isotretinoin
Accutane

Available forms
Available by prescription only
Capsules: 10 mg, 20 mg, 40 mg

Indications and dosages
 Severe recalcitrant nodular acne. Adults and adolescents: 0.5 to 2 mg/kg P.O. daily given in two divided doses and continued for 15 to 20 weeks.
 Keratinization disorders resistant to conventional therapy ◇, prevention of skin cancer ◇. Adults: Dosage varies with specific disease and severity of the disorder; dosages up to 2 to 4 mg/kg P.O. daily have been used. Consult current literature for specific recommendations.
 Squamous cell cancer of the head and neck ◇. Adults: 50 to 100 mg/m².

Pharmacodynamics
Antiacne action: Exact mechanism of action is unknown; isotretinoin decreases the size and activity of sebaceous glands, which decreases secretion and probably explains the rapid clinical improvement. A reduction in Propionibacterium acnes in the hair follicles occurs as a secondary result of decreased nutrients.
Keratinizing action: The mechanism is unknown. Isotretinoin has anti-inflammatory and keratinizing effects.

Pharmacokinetics
Absorption: When administered orally, drug is absorbed rapidly from the GI tract. Therapeutic range for isotretinoin hasn’t been established.
Distribution: Distributed widely. In animals, it’s found in most organs and is known to cross the placental barrier. In humans, degree of placental transfer and the degree of secretion in breast milk are unknown. Isotretinoin is 99.9% protein-bound, primarily to albumin.
Metabolism: Metabolized in the liver and possibly in the gut wall. The major metabolite is 4-oxo-isotretinoin, with tretinoin and 4-oxo-tretinoin also found in the blood and urine.
Excretion: Elimination process isn’t fully known, although renal and biliary pathways are known to be used.

Contraindications and precautions
Contraindicated in women of childbearing age unless patient has had a negative serum pregnancy test within 2 weeks before beginning therapy, will begin drug therapy on day 2 or 3 of next menstrual period, and will comply with stringent contraceptive measures for 1 month before therapy, during therapy, and for at least 1 month after therapy. Severe fetal abnormalities may occur if used during pregnancy. Also contraindicated in patients hypersensitive to parabens, which are used as preservatives.

Interactions
Drug-drug. Alcohol-containing preparations, medicated soaps and cleansers, medicated cover-ups, topical resorcinol peeling agents (benzoyl peroxide): Causes cumulative drying effect. Use cautiously.
Micro-dosed progesterone contraceptive pills that don’t contain estrogen: Decreased effectiveness of birth control. Advise patient to use additional contraceptive measures.
Phenytoin: May increase the risk of osteomalacia. Use together cautiously.
Tetracyclines: May increase the risk of pseudotumor cerebri. Avoid use together.
Vitamin A products: Causes additive toxic effect. Avoid use together.
Drug-lifestyle. Alcohol use: Increases plasma triglyceride levels. Discourage alcohol use.
Sun exposure: May cause photosensitivity reaction. Advise patient to take precautions.

Adverse reactions
CNS: depression, psychosis, suicidal ideation or attempts, suicide, aggressive and violent behavior, headache, fatigue, pseudotumor cerebri.
EENT: conjunctivitis, drying of mucous membranes, corneal deposits, dry eyes, visual disturbances, epistaxis,dry nose, hearing impairment, decreased night vision.
GI: nonspecific GI symptoms, gum bleeding and inflammation, nausea,vomiting, anorexia, dry mouth, abdominal pain, inflammatory bowel disease, acute pancreatitis.
Hematologic: anemia, elevated platelet count, elevated erythrocyte sedimentation rates.
Metabolic: hyperglycemia, hypertriglyceridemia.
Musculoskeletal: skeletal hyperostosis, calcification of tendons and ligaments, premature epiphyseal closure, decreases in bone mineral density, musculoskeletal symptoms (sometimes severe) such as back pain and arthralgia, arthritis, tendonitis, other types of bone abnormalities, elevated CK levels, rhabdomyolysis (rare).
Skin: rash, dry skin, facial skin desquamation, peeling of palms and toes, skin infection, photosensitivity, cheilitis, pruritus, fragility, petechiae, nail brittleness, thinning of hair.

Effects on lab test results
• May elevate AST, ALT, and alkaline phosphatase levels.
• May increase platelet count. May decrease hemoglobin and hematocrit.

Overdose and treatment
Signs and symptoms of overdose are rare and would be extensions of adverse reactions.

Special considerations
 ALERT A program, S.M.A.R.T. (System to Manage Accutane Related Teratogenicity) is in place to encourage the safe and appropriate use of the drug, which can cause birth defects and fetal death if taken by pregnant women.
• For women of childbearing age, a negative blood test for pregnancy must be obtained before therapy.
• Pregnancy tests must be repeated monthly to avoid administration of drug during pregnancy.
• Spontaneous reports of osteoporosis, osteopenia, bone fractures, and delayed healing of bone fractures have been seen in the Accutane population. While causality to Accutane hasn’t been established, an effect cannot be ruled out. Longer term effects haven’t been studied. It’s important that Accutane be given at the recommended doses for no longer than the recommended duration.
• Therapy usually lasts 15 to 20 weeks, followed by at least 8 weeks off drug before beginning a second course.
• Monitor patient for visual problems.
Pregnant patients
• Drug is a potent teratogen and shouldn’t be used in pregnant women.
Breast-feeding patients
• Breast-feeding isn’t recommended during therapy.

Patient education
• Advise patient to call immediately if she suspects she is pregnant.
• Recommend taking drug with or shortly after meals to ease GI discomfort.
• Caution against alcohol ingestion to reduce risk of hypertriglyceridemia.
• Warn patient to be cautious when driving, particularly at night because drug decreases night vision.
• Advise patient not to take vitamin supplements containing vitamin A while taking drug.
• Instruct patient to avoid prolonged exposure to sunlight or sun lamps to prevent photosensitivity.
• Contact lenses may become uncomfortable during treatment. Suggest that patient use artificial tears.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use