Isotretinoin
Isotretinoin (Accutane)
Isotretinoin
(eye-so- TRET-ih-noyn)
Pregnancy Category: X Accutane Accutane Roche Isotrex (Rx)

Classification: Vitamin A metabolite (antiacne, keratinization stabilizer)

Action/Kinetics: Reduces sebaceous gland size, decreases sebum secretion, and inhibits abnormal keratinization. Approximately 25% of the PO dosage form is bioavailable. Peak plasma levels: 3 hr. Steady-state blood levels following 80 mg/day: 160 ng/mL. Nearly 100% bound to plasma protein. t 1/2: 10-20 hr. Metabolized in the liver to 4-oxo-isotretinoin, which is also active. Approximately equal amounts are excreted through the urine and in the feces.

Uses: Severe recalcitrant cystic acne unresponsive to other therapy. Investigational: Cutaneous disorders of keratinization, cutaneous T-cell lymphoma (mycosis fungoides), leukoplakia, prevention of secondary primary tumors in those treated for squamous-cell carcinoma of the head and neck.

Contraindications: Due to the possibility of fetal abnormalities or spontaneous abortion, women who are pregnant or intend to become pregnant should not use the drug. Certain conditions for use should be met in women with childbearing potential (see package insert). Use during lactation and in children.

Special Concerns: Intolerance to contact lenses may develop.

Side Effects: Skin: Cheilitis, skin fragility, pruritus, dry skin, desquamation of facial skin, drying of mucous membranes, brittle nails, photosensitivity, rash, hypo- or hyperpigmentation, urticaria, erythema nodosum, hirsutism, excess granulation of tissues as a result of healing, petechiae, peeling of palms and soles, skin infections, paronychia, thinning of hair, nail dystrophy, pyogenic granuloma, bruising. CNS: Headache, fatigue, pseudotumor cerebri (i.e., headaches, papilledema, disturbances in vision), depression. Ocular: Conjunctivitis, optic neuritis, corneal opacities, dry eyes, decrease in acuity of night vision, photophobia, eyelid inflammation, cataracts, visual disturbances. GI: Dry mouth, N&V, abdominal pain, nonspecific GI symptoms, inflammatory bowel disease (including regional enteritis), anorexia, weight loss, inflammation and bleeding of gums. Neuromuscular: Arthralgia, muscle pain, bone and joint pain and stiffness, skeletal hyperostosis. CV: Flushing, palpitation, tachycardia. GU: White cells in urine, proteinuria, nonspecific urogenital findings, microscopic or gross hematuria, abnormal menses. Other: Epistaxis, dry nose and mouth, respiratory infections, disseminated herpes simplex, edema, transient chest pain, development of diabetes, hepatitis, hepatotoxicity, vasculitis, anemia, lymphadenopathy, flushing, palpitations.

Laboratory Test Alterations: Plasma triglycerides, sedimentation rate, platelet counts, alkaline phosphatase, AST, ALT, GGTP, LDH, fasting blood glucose, uric acid in blood, cholesterol, CPK levels in clients who exercise vigorously. HDL, RBC parameters, WBC counts.

Overdose Management: Symptoms: Abdominal pain, ataxia, cheilosis, dizziness, facial flushing, headache, vomiting. Symptoms are transient. Treatment: Symptoms are quickly resolved with drug cessation or decrease in dose.

Drug Interactions: Alcohol / Potentiation of serum triglycerides Benzoyl peroxide / Drying effects of isotretinoin Carbamazepine / Plasma carbamazepine levels Minocycline / Risk of developing pseudotumor cerebri or papilledema Tetracycline / Risk of developing pseudotumor cerebri or papilledema Tretinoin / Drying effects of isotretinoin Vitamin A / Risk of toxicity

How Supplied: Capsule: 10 mg, 20 mg, 40 mg

Dosage
?Capsules Recalcitrant cystic acne.
Adults, individualized, initial: 0.5-1 mg/kg/day (range: 0.5-2 mg/kg/day) divided in two doses for 15-20 weeks. Adjust dose based on toxicity and clinical response; if cyst count decreases by 70% or more, drug may be discontinued. If necessary, a second course of therapy may be instituted after a rest period of 2 months. Doses of 0.05-0.5 mg/kg/day are effective but result in higher frequency of relapses.
Keratinization disorders.
Doses up to 4 mg/kg/day have been used.
Prevent second tumors in squamous-cell carcinoma of the head and neck.
50-100 mg/m ².