milk

Protein binding: 99% to 100%

Metabolism: In the liver; major metabolite: 4-oxo-isotretinoin (active)

Half-life, terminal: Parent drug: 10-20 hours; Metabolite: 11-50 hours

Time to peak serum concentration: Within 3 hours

Elimination: Equally in urine and feces

Oral:

Children and Adults: 0.5-2 mg/kg/day in 2 divided doses (dosages as low as 0.05 mg/kg/day have been reported to be beneficial) for 15-20 weeks or until the total cyst count decreases by 70%, whichever is sooner

Dosing adjustment in hepatic impairment: Dose reductions empirically are recommended in hepatitis disease

Increased isotretinoin bioavailability when administered with food or milk

CBC with differential and platelet count, baseline sedimentation rate, serum triglycerides, liver enzymes

May cause sedation, depression, or psychosis; may rarely cause suicidal ideation

May increase the clearance of carbamazepine

No information available to require special precautions

>10% of patients experience dry mouth

Use exactly as directed; do not take more than recommended. Capsule can be chewed and swallowed, swallowed, or opened with a large needle and contents sprinkled on applesauce or ice cream. Do not take any other vitamin A products, limit vitamin A intake, and increase exercise during therapy. Exacerbations of acne may occur during first weeks of therapy. You may experience headache, loss of night vision, lethargy, or visual disturbances (use caution when driving or engaging in tasks requiring alertness until response to drug is known); photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); dry mouth or nausea (small frequent meals, sucking hard candy, or chewing gum may may help); dryness, redness, or itching of skin, eye irritation, or increased sensitivity to contact lenses (wear regular glasses). Discontinue therapy and report acute vision changes, rectal bleeding, abdominal cramping, or unresolved diarrhea. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant 1 month before, during, or for 1 month following therapy. Consult prescriber for instruction on appropriate contraceptive measures. This drug may cause severe fetal defects. Do not donate blood during or for 1 month following therapy (same reason). Breast-feeding is not recommended.

Capsules can be swallowed, or chewed and swallowed. The capsule may be opened with a large needle and the contents placed on applesauce or ice cream for patients unable to swallow the capsule.

Capsule: 10 mg, 20 mg, 40 mg

American Academy of Pediatrics Committee on Drugs, "Retinoid Therapy for Severe Dermatological Disorders," Pediatrics, 1992, 90(1 Pt 1):119-20.

Boyd AS, "An Overview of the Retinoids," Am J Med, 1989, 86(5):568-74.

Burrows NP and Roberts SOB, "Etretinate Hepatitis," J Dermatol Treat, 1995, 6:135.

Castleberry RP, Emanuel PD, Zuckerman KS, et al, "A Pilot Study of Isotretinoin in the Treatment of Juvenile Chronic Myelogenous Leukemia," N Engl J Med, 1994, 331(25):1680-4.

DiGiovanna JJ and Peck GL, "Oral Synthetic Retinoid Treatment in Children," Pediatr Dermatol, 1983, 1(1):77-88.

Hepburn NC, "Deliberate Self-Poisoning With Isotretinoin," Br J Dermatol, 1990, 122(6):840-1.

LaFontaine N, Tousignant J, Rozenfarb E, et al, "Thyroglossal Cyst and Isotretinoin," Eur J Dermatol, 1995, 5:225-6.

Lammer EJ, Chen DT, Hoar RM, et al, "Retinoic Acid Embryopathy," N Engl J Med, 1985, 313(14):837-41.

Lee AG, "Pseudotumor Cerebri After Treatment With Tetracycline and Isotretinoin for Acne," Cutis, 1995, 55(3):165-8.

Lotan R, Xu XC, Lippman SM, et al, "Suppression of Retinoic Acid Receptor-Beta in Premalignant Oral Lesions and Its Up-Regulation by Isotretinoin," N Engl J Med, 1995, 332(21):1405-10.

Mitchell AA, Van Bennekom CM, Louik C, et al, "A Pregnancy-Prevention Program in Women of Childbearing Age Receiving Isotretinoin," N Engl J Med, 1995, 333(2):101-6.

Rappaport EB and Knapp M, "Isotretinoin Embryopathy - A Continuing Problem," J Clin Pharmacol, 1989, 29(5):463-5.

Reynolds CP, Kane DJ, Einhorn PA, et al, "Response of Neuroblastoma to Retinoic Acid In Vitro, and In Vivo," Prog Clin Biol Res, 1991, 366:203-11

Taillan B, Chichmanian RM, Vialla I, et al, "Paroxysmal Nocturnal Hemoglobinuria and Hemolysis Induced by Isotretinoin," Therapie, 1994, 49(5):468.